Th
S P i!! ...... Wne 0996 No025
' i~ii~i! ii'i , : : a
Tony Angel and his hobby
Sheffield University
Jackie and Peter Hardcastle(with joint poster)
Russel Chess-Wyilliarns
Photography by Martin Rosenberg Stan White
TieFront procedure cover: A video-print of a ciona intestinalisfour cell stage embryo, held with a suction electrode and about to be microinjected with biotin. was performed by students on tie Plymouth Cell Physiology Course (see pg 33) with tie assistanceof David Becker and PeterMobbs. Courtesy of Jon Robbins. The Sheffield Meeting Form and Function and the New Biology, Biomedical Science in Sheffield - Peter Andrew ...... 1
Com mittee New s - ChristinaDocchar ...... 4 Members' News Changes in the Departments of Physiology at:- University of Bristol - Stephen Lisney ...... 5 University of Cam bridge - Alan Findlay...... 5 University of Hertfordshire - Wendy Purcell ...... 6 Hugh Bostcok, Personal Chair - PeterKirkwood ...... 6 Special Interest Group Forum Cardiovascular / Respiratory Control, Comparative & Invertebrate Neuroscience, Development & Plasticity, Epithelia & Membrane Transport, Heart & Cardiac Muscle, Human Physiology, Molecular Physiology, Neuroendocrinology, Renal Physiology, Respiratory Physiology, Sensorimotor Control, Sensory Functions, Somatosensory Physiology -Julian Paton,Bill Winlow, Meetings Secretary'sOffice, Barry Hirst,Godfre Smith, Ron Maughan,JanetAllen, Many Forsling,Dave Potts, Prein Kunar,John Riddell, Andy King, Rob Clarke...... 7 Science News and Views Revealed: A Novel K+ Channel Disorder in Insulin-Secreting Cells - Mark Dunne & Keith Lindley ...... 14 A Role for Endothelins as Neuromodulators in the Central Nervous System - H ugh Pearsonand BrigitteHeld...... 17
Policies & Politics Funding of Medical Research Shift from Government to the Private Sector - Lucie Clapp ...... 20
Young Physiologists A Positive Scientific Experience in Woods Hole, MA, USA - Ruth Eipson ...... 22
Letters Empson's 'Missing Dates' - John Haffenden ...... 24 Biography - John Hughes Bennet - Gordon Piller...... 24 Physiologists at Work A Decision in the Life of...... - Andrew Nicoll...... 25
Teaching and Technology Development of Electrical Impedance Tomography for Imaging Electrical Activity in the Brain - But Is It Physiology as We Know It? - David Holder...... 28 Softw are Review - Jin McGarrick ...... 31 Microelectrode Techniques for Cell Physiology, Marine Biological A ssociation, Plym outh - Jon Robbins...... 33 Molecular Physiology Techniques Workshop, University of Glasgow - Janet Allen ...... 35
Caption Co ntest ...... 36
Netwatch O nline Resources - D avid Davies ...... 37
Jo urnal Co ntents ...... 38 Noticeboa rd ...... 44
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,\rt,,r,,k & 1) I - s, Redm ,odAad,-n Ser,,rvoc',51 ,ccrgc I hcputal Medical5mlo ,[ FORM AND FUNCTION AND THE NEW BIOLOGY; BIOMEDICAL SCIENCE IN SHEFFIELD
W hen the Physiological Society was last in offer. It is extraordinary, and totally unexpected, Sheffield in April 1991, the Department that the control mechanisms by which various of Biomedical Science had recently been gene products are interrelated have often been created by merging the older Departments of dramatically and highly conserved throughout Anatomy and Physiology. Although part of a evolution, so that genes, their products and the general drive for greater financial efficiency, regulatory systems that operate in organisms this merger also recognised the convergence of such as the fruit fly or the nematode worm also the study of form and function. I must thank operate in higher animals including humans. my predecessor in the post of Chairman of It is remarkable, for example, that a single gene Biomedical Science, Professor Tony Angel, for (Pax-6), the deletion of which leads to a failure successfully managing the integration of two of eye development in mice and humans, distinct academic Departments and leaving a causes eye development when expressed in Department well positioned to exploit the new such unlikely sites as the wing or leg of a fruit opportunities in biology, fly; or, that a gene involved in patterning the embryos of flies (dpp) is closely related to genes At the same time, the remaining biology that are able to induce bone formation in departments of the University were also mammals, so that the Drosophila DPP protein combined into two larger units, the Departments itself is able to induce bone formation from of Molecular Biology & Biotechnology, and appropriate stem cells in mice and rats. This Animal & Plant Sciences. Together, we form conservation of regulatory functions now the School of Biology where we occupy allows us to make full use of a wide range of adjacent buildings. Increasingly, we are experimental model systems in a way that has working closely together to adopt an direct pertinence to human biology. integrated, multi-disciplinary approach to the study of biological problems, and in the recent Research Assessment Exercise this Department, for the first time, joined with the other Departments in the School to make a return as a single Unit of Assessment for Biology.
Revolutions in biological thinking/ The past 10 to 15 years have witnessed major changes in biology, both in experimental approaches and in our understanding of biological processes. The rapid development of molecular genetics has laid bare many of the nuts and bolts that make up complex organisms, and the Genome Project will undoubtedly soon reveal the nature and organisation of much of the human genome University entrance perhaps the culmination of a reductionist phase of biology that began with the great anatomists and physiologists of the 16th and Integrating traditional approaches with 17th centuries. Nevertheless, just as knowing molecular genetics the list of components used to construct a car engine does not tell us how the engine works, We, in the Department of Biomedical Science, so a list of genes that comprise the human are now in a strong position to integrate the genome will not tell us how the human body more traditional approaches of Physiology and functions. So, I now believe that we are poised Anatomy with these new developments in on the edge of a very exciting phase in biology, genetics. It is therefore with great pleasure that a synthetic phase in which we shall attempt to I welcome the Physiological Society to understand how the various components that Sheffield to hold its January meeting in 1997, make up an animal interact to produce the hosted by the Department of Biomedical whole. Here, another revolution in biological Science, at this very exciting time for biology, thinking of the past 10 years has something to for Physiology and for our Department. P S Meei
0 Cell Biology - The Department of the gastrointestinal tract, include Peter and Biomedical Science is divided into 3 major Jackie Hardcastle, and Roy Levin. They, areas of research interest, Cell Biology, together with newly appointed lecturers Neuroscience and Gastrointestinal Physiology. Jonathan Kibble and Louise Robeson, will Within the Cell Biology group my own interact closely with the new Laboratory. research focuses on the use of teratocarcinoma cell lines, isolated from testicular tumours, 0 Neuroscience - Released from the as tools to investigate the regulation of cell Chairmanship of the Department, Tony Angel differentiation during early human has been able to devote more time to his embryogenesis. Testicular cancer is one of the research into anaesthesia. In collaboration most common cancers of young men, and our with the Departments of Pharmacology, research also has implications for tumour Anaesthesia and Control Engineering, he has biology. The cells with which we work, apart set up a new Centre for Research into from resembling early human embryonic stem Anaesthetic Mechanisms (CRAM), with a cells, are able to differentiate into neurones in goal of integrating various interdisciplinary culture. In collaboration with Mark Dunne, approaches to the study of anaesthesia. A new Gavin Reynolds and Carl Pearson, we are laboratory to house this Centre is being using these to investigate the biology of refurbished within the Department. embryonic neurones, as well as for modelling Meanwhile Ken Clark continues to develop his aspects of human neurodegenerative disease. techniques for studying the motor control of gait and locomotion, and was recently rewarded with a grant from Proctor and Gamble to adapt his analytical techniques for assessing the efficacy of drugs that affect movement. Other neuroscientists within the . Department, notably Gavin Reynolds and Carl Pearson, are focused upon understanding the
- 11UI1111EEEEE..3.. mechanisms that underlie neurodegenerative p r"lU~~~g and psychiatric disease, particularly iil i. Alzheimer's disease, AIDS, schizophrenia and -. 'ii"Nilumg Huntington disease.
, ,! U0| |a|| oil lti i Gastrointestinal Science - Gastroenterology -1-41 has a long history in Sheffield and our current FAIR I research efforts divide into several strands: David Grundy investigates the neural The Alfred Denny Building regulation of gastrointestinal function, whilst Department of Biomedical Science Peter and Jackie Hardcastle focus on the regulation of transport in the intestinal * Electrophysiology is one of our strengths epithelia, particularly in relation to the defects and in an exciting new development we are associated with cystic fibrosis. Whereas the establishing a Laboratory of Membrane initial clinical symptoms of this disease are Function, bringing together Mark Dunne and usually associated with the respiratory tract, Stan White, who both run groups investigating defects are also found in other epithelial membrane function using electrophysiological systems throughout the body. In collaboration and other techniques. Mark Dunne recently with Chris Taylor in the Children's hospital, found that the congenital condition, the Hardcastles are using transgenic mouse hyperinsulinaemic hypoglycaemia of infants models to examine the mechanisms underlying (PHHI), involves a defect in a potassium the pathogenesis of cystic fibrosis. Roy Levin is channel that functions in the regulation of also interested in the regulation of transport by insulin secretion (see Science News & Views, the gastrointestinal epithelium, but especially this issue) Stan White is investigating the in dysfunction associated with malnutrition, a regulation of secretion across the kidney tubule condition that is a major cause of death epithelia and the differentiation of cells within throughout much of the world. From a that system. The new Laboratory of different perspective, Dave Rumsey continues Membrane Function will provide a focus for his long standing interest in diet and its effects further developments and recruitment of new upon gastrointestinal function. staff to focus on signal transduction mechanisms. Other members of the Department 0 Developmental Genetics in Sheffield with interests in membrane function and While Developmental Genetics may seem a far epithelial transport, particularly in relation to cry from the traditional interests of Physiologists, we believe that our new experience and to teach a range of generic skills program in this area, being established jointly that are likely to be essential in their with the Department of Molecular Biology & subsequent career. Biotechnology, will provide many new experimental approaches to our existing We continue to play a significant role in Physiology programs and allow us to establish teaching pre-clinical medical and related an interdisciplinary research grouping students, and our new Medical Curriculum, in uniquely positioned to exploit the recent which basic science and clinical sciences are advances in molecular genetics and to relate more closely integrated, has been well the structure and function of newly recognised received. As a result of an agreement between gene products to their role in the whole animal. the University and the new ASEAN Medical For example, the new program will include the School in Ipoh, Malaysia, beginning in 1997, establishment of a transgenic mouse unit we will be receiving an additional 120 medical within our animal facility, helping many of our students from Malaysia every year to existing research groups to take advantage undertake pre-clinical studies, so that our of transgenic techniques for answering medical student class will rise to about 320 traditional questions in physiology. We have students per year. The new teaching block been fortunate in recruiting Philip Ingham being built to accommodate the newly from the ICRF to the new Chair in increased class is giving us an opportunity to Developmental Genetics, and seven or eight re-organise both pre-clinical and science new posts are to be established as part of this teaching in a more efficient way. We will also new unit, with interests ranging from be appointing about 11 new staff members over Drosophila to Zebra Fish and the laboratory the next 3 years, providing another mouse. The teaching Symposium, organised opportunity for enhancing development of the by Stan White as part of the January meeting, is Department. designed to help introduce many of the new molecular genetic techniques to physiologists. Conclusion
Teaching in Sheffield I hope that, in this brief outline, I have been able to give you an idea of the many The Department teaches science undergraduate exciting developments taking place involving students in three honours schools of the Department of Biomedical Science. Physiology, Anatomy & Cell Biology and As highlighted in the recent Government Neuroscience, and also takes a lead role in the Foresight Exercise, multi - disciplinary more broadly based degree courses of approaches to the study of biological problems Biomedical Science and Biological Science, in are becoming increasingly important. I believe which students are able to select modules from that with the integration of Anatomy and all the pre-clinical sciences, or the full range of Physiology within one Department, and our biology subjects to meet their own specific close collaboration with the other Departments needs. The Biomedical Science course, now in within the School of Biology, will provide a its fourth year, is proving extremely popular strong basis in Sheffield for both teaching and and accounts for about half of our total science research in the new environment that student intake. The continuing rise in student Universities find themselves in the UK. My numbers is leading us to reassess the way in colleagues and I in the Department of which we teach our traditional subjects and is Biomedical Science hope that you enjoy your giving us an opportunity to develop courses in visit to Sheffield, and welcome the chance to which we are able to integrate much more show you how Physiology isthriving Inhere. closely the study of structure and function. We have recently established a CAL facility to help in this respect.
Our post-graduate students continue to play an important part in the research of the Department, which is now part of the newly established Graduate School. All post graduate students are now required to participate in an individually tailored training program, which includes a series of courses Peter Andrews organised by the Department in collaboration Arthur Jackson Professorof 4 with the Graduate school. These courses are Biomiedical Science designed to broaden a research student's Chairnmani of Department considered the met in Leeds on 10 In addition, the Committee The Committee half of the financial September, its first meeting since the financial report for the first membership subscription Society's AGM. This year there has been a year, approved indicated to the AGM of the substantial change in the composition of the changes already agreed revised charges for Committee. Kwabena Appenteng, Richard Society, and memberships of editorial boards Boyd, Janice Marshall, Noel McHale, John offprints. The were agreed. The process Widdicombe, David Miller, Laurence Smaje and subcommittees nominations for Honorary and Richard Vaughan-Jones have all left and of making of the Society was begun. Frances Ashcroft, Maynard Case, Clive Ellory, Membership abstracts were appointed for the Brian Harvey, and Alan North have become Scrutineers of a number of grants to Special members. This leaves the Committee coming year, and Designated Sessions were somewhat smaller than last year, and the work Interest Groups party was formed to load for each member somewhat larger. approved. A working plan celebrations for the 1000th Scientific which neatly falls in Charitable Expenditure meeting of the Society, Scientific and 1999 at the University of December with of the Society Birmingham. The annual meeting Press, who print and The main business of the September meeting is Cambridge University was considered, to start the process of decision making about distribute the Society Journals, of meetings of a number of the scientific and charitable expenditure of the as were the Minutes Notably, the Treasurer was Society during the following financial year. Subcommittees. that a contract had been signed Some of the work of the Society is now able to report University Press for the devolved to its Subcommittees, the with Oxford to the Body and that composition of which is given in the Grey publication of a Companion become cosponsor with the Book. Bids for expenditure were therefore the Society would the Genetical Society of a new made by those chairing Subcommittees as well Biochemical and and Function, to be published by as by the Officers of the Society. The journal, Genes Portland Press. This journal Committee had the task, after (sometimes Blackwells and physiological work on heated!) debate, of giving its assessment of would publish these bids by ranking them. The decision- transgenic animals. making process continues at the Treasurer's Advisory Subcommittee and at the November After very considerable discussion, which Committee Meeting. Inspection of the Society reflected differences of taste and opinion that Accounts in the Annual report of the Society are likely to run through the whole of the will show that the Society spends in all some Society, it was agreed to continue the practice £600,000 on its scientific and charitable of reading Minutes of the Scientific Meetings at purposes each year, while membership Society Dinners and of having after dinner subscriptions contribute about £120,000 only. speeches. But it was now with the stipulation Thus income from the Journalof Physiology and that brevity would be a requirement of from investments is crucial to the functioning speechmakers. of the Society. If you have any items that you feel the UK National Committee Committee should discuss, please contact the learned Committee Secretary, Peter Stanfield. Over the past year or so, a number of sciences have been societies in the biological Christina Docchar debating the possibility of collaborating in advancing the interests of cellular, molecular and physiological life sciences in a number of areas. These areas include Government and £5.8 billion other public policy, the formal education of scientists, public understanding of science, The Committee of Vice Chancellors and general media relations affecting learned Principals has estimated that by 2005/06 societies, and matters affecting career UK universities will face a funding gap of development of scientists. There has been approximately £5.8 billion. The article widespread support for the formation of a UK argues that filling that gap with increases National Committee, and it was agreed that the in student fees will not be easy. Physiological Society will become a member of this grouping, with the Committee Secretary THES 1246 20 September 1996 acting as the Society's representative. Source: SPIN CHANGES IN THE DEPARTMENT CHANGES INTHE OF PHYSIOLOGY, DEPARTMENT OF PHYSIOLOGY UNIVERSITY OF BRISTOL UNIVERSITY OF CAMBRIDGE
R ecent months have seen several changes to Jan Glynn retired in September 1995, and the staff in the Department of Physiology JtAlan Findlay became Head of Department in Bristol. The sad and untimely death of Reg for ten months until Roger Thomas moved Chapman at the end of 1995 has already been from Bristol to take over as Professor of reported in the Magazine and this, together Physiology and Head of the Department in with the election of Roger Thomas to the Chair August 1996. James Fitzsimons also retired in Physiology at the University of Cambridge from his personal Chair in September 1995, but and the appointment of Jonathan Ashmore to continues to teach and research as actively as the Bernard Katz Chair of Biophysics at UCL, ever. Denis New will retire from his meant there would be several vacant posts in Lectureship in September 1996. Three new the Department for this coming academic year. University Lecturers take up their posts this These have now been filled and we are year, and the Department also has a new delighted to have Roland Jones, Corn6 Kros Administrative Secretary. and Julian Paton joining our ranks. Fiona (Evelyn) Duncan became Secretary Immediately prior to this appointment, Roland of the Department of Physiology in April has been a Wellcome Trust Senior Research 1996. Fiona's first job, very appropriately, Fellow in the University Department of was a "Complaints Clerk" with International Pharmacology in Oxford. He has been Photofinishers in Cambridge. From there to appointed to a readership and he will form a the Scientific Periodicals Library as an focal point for cellular neuroscience research in Editorial Assistant, and later to the Bursar's, the Department. Corn6 Kros is currently a then the Senior Tutor's, offices in Newham Royal Society University Research Fellow in and Robinson Colleges respectively. She the School of Biological Sciences at the became known to many of us when, in 1990, University of Sussex. He is interested in the she became Administrative Officer (II) sensory transduction mechanism of the cochlea for Student Affairs at the Clinical School, and his work will complement that of Matthew when she was involved with things like Holley and Paul Kolston (existing members of organising admissions, 2nd MB exemptions, the Department), and Nigel Cooper (see and the clinical student timetable. She below), so creating a strong group in hearing was promoted in 1992 to the job of research. Corn6 will bring his Royal Society Administrative Officer (I) in charge of Fellowship to Bristol and hold a proleptic Resources at the Clinical School. lectureship. Julian Paton has already been a member of the Department for two years, as a Suzanne (Lee) Dickson became a University British Heart Foundation lecturer, but he has Lecturer in Phsiology in Au ust 1996. now been awarded a proleptic permanent Physiologyyeread (hegut year lectureship. He and his group will be Suzanne read Pharmacology (her third year continuing their work on the central control of subjects were Physiology, Pharmacology and the cardiovascular and respiratory systems. Pharmacological Physiology) at the University of Edinburgh. She became a graduate student There is a movement too amongst those at the Babraham Institute where she was holding fellowships of various sorts within the supervised by Gareth Leng for her work on Department. Christof Schwiening (Wellcome neural control of growth hormone secretion. Trust) left during the summer to take up a She gained her PhD in July 1993. Between lectureship in Physiology at Cambridge, January 1993 and September 1994, she Michael Evans (Wellcome Trust) has accepted remained at Babraham as a Higher Scientific a lectureship in the Department of Officer working on the central site and Communication and Neuroscience at the mechanism of action of growth hormone University of Keele, and Peter Skorupski releasing peptide, GHRP-6, funded by a grant (BBSRC) will be moving to Queen Mary and from Merck Research Laboratories, She was Westfield College in the New Year to take up a appointed to a Lectureship in Anatomy and lectureship in Biology. We wish them well in Human Biology at King's College, London in their new posts. In their stead we are pleased October 1994. Suzanne is the principal to welcome Nigel Cooper as a new Royal investigator on a 3-year MRC Project Grant Society University Research Fellow. held jointly with Professor Gareth Leng in Edinbugh. Stephen Lisney Christof Schwiening was appointed to a NEWS FROM DEPARTMENT OF University Lectureship in Physiology from BIOSCIENCES, UNIVERSITY OF August 1996. He read Physiology at the University of Bristol and then went to work on HERTFORDSHIRE a PhD on intracellular pH regulation in locust ollowing recent interviews Dr Wendy neurones under the supervision of Roger ollwa reetinterviews DrvWendy Thomas. He spent the year 1990-91 in the ILPurcell was appointed Head of Division of Department of Cellular and Molecular Physiology, Pharmacology and Toxicology Physiology at Yale University working with with Dr John Wilkinson as Deputy. Walter Boron on a NIH-funded Fellowship Dr Wendy Purcell was recently awarded a where he gained experience with fluorescent Media Fellowship with the BBC and selected as pH and calcium indicators as well as isolated The Wellcome Trust Media Fellow. She will mammalian cells. He then returned to Bristol spend some 6-8 weeks working with the BBC initially as a Research Assistant employed on a World Service Science Unit in order to facilitate MRC grant- and then, since 1994, as the holder the public understanding of science. Science of a Wellcome Trust Research Career and technology media fellowships are Development Fellowship. In his current work, intended to create a greater awareness and he is attempting to move away from the understanding of the workings of the media intracellular environment and instead is among practising scientists and engineers. The concentrating on trans-membrane ion fluxes, first hand experience of the conditions and using a technique which involves enclosing constraints of working journalists makes single cells in micro-droplets under oil. fellows better equipped to communicate their Christof is married and has two daughters. science to the general public, their students and their colleagues. Dino (Antonio) Giussani was born in La Paz, Wendy Purcell Bolivia - but is a British citizen. He was appointed to a University lectureship in Physiology from October 1996. According to HUGH BOSTOCK APPOINTMENT his curriculum vitae, Dino's education did not TO A PERSONAL CHAIR begin until he started at the University of UNIVERSITY COLLEGE LONDON London (Royal Holloway and Bedford New College) reading Physiology and Zoology in Tugh Bostock, of the Sobell Department of which he obtained a First Class Honours INeurophysiology at the Institute of degree in 1989. He then went to University Neurology in London (currently affiliated with College London (Department of Obstetrics and University College London) has recently been .Gynaecology), and obtained his PhD in August made a Professor of Neurophysiology in the 1992 for a thesis entitled 'The role of the carotid University of London. Hugh, who graduated chemoreceptors in the control of the fetal from Oxford with a BA in Chemistry and with cardiovascular system during acute an Msc in Physiology from UCL, will be well hypoxaemia'. He remained at University known to many members of the Society. He College until October 1993 during which time may have first come to their notice via his he also worked at the Universidad de Chile, elegant computer demonstrations at Society Tom Sears Santiago, Chile on cardiovascular and Meetings of his measurements with dorsal root endocrine responses to acute hypoxaemia in of action currents in demyelinated he had refined earlier the llama fetus. He then moved to the axons, in which and Sears so as to for Pregnancy and Newborn experiments of Rasminsky Laboratory demonstrate continuous conduction in the Research, College of Veterinary Medicine, internodes of these axons. He has continued to Cornell University, Ithaca, New York - the research in this area ever since. His studies Director of which is Peter Nathanielsz, from experiments in vivo, in vitro and in man, formerly a Lecturer in our Department. Dino in both normal and pathological conditions will be based there until September 1996, and have made him an authority on the has been working in a number of areas of distribution and function of sodium and perinatal and fetal physiology. He is fluent in potassium channels in myelinated nerve. Spanish and English, and has been honoured Recent measurements in man using for his football. measurements of "threshold electrotonus" (reviving ideas from the times of Lorente De Alani Findlay N6) have excited clinicians as providing new hypotheses into the aetiology of motor neuron disease, as well as possible means of monitoring the condition. Peter Kirkwood CARDIOVASCULAR I COMPARATIVE & INVERTEBRATE RESPIRATORY CONTROL NEUROSCIENCE
The Leeds Meeting C-ur Group is holding a symposium on O .Wednesday 28 May at the Plymouth The recent Leeds Meeting was full of interest Tand debate not only within the Meeting entitled 'Neuromodulation of Cardiovascular/Respiratory SessionAdutoc but also Synaptic Function'. There will also be a Designated Session on Comparative and in both the Respiratory Session and Autonomic Invertebrate Physiology and the Comparative Session and symposium. In our Designated Physiology Group is holding a Designated Session there were 16 Oral Communications, Session in 10 Poster Com munications, two Demonstrations the area of control of visceral function.fu ci n ForFo detailsde al oror ideasd as onn theth and one Demonstrated Communication. The latter was much appreciated despite the small symposium please contact either myself or technical problem of a burst perfusion line! I Roddy Williamson at Plymouth. Likewise, was also impressed by the demonstrations of comparative physiologists should contact Ted circulatory adjustment to orthostatic stress and Taylor at Birmingham: carotid baroreceptor stimulation in humans. In addition, I personally thought that the Bill Winlow inclusion of a one minute verbal presentation (Dept of Physiology, Leeds) with a single slide during the approval session Tel: (0113) 233 4247 for Posters and Demonstrations was a Email: [email protected] worthwhile improvement. I would appreciate hearing your opinions on this subject. Roddy Williamson (MBA, Plymouth) Future Dates for your Diary Tel: (01752) 633338 Email: [email protected] I would like to bring your attention to the symposium at the Sheffield Meeting which is Ted Taylor entitled: "Respiratory and Cardiovascular (Biological Sciences, Birmingham) Adaptation to Chronic Hypoxia" to be staged Tel: (0121) 414 5472 on 6 January 1997 with the Scientific Meeting to follow from 7-8 January. This symposium This looks like being a major meeting for will aim to cover both scientific and clinical comparative physiologists and we look aspects and looks to be most interesting, forward to a large number of attendees. The abstract submission period is from Monday 10 The next Designated Session will be held at to Thursday 20 February. Trinity College Dublin (24-26 March 1997); the deadline for submission of abstracts is 12 Bill Win low December 1996. I have invited Professor David Adams from the University of Queensland to # give a Designated Lecture. His field of A0 expertise concerns the role of intracardiac 199 IUPS Cogifwe.t'r x ganglia in control of the heart (exact title to be Important Deadlines announced shortly). 15
Finally, if you are intending to go to the 28 February 1997 First International Society for Autonomic 0 deadlines for registration and payment Neuroscience in Cairns, Australia next with lower registration fees. September please inform Joel Bornstein of you intentions; he has asked for this information and * deadline for payment for one night hotel his email is: [email protected]. or dormitory deposit.
I would like to finish by inviting you to 0 deadline for receipt of abstracts. contribute ideas for future speakers and themes for a symposium. Please contact me if 30 April 1997 you have any suggestions - now is your • deadline for full hotel and chance! dormitory payment
Julian Paton • deadline for all other remaining payments. DEVELOPMENT AND C Y Jung (Buffalo, NY) Proteins that interact with the glucose PLASTICITY transporter: implications for function Ontario) of the convenor of the R M Krupka (London, WAith the approval biological former Developmental Neurophysiology Channelling free energy into work in Special Interest Group and the Committee, processes this Group has been re-invented as the Development and Plasticity Group. Following In addition to the invited lectures, this the 'Mechanisms of Synaptic Plasticity' symposium willinclude OralCommunications symposium organised by Richard Ribchester on the topic of "Glucose Transport". There the evening, and David Price at the Edinburgh Meeting it will be a symposium dinner in a limited number of places, and the cost became clear, from the attendance and with be approximately f26.00. discussion, that 'development and plasticity' is will a major field of interest for many Members of During the Scientific Meeting, Professor Heini the Society. The revised Group will provide a (Zurich) will present the Epithelia & forum for presenting work on plasticity and Murer Transport Designated Lecture, development at the neuromuscular junction Membrane "Molecular mechanisms of proximal and development and plasticity of the visual entitled reabsorption of phosphate". system and the hippocampus. The Group will tubule have a Designated Session at the Dublin The Group will hold a short business meeting Meeting (24 - 26 March 1997). The new in Sheffield. The agenda for this meeting will include confirmation of Dr Peter Brown Dr Kevin Fox (Manchester) as the new convenor for the Physiology Unit, MOMED of Wales University PO Box 911 Barry Hlirst CARDIFF CF1 3US Tel (01222) 874 632 Fax (01222) 874 094 HEART AND CARDIAC MUSCLE Email [email protected].
Meetings Secretary's Office The recent Heart and Cardiac Muscle Designated Session at Leeds was well attended. At this meeting, authors of Posters EPITHELIA & MEMBRANE were asked to give a five minute talk with up voted on. TRANSPORT to two slides, before the Poster was This went very well, and I encourage colleagues to support this new format. The Sheffield Meeting will be preceded by a symposium in honour of Professor Wilfred The next Designated Session of the Group will Widdas, an active and regular contributor to the Group's Sessions, organised by Richard Naftalin: After three years in the position, I have decided Glucose Transport: a functional approach that my tenure as organiser of the Heart and Cardiac Muscle Special Interest Group should W F Widdas end. I have looked around the membership for The red cell glucose transporter - a functional a young and energetic replacement. After approach some discussions I approached Dr Stephen Dr Simon Harrison A Carruthers (Worcester, Massachusetts) O'Neill (Liverpool) and said they are keen to The kinetics of human erythrocyte sugar (Leeds) and both have So I would like to transport take up the position. propose to the membership that these two W D Stein (Jerusalem) people take on the role as joint organisers of the Kinetics of the multidrug transporter (P- Group. glycoproteins) and its reversal alternative suggestions G D Holman (Bath) If anybody has any myself or Chris Fry Relating the structure of the glucose please contact either to function (email: [email protected]). If there are no transporter objections I propose that their tenure begin on R Dev~s (Chile) 1 January 1997. System y+L: the broad-scope and cation modulated amino acid transporter HUMAN PHYSIOLOGY MOLECULAR PHYSIOLOGY
he next Designated Session of the Human ne of the great difficulties in introducing a Physiology Group will take place at the O.,,new technique into an established Sheffield Meeting, to be held on 7-8 January discipline is language. Molecular biology has 1997. This Session will feature a Designated evolved its own "jargon" that eases Lecture by Professor Eric Hultman of communication between like-minded scientists Stockholm who will review the metabolic basis but which makes it incomprehensible to of fatigue. The annual business meeting of the anyone outside the subject. As a result, it has Group will be held at some point during the proved difficult to realise the enormous value Meeting. Details of the time and the agenda that molecular biology can offer to the study of will be circulated when the Meeting physiology. It provides potential to the study programme is known. of the structure-function relationships for proteins and the dynamics of gene expression. The second Designated Session of the year will By way of reverse, physiologists are needed to be held at the Cambridge Meeting in unravel the ever increasing sophistication of December, and will feature a symposium to be transgenic and gene knock-out animals. organised by Tony Sargeant. In an effort to bridge the communication gap, In addition to these two Designated Sessions, we will hold a one day teaching symposium at the Human Physiology Group has been the Sheffield Meeting of The Physiological invited to participate in the meeting of the Society. This has been co-organised by Dr Irish Section of the Nutrition Society. This Stanley White at Sheffield University and Janet meeting will take place in Dublin on 16 - 18 Allen at University of Glasgow. It will take June 1997, immediately preceding the 8th place on Thursday 9 January 1997. A line-up of European Congress on Obesity which will also superb communicators have accepted the take place in Dublin. The meeting will feature challenge and agreed to contribute to the a symposium on nutritional aspects of symposium which has been provocatively exercise, and there will be opportunities labelled: "Jargon-Free Molecular Biology for for the presentation of oral and poster Physiologists". communications. Discussions are also under way for a joint meeting with the Scandinavian Topics and speakers include: Society for Physiology to be held in Oslo C A R Boyd (Oxford) - in October 1997, and further details will Molecular Physiology follow very shortly. In addition to this why it matters for physiologists rather hectic programme there will certainly be a number of papers D Hornby (Sheffield) - of interest to human How to clone your gene of interest physiologists at the K Page (London) Physiological Society RT-PCR in tissues and cells Meeting at Trinity College Dublin (24 G Gould (Glasgow) 6: 26 March), even How to express your gene of interest iF I though it was not M Leyland (Leicester) - possible to hold a Mutagenesis Designated Session of the Group. A C Dolphin (London) - Uses of antisense technology
Trinity College Dublin A workshop on R Dimaline (Liverpool) - laboratory methods Quantitation of messenger RNA in Human Physiology is planned for Easter 1997. This will take the same form as the earlier C Pearson (Sheffield) workshop which covered aspects of blood In situ hybridisation sampling and analysis. The proposed W Brammar (Leicester) - workshop will cover cardiovascular and Regulation of gene expression respiratory measurements. Further details will follow shortly. W Colledge (Cambridge)- Transgenic approaches to physiology
Ron Maughan Janet Allen NEUROENDOCRINOLOGY RENAL PHYSIOLOGY
T here have been two successful meetings of A meeting of the Renal Special Interest the Special Interest Group for -Group was held at the Leeds Meeting of Neuroendocrinology this year. The first at the Society. A broad range of topics within University College London included a renal physiology was covered in nine Oral symposium on the non-reproductive effects of Communications and four Posters. At the gonadal steroids, chaired by Professor Julia Poster approval session a one minute Buckingham. This was followed by a Poster presentation for each Poster facilitated session in the afternoon, a Designated Session discussion and seemed to work well. with 11 Communications and the G W Harris lecture on the neuroendocrine control of In view of the ISN meeting in May and the growth given by Professor I C Robinson. IUPS Conference at St Petersburg in June/July Professor E E Baulieu opened the symposium 1997 the next formal meeting of the Group will with a review of the neurosteroids. Dr G Gillies be held at the St Thomas' Meeting of the then discussed her studies on steroids and Society, 7-8 November 1997. neural development and was followed by Dr R Stanhope who presented some clinical aspects Physiological Society recommendations are of steroids and growth hormone release. After that Special Interest Group convenors should the break the topics were the effect of ovarian be rotated every three years or so and it is now steroids on the hypothalamic-pituitary-adrenal time for me to hand over to a successor. The axis and on the neurohypophysial system, normal procedure is to elect a new convenor at Drthe speakersJ Morris beingand ProfessorDr M L GForsling. P Chrousos, The a businessa procee meeting is of tethe Group.a newonve It would be Dr Ms andtr pLreseion T s helpful if anyone within the Renal Special Communications and Poster presentations Interest Group who would like to take on this covered a wide variety of topics, many of them role would write to me in the first instance. related to the theme of the symposium.
There was another Designated Session at the Dave Potts Meeting in Edinburgh in July. Many of the Special Interest Group attended the oral presentations and there was much discussion RESPIRATORY PHYSIOLOGY following each paper and during the Poster Session. The sessions also highlighted the wide ranging interests of the Group. However, The Leeds Meeting ii was a long day with the final poster being They say you can tell a Yorkshireman - but approved at around 18.25. Lyou can't tell him much. Well, any Yorkshireman that inadvertently ventured into More meetings are being planned including a Lecture Theatre 2 of the Roger Stevens joint meeting next year with the Special Building at Leeds University on Wednesday 11 Interest Group for Renal Physiology which will September would have been told quite a lot deal with recent developments in the about the control of breathing during what was eetingd ur Group neuroendocrine control of fluid balance. We out the otol are always inarealwys nedneed off nsggetiossuggestions frfor ecitngexciting onefor someof the time.mostAnotherlively meetings9am startof guaranteedour Group and sending them in for mAny in wat ustehv workshops andis nwsymposia esierevn e-ail hem an extra night for many in what must have is now even easier: e-mail them to been some of the most bizarre accommodation [email protected], ever offered to Phys Soc delegates. It was Mary Forsling certainly a common topic for the week - suffice to say that to be ruled by your own bladder is bad enough, but to be held hostage by and undertrained someone else's is quite something else! If Imay PhD__tutors__reunderpaid__ndundertrainedPhD tutors are underpaid paraphrase Professor Milledge's quote on report by the Association of University Teachers, the auemuti ikes N-n isfo sleeping in the Henry Price Building but many National Union of Students and the National wish they could". Postgraduate Committee reveals that PhD students are poorly paid and untrained for their teching duties. The article 16 Oral Communications and one Designated discusses what steps can be taken to remedy this problem. Lecture were given including presentations Guardian10 September 1996 p.9 from colleagues in Germany (Dr Pierrefiche), USA (Professor Mitchell), France (Dr Benchetrit) Source: SPIN and Japan (Professor Honda) and once again The Sheffield Meeting these demonstrated the breadth of interests within our Group. The first Pfizer round in our Just enough space left to remind everyone of Special Interest Group also took place and I the Symposium on "Respiratory and was certainly pleased not to have been in the Cardiovascular Adaptation to Chronic position of having to make a choice between Hypoxia" at Sheffield University on Monday 6 the entrants who were all excellent. In the end January 1997. More details elsewhere. It the selection committee chose Rachel Landauer promises to be a great day intellectually and for her talk on the reversible and age- socially and I hope to see you all there. PS for dependent effects of chronic hypoxaemia the Londoners - bring a jumper! upon peripheral chemoreceptor sensitivity. Congratulations also go to Simon Gladwell Notice of Future Meeting who was the prize winner from the Trinity College Dublin: 24 - 26 March Cardiovascular/Respiratory Control Pfizer 1997. Abstracts please for the Designated round. I shall make further bids to have more Respiratory Session at this Meeting. Pfizer rounds in the future, so watch for details. Submission dates 2-12 December 1996. There A highlight are few places in the UK with a stronger of the day was the Designated tradition of respiratory physiology than Dublin Lecture given by Professor Gordon Mitchell of so please try to get an abstract in. the University of Wisconsin, Madison USA entitled "Modulation and Plasticity in Prem Kunar Respiratory Control". In exemplary fashion, Professor Mitchell described the significant SENSORIMOTOR CONTROL adaptive potential that exists in respiratory control and it appears that you certainly can ext year looks like being an interesting teach an old goat new tricks. Gordon's Ni comparative and busy year for the Group. The first of neuroscience background made three Sessions planned for 1997 will take place for an absorbing lecture which ended with a at the Trinity College Dublin Meeting in March. slide showing that LTP could be abolished at a I am delighted that Dr Daniel Wolpert has Pco 2 of 80mmHg. Not sure how much I'd want accepted an invitation to give a Designated to remember if I let my pH fall so low! Lecture to the Sensorimotor Control Group at this Meeting. Daniel has The Session recently established a began with the London PET research group at the Sobell Department of group's experiments into the motor control of Neurophysiology, Institute of Neurology, speech. Dr Murphy's first slide had the words after working for three years at the MIT in "BUY BOBBY A POPPY" written in so large a Boston. Daniel's interests are in the neural format that whenever I shut my eyes I can still computations involved in motor control which see them in all their 256 point magnificence. Dr he is investigating using a novel experimental Murphy also explained that in the pre- approach in which computer controlled circulated abstract booklet his figure had been apparatus is used to create "virtual accidentally misprinted by leaving out all the environments". In Dublin, Daniel will talk grey scales from his averaged PET scans but that about recent work on internal models of these had now been put back in. And I thought sensorimotor integration and visuomotor the aim of science was to remove the grey areas! learning in a lecture entitled: "Internal models in human motor control: a computational and The willingness of undergraduates to partake in psychophysical perspective". I hope as many somewhat-heroic respiratory experiments, as of us as possible will cross the water to make typified by communications given by Dr this a lively Session (deadline for abstracts; 12 Corfield and 'soon-to-be Dr' Pedersen, is to be December). commended but I think we had a first with a recurring discussion on the relative intelligence In the second half of the year there will be two of these undergraduates when compared to further Sessions of the Group. In September we ducks. Not quite as obvious as one might meet in Bristol where there will also be a Motor initially think and at time-out I think the Control Symposium organised by Dr Richard undergraduates had it by a head by virtue of Apps. In November we meet in London at St knowing to stop breathing if someone(thing) Thomas' at what is likely to be the last else was looking after their bloodgases for them. Physiological Society Meeting to be held at the J G Tansley mumbled something about his Sherrington School of Physiology. Several subjects at Oxford not being as stupid as ducks special events are being planned for this but intriguingly offered no direct evidence. Meeting including the Sherrington Lecture which will be given by Professor Anthony Taylor. S I Grou Forum
Turning to more mundane matters, can I take SOMATOSENSORY this opportunity to remind you that it is PHYSIOLOGY important, when filling in abstract submission forms, to complete the box indicating the Special Interest Group Session at which you Edinburgh Meeting 2-3 July 1996 wish to present your Communication. If you forget to complete this box there is a risk that m'he Group convened at the Edinburgh the your Communication will be programmed I Meeting for a symposium on "Interactions in a General Session. This has, unfortunately, in Spinal Somatosensory Processing happened at recent Meetings. Pathways", organised by Sue Fleetwood- Walker, on the Wednesday, followed by a full Finally, now that we have a Society magazine, day of free Oral and Poster Communications. expensive surface mailings to members of The symposium, held in the grand Special Interest Groups have become more surroundings of The Royal Society of difficult to justify. In order to maintain the Edinburgh, made for a good start to the possibility of disseminating information to the Meeting. Alan Brown reported some very Group in between publication of the Magazine interesting data on collateral connections I intend to experiment with "email shots". If between spinal neurones giving rise to you have recently started using e-mail or if different ascending tracts, showing that your address now differs from that shown in transmission in each ascending pathway is not The Grey Book, I should be grateful if you would completely independent of activity in the let me know (email: [email protected]). others. This was followed by a series of talks on amino acid and peptide transmitters in Hope to see you in Dublin. nociception and in the central sequelae of peripheral inflammation. There was a good Joh/ Riddell deal of information on interactions between glutamate and peptide transmitters, particularly the tachykinins, in the spinal cord. SENSORY FUNCTIONS There is general agreement that substance P can enhance responses to glutamate, but there remains some controversy as to whether this second Sensory Functions Session for this enhancement is specific to events mediated year was held in September at the Leeds through NMDA receptors. Methinks there is Meeting. This attracted a rather modest eight yet some mileage in this debate. In the middle Oral Communications, which nonetheless covered a broad range of subjects. I have again scheduled Designated Sessions at two Meetings in 1997. The first will be at the Bristol Meeting, which takes place from 2-4 September. Professor Peter Dallos from Northwestern University in Evanston has agreed to deliver a Designated Lecture at this Meeting on cochlear biophysics. A Sensory Functions Session will also be part of the programme at the Cambridge Meeting (15-17 December 1997). I hope that members as well as others working on any aspect of sensory physiology from transduction to cognitive function will consider contributing papers to one or both of these Meetings. .
The Committee recommends that Special McEw'ani Hall, Edinburgh University Interest Group convenors should change about every three years. As I will have run the of all this, Steve Thompson introduced us to a Sensory Functions Group for three years by the "new" neurotrophin (Leukaemia Inhibitory second half of next year, a Group business Factor, LIF) which, like NGF, seems to be meeting will be arranged in Cambridge with a involved in some of the changes in view to appointing a successor. neuropeptide content of primary afferents after to the Andy King nerve damage and may thus contribute changes in sensory processing which flow from such damage. In the last talk, Zsuzsanna Wiesenfeld-Hallin talked in more detail about the changes in spinal neuropeptides which accompany peripheral inflammation, including factors which may militate against successful analgesic intervention such as increased production of CCK. The day was informative and hugely enjoyable, and thanks must be due to Sue for organising such a splendid day.
The Group's Session in the Meeting proper saw 14 Oral and 10 Poster Communications. This was a fantastic turn out and I am very grateful to all of those who made presentations. We learnt how stimulation in the PAG appears not to suppress responses of spinal cord cells evoked by thin myelinated axons; marvelled at the richness of the innervation of the Echidna Appleton Tower, Edinburh University snout; puzzled over how destruction of the VPL nucleus of the human thalamus has quality of the work presented made one different sensory consequences to those of optimistic for the future of somatosensory spinothalamic tract section; discovered that the physiology in the UK. mysterious imidazoline receptors are involved in the central nervous adjustments to The Group will convene again at Bristol in peripheral inflammation; and were intrigued September next year. There may be a by the finding that female rats seem to be less symposium and we will have another bash at sensitive to painful stimuli in oestrus than in winning a Pfizer prize. I also intend this to be pro-oestrus. These are just some of the findings my last meeting as convenor. You have been which stuck in my mind: there were lots of warned.... other stimulating papers and the abstracts are worth reading. The level of attendance and the Rob Clarke
M edinfar wishes to announce that it has established, with the official sponsorship of the President of the Portuguese Republic, a biannual prize for contributions to mammalian physiological science by an investigator aged under 40 years. The prize of £25000 (twenty five thousand pounds) will be awarded for the first time in 1997. The recipient will be required to deliver a lecture in the University of Lisbon.
S'MEDINFAR Applications for the prize will be restricted to European PRIZE nationals (subjects of EU nations and resident in an EU IN PHYSIOLOGY nation at the time of nomination).
National Physiological Societies are requested to make three nominations, Heads of Academic Departments or Research Institutes a single nomination.
The prize will be awarded on the recommendation to Medinfar of an international Jury: Chairman Professor K M Spyer, UCL London; Professor David Eisner, University of Liverpool; Professor Charles Michel, Imperial College, University of London; Professor D W Richter, University of Gottingen, Germany; Secretary Professor Luis Silva-Carvalho, University of Lisbon.
Nominations must be received by February 28th, 1997. Further information and application forms may be obtained from Medinfar.
Medinfar Apartado 6648 Venda Nova 2700 Amadora Portugal Tel (351) (1) 476 12 00 Fax (351) (1) 476 55 21 E-mail: [email protected] REVEALED: A NOVEL K+ CHANNEL DISORDER IN INSULIN - SECRETING CELLS
.,ii-, Mark Dunne and Keith Lindley 11111111111 explain how molecular studies of a rarediseasehelped in understanding the control of insulin secretion and 1111111 how basic science could lead to ,,.... novel approaches to therapy.
T he study of "natures experiments" in the The ionic control of insulin release form of inherited diseases has proven a recognized that time honoured method of improving our Since the late 1960s it has been from 3-cells understanding of normal human physiology, control of the secretion of insulin is related Within the last 10 years a number of human of the pancreatic islets of Langerhans 3-cells are diseases have been more fully explained in to the cell membrane potential. presence of terms of abnormalities of cell membrane ion electrically active, and in the of glucose channels. Perhaps the best known and most stimulatory concentrations they will fully described example of changes in (typically greater than 5.5mM) being associated depolarize and generate Ca-dependent action membrane ionic conductance 2+ phenotype is cystic fibrosis in potentials. This will result in Ca influx and with a disease 2 which over 500 different mutations of the gene the release of insulin through Ca +-regulated encoding the cystic fibrosis transmembrane exocytotic events; fusion of secretory granules regulator protein, a cAMP-regulated chloride with the plasma membrane and release of their conductance, are described. It is becoming contents (Fig 1). Not until the mid-1980s, increasingly important to recognize that ion through the application of patch-clamp channel defects are coupled to altered techniques to study isolated P-cell function, physiological processes and pathogenesis. were these events further resolved. Our Our efforts in this area of physiology are current hypothesis to account for how glucose directed towards unraveling a potentially will cause changes in the cell membrane lethal infantile disorder associated with potential is summarized in Figure 1. In the hypersecretion of insulin; persistent normal resting 3-cell the membrane potential is hyperinsulinaemic hypoglycaemia of infancy, maintained by the combination of an GLUCOSE
N a ' Na *
K ( K ' A
CI K P channel c1 METABOLISM K channel
caK' Ka+in
: , M Cal2+-' CALCIU cations Cal- A Ca2* CALCIUM atio
2 Ca'Ca + a
INSULIN INSULIN RESTING STIMULATED
Fig 1. Schematic representationof the major ion channels in pancreatic/-cells and their role in stinulus response coipling,. Under basal conditions the 'resting'-cell menibrane potential is taintined by open K~11, channels. In the presence ofstinnlatory concentrationsof glucose, the intracelldarATPIADP ratio is elevated, 2+ KAF, channels close and the membrane depolarizes. This leads to the activationof voltage-gated Ca channels 2 and an elevation of the cytosolic concentrationof Ca ' which triggers exociytosis. electrogenic Na+-K ATPase pump and opening of ATP-sensitive potassium (KATP) KIR6.2 channels which allow K to exit the 3-cell down its electrochemical gradient. These N - " E a channels may be considered as an "on-off" switch for secretory events, since changes in their activity essentially governs changes in the SUR 1 cell membrane potential. Thus, in low glucose concentrations, normal P-cells are electrically quiescent, but at high glucose concentrations KATP channel openings are reduced, resulting in a depolarization of the 1-cell membrane and the activation of voltage-dependent Ca2+ channels. KATP channels are inhibited by N Fl intracellular ATP, and their gating governed by NBF2 changes in the availability of intracellular ADP. KATP channels are therefore metabolically sensitive, and as a result of this, these channels CFTR will close as a consequence of glucose metabolism and a concomitant elevation of the intracellular ATP/ADP ratio. The KATPchannel has therefore a pivotal role in stimulus response coupling events. The channel is also of clinical importance as compounds that inhibit these channels will tend to mimic the J effects of glucose and act as insulin secretagogues. Indeed, this is the basic mechanism by which sulphonylureas promote insulin release from the pancreas of non insulin dependent diabetic patients. R-domain NBF1
Molecular architecture of the P3-cell Fig 2.Schematic representationof the reconstituted KATP channel KATP channel in pancreaticfl-cells; SUR1 represents the high affinity receptorfor Two major advances in this field over the past suilphonylureasand KIR6.2, an inward rectifierK' channel. Both SUR1 12 months have provided convincing evidence and CFTR are members of the ABC family of proteins. that the hypothetical model outlined above does nucleotide binding folds, Fig 2. Neither K11 6.2 indeed provide the cornerstone to our understanding the regulation of insulin nor SURt appear to conduct potassium ions secretion. First, the molecular architecture of alone, but when co-expressed will generate ion the 0-cell KATp channel has been partially channel.channel currentsSURi alsovery appearssimilar toto controlthe native the resolved, and secondly studies of a rare major regulatory and pharmacological neonatal disorder have revealed that properties of the channel complex. The genes uncontrolled, hypersecretion of insulin occurs that encode SURI and KIR6 .2 are found in in association with the absence of functional KATP channels. humans on the short-arm of chromosome 11, at a locus that is associated with familial forms
Molecular clues suggest that KATP channels are of so called persistent hyperinsulinaemic o hypoglycaemia of infancy (PHHI). We now composed of at least two subunits. One believe that defects in the SUR1 gene in these subunit is a member of the family of inward patients cause loss of functional KATP channels rectifier / ATP-sensitive K channel pore proteins, KIR6 .2, also termed BIR ('3-cell Persistent hyperinsulinaemic inward rectifier'). The other subunit is a larger hypoglycaemia of infancy protein - the high affinity receptor for sulphonylureas (SUR1). SUR1 is composed of Hypoglycaemia is a common metabolic 1632 amino acids, and like the cystic fibrosis abnormality seen in childhood, and when this transmembrane conductance regulator (CFTR) is persistent or recurrent, it is frequently a it is a member of a superfamily of ATP binding consequence of hyperinsulinism; PHHI. The cassette (ABC) proteins all of which have two pathophysiology of PHHI is incompletely understood, although a defect in the pancreatic the Great Ormond Street Hospital for Sick P-cell's stimulus-response coupling events was Children, London we recently showed that first being alluded to in the 1980s. In recent hypersecretion of insulin in a PHHI patient can months we have shown this to be a be successfully treated in vivo with nifedipine. consequence of an absence of functional P-cell ATP-sensitive potassium channels. The This type of study reveals how important condition is thought to be rare in the UK, but lessons in biomedical science can be learned the incidence of PHHI in communities with from attempting to understand the high rates of consanguinity, approaches that of pathogenesis of rare diseases. From a clinical we have now begun to unravel one cystic fibrosis, i.e. approximately 1/2,500 live perspective births. PHHI has a variable clinical phenotype, of the key subcellular defects associated with usually presenting within the first few insulin-secreting cell pathophysiology. We hours/days of birth as severe and maintained have shown how KATp channel defects are hypoglycaemia due to unregulated causally related to alterations in the control of hypersecretion of insulin. Failure to recognize insulin release from 3-cells, and our efforts to and treat the hypoglycaemia promptly and date have already alluded to a novel approach adequately carries a substantial risk of severe in the clinical management of the condition. brain damage because of a lack of alternative Finally, in the wider context, these studies have fuels to sustain brain metabolism. Medical placed more emphasis upon what we therapy for the disorder involves increased understand to be important for the control of carbohydrate intake to meet the elevated insulin secretion under normal conditions; requirement, and usually one or more drugs reaffirming the consensus opinion of the role which inhibit insulin secretion. One such agent and regulation of ion channels, particularly the is diazoxide, which was first introduced to KATP channel, in stimulus-secretion coupling treat hyperinsulinism in the 1960s. Diazoxide mechanisms. is a specific agonist of the KATP channel, and Dunne tends to hyperpolarize the P-cell membrane Mark of Biomedical Science potential and eliminate voltage-dependent Department University of Sheffield Ca2 + influx in normal 03-cells. However, the responsiveness of children with PHHI to Keith Lindley diazoxide is highly variable from extreme Institute of Child fealth sensitivity through to total drug resistance, and University of London patients who do not show adequate responses to diazoxide (alone or in combination with other compounds) usually require a subtotal Recommended further reading: ,pancreatectomy to prevent recurrent Aynsley-Green A,Polak JM, Bloom SR, Gough MH, Keeling RC and Baum JD (1981) Archives of hypoglycaemia. The variability in sensitivity J,Ashcroft SJH, Turner Diseases in Childhood 56: 496-508. to diazoxide has until now been unexplained, (1985). but is probably related to the absence of KATP Sturgess NC, Ashford MLJ, Cook DL and Hales CN Lancet. 2:474-475. channels. Dunne MJ and Petersen OH (1991). Biochin Biophys Acta 1071:67-82. Altered ionic control of the P-cell Glaser B, Chiu KC, Anker R, Nestorowicz A, Landau H, Ben membrane potential BH, Shlomai Z, Kaiser N, Thornton PS and Stanley CA (1994). Nature Genetics 7:185-188. of the loss of ATP-sensitive One consequence SW, Clement IV JP, + hyperinsulinsm will be Aguilar-Bryan L, Nichols CG, Wechsler K channels in neonatal Boyd III AE, Gonzalez G, Herrera-Sosa H, Nguy K, Bryan J that PHHI 1-cells no longer effectively control and Nelson DA (1995). Science 268:423-426. their cell membrane potential and this will Inagaki N, Gonoi T, Clement IV JP, Namba N, Inazawa J, result in spontaneously electrically active cells. Gonzalez G, Aguilar-Bryan L, Seino S and Bryan 1 (1995). Electrophysiological recordings of isolated Science 270:1166-1170. cells reveal that they are persistently firing Sakura H, Ammli C, Smith PA, Gribble FM and Ashcroft action potentials, and it is this hyperactivity of FM (1995). FEBS Letts 377:338-344. 2+ Ca channels, resulting from the KATp channel Lindley KJ, Dunne MJ, Kane C, Shepherd RM, Squires PE, defect, that we now believe to account for the James RFL, Johnson PRV, Eckhart S, Wakeling E, Dattani M, unregulated secretion of insulin. Since voltage- Milla PJ and Aynsley-Green A (1996). Archives of Diseasesin 2 + 74:373-378. gated Ca channels in 1-cells can be inhibited Childhood by nifedipine and verapamil we proposed that Ammili C, Moorehouse A and Ashcroft FM (1996). fournal these compounds may be of therapeutic value of Physiology 494:709-714. in alleviating the symptoms of hypersecretion, Seino S,Inagaki N, Namba N and Ganoi T (1996). Diabetes and as a result of our close collaboration with Reviews 4:177-190. A ROLE FOR ENDOTHELINS AS NEUROMODULATORS IN THE CENTRAL NERVOUS SYSTEM B 0mV
ET-1 I -100mV Endothelins are well known for their vasoconstrictoractions but new evidence shows they may also be important neuromodulators. Hugh Pearsonand I o.2pA Brigitte Held report. 50ms
Introduction
The discovery of the existence of the hypothalamus and the granule layer of the vasoconstrictor peptides of the endothelin cerebellum. Many cultured neurones also family in the mid- to late eighties, led to a great possess binding sites for ETs, in particular deal of excitement over their potential role in primary cultures of cerebellar granule cardiovascular homeostasis and their possible neurones. These cells possess both ET-A and therapeutic potential. The isolation, ET-B receptors, relative levels of which alter purification and sequencing of the endothelins with time in culture. (ETs) has since allowed the development of both peptide and non-peptide antagonists Second messenger pathways coupling selective for the endothelin-A (ET-A) and -B to ET receptors (ET-B) receptors, which have also been cloned. The ET receptors are members of the rhodopsin It was clear from early studies that the superfamily of G-protein coupled receptors, distribution of ETs and their binding sites are having seven putative membrane spanning not confined solely to the cardiovascular regions with an extracellular NH 2-terminal system. Significant levels of radiolabelled ET domain and intracellular COOH-terminal binding were discovered in kidney, lung, domain. They are believed to couple to adrenal gland and intestine. High levels of ET phospholipase C resulting in production of binding were also observed in the central nervous system. This suggested that, in addition to their actions to contract vascular Vascular smooth muscle smooth muscle, ETs might have other physiological functions. In particular, the ROC notion that ETs might act as neurotransmitters or neuromodulators in the central nervous system has led to interest over their possible VGt roles in the pathology of neurological disorders , ) ... -protein such as Alzheimer's disease. ( "
Distribution of ET and ET receptors in I .... the CNS - IP, + DAG
Localisation of ET immunoreactivity in human 2+ brain indicates a widespread, but diffuse, Ca distribution of the peptide in neurones. Fig 1.Second messenger pathways coupled to ET receptors in Highest levels were found in the vascular smooth muscle. The G-proteincoupled ET receptors activate hypothalamus, with pyramidal neurones in the phospholipaseC (PLC) resultingin increasedproduction of lP3. 1P3 can CA3 region of the hippocampus and neuronalthen act to release Ca2' froni intracellularstores. ET receptoracivation processes in the temporal cortex also showing also causes the opening of receptoroperatedchannels (ROC) in the cell ET immunoreactivity. meibrane that allow influx of Ca2 +from the extracellularniediuni. This causes depolarisationof the cell which opens voltage sensitive calcium Autoradiographic localisation of [1251]ET-1 channels (VSCC). Ca2 entering the cells by ROCs and VSCCs caii also binding sites in rat brain indicate high El stiiulate release of Ca2 'froin intracellularstores. A third pathway receptor concentrations in a number of couples to VSCCs, increasingthe probabilitythat they will open in brain regions, particularly the hippocampus, response to depolarisation. effects of ET receptor inositol 1,4,5 - trisphosphate (P 3) and Functional diacylglycerol. In vascular smooth muscle activation in CNS neurones activation of both ET-A and ET-B receptors 2+ have important roles in results in increased Ca influx and release of ETs appear to function of central Ca2+ from intracellular stores by a variety of modulating the normal vasopressin pathways, some of which remain to be neurones. They cause release of slices and characterised (Fig 1). In cells with a neuronal and substance P from hypothalamic phenotype activation of ET receptors also release of a wide range of homones from results in a rise in intracellular Ca 2+ , again due both the anterior and posterior lobes of the release of to release from2 +intracellular stores and pituitary. ETs can also cause the partly of Ca from the extracellular neurotransmitters from neurones of the central partly to influx The application of ETs to medium. In some neuronal cell types however, nervous system. 2+ stores is striatal slices or cultured rat cerebellar granule d the release of Ca from intracellular 2 ones o r the r e ebe llar inan on the presence of Ca in nr entirely dependent the release of dopamine and and may not b neurones evokes the extracellular medium Thus it has become may, therefore, aspartate respectively. dependent on IP3 production. It to apparent that ETs have an important role be dangerous to assume that the second in play in altering neuronal function. messenger pathways activated by ETs central neurones are the same as those by which ETs alter neuronal activated by ETs in smooth muscle cells. The mechanisms
A B 0mV 0mV OmV -100m v 1 oo-100mV -1mV ET-1
Control
OrIj-1 '41100 0.2pA 5Oms I! C
ET-1
" Control ET-1 IpA. 50ms 20 30 40 50 60 70 80 time (sec)
2+ granule neurones Fig 2. Effect of ET-1 on Ca channel currents in cultured rat cerebellar on the soma of agranule neurone. Application A. Calcium channel currents recordedfroni a cell-attached patch with no effect on mean open time. of ET-1 to the bath causes a reduction in channel openingfrequency of ET-1 the Ca2+ currentwas reduced B. Averaged currentsfrom the same cell-attachedpatch. In the presence by more than 90%. 2 bathed in the same solution used for cell C. ET-1 did not alter the intracellularCa > concentration in cells of intracelludarCa2+ levels and attached recording.Cells were loaded with fura-2for fluorescent measurement tracesfrom 8 different somata are shown. ET-1 was added at the arrow. Cerebellar granule neurones g 3.Second ,,essenger pathwaYS coupled to ET receptors in cerebellar granule neurones. The G-protein ROC coupled ET receptors activate phospholipase C resultingin increased
production of P3 . However, release of 2 Ca +fromIP 3 sensitive stores does not VSCC appearto be involved in responses to ET, although other agonists can .4-protein/po stimulate release-fromn 1P -sensitive (+) ,'" stores in these cells. As with3 v~ascular ," smooth munscle, ET receptoractivation
also causes the opening of receptor H " operated channels and the resultant are not fulyuddepolarisation/ calciuni channels.opens Ca2+ voltageinduced sensitive Ca2+
ereleasefro intracelludarstores is also I P 3 + DAG seen. In granuilecells ET receptor , activ~ation reduces the open probabilitt! k~l~L-I "P+ 9of VSCCs in direct contrastto the Ca 2+ increaseseen in vascularsmnooth inuscle.
function are not fully understood at present. (Fig 2C). Neither is the inhibition due to G While it is clear that a rise in intracellular Ca 2+ proteins directly inhibiting the Ca2 + channels, may underlie many of the effects of ETs, the although, a cytosolic second messenger exact means by which this rise occurs varies pathway is probably involved. The interaction between cell types. The dependence of release of ETs with voltage-sensitive Ca 2+ channels in from intracellular stores on influx of external these cells therefore appears to be very 2 + Ca in some cell types, suggests that IP 3 different to that in smooth muscle cells (Fig 3). dependent release may not be as important as activat oflea + conductngepathsmay ianth aIn a ctiva tion of Ca cond u cting summary, there is increasing evidence which pa thw ays in th e p o n s t w r s a i m r a t r l e f r E n cell membrane. Since it has been reported that2+ points towards an important role for ETs in ETs can cause prolongation of L-type Ca modulating the function of neurones in the CNS. However, there may be substantial channel openings in vascular smooth muscle to differences in the signalling pathways utilised 2+ promote Ca influx, it might be expected that and / or the effects of activating these pathways they would do the same in central neurones. between smooth muscle cells (where ETs were first shown to act), and central neurones. the However, this is not the case. Fig 2A shows effect of ET-1 on Ca 2 + channel currents recorded from a cell-attached patch in cultured rat cerebellar granule neurones. ET-1 has no Hugh Pearson and BrigitteHeld effect on the duration of channel openings in Department of Pharmacology these cells. The main effect of ET-1 on these University of Leeds channels appears to be a prolongation of the closed duration of the channels, which results in a decreased probability that the channnels Further reading will open in response to depolarisation. The overall effect is one of inhibition rather than C Koseki, MImai,Y Hirata, M Yanagisawa and T Masaki 2 + augmentation of Ca influx through these (1989). Am I Physiol 256: R858-R866. channels, as is shown by the current averages GM Rubanyi and MA Polakoff (1994). PharmR'z 46: in Fig 2B. This effect is mediated by ET-A 325-415.3254)5 receptors. It is not due to a rise in intracellular 2+ Ca directly inhibiting the channels since Ca 2+ SS Stojilkovic and KJ Catt (1992). TiPS 13: 385-391. is absent from the extracellular medium. In the 2+ absence of extracellular Ca a rise in M D'Amico, MR Dashwood and TD Warner (1996). B I 2 intracellular Ca + does not occur in these cells Pharmacol118: 21-26. FUNDING OF MEDICAL RESEARCH SHIFT FROM GOVERNMENT TO THE PRIVATE SECTOR
t was with the establishment of Medical and this year saw a 5% overall cut in grants Research Council (MRC) in 1920, that the amounting to -£150 million. These latter cuts UK developed a structure that enabled will particularly burden the charitable sector physiological research to be actively who are under ever increasing pressure to fund encouraged and pursued nation-wide. The university and hospital infrastructural grants MRC was originally set-up to implement the to support the provision of major equipment, National Insurance Act of 1911 which stated maintenance of buildings and essential that a penny per annum per head of the support staff. It is also somewhat alarming to insured population would be allocated to note that 40% of all staff in universities are now research. Its principal objective was to on short term contracts funded largely from "advance knowledge so as to improve physical outside sources compared to only 20% 10 years and mental health and develop the biomedical ago. sciences as such, to maintain a fundamental capacity for research and to support higher The Wellcome Trust has unquestionably education". To this end, the Council runs two cushioned biomedical research against some of large institutes and a number of other the worst cuts, funding over 3000 people establishments located within university (including many support staff) in research and departments, medical schools and hospitals investing a substantial amount in the and supports project grants, fellowships, and refurbishment of laboratories, particularly in studentships. In 1978, the MRC budget was £62 universities. This huge financial commitment million and currently stands at £260 million, has only been possible through investment of money raised from the sales of its shares in Wellcome plc, which gave the Trust an income The Thatcherite Era of £340 million in 1995. I believe this money, along with substantial funds from charities like However, during the Thatcherite era of the late Imperial Cancer Research (£48 million) and the 70's and 80's, the source and structure of British Heart Foundation (£31 million), has research funding began to change. The proved essential in maintaining our government urged scientists to forge greater momentum and competitiveness in medical links with industry (particularly the related research abroad. However, obtaining pharmaceutical and chemical industries) and funds from the charitable sector will become the charitable sector. This was probably an increasingly more competitive, in a climate the MRC turns down the majority of attempt to focus research efforts into the where projects and the pharmaceutical development of technology which could "alpha-rated" eventually be translated into increased industries are now significantly reducing economic wealth.
Figures from the Association of Medical Research Charities (AMRC) show that industry now 10.2% 8.1% funds well over 50% of all health- NHS MRC 2.7% related research with the Dept. of Health charitable sector (combined 9.3% income of £360 million in Universities 1994/95) out-funding the MRC. Whilst this shift has benefited certain aspects of research, it is 12.9% becoming increasingly obvious Charities that the private sector is being asked to compensate for the reduction in government 0.5% spending in research and Other Research development, which has fallen by Councils £1 billion a year over the last 56.3% decade, and set to fall by a further 56.3% Industry £400 million in the next 4 years. Furthermore, university funding has continued to decline annually oliticsa
spending on research and development, disabling diseases. If one does however, Furthermore, the extra money that the manage to succeed in meeting the initial government made available after the 1993 criteria, then the application must first be White Paper on Science and Technology, has peered reviewed by the appropriate charity, been skimmed off existing research council receive an alpha rating, but even then only one budgets and shifted to joint ventures with application per charity will be accepted by the industry. NLCB. Thus, whilst the majority of the public wants medical research to be supported by the The National Lottery - a "double Lottery, legislation will largely prohibit whammy" for medical research applications unless it primarily targets small sections of the community and is from an Biomedical research in the UK is likely to suffer organization who has not yet attracted in more ways than one from the National substantial funding. Lottery. In the first four months of this year, charities say they have lost approximately £70 Lucie Clapp million, and it will be virtually impossible for The Rayne Institute them to recoup this money from the lottery due St Thomas' Hospital to strict criteria imposed by the National Lottery Charities Board (NLCB). However, it is hard at this stage to determine exactly what the long term effect will be, since the Lottery has The Wellcome Trust Prizet only been in existence for just under two years. Lis a unique opportunity Could you write There is however, a general feeling that the for professional Life the wxte Lottery will continue to siphon off donations Scientists to realize their the next best-selling from those charities who have little legacy dream of telling the world popular science funding and who therefore rely heavily on about their work. book? public donations. The hardest hit appears to be the cancer charities; one in particular lost a The Prize of £25,000 will great deal of money when it was forced to enable the winner to take a abolish its scratchcard game because of falling break from their normal demand after the Lottery was introduced, routine in order to write a Despite this, the total annual research budget book about the work to of the AMRC is still rising, although one which they are devoting should bare in mind that the average cost of a their career. project grant has nearly doubled in the last five years. The aim is to write a book that will educate, captivate After complaints by the research charities who and inspire the non-specialist were excluded from the first round of grants lay reader. awarded by the NLCB, it was announced that grants in 1996/1997 will concentrate on health, Leading popular science disability and care. Thus, charities were publishers HarperCollins! optimistic of receiving a sizeable amount of the Flamingo will be publishing and promoting the winning £150 million the NLCB will be responsible for work. distributing annually. However, it was recently conceded by Timothy Hornsby, chief executive Entrants must be professional Life Scientists who have had of the NLCB, that medical research would face no popular science books published to date. They must be fundamental barriers in securing support, not permanently resident in the UK or the Republic of Ireland. least because the Board's primary aim is to "make an impact on the lives of people For further information contact: suffering poverty, disadvantage and discrimination". This will mean that Marketing Officer applications will have to target people in these The Wellcome Centre for Medical Science groups. It seems ironic that such a policy will 210 Euston Road discriminate against a large fraction of medical London research which seeks to understand the NW1 2BE fundamentals of physiology and to develop medical technology. Such research may take Tel: 0171 611 8351 years to have an impact clinically, and yet Fax: 0171 611 8526 nonetheless, offers vital hope to eventually curing certain types of life-threatening or A POSITIVE SCIENTIFIC EXPERIENCE IN WOODS HOLE, MA, USA. science at the MBL. I was fortunate enough to be enthusiasm that epitomises This year the lab (15 invited, with Antony Galione, to the In addition to long days spent in is plenty of Marine Biological Laboratory (MBL) to teach hours is not unusual) there from a wide diversity of the Ca 2+ and Signalling Section of the Summer opportunity to learn are also going on at the Physiology Course at the Marine Biological seminars and talks that on the Courses uses Laboratory in Woods Hole, Massachusetts in MBL. The science taught as much as possible and the the USA. Two summers ago I had been to the marine organisms is testimony to MBL as a student on the Neural Systems and Physiology Course tee-shirt a tradition of all the courses Behaviour Course. Both courses were such this. Tee shirts are are usually thought up and positive experiences I wanted to bring the MBL at the MBL and of hours before the and the summer courses to the attention of designed in a couple to the printers! young physiologists in Britain. deadline of getting them
The MBL is an independent non-profit making Student section research and educational institution and was selected on very different bases, founded in 1888, so in American terms it has a Students are depending upon the course. In rich tradition. Since 1888 it has been a "mecca" often the students tend to be relatively for scientists in the summer largely because it Physiology graduate students (eg in their second or provides an excellent opportunity to use the young year - in the States this means that diverse marine organisms from the rich waters third their lab rotations they have decided of Cape Cod as models for understanding following lab in which to do their Ph.D) although fundamental aspects of biology. The summer on a were nearing or had just completed courses are a major part of life at the MBL several Ph.D. In addition the courses are although a smaller scientific community exists their value for students who have not there all the year round. A number of the long excellent in a physiological science before summer courses are of interest to specialised this years course there were 2 physiologists: and on mechanical engineers and 1 aeronautical engineer. None of them knew how to 0 Embryology: Cell differentiation and gene expression in early use a Gilson pipettman at the d nee pen start of the course and so all enjoyed a very steep learning curve! However knowledge Behaviour is not that important; the Neuroioly course is there to teach and one thing that the students had in common was their * Physiology: Cellular enthusiasm most often and Molecular Cell coupled with intelligence, Biology creativity and the ability to In i twork hard. This makes the In addition there are a number of teaching both easy and challenging! including imaging short courses techniques, computational neuroscience, Learning a wide variety of techniques vision research and rapid electrochemical measurements. The subject base of the Physiology course is really cell biology in the broadest sense. The longer courses tend to last from 6-8 weeks. Students learn a wide variety of techniques Physiology lasts for 6 weeks and then a such as protein and nucleic acid purification, proportion of the students have the cell and organelle fractionation and become opportunity to stay and do some post-course expert in their use of advanced light research on some aspect that they have found microscopy (including a number of different particularly interesting. Six weeks seems a long confocal microscopes) to study the actions of time but because of the pace of the Course time these proteins in vivo. A large feature of the goes very quickly; the course is intense in true course is the understanding of the cell cycle, American style but no less enjoyable for that. something I found as a neurophysiologist quite 2+ As both a student and a faculty member enlightening ! In the Ca and Cell Signalling I found it a very refreshing approach and section this year the students used fluorescence thoroughly enjoyed the openness and video microscopy on sea urchin eggs to study The 1996 Physiology Course T-Shirt
FRONT
BACK
Protocol for the MBL Physiology Course
1.Dounce homogenise brains in sea water (Woods Hole, MA)
2. Every morning, incubate in an alternating light dark cycle in Lillie Auditorium for 60 min ± 2 hours .... nap frequently
3. Macroinject 10 X Caffeine
4. Add glucose - PASTRIES AND COOKIES
5. Spin at high speed to remove cytoskeletal and membrane components
6. Add Big Daddy Moose (Big Daddy Moose)
7. Add SWOPE ATP regenerating system 3 times daily (the morning application may be skipped)
8. Triturate in Xs ice cold beer, kindly provided by Captain Kidd
9. At 3am transfer into 55C water bath at Stony Beach
10. Allow 1 picosecond sleep
Ca2+ signalling events at fertilisation as well as privilege to study at the MBL and presents a membrane events by actually recording from great opportunity. If your appetite has been the eggs (eggs are surprisingly excitable cells), whetted by this small introduction you can To complement the physiology they also used find out more by browsing the MBL web page sea urchin egg homogenates to look more or by writing directly for a Prospectus. Closing closely in vitro at mechanisms of Ca 2+ dates for applications are in March. mobilisation. All this and time for mini projects in 9 days ! http://www.mbl.edu As a scientific experience the courses at the The Marine BiologicalLaboratory MBL are second to none. If you feel that you 7 MBL Street have the drive and enthusiasm to participate it Woods Hole will provide you not only with new techniques MA 02543-1015 and knowledge but also with contacts and friends in the US. As far as funding goes, if you are accepted on a course then a number of grants are made available to you to pay the tuition fees; it is then up to you to find money to pay for the flight and the accommodation Ruth Einpson (which is quite frugal but cheap). I was Dept of Pharmacology fortunate enough to obtain a generous grant University of Oxforid from the Dale and Rushton Fund in 1994 which went part way towards the cost. It is indeed a / The other crux features in a poem called 'Invitation to Juno' (as the title implies, it is a T he Editor and Members of the wooing poem and concerns the mating, LMagazine Subcommittee wishes twinning or correlating of unlikely partners), which was first published in the Cambridge all our readers a Happy Christmas and Review in May 1928: and would like a prosperous New Year Weren't strips of our contributors who have Courage. to thank all heart culture seen supported our efforts over the last Of late mating two periodicities? twelve months. Please keep your I would greatly appreciate any information or ideas and suggestions rolling in so that suggestion about these cruces. The Magazine can represent all aspects p-, f the Society's work and interests. rfesrofEgihJohn HaffendenLiteaure Professor of English Literature University of Sheffield Sheffield Empson's 'Missing Dates' 2TD
Dear Editor, Biography - John Hughes Bennett I am working on an annotated edition of the poems of the late Professor Sir William Empson, for publication in the Penguin Dear Editor English Poets series, and would be most Following the symposium held last year in grateful if any of your readers can enlighten Edinburgh to mark the 150th anniversary of me with points of reference or clarification in the first identification of the disease leukaemia respect of two cruces that leave me quite by John Hughes Bennett (1812-1875), I am baffled. being encouraged to write the biography of Bennett. refer to an experiment The first, which seems to in transfusion (or perhaps perfusion?), features Initial research has revealed how little has been in one of Empson's best-known poems written on Bennett's life and his considerable achievements as a leading Edinburgh and teacher of the last They bled an old dog dry yet physician, physiologist how much of what did the exchange rills century and, indeed, more on conjecture than fact. Of young dog blood gave appear was based but a mouth's desires Bennett's reputation in France and the USA was equally high and he was one of the very authors of the period whose work That couplet appears to refer to an experiment few British translated into Japanese. in which an old dog was given a transfusion was with the blood of a young dog, but that the process unhappily revived the old dog's I have made reasonable progress on tracing his (sexual? carnal?) appetite for no more than a family history, although latterly this has been month. Indeed, it is perhaps meaningless, somewhat hindered by the fact that Bennett left though I may be incorrect in my layman's four daughters and his only son, a physician, understanding that a blood transfusion either died a bachelor. I have also been able to study
works within half an hour or so or else it some of Bennett's papers, and a number of who recall working to the John doesn't work at all? (Of course, it is also quite physiologists Bennett Laboratory established in 1901 possible that I am misconstruing the verses.) Hughes physiology have kindly However, Empson in his own note to the poem for experimental memories with me. I wonder if stated, 'It is true about the old dog, ot at least I shared their have particular information on reported somewhere'. The poem was any readers saw it or any Bennett 1937, and I believe he must Bennett and his work, published in or copies of textbooks written by certainly havecertinl read sucsuchhav aola reorreport (hegte(he may memorabilia, toheraro I would be delighted to hear from misremember it but he wouldn't make it up), him. If so, scientific in a newspaper or more probably in a journal of the time. (He had been acquainted Gordon Piller with J B S Haldane since 1929, and took a lively Ab'botswold, Great Wolford on Stour interest in all the sciences.) Shipstoi Warwickshire, CV36 5NQ P s l i at W
A DECISION IN THE LIFE OF ...... experience at the junior end of the scale, things are not necessarily better on the other side of the Atlantic. At the postdoctoral/junior Andrew Nicoll has decided to leave academic level, the salary to cost of living ratio researchand academiaand go into school is not particularly favourable in many parts of teaching. In this articlehe outlines what the USA: and you can forget getting a credit he thinks is good about British science, card or buying a house as a foreigner in America! In the UK, we have more five/ten but why he made the decision to leave it. year fellowship schemes than in the USA and more is done here to encourage junior am a fixed term lecturer in physiology at researchers to obtain their own grants. At the Bristol University and have decided to leave senior end, of the Ivy League universities only my post in January to become a school teacher. Brown and Harvard pay tenured staff a full In this article I would like to explain the reason salary, and "professors" in most of those behind my decision but at the same time to institutions have to find large chunks of their consider what I think are the good points salaries from external grant income. At some about British science. In a recent article in universities, upto eighty percent of an The Physiological Society Magaziiie (No. 23, individual academic's salary is derived from Summer 1996) Andy Randall described his external funding. experiences of returning to UK science. I do not share all of his often unfavourable Areas of concern comparisons between British and American science. In my view Britain is, in many ways, a Having said all of the above, there are rather good country in which to do research obviously difficulties here in Britain, especially and the problems we currently face are also the current low success rate in obtaining project being experienced in other countries. For me it grants. With the exception of the organisation of has sadly been the obstacles which have teaching (see below), many of our problems are outweighed the benefits of science in the UK. also found in the USA:
UK versus USA * Structural imbalances. As in the USA, only a minority of grant applications are * The general scientific environment. The funded in the UK, and this is only partly a atmosphere in the average British science result of lack of funds owing to this country's department seems to me to be co-operative, large social security and defence bills. The democratic and social. Although I personally Research Assessment Exercise has increased had good experiences in the American grant "demand" too. Every lecturer in our laboratory in which I worked, it is not difficult to find unhealthy competition between postdoctoral research assistants within scientific groups in the States. I have yet to come across one academic department in an American university with a common room!
* Funding. Funding is tight, but the amount of money per head of research worker in the USA is not orders of magnitude greater than here and is presently declining. The UK produces more scientific papers per unit funding than any other country, and the Wellcome Trust is the biggest medical charity in the world (larger than the US Howard Hughes). I worked in an Ivy League university neuroscience department as a postdoctoral assistant, where the roof leaked every time it rained and the department did not posses any specialist electronics technicians or a mechanical workshop.
* Career conditions. It is true that most senior American academics are better paid Measuringa students'oxygen consumption in a than their British counterparts, but in my physiology practicalclass. Project Grant Applications whether or not the problem is solved, and the 1989-1994 second is the notion that a project cannot be 1500 properly conceived unless it is testing a hypothesis. The potential negative effects on been Number of applications research of this approach have opinion. Obviously, anyone - Number of awards overlooked in my can frame a grant application in terms of a 1200 -hypothesis if they so wished, but by its very nature, science is open ended and many areas of study are not suitable to be hypothesis driven. In my own field (cortical circuitry), I Wcannot "test" the "function" of, say, strong Msuperficial layer inhibition but I can say with E 900 ------certainty that we will not understand the brain :unless we record from its cells! I also detect an Z even worse trait among reviewers of papers and grants: bandwagonism. Unless you are using molecular biology, laser 600 ------ photostimulation, infrared microscopy and triple whole cell patch recording (or whatever else is fashionable), then you must be asking the wrong question!
know, the 300 0 Teaching. As we all <9, <9<9" staff/student ratio is declining in British ,, Lt9 universities, approaching that in US and
, 0, ' Australian universities. We cannot go on V $teaching students in the way we have done so Financial Year up to now (regrettably). It is no longer justifiable to give individual student tutorials Reprintedfrom Grants and Supportfor Biomedical Research Welcome Trust, or have twenty academics spending hours 1995, with permission. agonising over degree classifications, average graduate is going eighty plus universities now wants to be especially when the or stock broker. armed with project grants and a platoon of to get a job as an accountant be academics who postdoctoral workers; every Head wants There must also, in future, and those who his/her department to be equipped with concentrate on research but this will only be programme grants and armed with a batallion concentrate on teaching, lecturers are not of research fellows. Hence there has never achieved when teaching class citizens. The been a better time to find a postdoctoral regarded as second to these facts many years appointment, either here or in the States. Americans woke up in my present However, the structural consequences of this ago: contact time for academics hours a year plus a are obvious: too many scientists being department average 130 My former supported by insufficient grant money and hefty load of administration. felt hard done by with being trained for jobs which will not be there supervisor in America administrative duties and later on in a career. I think I am correct in comparatively light saying that only one in seven postdoctoral only fifty student contact hours. workers in biomedical sciences in Britain will eventually take up a lectureship, a similar An offer I could not refuse number to that in the USA. A system in which work in everyone has a laboratory with five I completed my D.Phil in 1992, went to been in postdoctoral workers for every PhD student is the USA for a year and I will have Since clearly unstable and represents, without more Bristol three years by the time I leave. out of the secure long term prospects, a misuse of the being here, I have been awarded two applied temporary staff concerned, three project grants for which I have and I have also undertaken what I hope has and • Short termism. One of the hallmarks of been regarded as a fair share of teaching I have British science was always our willingness to administration in the department. before the end of undertake good quality work even if it does decided to finish two years feel I can compete not produce instant rewards. This potential is my contract because I do not research market and being undermined by two trends: the first is long term in the present efforts will the need to produce quick publications do not feel that any of my teaching ultimately benefit my career. There Output of academic papers published between seem to be too many good people in 1981-1990 their late thirties struggling to find permanent appointments and in Number of papers present circumstances, I do not foresee the much expected large number of 2000 vacancies becoming available when the "bulge" of academics appointed in the 1500 1960s begins to retire. Under the 1000 present academic regime, the current fashion of making so-called proleptic 500 lectureship appointments, while understandable, is rather short sighted 0- E M = 1 and potentially damaging to academic .,T, Q e, departments. A most stressful part of a 4 %. lectureship is the constant sense of Ql/j under achievement, whether that be from sweating over the outcome of Number of papers per $billion GNP (probably ultimately unsuccessful) grant applications or sitting in pointless 500 committee meetings re-inventing 400 the wheel with "exciting" teaching ventures. In short, there seems to be so 300 little reward for the effort one has to 200 put into the job. My new post teaching biology involves three hundred contact 100 hours per year, few extracurricular 0 activities and offers a significantly QL greater salary, a permanent contract •" '20,64 and "real" Summer holidays. My new school is largely boarding, and as they are giving me a house to live in as well, Redrawnfrom 'Science' Vol 258, pp 564 (1992). it was an offer I could not refuse. Source: Science and Technology Agency: ISI Science IndicatorsData Base. Obviously, I would have preferred to stay in higher education (HE), but post-16 education Researchers try crystal ball gazing to in the UK is changing and I hope my move into predict future school teaching will not necessarily be a one way jump. With universities offering access A team of futurologists put together by courses and schools going into college level British Telecom has tried to predict when certificate teaching, I think the boundaries artificial hearts, livers, and kidneys will come between school and university teaching into clinical use. It estimates that there will responsibilities are becoming blurred. What is be an artificial pancreas by 1998; artificial more or less certain is that whoever wins the blood by the year 2000; and artificial heart by next election, the state funded higher 2010; and the individual's genome will be education sector will not get significantly more part of their medical record by 2015. money. This means that, unlike the salaries of MPs, academics will not get a 30% pay rise to BMJ 313 21 September 1996 p.70 6 bring them back to 1970s levels. Hence, Source: SPIN improvement in conditions in HE will have to be brought about by changes the structure of Research 'golden egg' research and teaching in the UK. I therefore leave HE with mixed feelings. Teaching the t rim Radford, Science Editor, states that Tiffanys and Jamies of this world will be, as J leading scientists have warned the they say, a challenge, but the aims and Government that "ignorant and insensitive" execution of the job are clearly defined and plans to manage university research on therefore I hope the results will ultimately be business lines "would kill a goose that was more rewarding. still laying golden eggs". Andrew Nicoll Departmentof Physiology Guardian 10 September 1996 p.9 University of Bristol Source: SPIN FOR DEVELOPMENT OF ELECTRICAL IMPEDANCE TOMOGRAPHY - BUT IS IT IMAGING ELECTRICAL ACTIVITY IN THE BRAIN PHYSIOLOGY AS WE KNOW IT ? depolarizations) with a time course of Iremember standing near the passenger milliseconds, and a spatial resolution of a few arrivals exit at San Francisco airport, on cubic mm. CT scanners were just coming into August 30th 1982. I had several problems, but clinical use at that time; my idea was to try and the most pressing was very practical : I had develop a device which used similar image two suitcases, each weighing 70 lb (Continental reconstruction procedures, but was a thousand Airlines allowed that much in those days). I times faster and produced images of brain needed some US change in order to borrow a activity. trolley, and the nearest foreign exchange booth was miles away, farther than I could carry my In my second year at Berkeley, I sat in the bags. I had heard about America, and knew library, and attempted to analyze every my bags would probably be pinched appropriate technique I could find. Somewhat immediately, or detonated by the bomb squad, to my surprise, two techniques did appear to if I left them unattended to get the change. be suitable in principle - Electron Spin Resonance and Electrical Impedance The trouble was, this was the least of my measurement (Holder, 1989); the latter has problems .... I had just left a promising medical been the focus of my efforts since, because the career and my wife to be, in London, in order is more advanced. Of course, to embark on a research plan which was technology Positron Emission Tomography (PET) and now uncertain to say the least, and clearly foolhardy functional Magnetic Resonance Imaging can in the opinion of several of the experts I had produce good images of brain function, but consulted. With great ingenuity, I managed to this is of metabolic recovery processes such as solve the immediate problem. Within suitcase blood flow or glucose utilization, which occur carrying distance was a car rental booth. with a time course of tens of seconds. They do Instead of taking the bus to Berkeley, where I not give any information about the electrical was to start a Master's degree in Biophysics at activity over milliseconds, which is the ripe old age of 29, I rented a car. This way presumably the immediate substrate of brain I had an easier ride and retained possession of function. The idea was : electrical impedance my worldly goods for the outset of my research across neuronal membranes is well known to career; on the other hand, it did cost more. This change during activity, due to the opening of seemed like an omen; there were clearly going ion channels. It must therefore also change to be numerous obstacles, but I hoped that across volumes of tissue during activity when optimism and initiative would always be able measured with external electrodes. This could, to overcome them. in principle, be reconstructed into tomographic as images of impedance can be - a technique for imaging images, Required a method similar to X-ray CT. The depolarization produced by neuronal unknown factor was whether the impedance resulting from depolarization would It mainly started with Colin Blakemore and Joe changes enough to yield scientifically useful Herbert in 1973, who captivated many of my be large year of medical students at Cambridge with images. their lectures on the CNS. A year later, during Physiology Part II, John Robson intrigued us How it works with lectures on how the CNS coded Electrical Impedance Tomography (EIT) works information. I felt that I could think of no by making multiple measurements from a ring better career than to research into information a electrodes placed around the body part of processing in the CNS. Later, as a clinical interest. Many such measurements are made student at UCH, this was realized in concrete rapidly from differing electrode combinations, form. It seemed to me that there was a gulf which are then processed rapidly on a PC to in neuroscience between the behavioural produce a single tomographic "slice" image sciences and cellular physiology - it was not through the plane of the electrodes. The known how information was moved around advantages of EIT are that it is fast, completely the CNS, and in what form. The reason safe (as far as is known at present), inexpensive appeared to be that no suitable measurement and portable (Holder, 1993). The first technique was available; what was needed was commercially available prototype, called the a medical imaging device that could image "Sheffield Mark 1", produced images at up to neuronal depolarization (either as action 24 per second, using an applied current of 5 potentials in white matter, or synaptic graded w4ZP mA or less at 50 kHz, cost about £15,000, and to current flow. I have now built up a group of comprised a box about the size of a video 6 or so medical physiologists, clinicians and recorder attached to a PC (Fig 1). There has engineers, and we have solved most of these been burgeoning interest in the method: about problems, at least in saline-filled tank thirty groups world-wide are now working simulations. For example, we can image actively in developing new systems. Almost cranial contents using scalp electrodes, by all are based in medical physics or engineering injecting current through diametrically departments. It has been used to image opposed electrodes. This reduces spatial pulmonary ventilation and perfusion, the heart resolution, but this can be restored by using beating, gastric emptying, and, more recently, more electrodes - we now use 64. We now have lung water, but has not yet found a widespread two newly designed systems, ready for clinical clinical use. The main problems are a relatively trials in human subjects. From a physiological poor spatial resolution of about 15% of the point of view, I elected, as a first step, to image electrode ring diameter (with 16 electrodes), the relatively large and long-lasting impedance and a wandering baseline, changes which occur in the brain during events such as stroke or epilepsy, due to cell swelling during anoxic depolarization, or accompanying blood flow and temperature changes. We have therefore produced the first EIT images of cerebral ischaemia, spreading depression (Boone et al, 1994, Fig 2), visual and sensory evoked responses (Rao et al, 1996, Fig. 3), and, recently, epilepsy (back cover), all in anaesthetized rats or rabbits with electrodes placed directly on the brain. These are in descending order of difficulty; during stroke, impedance changes by about 50% of the baseline value and this lasts tens of minutes, whilst those during evoked responses or epilepsy are a few per cent over a minute or two. Baseline variability in the images is, by contrast, about 1% over a few minutes.
How far are we away from the final goal of imaging neuronal depolarization ? The problem may be reduced to two simple numbers - the size of the impedance change during activity, and the sensitivity of the EIT Fig 1. The Sheffield Mark 1 EIT system being used to machine. Our best estimate at present is that image lungfunction. images were collectedfrom there is a gap of about two orders of either the upperor lower ring of electrodes. magnitude. We have measured square wave impedance changes during evoked activity in crab nerve and brain. Whilst a healthy 1% or Developing EIT systems for imaging so in crab nerve, it is about 0.03% in brain the brain during physiologically evoked responses, presumably because a lesser proportion of On return from Berkeley, I decided to try and neurones are discharging and they are less combine the development of EIT systems for synchronous (Boone, 1995). On the other hand, this purpose with a career in clinical existing EIT systems have a baseline noise of neurophysiology. Following two years as a about 1%. However, this is in existing systems registrar in Neurology, I moved to the which operate with applied frequencies of Physiology Department at UCL in 1986, and hundreds of Hz or more. In single channel have remained here since, maintaining various prototype square wave impedance systems we concomitant degrees of clinical activity. I now have designed, the noise can be reduced to far spend about half my time performing hospital less - about 0.01%, with averaging. Even if the work in Clinical Neurophysiology. device works, will it be scientifically useful ? I think so :At the least, it could provide similar It became rapidly apparent that imaging in the information to PET scans of brain activity, but head had particular problems, for which no be inexpensive and non-invasive and, existing device was suitable. The major furthermore, show the order in which different difficulty is that the skull presents an obstacle areas are activated. At the best, it could enable Techn An Tecnoog
:ecrd lDiagramn of cortical spreading -- >-TL:< , depression Xi' - " " ring Ant
18-20mm R
Post IT images every Impedance change 15s 15r
spreadingdepression in Fig 2. Electrical impedance tomography (EIT) images collected every 15s during cortical of the exposed brain. The the anaesthetised rabbit, using a ring of 16 electrodes placed on the superiorsurface above. Cell swelling during regions of brain affected by the spreading depression are shown diagramatically The onset is correctly seen in spreadingdepression causes an impedance increase,which is seen in the EIT images. of the EIT system renderit the images; later spread is seen to occur with the correct time course, but the physics Physiol Meas, 15, A189-A198). more sensitive to changes at the edge. (Boone K, Lewis AM and Holder DS (1994)
mathematical analysis of the envelope Is this physiology? waveforms of activity along white matter tracts a personal point of view, this last decade or grey matter nuclei. With a resolution of a From been easy. It has not only been that few cubic mm, it obviously could never has not is interdisciplinary - it covers address the cellular coding of information the research medicine, whole animal and processing, but I think it could be of vital clinical physiology, electrical engineering and assistance in pointing to which areas were cellular In fact, the bulk of the work over involved in different tasks, and which were mathematics. past three years has been in developing abnormal in different disease states. It is not the reconstruction algorithms and hardware, yet clear whether we will be able to overcome new the emphasis will revert to the technical difficulties and produce the although once the new systems are working. "dream" machine. Our current position is that physiology main difference is that this research is "top we are confident we can measure impedance The (i.e. there is a clear application, and the changes during evoked activity in the brain, down" sciences covered serve as a means to with electrodes placed directly on the brain; various in contrast to the "bottom-up" whether it will be possible with an imaging an end), approach of almost all of my system with electrodes placed all over the scalp investigative colleagues. is still a formidable, but not necessarily physiological intractable, problem.
Electrode Ring
LRj~
Expected response
LIT images every 30 seconds was carriedout over 2.5 Fig 3. Example ofEIT images recordedduringbinocularphotic stimulation. Stimulation Orientation : Up - anterior, minutes (indicated by the line) at 10 Hz. Images were recorded every 30 seconds. left/right as shown. The principal impedance decrease of 2.5% is over the occipital cortex. As a result, my efforts seem to sit uncomfortably objective procedures for calibrating new within any of the traditional disciplines in the multifrequency EIT systems using biological life sciences or medical physics. It feels like I objects in fluid filled tanks. However, deep have had to divert a lot of energy in down, I feel that research should be like cricket establishing a physical base, creating new : it is the playing, not the winning, that matters. equipment from scratch, and setting up an As long as the question is worthwhile, the interdisciplinary group. On the other hand, outcome should be useful, whether positive or the novelty of the ideas appears to have made negative, provided the work is technically funding the least of the problems - I have been satisfactory. Combination with a clinical career generously supported by the MRC, first as a has meant a dilution of the time I have had training fellow and, latterly, with project been able to devote to acquiring the difficult grants, and by the Royal Society under its skills for physiological research. On the other magnificent University Research Fellow hand, the scientific compensations are the scheme, which gave me the medium term opportunity to be stimulated by real life security to build up my group. Is it Physiology problems in the patients, and the financial ? My group is presently based in a department security to pursue difficult problems with an of Physiology, which, I believe, is the most uncertain outcome. Would I do it all over again appropriate base. With a medical ? - definitely, but next time I think I would pack / physiological training, I think that our lighter suitcases and take the bus. principal advantage is the ability to define the application, and then refine the engineering David Holder design in the light of rigorous experiments in Departmentof Physiology humans or physiological preparations. At University College London present, whilst we are trying to develop the References: technology, this does not address any fundamental physiological issues, but it Holder DS (1987). The feasibility of developing a certainly requires some rigorous applied method of imaging neuronal activity in the human physiology in designing and running the brain: A theoretical review. Med Biol Eng Cotnput 25:2-11 experiments, and understanding the results. Holder DS (ed.) (1993). Clinical and physiological applications of electrical impedance tomography. UCL Will it all been worth it ? Press, London I don't know yet whether the ultimate goal will Boone K, Lewis AM and Holder DS (1994). Imaging of at cortical spreading depression by EIT: implications for be achieved, but it seems very probable that, localisation of epileptic foci. Physiol Meas 15: A189-A198 least, lesser spin-offs will occur along the way. For example, there is a good chance that our Rao A, Hanquan Y and Holder DS. Non-invasive EIT systems could be used as an early warning imaging of cortical evoked responses by Electrical system for brain injury in neonates or to Impedance Tomography in the anaesthetized rabbit. ]. localize epileptic foci in severe epileptics prior Physiol. (in press). to surgery. We have also made several Boone K (1995). The possible use of applied potential technical contributions to EIT - for example, a tomography for imaging action potentials in the brain. new class of algorithm, and the pioneering of PhD thesis, University of London. SOFTWARE REVIEW 0 The CardiovascularSystem # Andromeda Interactive Inc.
A ndromeda Interactive, whose UK division word. The product can, at its simplest, run is based in Abingdon, have launched a directly from the CD on a stand-alone machine, series of computer assisted learning programs without eating up valuable hard disk space, or, supplied on CD rom which run on both licence permitting, sit on a network such as Macintosh and PC machines and cover, in Windows NT. some detail, the anatomy, histology and physiology of the cardiovascular system.. The I received three modules to review. The first, investment in this product is considerable, and entitled Functional Anatomy of the Heart; the has involved the consultation of an impressive second Cellular Mechanisms in CardiacPhysiology, team of experts in the cardiovascular field. and the third; Cardiac Muscle Action and Blood Consequently, the material, in its tangible and Flow. The format of all three is based upon a visible form, is not cheap in either sense of the menu-selected set of tutorials which are richly TecigAn Tecnoog
in the heart and .7 .events the cardiac cycle.... an ever popular target for computer-animated courseware quickies. Here though, some of the best graphical animations of its type are to be found.
Each module comes :K with a quiz bank which links back to the taught material. There are also glossary files and reference lists linked to the material, as well as a separate disk of images that can be used for bona fide teaching purposes.
No product like this is going to be perfect. I found my attention A capturedframe from part of the tutorialon arterialbaroreceptors, repeatedly thrown The originalis of course in full colour, every time I heard the "glommy-ruler" graphical voice annotated sequences which American-accented voice say capillary ball, and the user can move through and jump around. in reference to that little hiccups in starting Seeing the graphics for the first time reminded there were some minor on the latest me of my first exposure to Netter's artwork in Module 1 on a PC (not a problem Gray's Anatomy and Scientific American. The release). voice-overs, in clear-honeyed American, can well in a library that also be viewed or printed as text, although it is This resource would work CDs. The best to listen as you watch, especially in the offers facilities to run multimedia guided teaching build up diagrams and animations. Some of material could also be used in around a the less interactive parts the tutorials feel as sessions of up to four people if the though they are being delivered via a machine, or even in the lecture theatre, the necessary broadcast-quality video with the user holding teacher is lucky enough to have I was not a remote control. Each topic can be followed in projection resources at his disposal. a network, a logical progression by default, thanks to able to test the product over subject to simple intuitive navigation controls, and it is although it can be used in this way and a large also possible to set up a prescribed sequence of appropriate licence agreement, material, or to jump from topic to topic. reserve of disk space!
by the For obvious reasons I concentrated on modules Free 30 day trial copies are offered 2 and 3 which cover the more physiological manufacturer. aspects of the cardiovascular system. Module at 9-15 The 2 covers the basics of muscle contraction (and Andromeda Interactive Ltd are 3PX, this area is useful for teaching the sliding Vineyard, Abingdon, Oxfordshire, OX14 filament concept as applied to skeletal muscle Tel: 01235 529595, Fax: 01235 559122, too), autonomic control, and control of blood email: [email protected],Web pages: pressure by nervous and renal mechanisms. As http://www.andromeda.co.uk/medical.html a lecturer and courseware developer in this area I was impressed by the attempt to cut through the confusing issues and yet still put over a coherent explanation of current Jim McGarrick thinking. (j. [email protected]) Deartinentof Plnlsiology basics of circulatory Module 3 deals with the St Thomas' Campus plumbing, and the relationships of pressure, moving on to the electrical flow and resistance,
iI TcnAnd T
MICROELECTRODE TECHNIQUES FOR CELL PHYSIOLOGY 4 -18 SEPTEMBER 1996 MARINE BIOLOGICAL ASSOCIATION, PLYMOUTH
Now in its thirteenthyear and still in greatdemand, this workshop is taught by and has taught many of The Society's members. Furthermore, through the Dale and Rushton Funds, The Society provides bursariesfor students *to attend this course.Jon Robbins highlightswhy this course is so successful, from both sides of the educationalinterface. The Students' Perspective Sixteen lucky participants from the UK, The students would like to thank the Poland, Australia and Germany gathered at the organisers, teachers, companies and grant Plymouth Aquarium, home to the Marine authoritiesfor their support. They hope that Biological Association (MBA), to attend this m m year's workshop which was organised by y more generationsof young researchers David Ogden from the National Institute for will be given the chance to widen their Medical Research, London, and Colin scientific horizons in Plymouth. Brownlee, Deputy Director of the MBA in Plymouth. With the historic background of the A Teacher's Perspective squid giant axon work by Hodgkin and Huxley in the 1950s, Plymouth is ideally suited The advertisements for this year's course went for these annual workshop. out in November 1995 with the characteristic squid-action potential motif, which was Over a period of two weeks the course covered originally drawn by Barbara Fulton. The a wide range of currently used cell advertisements obviously work, as around 60 physiological techniques ranging from voltage applicants apply each year for the sixteen clamp to more recent methods such as single places. This means that in May 1996 a number cell RT-PCR and flash photolysis using of people involved with the course had a preparations mainly from locally collected difficult task assessing the applications and marine animals. The students were given the selecting students. This procedure is carried opportunity to work on a variety of out in a secret location (near the old M15 experimental set-ups to gain 'hands on' building in London) and involves much experience. For the students to be taught by so discussion until a consensus is reached. many experts in their fields (students were outnumbered by teachers by approximately Things then go quite for a few months until a 2:1) is a rare and invaluable experience. For few weeks before the course is due to start, most of the teachers, the Plymouth Workshop when David Ogden gently reminds you of a has a firm place in their calendar and they commitment you made in a weak (relaxed) have been coming for several years. The moment, to teach on the course, again or for commitment of the teaching staff is the essence the first time. Then a round of frantic phone of the course and the wide ranging knowledge calls ensue, organising equipment, people, and experience was very much appreciated by accommodation and food. From a teachers all. Most research institutions cannot match point of view the course is spilt into two the variety of techniques taught in Plymouth sections: The first "week", involves arriving at and therefore workshops such as this are the MBA to an empty room, a pile of boxes and important to allow young scientists to the prospect of building three patch clamp, two appreciate the scope of electrophysiological single electrode voltage clamp (SEVC), a twin techniques available. After long hours in the electrode voltage clamp (TEVC), one ion lab, staff and students raised the profit of a sensitive recording, one dye injection and one local pub which is, conveniently situated dual excitation fluorescent indicator set ups in between the Aquarium and the accommodation, three days (Details on these and other Not even the weather gave any reason for techniques will be found in the course book, complaint, apart from the permanent temptation Ogden, 1994). As you might imagine its not just to take the rigs outside. Unfortunately, due to a the soldering ions that get hot! However, lack of portable power supplies, this was not without fail the set-ups are ready for the first possible. round of student practical workshops, the Tahn An Technology
of demonstrations occur throughout the course, including capacitance measurements of exocytosis and endocytosis, flash photolysis in .... [k~i///techniques squid skin andand approachessingle cell areRT-PCR. supported All theby
lectures given by specialists in the field.
Although teaching on the course can be as much of a test for the teachers as the students, ° -the fact that many teachers come back year after year is due the great satisfaction we get from seeing the students succeed as well as the help and support we are previliged to from the - __- members of the MBA.
Thanks to all the students, teachers, MBA staff, - - companies and funding bodies who make this annualevent possible. In particular,I am grateful ° -______to Peter Appenrodt, Brigitte Held, Alastair 1 Miller and Amanda Smith for their contributions to this article.
For information on next year's course contact: Dr. D. Ogden, NIMR, The Ridgeway, Mill Hill, Fig 1. Calcium (upper) and inward rectifier (lower) D o den, N MR T d , H current traces recordedfrom ciona intestinalis London, NW7 1AA. gametes during this year's workshop. Currents were recorded using single electrode voltage clamp. Jon Robbins Calcium currents were evoked by depolarisingvoltage PharmacologyGroup steps from -80 m V and inward rectifier currents were Biomedical Science Division evoked by hyperpolarisingsteps from -50 m V King's College, London Reference students having already honed their skills at using microscopes and building electronic Odgen, D. (1994) Microelectrode Techniques: The circuits. Plymouth Workshop Handbook (2nd Edition), Company of Biologists Limited, Cambridge. The second "week" usually involves a fresh set II of teachers who take over and run two more workshop rounds. Teaching on the second ToI's week means that you do not have to construct r the set ups but it does involve packing up at the end. How we get everything back in the -F 7 right boxes is surely evidence of telepathy! What all teachers on the course have to do, what ever week they are teaching, is go through a crash course on marine biology, as in the tradition of Hodgkin and Huxley we use marine (or at the very least invertebrate) preparations whenever possible. The gametes from ciona intestinalis (sea squirt) are used for SEVC, a ganglion from helix aspersa (garden snail) for TEVC, the patch clampers used dissociated alloteuthis subulata (squid) stellate Kneeling from left to right: Roddy Williamson, Amanda Smith, Alistair Peter ganglion cells and raja clabata (skate) cerebella Miller, Tim Cheek, Lucia Sivilotti, Peter Mobbs, John Rostas, Dempster. slices. Astacus fluviatilis (crayfish) muscle are Appenrodt, John used for the ion selective electrode experiments and their swimmeret ganglion for the dye Standingfrom left to right: Grace Wo/cik, Kei McLeod, Virgiiia Owen, Gunthrope, injection experiments. The only preparation Ken Waim, Eleanor Strain, Michael Pasternack, Martin that could be called "mammalian" are the PC12 Nick Manison, Peter Wood, Jane Crawford, Boris Barbour, Held, Michael Ackley, cells which are used for intracellular calcium Kate Wareham, Edward Childs, Brigitte Maike Glitsch, measurements. Paul Goodwin, Geralad Finnerty, Marti Thomas, Gregor Zupawcic, Maggie Riccio, David Ogden, Thierry Capiod, As well as the "permanent" set-ups, a number Jon Robbins, Alasdair Gibb. Techn An Tecnolgy
MOLECULAR PHYSIOLOGY TECHNIQUES WORKSHOP 2-14 SEPTEMBER 1996 UNIVERSITY OF GLASGOW
Both physiology and molecular biology can gain from applying their technology to the either discipline. For a number of reasons, molecular biology has been slow to make an impact in physiological studies in the UK. Many of the problems stem from the very specialised language that has evolved to assist communication between 3like minded molecular biologistsbut now acts as a barrier. Photographof University Tow7er: University of Glasgow.
T he first Molecular Physiology Techniques response to the "flier" distributed to members Workshop was held during the first two through the Magazine. At the last count, over weeks of September at the University of 110 full applications were received by the Glasgow. The intensive two weeks of "hands- Society. on" learning resulted from the hard work and relentless enthusiasm of Richard Boyd. While On the 1 September, the 12 participants of the Committee Secretary of the Physiological workshop arrived in Glasgow and the weather Society, he began to explore the possibility of met everyone's expectations for the West of establishing a workshop to teach molecular Scotland - overcast, cold and very wet. All biology to physiologists in training that was the participants were young scientists (pre unashamedly based on the successful doctoral or post-doctoral) located in laboratories Plymouth "Microelectrodes" course. The ethos all over the UK and even St Petersburg. I must was to create a course where we could teach as admit that I had grave reservations; firstly, that much as possible by "hands-on" laboratory it would be possible to teach molecular biology practical work, where students would be given from scratch to really very sophisticated a series of lectures mixing "how-to-do" type techniques in the space of two weeks and, lectures with talks describing the successful secondly, that we could cater for the different application of molecular biology techniques to levels of background knowledge of the physiological science and finally, to provide an participants and keep everyone occupied and environment where the students and teaching learning. However, the course was a success; staff could interact and form friendships, even the rain stopped for the entire two weeks and the sun shone most of the time. An Overwhelming Response
After the first meeting to discuss the feasibility V of arranging such a course, the process slowly MS_; evolved over the last few years. A financial commitment was made by the Society. The Wellcome Trust were persuaded by Richard Boyd providedand by Peter the Society.Stanfield Last to matchsummer the Richard funds '/ - visited the University of Glasgow to persuade the newly formed Institute of Biomedical and Life Sciences to host the course. Over this last __ - year, the course slowly took shape, guided by a ", .. committee comprising Richard Boyd, Peter Ale Stanfield, David Miller, Annette Dolphin and me. While we were all committed to idea of introducing molecular biology techniques to The 12 participantsof the Molecular Physiology Techniques Workshop physiology, I wasn't prepared for the together with teaching staff and the technical support staff involved in overwhelming number of applicants in thefirst week. A Full Programme The first week essentially provided a basic Glasgow to lecture. A feature of the success of cloning type practical run in parallel with the course is an "email group" has been measuring fos mRNA by Northern. The formed to encourage everyone to keep in touch second week emphasised more specialised and help teach. techniques including COS cell and oocyte expression, sequencing and mutagenesis The original intention was that the course and finally, a two day practical organised by be run annually, as is the Plymouth course, Annette Dolphin on antisense technology with initial funding from the Wellcome and single cell RT-PCR. The Trust (who have generously days were long; always provided partial funding for starting at 9 am and on - three years to IBLS at the many evenings a lecture was University of Glasgow) being organised for 6pm. The only matched by The Society. The free day was Sunday as f obvious great success of the a computer practical on first course suggests that this accessing the databases expectation is reasonable and through the web was that the clearly-apparent organised on the Saturday. need for such training of Despite the attractions of many younger Physiologists Glasgow night-life all 12 throughout the British Isles participants turned up for every session. will require a continued financial commitment by the Society to this venture, although at a The success of the course entirely resulted from level which the committee feels is appropriate the enthusiasm and commitment of everyone given the many competing financial calls as the who took part; the participants who were fun St Petersburgh IUPS Congress approaches. to teach and interact with, all the people who Janet Allen ran and organised the practical sessions and Instituteof Biomedical & Life Sciences everyone who made the long journey to University of Glasgow
W hat is Derek ., Bacon, who was Michael de Burgh daly's 4 technician for over 30 years, saying to Tilli Tansey during an oral history interview for the Society archives?
(Photographby the courtesy of Martin Rosenberg.) A bottle of wine will be awarded to the person L who, in the opinion of the judges, submits the most amusing caption for this photograph. Entries should reach the following address by 6 January 1997: Saffron Whitehead (Caption Competition) Department of Physiology St George's Hospital Medical School Cranmer Terrace Tooting. London SW17 ORE IMF ONLINE RESOURCES with a wide range of subject areas covered there will almost certainly be projects of n this issue of the Netwatch column we'll interest to most physiologists involved in take a look at some of the online resources teaching undergraduates. Much of the available that should be of interest to software is free to download directly from the physiologists though much of what follows TLTP WWW site. will also be of general interest. The Computers in Teaching Initiative It seems that these days one connot escape (CTI) was set up as an ongoing service to reading about the Internet and World Wide the higher education community to Web (WWW). It may come as a surprise encourage and support the use of computers therefore to hear than many members do not in teaching. There are CTI centers realise the Physiological Society has been for most academic disciplines though running its onw WWW server for some time as physiologists the centers of most interest not. Developed in association with Cambridge are the CTI Center for Medicine University Press, Physiology Online contains a (http://www.ets.bris.ac.uk/cticm/home2.ht) wealth of useful information and makes an and the CTI Center for Biology ideal starting point for the novide WWW (http:/ /www.liv.ac.uk/ctibiol.html). Both sites physiologist. As well as being able to search the list details of most of the important projects contents of all journals produced by the involving all aspects of the use of computers in Physiological Society there is now the facility biomedical education. Both sites also have lists to view abstracts from recent issues of the of software teaching packages many of which Journal of Physiology online. Another of are free to download. Armed with the Physiology Online's useful features is a list of combined URLs of the CTI centers and the all know physiology department WWW sites TLTP projects even the most sceptical Internet both in the UK and abroad. Naturally there is user could not fail to find some project of an online noticeboard on which you can read interest, often including free software to the latest news from the Society and there's download and especially of interest to those even a situations vacant page. physiologists involved in teaching.
Physiology Online can be found at As ever we are always interested to hear about http: / /physiology.cup.cam.ac.uk/ any IT initiatives members of the Society are involved in, so please keep those messages The fact that you can now read the abstracts of coming in. As we reported in the last issue of papers in recent issues of the Journal of the Magazine, the Physiological Society has Physiology is just one indication of the trend started its own computers in education towards electronic journals. There are now initiative, the Teaching Resource, so if any many peer-reviewed scientific journals that are member of the Society would like further available in some form on the Internet information of that and any other IT including high profile journals such as Science project, please do get in touch. Please (http: / / www.science.com /) and Nature address all correspondence to myself at (http://www.nature.com/). New Scientist is [email protected] or telephone 0121 414 also online (http://www.newscientist.com/) 3255. as is Scientific American (http://www.sciam.com/) and the former has a very comprehensive site avid Dvies including a searchable jobs database. There are Departmentof Physiology several good starting point to find other discipline specific online journals. One of the best is the WWW Virtual Library index of academic reviewed journals (http://www.edoc.com/ejournal/academic.ht From science to psychic snake oil ml). The range of subjects covered by these journals is quite staggering. Christopher Dunkley describes the decline of British state television in broadcasting Finally, we move from online journals to online science programmes. It seems that teaching projects and initiatives. Many projects astrology, aromatherapy, ley lines and the funded by the Teaching and Learning like have replaced "serious" screening Technology programme (TLTP) have now entered their final stage, the delivery phase. Financial Times 4 September 1996 p.19 Details of all TLTP funded projects can be found at http: //www.icbl.hw.ac.uk / tltp / and Source: SPIN in Natriuretic effect of non-pressor doses of endothelin-1 August 1996 Vol. 494 part 3 conscious dogs SANDGAARD N. C. F. & BIE P. cl S E809 R ate tas por in s e p e a calcium -activated c on calcium in turtle hair cells with Monitoring transport in sheep parotid secretory cellsSTEWARD TUCKER T. R. & FETTIPLACE R. 613 Bicarbonate potassium channel M. C., PORONNIK P. & COOK D. I. 819 Ca2 influx and activation of a cation current are coupled to intracellular Ca"+ release in peptidergic neurons of Aplysia Calorigenic effect of diiodothyronines in the rat LANNI A., californica KNox R. J., JONAS E. A., KAO L.-S., SMITH P. J. S., MORENO M., LOMBARD! A. &GOGLIA F. 831 CONNOR J. A. & KACZMAREK L. K. 627 Growth and differentiation of fast and slow muscles in fetal and the effects of hypophysectomy JAVEN I., WILLIAMS N. Calcium gradients during excitation-contraction coupling in cat sheep, I. R., LUFF A. R. & WALKER D. 839 atrial myocytes HiSER J., Lipsius S. L. & BLATrER L. A. 641 A., YOUNG 2 afferents evoke disynaptic EPSPs in cat Effect on the indo-1 transient of applying Ca " channel blocker Group I extensor motorneurones during fictive locomotion for a single beat in voltage-clamped guinea-pig cardiac hindlimb extensor M. GUERTIN P., JIM] NEZ I. & MCCREA D.A. 851 myocytes LEVI A. J., Li J., SPITZER K. W. &BRIDGE J. H. B. 653 ANGEL J., of human locomotion BORGHESE N. A., Cyclic GMP-gated channels of bovine rod photo-receptors: Kinematic determinants F. 863 affinity, density and stoichiometry of Ca-calmodulin binding BIANCHI L. & LACQUANm sites BAUER P. J. 675 Respiratory mechanics during exhaustive sub-maximal exercise humans CIBELLA F., CuTrrrrA G., The mechanism of calcium channel facilitation in bovine at high altitude in healthy M., ROMANO S. & SAIBENE F. 881 chromaffin cells ALBILLOS A., GAND(A L., MICHELENA P., KAYSER B., NARICI GILABERT J., DEL VALLE M., CARBONE E.&GARcAA. G. 687 Eccentric exercise decreases maximal insulin action in humans: + AsP S., DAUGAARD J.R., KRISTIANSEN effects of fl-stimulation on the Na-K pump muscle and systemic effects The 891 current-voltage relationship in guinea-pig ventricular S., KIENs B.& RICHTER E. A. myocytes GAO J., MATHIAS R. T., COHEN I. S., SHI J. & BALDO G. J. Mechanisms of activation of muscle branched-chain ,,-keto acid 697 dehydrogenase during exercise in man VAN HALL G., MACLEAN 899 The sulphonylurea receptor confers diazoxide sensitivity on D. A., SALTIN B.&WAGENMAKERS A. J.M. the inwardly rectifying K+ channel Kir6.1 expressed in human FINKG. R., ADAMS L., WATSONJ. D. G., INNESJ. A.,WUYAM B., embryonic kidney cellsAMMAL C., MOORHOUSE A.&ASHCROFr KOBAYASHI I., CORFIELD D. R., MURPHY K., JONES T., FRACKOWIAK F.M. 709 R. S. J.&Guz A. The properties and distribution of inward rectifier potassium currents in pig coronary arterial smooth muscle QUAYLE J. M., August 1996 Vol. 495 part 1 DART C. & STANDEN N. B. 715 Kinetics of desensitization induced by saturating flashes in toad + Voltage- and time-dependent block of delayed rectifier K and salamander rods MURNICK J. G. &LAMB T. D. 1 2 Mgcurrent 2+ Ho in W.-K., rabbit EARM sino-atrial Y. E., LEEnode S. H.,cells BROWN by external H. F. & CaNOBLE" and D. Effects of repetitive tetanic stimulation at long intervals on 727 excitation-contraction coupling in frog skeletal muscle BRUTON J. D., LANNERGREN J. & WESTERBLAD H. 15 Novel glial-neuronal signalling by coactivation of metabotropic 2 glutamate and 8l-adrenergic receptors in rat hippocampus Modulation of Ki conductances by Ca tand human chonionic mature rat testis DESAPHY WINDER D. G., RITCH P. S., GEREAU R. W. IV &CONN P. J. 743 J.-F.,gonadotrophin ROGIER C. & inJOFRE Leydig M. cells from 23
primaryMechanisms visual underlying cortex of orientationthe macaque selectivity SATO H., of KATSUYAMA neurons in theN. Oxidized glutathione mediates cation channel activation in calf TAMURA H., HATA Y. &TSUMOTO T. 757 vascular endothelial cells during oxidant stress KOLWAD S. K., ELLIOTr S. J. &KUNZE D. L. 37 Pancreatic secretion evoked by cholecystokinin and non-cholecystokinin-dependent duodenal stimuli via vagal External-anion-dependent anionic current in blasto-derm cells afferent fibres in the rat LI Y. & OWYANG C. 773 of early medaka fish embryos SHIGEMOTO T.& OKADA Y. 51 loader in the guinea-pig Non-ionic diffusion and carrier-mediated transport drive Novel chloride-dependent acid acid-loading mechanism extracellullar pH regulation of mouse colonic crypts CHU S. & ventricular myocyte: part of a dual VAUGHAN-JONES R. D. 65 MONTROSE M. H. 783 SUN B., LEEM C. H. & of the embryonic form of A model for the kinetics of neutral and anionic Open channel and competitive block myotubes by (+)-tubocurarine dipeptide-proton cotransport by the apical membrane of rat the nicotinic receptor of mouse H., FRANKE CH.& DUDELJ. 83 kidney cortex TEMPLE C. S., BAILEY P. D., BRONK J. R. & BUFLER J., WILHELM R.,PARNAS BOYD C. A. R. 795 Dopamine D,-like receptor-mediated presynaptic inhibition of Impaired sympathetic vascular regulation in humans after excitatory transmission onto rat magnocellular basal forebrain acute dynamic exercise HALLIWILL J. R., TAYLOR J.A. & ECKBERG neurones MOMIYAMA T., SIM J. A. & BROWN D. A. D. L. 279 * Increased neuronal excitability during depolarization- Phase-shifting human circadian rhythms: influence of sleep induced suppression of inhibition in rat hippocampus WAGNER timing, social contact and light exposure DUFY J. F., KRONAUER J. ALGER J. & B.E. 107 R. E. & CZEISLER C. A. 289 2 Sr " and quantal events at excitatory synapses between mouse September 1996 Vol. 495 part 2 hippocampal neurons in culture ABDUL-GHANI M. A., VALIANTE T. A. & PENNEFATHER P.S. 113 * Modulation of glycogen synthesis in rat skeletal muscle by A role for synaptic and network plasticity in controlling changes in cell volume Low S. Y., RENNIE M. J. &TAYLOR P. M. 299 epileptiform activity in CA1 in the kainic acid-lesioned rat Effects of photoreceptor metabolism on interstitial and glial cell hippocampus in vitro BERNARD C. & WHEAL H. V. 127 pH + in bee retina: evidence of a role for NH4 COLES J. A., MARCAGGI P., VWGA C. &COTILLON N. 305 Effects of background noise on the response of rat and cat motoneurones to excitatory current transients POLIAKOV A. V., Necrosis and apoptosis associated with distinct Ca2" response POWERS R. K., SWACZUK A. & BINDER M. D. 143 patterns in target cells attacked by human natural killer cells OSHIMI Y., OSHIMI K. & MIYAZAKI S. 319 Reversible inactivations of the cerebellum prevent the extinction of conditioned nictitating membrane responses in Differentiation of the human monocytic cell line U937 results in rabbits RAMNANI N. & YEO C. H. 159 an upregulation of the calcium release-activated current, ICRAC - FLOTO R. A., MAHAUT-SMITH M. P., ALLEN J. M. & Accumulation of intracellular HCO3- by Na-HCO3 cotransport SOMASUNDARAM B. 331 in interlobular ducts from guinea-pig pancreas ISHIGURO H., STEWARD M. C., LINDSAY A. R. G. & CASE R. M. 169 ADP-induced rapid inward currents through Ca2+-permeable cation channels in mouse, rat and guinea-pig megakaryocytes: Bicarbonate a secretion in interlobular ducts from guinea-pig patch-clamp study KAWA K. 339 pancreas ISHIGURO H., STEWARD M. C., WILSON R. W. & CASE R. M. 2 179 Sources of Ca2+ for different Ca +-activated K' conductances in A novel physiological function for platelet-derived growth IRELANDneurones D. ofR. &McLACHLANEF.the rat superior M.cervical ganglion DAVIES P.353J., factor-BB in rat dermis RODT S. A., AHLtN K., BERG A., RUBIN K. &REED R. K. 193 Somatic voltage-gated potassium currents of rat hippocampal
Contribution of oxygen-sensitive neurons of the rostral pyramidal cells in organotypic slice cultures Bossu J.-L., CAPOGNA ventrolateral medulla to hypoxic cerebral vasodilatation in the M., DEBANNE D., MCKINNEY R. A. &GXHWILER B. H. 367 rat GOLANOV E.V. & REIS D. J. 201 Distinct modes of channel gating underlie inactivation of Red nucleus lesions abolish the biphasic respiratory response to Bossusomatic J.-L. K' ¤t GXHI-IE~R in ratB. H.hippocampal pyramidal cells in vitro383 isocapnic hypoxia in decerebrate young rabbits WAITEs B. A., ACKLAND G. L., NOBLE R. &HANSON M. A. 217 Developmental adaptation of withdrawal alteration reflexes to early of peripheral innervation in the rat HOLMBERG H.& The effect of low-dose acetazolamide on the ventilatory CO, SCHOUENBORG J. 399 response curve in the anaesthetized cat WAGENAAR M., TEPPEMA L., BERKENBOSCH A., OLIEVIER C. & FOLGERING H. 227 Calcium-induced inactivation of NMDA receptor- channels Rostrocaudal evolves independently of run-down in cultured rat brain gradient of mechanical advantage in the parastemal neurones MEDINA I., FILIPPOVA N., BAKHRAMOV A. & intercostal muscles of the dog TROYER A. D., LEGRAND A. & BREGESTOVSKI P. 411 WILSON T. A. 239
Rostrocaudal PGE2 modulates the tetrodotoxin-resistant sodium current in gradient of electrical activation in the parasternal neonatal rat dorsal root ganglion neurones via the cyclic intercostal muscles of the dog LEGRAND A., BRANCAT1SANO A., AMP-protein kinase A cascade ENGLAND S., BEVAN S. & DECRAMER M. & TROYER A. D. 247 DOCHERTY R. J. 429 Central effects of 5-HT on activity of respiratory and * The chloride current induced by expression of pICl in hypoglossally n innervated muscles in newborn kittens KHATER- Xenopus oocytes differs from the endogenous volume-sensitive BOIDIN J., ROSE D. & DURON B. 255 chloride current VOETS T., BUYSE G., TYTGAT J., DROOGMANS G.,
Neuropeptide Y-like substances are released from the rostral EGGERMONT J. &NILiuS B. 441 2 brainstem of cats during the muscle pressor response WILLIAMS Ca -dependent inactivation of NMDA receptors: fast kinetics C.A. 2 267 and high Ca "sensitivity in rat dorsal horn neurons KYROZIS A., ALBUQUERQUE C., Gu J. &MACDERMOTT A. B. 449 The ionic dependence of the histamine-induced depolarization Glial potassium channels activated by neuronal firing or of vasopressin neurones in the rat supraoptic nucleus SMITH B. intracellular cyclic AMP in Helix GOMMERAT I. & COLA M. 649 N. &ARMSTRONG W. E. 465 Inwardly rectifying currents in hair cells and supporting cells in Potentiation of IPSCs by nitric oxide in immature rat sympathetic the goldfish sacculus SUGIHARA I. &FURUKAWA T. 665 preganglionic neurones in vitro Wu S. Y.&DUN N. J. 479 Protein kinase C inhibition of cloned inward rectifier Electrotonic coupling between rat sympathetic preganglionic (HRK1/KIR2.3) K' channels expressed in Xenopus oocytes neurones in vitro LOGAN S. D., PICKERING A. E., GIBSON I. C., HENRY P., PEARSON W. L. & NICHOLS C. G. 681 NOLAN M. F. & SPANSWICK D. 491 Angiotensin II activation of protein kinase C decreases delayed Release properties of isolated neuromuscular boutons of the rectifier K' current in rabbit vascular myocytes CLtMENT- garter snake WILKINSON R. S., SON Y.-J. & LUNIN S. D. 503 CHOMIENNE 0., WALSH M. P. & COLE W. C. 689 2 + Possible role of diadenosine polyphosphates as modulators of Block of large conductance Ca +-activated K channels in rabbit 2+ + cardiac sensory-motor neurotransmission in guinea-pigs vascular myocytes by internal Mg and Na MORALES E., COLE RUBINO A. & BURNSTOCK G. 515 W. C., REMILLARD C. V. & LEBLANC N. 701
Neuropeptide Y-enhanced diuresis and natriuresis in Activity-dependent modulation of the presynaptic potassium anaesthetized rats is independent of renal blood flow reduction current in the frog neuromuscular junction MIRALLES F. & BISCHOFF A., ERDBRIJGGER W., SMITS J. & MICHEL M. C. 525 SOLSONA C. 717
The dipeptide carnosine constricts rabbit saphenous vein as a zinc Amino acid substitutions in the rat Na+,K+-ATPase ,2-subunit complex apparently via a serotonergic receptor O'DOWD A., alter the cation regulation of pump current expressed in HeLa O'DowD J. J. & MILLER D. J. 535 cells YAMAMOTO S., KUNTZWEILER T. A., WALLICK E. T., SPERELAKIS N. &YATANI A. 733 Isolated mesenteric arteries from pregnant rats show enhanced flow-mediated relaxation but normal myogenic tone COCKELL Distinct voltage-dependent gating behaviours of a swelling A. P. & POSTON L. 545 activated chloride current in human epithelial cells BRAUN A. P. & SCHULMAN H. 743 Studies on the roles of ATP, adenosine and nitric oxide in mediating muscle vasodilatation induced in the rat by acute Ryanodine produces a low frequency stimulation-induced systemic hypoxia SKINNER M. R. & MARSHALL J.M. 553 NMDA receptor-independent long-term potentiation in the rat dentate gyrus in vitro WANG Y., Wu J., ROWAN M. J. & ANWYL R. Attenuation of the hypoxic ventilatory response in adult rats 755 following one month of perinatal hyperoxia LING L., OLSEN E.B. JR, VIDRUK E. H. &MITCHELL G. S. 561 Membrane potentials and microenvironment of rat dorsal vagal cells in vitro during energy depletion BALLANYI K., DourHEIL J.& Force-velocity properties of human skeletal muscle fibres: BROCKHAUSJ. 769 myosin heavy chain isoform and temperature dependence BOTIrNELLI R., CANEPARI M., PELLEGRINO A. M. ®GIANI C. 573 Regional differences in the response of the isolated sino-atrial node of the rabbit to vagal stimulation KODAMA I., BoYETT M. R., Effect of muscle acidity on muscle metabolism and fatigue SUZUKI R., HONJo H. &TOYAMA J. 785 during intense exercise in man BANGSBO J., MADSEN K., KIENS B. &RICHTER E.A. 587 Glycosaminoglycan concentration in synovium and other tissues of rabbit knee in relation to synovial hydraulic resistance PRICE September 1996 Vol. 495 part 3 F. M., LEVICK J.R. & MASON R. M. 803
Activation of MAP kinases and phosphorylation of caldesmon Changes in glycosaminoglycan concentration and synovial in canine colonic smooth muscle GERTHOFFER W. T., YAMBOHEV permeability at raised intra-articular pressure in rabbit knees 821 I. A., SHEARER M., POHL J., HAYNES R., DANG S., SATO K. & PRICE F. M., LEVICK J. R. & MASON R. M. SELLERS J. R. 597 Regulation of soleus muscle spindle sensitivity in decerebrate Effects of cardiac glycosides on excitation-contraction coupling and spinal cats during postural and locomotor activities 835 in frog skeletal muscle fibres SARKOZI S., SZENTESI P., JONA I. & BENNETT D. J., DE SERRES S. J. & STEIN R. B. CSERNOCH L. 611 Membrane potentials of respiratory neurones during dizocilpine in adult cats HAil A., PIERREFICHE 0., TAKEDA R., Dopamine (D2) receptor regulation of intracellular calcium and induced apneusis membrane capacitance changes in rat melanotrophs LEE A. K. 627 Fourz A. S., CHAMPAGNAT J. & DENAVIT-SAUBIt M. 851
*Axonal calcium entry during fast 'sodium' action potentials in Nitric oxide and exercise in the horse MILLS P. C., MARLIN D. J., rat cerebellar Purkinje neurones CALLEWAERT G., EILERS J. & DEMONCHEAUX E., SCOTT C., CASAS I., SMITH N. C. & 863 KONNERTH A. 641 HIGENBOTTAM T. Ventilatory chemoreflexes at rest following a brief period of Studies on the blocking action of human Kv3.4 inactivation heavy exercise in man CLEMENT I. D., PANDIT J.J., BASCOM D. A. & peptide variants in the mouse cloned Kvl.1 K+ channel ROBBINS P. A. 875 STEPHENS G. J., OWEN D. G., OPALKO A., PISANO M. R., MACGREGOR W. H. & ROBERTSON B. 145 Effects of arterial perfusion pressure on force production in working human hand muscles FITZPATRICK R., TAYLOR J. L. & Effect of metabolic inhibition on K' channels in pyramidal MCCLOSKEY D. I. 885 cells of the hippocampal CA1 region in rat brain slices HYLLIENMARK L. &BRISMAR T. 155 October 1996 Vol. 496 part 1 * Dimensions and ion selectivity of recombinant AMPA and Increase in ATP consumption during shortening in skinned kainate receptor channels and their dependence on Q/R site fibres from rabbit psoas muscle: effects of inorganic phosphate residues BURNASHEV N., VILLARROEL A. &SAKMANN B. 165 POTMA E. J. & STIENEN G. J. M. 1 Histamine H3 receptor-mediated depression of synaptic A HERG-like K' channel in rat F-11 DRG cell line: transmission in the dentate gyrus of the rat in vitro BROWN R. E. pharmacological identification and biophysical characterization &REYMANN K. G. 175 FARAVELLI L., ARCANGELI A., OLIVOTTO M. & WANKE E. 13 Binding sites contribute unequally to the gating of mouse 2 Ca " mobilization and interlayer signal transfer in the nicotinic ,D20ON acetylcholine receptors AKK G., SINE S. & heterocellular bilayered epithelium of the rabbit ciliary body AUERBACH A. 185 SCHUTrE M. & WOLOSIN J. M. 25 Retrograde signalling in depolarization-induced suppression Lasting effects of glutamate on nuclear calcium concentration in of inhibition in rat hippocampal CA1 cells ALGER B. E., PITLER cultured rat hippocampal neurons: regulation by calcium stores T. A., WAGNER J. J., MARTIN L. A., MORISHITA W., K1ROV S. A. & KORKOTIAN E. & SEGAL M. 39 LENZ R.A. 197
The mechanisms controlling physiologically stimulated Salbutamol changes the molecular and mechanical properties changes in rat brain glucose and lactate: a microdialysis study of canine skeletal muscle ZHANG K.-M., Hu P., WANG S.-W., FRAY A. E., FORSYTH R. J., BOUTELLE M. G. & FILLENZ M. 49 FEHER J. J., WRIGHT L. D., WECHSLER A. S., SPRATr J. A. & BRIGGS F. N. 211 Single L-type calcium channel conductance with physiological levels of calcium in chick ciliary ganglion neurons CHURCH P. J. Salbutamol and chronic low-frequency stimulation of canine & STANLEY E. F. 59 skeletal muscle Hu P., ZHANG K.-M., FEHER J. J., WANG S.-W., WRIGHT L. D., WECHSLER A. S., SPRATr J. A. &BRIGGS F. N. 221 Properties of the cAMP-activated Cl- current in choroid plexus epithelial cells isolated from the rat KIBBLE J.D., TREZISE A. E.O. Conducted depolarization in arteriole networks of the &BROWN P. D. 69 guinea-pig small intestine: effect of branching on signal dissipation SEGAL S. S. & NEILD T. 0. 229 Single axon IPSPs elicited in pyramidal cells by three classes of intemeurones in slices of rat neocortex THOMSON A. M., WEST M, muscarinic receptor-induced facilitation of ACh and D. C., HAHN J. & DEUCHARS J. 81 noradrenaline release in the rat bladder is mediated by protein kinase C SOMOGYI G. T., TANOWITZ M., ZERNOVA G. & DE GROAT + * Contrasting effects of hypoxia on cytosolic Ca" spikes in W. C. 245 conduit and resistance myocytes of the rabbit pulmonary artery URE&A J., FRANCO-OBREG6N A. &LOPEZ-BARNEO J. 103 Ca2 + - and GTP-dependent exocytosis in mouse pancreatic #l-cells involves both common and distinct steps PROKS P., The relationship between mitochondrial state, ATP hydrolysis, ELIASSON L., AMMAL.A C., RORSMAN P. & ASHCROFT F. M. 255 [Mg 2+] and [Ca2+]l studied in isolated rat cardiomyocytes LEYSSENS A., NOWICKY A. V., PATTERSON L., CROMPTON M. & Interactions between secretin and acetylcholine in the regulation DUCHEN M. R. 111 of fluid secretion by isolated rat pancreatic ducts EVANS R. L., ASHTON N., ELLIOTT A. C., GREEN R. & ARGENT B. E. 265 Differential effects of protein kinase C activation on 5-HTiA + receptor coupling to Ca" and K' currents in rat serotonergic Two human paramyotonia congenita mutations have opposite neurones CHEN Y. &PENINGTON N. J. 129 effects on lidocaine block of Na + channels expressed in a mammalian cell line FAN Z., GEORGE A. L. JR, KYLE J. W. & 2 * Tyrosine kinase inhibitors enhance a Ca +-activated K' MAKELSKI J.C. 275 current (IAHp)and reduce IAHP suppression by a metabotropic glutamate receptor agonist in rat dentate granule neurones In vivo human gastrocnemius architecture with changing joint ABDUL-GHANI M. A., VALIANTE T. A., CARLEN P. L. & angle at rest and during graded isometric contraction NARICI PENNEFATHER P.S. 139 M. V., BINZONI T., HILTBRAND E., FASEL J., TERRIER F. & CERRETELLI P. 287 in Protein kinase C-mediated enhancement of glycine response October 1996 Vol. 496 part 2 rat sacral dorsal commissural neurones by serotonin Xu T.-L., &AKAIKE N. 491 proton current in eosinophils from human NABEKURA J. Voltage-activated rdcini bloodROBINSON GORDIENKO C. &BOLTON D. V.,T. B.TARE M., PARVEEN S., FENECH C.299J FredpnetadfreidpnethaForce-dependent and force-independent heat production in Xenopus laevis single slow- and fast-twitch muscle fibres from G. J. M. & in intact BUSCHMAN H. P. J., VAN DER LAARSE W. J., STIENEN Role of Rho proteins in carbachol-induced contractions 503 ELZINGA G. and permeabilized guinea-pig intestinal smooth muscle Orro B., STEUSLOFF A., JUST I., AKTORIES K. & PFITZER G. 317 Interganglionic segregation of distinct vagal afferent fibre W., channels in rat phenotypes in guinea-pig airways Riccio M. M., KUMMER * Calcium permeability increase of endplate 521 & BIGLARI B., MYERS A. C. &UNDEM B. J. muscle during postnatal development VILLARROEL A. SAKMANN B. 331 Skin blood flow responses to the iontophoresis of acetylcholine 2 sodium nitroprusside in man: possible mechanisms MORRIS + Absence of Ca " current facilitation in skeletal muscle of and S. J.& SHORE A.C. 531 transgenic mice lacking the type 1 ryanodine receptor FLEIG A., TAKESHIMA H.& PENNERR. 339 Relationship between limb and muscle blood flow in man U., TERkS M., ERONEN E., at voltage-clamped excitor and RAITAKARI M., NUuTILA P., RUOTSALAINEN Presynaptic calcium currents M. J.& YKI-JARVINEN WRIG-T S. N., BRODWICK M. LAINE H., RAITAKARI O. T., IIDA H., KNUUT inhibitor nerve terminals of crayfish 543 S. &BITrNER G.D. 347 H. Changes in maximal voluntary force of human adductor pollicis Calcium currents, transmitter release and facilitation of release muscle during the menstrual cycle PHiLLIPS S. K., SANDERSON at voltage-clamped crayfish nerve terminals WRIGHT S. N., A. G., BIRCH K., BRUCE S. A. & WOLEDGE R. C. 551 BRODWICK M. S. & BrITrNER G.D. 363 somatic attention: the rat supraoptic neurones Non-averaged human brain potentials in Oscillatory bursting of phasically firing C. & 2 + + 2 short-latency cognition-related P40 component TOMBERG in low-Ca medium: Na influx, cytosolic Ca " and gap J.E. 559 junctions LI Z. &HATrON G. 1. 379 DESMEDT 2 and sarcoplasmic reticulum transport both of muscarinic synaptic modulation of the * Ca " diffusion Temporal specificity 2 during Ca2" sparks in rat + (IsAHp) in rat hippocampal neurones contribute to [Ca +] decline Ca +-dependent K current J. & ventricular myocytes G6MEz A. M., CHENG H., LEDERER W. ZHANG L., HAND. & CARLEN P. L. 395 BERSD.M. 575 Properties of a novel K current that is active at resting potential energy * Myosin heavy chain isoform expression and high in rabbit pulmonary artery smooth muscle cells EVANS A. M., phosphate content in human muscle fibres at rest and OSIPENKOO. N. &GURNEY A. M. 407 post-exercise SANT'ANA PEREIRA J. A. A., SARGEANT A. J., H. J., DE HAAN A. & VAN MECHELEN W. 583 Regulation of ram scrotal temperature during heat exposure, cold RADEMAKER A. C. exposure, fever and exercise MALONEY S. K. &MITCHELL D. 421 * Reflex 'unloading' and 'defensive capitulation' responses in 2 CORNA S., ITO Y., VON BREVERN M., Voltage-dependent blockage of Ca +-permeable AMPA human neck muscle M. A. 589 receptors by joro spider toxin in cultured rat hippocampal BRONSTEIN A. M. &GRESTY neurones ITNO M., KOIKE M., ISA T. &OZAWA S. 431
Substance P suppresses GABAA receptor function via protein K. & * Short Paper given rapid review kinase C in primary sensory neurones of bullfrogs YAMADA AKcAsu T. 439
Regulation of EPSPs by the synaptic activation of GABAB autoreceptors in rat hippocampus DAVIES C. H. & COLLINGRIDGE G. L. 451 * Bidirectional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus MCLEAN H. A., CAILLARD 0., BEN-ARI Y. &GAIARSA J. 471
Induction and maintenance of ganglionic long-term potentiation require activation of 5-hydroxytryptamine (5-HT,) receptors ALKADHI K. A., SALGADO-COMMISSARIAT D., HOGAN Y. H. &AKPAUDO S. B. 479 September 1996 Vol. 81 No. 5
Full-length papers
The relationship between the intracellular Ca2" transient and the isometric twitch force in frog muscle fibres SUN Y.-B., Lou F. & EDMAN K. A. P. 711
Two components of the delayed rectifier potassium current, I K , in rabbit sinoatrial node cells LEI M. &BROWN H. F. 725 Inward rectification of the large conductance potassium channel in smooth muscle cells from rabbit pulmonary artery SNETKov V. A., GURNEY A. M., WARD J. P. T. &OSIPENKO O. N. 743
The effect of bile acid on the activation of amiloride-sensitive sodium channels in frog skin LIMA M. S., FERREIRA H. G. & FERREIRA K. T. G. 755
Transepithelial fluid shift generated by osmolarity gradients in unstimulated perfused rat submandibular glands NAKAHARI T., YOSHIDA H. &IMAi Y. 767
5-Hydroxytryptamine induces forestomach hypomotility in sheep through 5-HT 4 receptors PLAZA M. A., ARRUEBO M. P. & MURILLO M. D. 781
Ion channels in freshly isolated and cultured human bronchial smooth muscle cells SNETKOV V. A., HiRsT S. J.& WARD J. P. T. 791
The influence of age on the assessment of motor unit activation in a human hand muscle SPIEGEL K. M., STRAT'ON J., BURKE J. R., GLENDINNING D. S. & ENOKA R. M. 805
The effect of H-wave therapy upon conduction in the human superficial radial nerve in vivo McDOWELL B. C., LowE A. S., WALSH D. M., BAXTER G. D. &ALLEN J. M. 821
The effect of climatic heat stress on intermittent supramaximal running performance in humans MAXWELL N. S., AITCHisON T. C. &NIMMO M. A. 833
Effects of ingested fluids on exercise capacity and on cardiovascular and metabolic responses to prolonged exercise in man MAUGHAN R. J., BETHELL L. R. & LEIPER J. B. 847
Frequency and degree of milk removal and the short-term control of human milk synthesis DALY S. E.J., KENT J.C., OWENS R. A. & HARTMANN P. E. 861
Rapid Communications
Possible role of calcium release from the sarcoplasmic reticulum in pacemaking in guinea-pig sino-atrial node RIGG L. & TERRAR D.A. 877
Hypothalamic and plasma nitrate/nitrite concentrations in spontaneously hypertensive rats ALAGHBAND-ZADEH J., DAS I., HANSON M. R., MACGREGOR C. A. J., DE WARDENER H. E. & LAYCOCK J.F. 881 No notice is carriedfor more than three Designated Sessions at Scientific Bedroom Accommodation and Meeting successive editions. Notices are starred so Meetings Facilities at The Ciba Foundation that readers can see at a glance whether this The Society has agreed that part of each Any graduate in a scientific discipline on a to London, or travelling via is the first (one star) or final (three stars) Meeting can be set aside in advance for a working visit Designated Session on a special topic. Such London, is welcome to use one of bedrooms for appearance of the notice. Notices for the Sessions will run in parallel with the other a period of up to two weeks. Charges as from 1 Spring 1997 edition (to be distributedon 14 sessions of Communications. Suggestions from January 1996 are £37 for a single and £47 for a February) should reach the Administration Members for Designated Sessions at future twin room which includes breakfast. Further Office by 13 January. Meetings can either be made directly to the details from: Sue Venables, The Ciba Special Interest Group organiser or to the Foundation, 41 Portland Place, London WIN Meetings Secretary. 4BN, tel (0171) 636 9456. European Congress on the ETHICS OF ANIMAL EXPERIMENTATION NEUROLOGY FOR NEUROSCIENTISTS 17-18 December 1996 Palais des Congres, Brussels March 24, 25 1997 Members of the animal research community Magdalen College, Oxford, U.K. Visiting Scientists Foreign visitors of the status of at least post and animal protection community are invited A 2 day conference for young neuroscientists graduate student, working in laboratories of to debate the future regulation of animal on how clinical neurology can illuminate Members of the Society, may be made "Visiting experimentation. Organised by the European neural function: imaging of disability and Scientists" by the Society. The names of such Biomedical Research Association (EBRA) and recovery, neuroimmunology and sponsored persons, with the dates of their visits and a the Federation of European Laboratory Animal neurooncology. This conference is Brain. letter of support, should be sent to the Foreign Science Associations (FELASA). Posters are and subsidised by the Guarantors of Secretary, Professor 0 H Petersen, The invited on the following subjects: Further information Prof. JB Clark. Sq. Physiological Laboratory, University of * The regulation of Animal Experiments Neurochemistry, National Hospital, Queen Liverpool, PO Box 147, Crown Street, Liverpool Animal Biotechnology London WCIN 3BG. 44-71 829 8722; " L69 3BX. * Replacement Alternatives [email protected]. " Refinement of Animal Experiments * The Use of Primates in Experiments European Congress for Molecular Cell Reunion at Bristol " Public Understanding of Animal Research Biology In July 1997 the University of Bristol * Improved Animal Models Department of Pharmacology will be hosting " General 22-25 March 1997 the summer meeting of the British Participation fee: ECU 200. Languages: Brighton Conference Centre Pharmacological Society. This coincides with English, French & German. Further This congress organised by "Traingle 3" will 21 years of Pharmacology graduates from information from Congress Secretariat, BW & cover topics across the full spectrum of Bristol. A reunion for former students and staff Partners, 9 rue du Moniteur, B-1000 Brussels. contemporary molecular cell biology. The is being planned and details will be circulated Fax: +32 2 219 32 15. *** plenary symposia and poster sessions will be to graduates in advance of the event. Further complemented by twenty or more concurrent information is available from Peter Taberner symposia. To receive details of the congress, c/ o the Depatment of Pharmacology, School of Open Meeting at The Royal Society send an email to [email protected] with Medical Sciences, University Walk, Bristol, BS8 DISCUSSION MEETING the subject of
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Biomedical Science office staff
Some members of the NeurogastroenterologyGroup.
Photography by Martin Rosenberg
At the Leeds Meeting....
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ProfessorJohn Morrison (Left) and Professor Wilfred Idnig (Left to right behind) Dr Malcoln Lidierth, DrPhilip Harrison, admiring the mask used by The Royal Armouries Dr Preni Kumar and (infront) Dr Bridget Lumb
Interpretationof sword fightiigby Samurai Warriors (Left) Dr David and Mrs Mary Cotterrell and (right) Professor Brian and Benita Jewell
Photographyby Kathleen Rayfield
Back cover: Electrical impedance tomography (EIT) images collected duringartificiallyinducedfocal epilepsy in the anaesthetisedrabbit, using a ring of 16 electrodes placed on the superiorsurface of the exposed brain. The electrocorticogramwas concomitantly measuredfrom the 16 electrodes, and blood flow was measured at two sites sing a Laser-Dopplerflowmeter. Impedance changes causedby the epilepticactivity may be seen in the EIT images. These were collected every 5 s; only a selection is shown. Courtesy of David Holder. 2
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