DOCSLIB.ORG

Outer Hair Cells and Electromotility

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Outer Hair Cells and Electromotility Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Outer Hair Cells and Electromotility Jonathan Ashmore University College London Ear Institute, London WC1X8EE, United Kingdom Correspondence: [email protected] Outer hair cells (OHCs) of the mammalian cochlea behave like actuators: they feed energy into the cochlear partition and determine the overall mechanics of hearing. They do this by generating voltage-dependent axial forces. The resulting change in the cell length, observed by microscopy, has been termed “electromotility.” The mechanism of force generation OHCs can be traced to a specific protein, prestin, a member of a superfamily SLC26 of transporters. This short review will identify some of the more recent findings on prestin. Although the tertiary structure of prestin has yet to be determined, results from the presence of its homologs in nonmammalian species suggest a possible conformation in mammalian OHCs, how it can act like a transport protein, and how it may have evolved. he outer hair cells (OHCs) of the mammali- frequency hearing. Although several extensive Tan cochlea are an identifiable group of cells reviews have been published (Ashmore 2008; of the inner ear, which are responsible for many He et al. 2014; Corey et al. 2017; Santos-Sacchi of the distinct features of our hearing (Fig. 1). et al. 2017), the emphasis here will be on a num- These features include absolute sensitivity to ber of outstanding issues. low sound pressure levels, selectivity to frequen- cies over many octaves, and the dependence ELECTROMOTILITY of cochlear performance on physiological status. These properties have collectively defined a The OHCs of the organ of Corti, the neurosen- process known as “cochlear amplification.” sory epithelium of the mammalian cochlea, are Although other orders of terrestrial animals organized in three (and sometimes four) rows also have cells homologous to the mammalian along the full length of the cochlear partition. www.perspectivesinmedicine.org OHCs, it seems that the evolution of hearing Viewing the cochlear partition in cross section organs has taken slightly different routes in dif- suggests that OHCs are placed in a position to ferent species. This review will focus specifically have the maximal mechanical influence on the on mammalian OHCs, their loss or functional flexure of the basilar membrane. failure being a major cause of hearing deficiency, The original observation that OHCs were including that caused by age. Thus, although cells that were “motile” was made by Brow- hair cells in all vertebrate species share com- nell and his coworkers in Geneva (Brownell et mon molecular features (see Köppl and Manley al. 1985). They showed, using intracellular re- 2018), there have been particular specializations cording electrodes, that the cells could be driven in mammalian hearing to enable and favor high- to change length when the membrane potential Editors: Guy P. Richardson and Christine Petit Additional Perspectives on Function and Dysfunction of the Cochlea available at www.perspectivesinmedicine.org Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a033522 Cite this article as Cold Spring Harb Perspect Med 2019;9:a033522 1 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press J. Ashmore AB K+ Apical transducer Prestin/ Transport SLC26A5 Basal synapses and K channels 10 µm Figure 1. The elements of the mammalian outer hair cell (OHC). (A) An isolated OHC from turn 2 (∼5–10 kHz region) of the guinea pig cochlea. The apical stereocilia are apparent at the apical surface. (B) Schematic OHC showing the location of prestin/SLC26A5 down the basolateral surface, generating longitudinal forces. Transport + to regulate pHi is presumed to be collocated as a parallel property of prestin. K ions from scala media enter through the mechanoelectric transducer channels at the apex and exit through the basally located K+ channels. Both afferent (red) and efferent (blue) terminals are located at the base of the cell. was changed. The term “electromotility” was from energy sources within the cell. A back-of- used as shorthand to describe this behavior the envelope calculation using the stiffness of and has stuck, even though it might imply that the cell shows that the maintenance of the cell “motile” means that the cells are migrating membrane potential at −50 mV allows suffi- somewhere. It required the widest electrical cient extraction of energy from the electric field www.perspectivesinmedicine.org bandwidth possible with patch clamp recording to explain the work done by the OHC against the to show that such length changes were rapid and mechanical constraints of the tissue in which certainly fast enough to claim that OHCs could they are embedded (Dallos 1991). be force-generating elements and are involved in Mammalian OHCs possess a very character- shaping cochlear mechanics at acoustic frequen- istic V-shaped bundle of stereocilia, serving cies (Ashmore 1987). Since then, a variety of to inject current into the cells when deflected. different biophysical techniques have shown As sensors of the movement of the basilar that the electromotile mechanism can be driven membrane, OHCs thus form part of a local me- over the full range of frequencies known to be chanical-electrical-mechanical feedback loop to encoded by most mammalian hearing organs, control basilar membrane tuning. The intimate and certainly up to 80 kHz (Frank et al. 1999). role of OHCs in such feedback has meant that It is strictly more accurate to describe the their function in the in vivo cochlea often has OHC as an “actuator” as the source of the energy to be interpreted by appeal to cochlear models. because the force generation derives from the When studied in isolation a property such as potential across the mechanoelectrical trans- electromotility gives an exaggerated impression ducer channels: it is not produced seemingly of the length change that an OHC may exhibit in 2 Cite this article as Cold Spring Harb Perspect Med 2019;9:a033522 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Outer Hair Cells and Electromotility a fully functioning cochlea. In vivo, when cells IDENTIFICATION OF THE MECHANISM are constrained by their surrounding cells, they operate more like force-generating elements. A number of hypotheses could explain the phe- A number of other features of OHCs should nomenon of OHC electromotility. There are also be considered when discussing electromo- several constraining observations: (1) the lateral tility. First, although they are neuroepithelial membrane of the OHC is packed with a particle cells specialized so that the apical surface facing about 8 nm in diameter; (2) a change in the scala media is mechanosensitive and the basal OHC membrane potential is accompanied by surface contains synaptic machinery, OHCs are a gating charge movement, or equivalently the relatively sparsely innervated by afferent fibers cell membrane capacitance is voltage dependent; in comparison to inner hair cells. It is clear that (3) the charge movement is blocked by the am- OHCs can generate activity in the type II audi- phiphilic anion salicylate (aspirin, with an addi- tory nerve fibers (Weisz et al. 2009), but this tional methyl group has the same effect); and information may be used in a very different (4) OHCs only acquire motile properties pro- way from the major sensory pathways from the gressively during a short period of development. sharply tuned type I fibers forming the majority The identification of prestin (Zheng et al. of the auditory nerve. Second, OHCs are the 2000) by using a subtracted complementary target of a descending pathway, the fibers of DNA (cDNA) library prepared from the mes- the medial olivocochlear bundle. These fibers, senger RNA (mRNA) of isolated hair cells in releasing acetylcholine (ACh), activate hetero- principle solves most of these problems. Mam- meric α9/10 AChRs on OHCs and serve to malian prestin is a 744 amino-acid protein with control the membrane conductance of the cell a predicted molecular mass of 81 kDa, and when (to K+). The net effect is to both hyperpola- it is expressed in heterologous cells they exhibit rize the cells and to reduce the amplitude of voltage-dependent movements and a nonlinear the receptor potentials in the cell and thus capacitance (NLC), which are indicative of pro- to reduce the mechanical OHC loop gain and tein rearrangements when under the influence overall cochlear sensitivity. The role of the effer- of the membrane potential. The surprise is that ent system is contentious but its effect on me- prestin is member of a superfamily of membrane chanical tuning (Murugasu and Russell 1996) transporters SLC26A5, a family whose other and distortion product emissions (e.g., Maison members are chloride-bicarbonate exchangers et al. 2007) is clear. There is also the suggestion, (Fig. 2) (Lohi et al. 2000). from studies in a mouse where the efferent cho- There are some differences in the behavior linergic receptor had been deleted, that the ef- of the NLC when it is studied in heterologous www.perspectivesinmedicine.org ferent system activity might even slow auditory cells (e.g., HEK293, TSA201, or CHO cells) and aging (Liberman et al. 2014). in isolated OHCs ex vivo. The difference seems ABChloride Bicarbonate Compact Extended 14 TM helices in cell membrane STAS domain in cytoplasm Figure 2. Models for prestin. (A) Organization of prestin/SLC26A5 in the membrane as a monomer. Two mobile components of the protein are placed in the membrane (Gorbunov et al. 2014; Geertsma et al. 2015), whereas the carboxy-terminal region, containing the sulfate transporter and anti-sigma factor antagonist (STAS) domain is cytoplasmic (Mio et al. 2008). (B) Hypothetical model for coassembly into a tetramer. The carboxy-terminal region (red) forms a base against which the oligomer can deform, rapidly shifting between a compact (cell depolarized) and an extended configuration (cell hyperpolarized).
Load more

Recommended publications
  • Macromolecular and Electrical Coupling Between Inner Hair Cells in the Rodent Cochlea
    ARTICLE https://doi.org/10.1038/s41467-020-17003-z OPEN Macromolecular and electrical coupling between inner hair cells in the rodent cochlea Philippe Jean 1,2,3,4,14, Tommi Anttonen1,2,5,14, Susann Michanski2,6,7, Antonio M. G. de Diego8, Anna M. Steyer9,10, Andreas Neef11, David Oestreicher 12, Jana Kroll 2,4,6,7, Christos Nardis9,10, ✉ Tina Pangršič2,12, Wiebke Möbius 9,10, Jonathan Ashmore 8, Carolin Wichmann2,6,7,13 & ✉ Tobias Moser 1,2,3,5,10,13 1234567890():,; Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers pre- synaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding. 1 Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany. 2 Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
    [Show full text]
  • IEB at 50: a Scientific Timeline
    IEB at 50: a scientific timeline Alcalá de Henares, 12 September 2013, Jonathan Ashmore When the Inner Ear Biochemistry Workshop started in 1964, we knew of giants who had given us some the key ideas. They included Alfonso Corti Robert Barany Georg von Bekesy Halliwell Davis and many others…… What science had happened be fore the workshop started? 1 Elsewhere we had seen the birth of molecular biology “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying method for the genetic material.” Elsewhere: we had seen the birth of cellular biophysics Alan Hodgkin and Andrew Huxley J. Physiol 1952 2 As Jochen Schact describes, Sigurd Rauch convened the first workshop to enable a research interface between clinicians and biochemists: Sigurd Rauch Invitation: 1st Workshop November 6 & 7, 1964 To be followed in 1965 by a 2nd Workshop on Inner Ear Biochemistry Topics Mucopolysaccharides in the inner ear Inner ear fluids: composition, secretion and absorption Membrane problems : electron microscopy and electrophysiology Ototoxicity: pharmacology and pathology 3 How the 1965 discussions were divided up Mucopolysaccharides Ototoxicity Electrophysiology and electron microscopy Inner ear fluids Timelines : 1964 1st Workshop on Inner Ear Biochemistry 1968 5th Workshop on Inner Ear Biology SfN 1971 ARO 1976 MoH 1980 MBHD 1992 2013 4 How has inner ear biology developed? Here are (some!) enabling technologies 1950s - Electron microscopy 1960s - Recording from nerves and cells (1976 – low noise patch
    [Show full text]
  • The Role of Potassium Recirculation in Cochlear Amplification
    The role of potassium recirculation in cochlear amplification Pavel Mistrika and Jonathan Ashmorea,b aUCL Ear Institute and bDepartment of Neuroscience, Purpose of review Physiology and Pharmacology, UCL, London, UK Normal cochlear function depends on maintaining the correct ionic environment for the Correspondence to Jonathan Ashmore, Department of sensory hair cells. Here we review recent literature on the cellular distribution of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK potassium transport-related molecules in the cochlea. Tel: +44 20 7679 8937; fax: +44 20 7679 8990; Recent findings e-mail: [email protected] Transgenic animal models have identified novel molecules essential for normal hearing Current Opinion in Otolaryngology & Head and and support the idea that potassium is recycled in the cochlea. The findings indicate that Neck Surgery 2009, 17:394–399 extracellular potassium released by outer hair cells into the space of Nuel is taken up by supporting cells, that the gap junction system in the organ of Corti is involved in potassium handling in the cochlea, that the gap junction system in stria vascularis is essential for the generation of the endocochlear potential, and that computational models can assist in the interpretation of the systems biology of hearing and integrate the molecular, electrical, and mechanical networks of the cochlear partition. Such models suggest that outer hair cell electromotility can amplify over a much broader frequency range than expected from isolated cell studies. Summary These new findings clarify the role of endolymphatic potassium in normal cochlear function. They also help current understanding of the mechanisms of certain forms of hereditary hearing loss.
    [Show full text]
  • FM1-43 Reveals Membrane Recycling in Adult Inner Hair Cells of the Mammalian Cochlea
    The Journal of Neuroscience, May 15, 2002, 22(10):3939–3952 FM1-43 Reveals Membrane Recycling in Adult Inner Hair Cells of the Mammalian Cochlea Claudius B. Griesinger, Chistopher D. Richards, and Jonathan F. Ashmore Department of Physiology, University College London, London WC1E 6BT, United Kingdom Neural transmission of complex sounds demands fast and surface area of the cell per second. Labeled membrane was sustained rates of synaptic release from the primary cochlear rapidly transported to the base of IHCs by kinesin-dependent receptors, the inner hair cells (IHCs). The cells therefore require trafficking and accumulated in structures that resembled syn- efficient membrane recycling. Using two-photon imaging of the aptic release sites. Using confocal imaging of FM1-43 in ex- membrane marker FM1-43 in the intact sensory epithelium cised strips of the organ of Corti, we show that the time within the cochlear bone of the adult guinea pig, we show that constants of fluorescence decay at the basolateral pole of IHCs IHCs possess fast calcium-dependent membrane uptake at and apical endocytosis were increased after depolarization of their apical pole. FM1-43 did not permeate through the stereo- IHCs with 40 mM potassium, a stimulus that triggers calcium cilial mechanotransducer channel because uptake kinetics influx and increases synaptic release. Blocking calcium chan- were neither changed by the blockers dihydrostreptomycin and nels with either cadmium or nimodipine during depolarization D-tubocurarine nor by treatment of the apical membrane with abolished the rate increase of apical endocytosis. We suggest BAPTA, known to disrupt mechanotransduction. Moreover, the that IHCs use fast calcium-dependent apical endocytosis for fluid phase marker Lucifer Yellow produced a similar labeling activity-associated replenishment of synaptic membrane.
    [Show full text]
  • Cochlear Outer Hair Cell Motility
    Physiol Rev 88: 173–210, 2008; doi:10.1152/physrev.00044.2006. Cochlear Outer Hair Cell Motility JONATHAN ASHMORE Department of Physiology and UCL Ear Institute, University College London, London, United Kingdom I. Introduction 174 II. Auditory Physiology and Cochlear Mechanics 174 A. The cochlea as a frequency analyzer 175 B. Cochlear bandwidths and models 175 C. Physics of cochlear amplification 177 D. Cellular origin of cochlear amplification 177 Downloaded from E. OHCs change length 178 F. Speed of OHC length changes 178 G. Strains and stresses of OHC motility 179 III. Cellular Mechanisms of Outer Hair Cell Motility 181 A. OHC motility is determined by membrane potential 182 B. OHC motility depends on the lateral plasma membrane 182 C. OHC motility as a piezoelectric phenomenon 183 physrev.physiology.org D. Charge movement and membrane capacitance in OHCs 184 E. Tension sensitivity of the membrane charge movement 185 F. Mathematical models of OHC motility 186 IV. Molecular Basis of Motility 186 A. The motor molecule as an area motor 186 B. Biophysical considerations 187 C. The candidate motor molecule: prestin (SLC26A5) 187 D. Prestin knockout mice and the cochlear amplifier 188 E. Genetics of prestin 188 on February 28, 2012 F. Prestin as an incomplete transporter 189 G. Structure of prestin 190 H. Function of the hydrophobic core of prestin 190 I. Function of the terminal ends of prestin 191 J. A model for prestin 191 V. Specialized Properties of the Outer Hair Cell Basolateral Membrane 192 A. Density of the motor protein 192 B. Cochlear development and the motor protein 193 C.
    [Show full text]
  • Women Physiologists
    Women physiologists: Centenary celebrations and beyond physiologists: celebrations Centenary Women Hodgkin Huxley House 30 Farringdon Lane London EC1R 3AW T +44 (0)20 7269 5718 www.physoc.org • journals.physoc.org Women physiologists: Centenary celebrations and beyond Edited by Susan Wray and Tilli Tansey Forewords by Dame Julia Higgins DBE FRS FREng and Baroness Susan Greenfield CBE HonFRCP Published in 2015 by The Physiological Society At Hodgkin Huxley House, 30 Farringdon Lane, London EC1R 3AW Copyright © 2015 The Physiological Society Foreword copyright © 2015 by Dame Julia Higgins Foreword copyright © 2015 by Baroness Susan Greenfield All rights reserved ISBN 978-0-9933410-0-7 Contents Foreword 6 Centenary celebrations Women in physiology: Centenary celebrations and beyond 8 The landscape for women 25 years on 12 "To dine with ladies smelling of dog"? A brief history of women and The Physiological Society 16 Obituaries Alison Brading (1939-2011) 34 Gertrude Falk (1925-2008) 37 Marianne Fillenz (1924-2012) 39 Olga Hudlická (1926-2014) 42 Shelagh Morrissey (1916-1990) 46 Anne Warner (1940–2012) 48 Maureen Young (1915-2013) 51 Women physiologists Frances Mary Ashcroft 56 Heidi de Wet 58 Susan D Brain 60 Aisah A Aubdool 62 Andrea H. Brand 64 Irene Miguel-Aliaga 66 Barbara Casadei 68 Svetlana Reilly 70 Shamshad Cockcroft 72 Kathryn Garner 74 Dame Kay Davies 76 Lisa Heather 78 Annette Dolphin 80 Claudia Bauer 82 Kim Dora 84 Pooneh Bagher 86 Maria Fitzgerald 88 Stephanie Koch 90 Abigail L. Fowden 92 Amanda Sferruzzi-Perri 94 Christine Holt 96 Paloma T. Gonzalez-Bellido 98 Anne King 100 Ilona Obara 102 Bridget Lumb 104 Emma C Hart 106 Margaret (Mandy) R MacLean 108 Kirsty Mair 110 Eleanor A.
    [Show full text]
  • Mode Conversion in the Cochlea?
    Mode conversion in the cochlea? Robert S. MacKay∗ Mathematics Institute and Centre for Complexity Science, University of Warwick, Coventry CV4 7AL, U.K. August 28, 2008 Abstract It is suggested that the frequency selectivity of the ear may be based on the phenomenon of mode conversion rather than critical layer reso- nance. The distinction is explained and supporting evidence discussed. PACS numbers: 43.64.Kc, 43.66.Ba Keywords: Cochlea, travelling wave, mode conversion Running title: Mode conversion in the cochlea ∗Electronic mail: [email protected] 1 1 Introduction The cochlea is the part of the ear where mechanical vibrations (forced by sound waves in the air) are turned into neural signals. There is a huge literature about it, both experimental and mathematical (for summaries, see Robles & Ruggero, 2001, or Ch.23 of Keener & Sneyd, 1998). There are large differences between the cochleae of different species (especially between mammals, birds and reptiles); in this paper attention is restricted to mammalian and usually human cochleae. Most current explanations for the function of the mammalian cochlea are based on “critical layer resonance”, the build up of wave energy at a frequency-dependent place where the wavelength goes to zero, e.g. Lighthill (1981), Nobili, Mammano & Ashmore (1998), de Boer (1996), Hubbard & Mountain (1996), even if the words and mathematical theory are not always used and it is disputed by some (e.g. the discussion in section VII of Olson, 2001). The goal of this paper is to suggest that critical layer resonance is not the right explanation: rather it might be “mode conversion”, the propagation of a wave to a frequency-dependent place where it turns round and comes back out in another wave mode, the energy density forming a peak at the turning point.
    [Show full text]
  • Montpellier 2016
    IEB 201 Montpellier © Marc Ginot SYMPOSIUM - September 18, 2016 New horizons in hearing rehabilitation © Agnès Lescombe © Ville Montpellier © Ville Montpellier © OT Organizing Committee Jean-Luc Puel, PhD (President) Rémy Pujol, PhD (Honor. Pres.) Jérôme Bourien, PhD Gilles Desmadryl, PhD Régis Nouvian, PhD Jean-Charles Ceccato, PhD Michel Eybalin, PhD Frédéric Venail, MD, PhD François Dejean, MS Marc Lenoir, PhD Alain Uziel, MD, PhD Benjamin Delprat, PhD Michel Mondain, MD, PhD Jin Wang MD, PhD For more information: [email protected] www.IEB2016.com Welcome to the Inner Ear Biology 2016 IEB For the 4th time after the successful meetings in 1981, 1994 and 2006, Montpellier has the privilege to organize the Inner Ear 201 Biology (Sept 17th to 21st, 2016). Montpellier We aim to reflect the dialogue that exists between basic and applied research, by complementing the usual scientific program with an opening day focused on clinical aspects (last advances, future directions and challenges in innovative therapies and rehabilitation of the inner ear diseases). Located on the Mediterranean seashore, Montpellier (pop. 270,000) stands as a recognized high-tech pole. However, the city keeps the spirit of the past, when doctors and scientists came from all around the world, to share their knowledge in medicine, law and philosophy: its Medical School runs since the 12th century and now its Universities amount 65,000 students. Welcome to Montpellier! Join us for the 53rd IEB workshop and its Symposium! COMMITTEES de Montpellier - Elohim Carrau Ville © LOCAL COMMITTEE INTERNATIONAL SCIENTIFIC Jean-Luc Puel, PhD (President) COMMITTEE Rémy Pujol, PhD (Honor. Pres.) Jonathan Ashmore Jérôme Bourien PhD Gaetano Paludetti Jean-Charles Ceccato PhD Graça Fialho François Dejean MS Anthony J.
    [Show full text]
  • The Cochlea: Mechanics and Transduction Jonathan Ashmore Neuroscience, Physiology and Pharmacology University College London
    21/05/2015 Neurobiology of Hearing Salamanca, 20th May 2015 The cochlea: mechanics and transduction Jonathan Ashmore Neuroscience, Physiology and Pharmacology University College London [email protected] Not all tuning mechanisms use the same cellular design BM Hair cell frogs reptiles BM Hair birds cell Sound Soundinput Sound Soundinput BM Hair cell mammals 1 21/05/2015 In non-mammals, hair cells are electrically tuned: Neural tuning = intrinsic hair cell tuning Found in frog hair cells (Hudspeth et al); Turtle hair cells (Fettiplace et al.) In mammals, neural tuning = basilar membrane tuning Post-mortem 2 21/05/2015 The mammalian cochlea is a mechanical spectrum analyser B A Stapes Basilar membrane Fluid Fluid in motion at Round rest window BM stiffness high low Does the spiral contribute to cochlear performance? Only in a minor way. high frequencies low frequencies Sound enters from middle ear From Manoussaki et al., Phys Rev Letts E 2006 3 21/05/2015 Stapes Basilar membrane Fluid Fluid in motion at Round rest window d 2 x dx Simple m i h i k x f (t) , oscillator i dt 2 i dt i i i N 2 j i d xi dxi dxi dxi1 dxi1 Gi mi j 2 hi Ui (yi ) si 2 ki x Gi aS (t) j1 dt dt dt dt dt x = BM displacement ‘undamping’ y = tectorial membrane displacement 4 21/05/2015 What in silico models of the cochlea do: Inform intuition! Natural framework for functional genomics They indicate that there may be : Cochlear gradients of the mechanotransduction channel Cochlear gradients of K channel densities A small degree of longitudinal coupling along the cochlea From Robles & Ruggero, 2001 5 21/05/2015 Raw data from interferometry BM velocity normalised velocity (gain) i.e.
    [Show full text]
  • Inside Living Cancer Cells Research Advances Through Bioimaging
    PN Issue 104 / Autumn 2016 Physiology News Inside living cancer cells Research advances through bioimaging Symposium Gene Editing and Gene Regulation (with CRISPR) Tuesday 15 November 2016 Hodgkin Huxley House, 30 Farringdon Lane, London EC1R 3AW, UK Organised by Patrick Harrison, University College Cork, Ireland Stephen Hart, University College London, UK www.physoc.org/crispr The programme will include talks on CRISPR, but also showing the utility of techniques such as ZFNs and Talens. As well as editing, the use of these techniques to regulate gene expression will be explored both in the context of studying normal physiology and the mechanisms of disease. The use of the techniques in engineering cells and animals will be explored, as will techniques to deliver edited reagents and edited cells in vivo. Physiology News Editor Roger Thomas We welcome feedback on our membership magazine, or letters and suggestions for (University of Cambridge) articles for publication, including book reviews, from Physiological Society Members. Editorial Board Please email [email protected] Karen Doyle (NUI Galway) Physiology News is one of the benefits of membership of The Physiological Society, along with Rachel McCormack reduced registration rates for our high-profile events, free online access to The Physiological (University of Liverpool) Society’s leading journals, The Journal of Physiology and Experimental Physiology, and travel David Miller grants to attend scientific meetings. Membership of The Physiological Society offers you (University of Glasgow) access to the largest network of physiologists in Europe. Keith Siew (University of Cambridge) Join now to support your career in physiology: Austin Elliott Visit www.physoc.org/membership or call 0207 269 5728.
    [Show full text]
  • Xi. International Tinnitus Seminar
    ITS 2014 1 XI. INTERNATIONAL TINNITUS SEMINAR 21 – 24 MAY 2014 · BERLIN, GERMANY LANGENBECK-VIRCHOW-HAUS www.international-tinnitus-seminar-2014.com FINAL PROGRAMME ITS 2014 3 TABLE OF CONTENTS 04 // WELCOME ADDRESSES 08 // CONGRESS ORGANISATION AND COMMITTEES 10 // GERMAN TINNITUS FOUNDATION CHARITÉ 10 // ÖFFENTLICHE VERANSTALTUNG (German only) 11 // CONGRESS INFORMATION 13 // FORMATS & TOPICS 14 // PROGRAMME OVERVIEW 14 a Wednesday, 21 May 2014 15 a Thursday, 22 May 2014 16 a Friday, 23 May 2014 17 a Saturday, 24 May 2014 18 // SCIENTIFIC PROGRAMME 18 a Wednesday, 21 May 2014 22 a Thursday, 22 May 2014 24 a Friday, 23 May 2014 29 a Saturday, 24 May 2014 32 // INDUSTRY-SPONSORED SESSIONS 33 // SPONSORING & EXHIBITION 35 // SOCIAL EVENTS 37 // INDEX ORGANISER German Tinnitus Foundation Charité Luisenstraße 13 10117 Berlin, Germany CONGRESS AND EXHIBITION OFFICE CPO HANSER SERVICE GmbH Paulsborner Straße 44 14193 Berlin, Germany Tel.: +49 – (0)30 – 300 669 0 CONGRESS VENUE Langenbeck-Virchow-Haus Luisenstraße 58 / 59 10117 Berlin, Germany 4 ITS 2014 WELCOME ADDRESS GOVERNING MAYOR OF BERLIN Berlin extends a warm welcome to the participants of the XI. International Tinnitus Seminar 2014. It is an honour for our city to host this important medical-scientific congress. For many people tinnitus poses a serious threat to health and quality of life. It is estimated that, in Germany alone, more than eleven million people at least temporarily suffer from the irritating tinnitus noises. And experts predict that the number of those affected will continue to rapidly increase. Which makes it all the more important that considerable effort continue to be made in the research, diagnoses and treatment of this widespread disease.
    [Show full text]
  • Newsletter 5
    Newsletter-AcdMedSci-July 01 16/7/01 2:54 pm Page 1 Fellowship Newsletter 5 The continuing battle against infectious disease It was the perceived wisdom in the 1970s that communicable diseases were under control thanks to the dramatic successes of immunisation and chemotherapy, and that there was no longer a specialist career in this field. How wrong we were. HIV/Aids, MRSA, exotic viruses emerging from the bush, prion diseases, tuberculosis... arguably pose, yet again, the single greatest challenge to science, public health and clinical practice. The Academy has responded to this with a major, in-depth review of the issues and has produced a disturbing and challenging report, Academic Medical Bacteriology in the 21st Century, which is summarized on page 12. Professor Brian Spratt, chairman of the Academy working group on academic medical bacteriology, presents the findings of the in-depth study at the report launch in July. As the General Election loomed, the last issue set out the challenges facing the medical sciences and healthcare in the UK and the aspirations of the Secretary of State for Health. Now, post-election, with continuity preserved through Alan Milburn, John Hutton, Philip Hunt and Yvette Cooper, together with familiar colleagues in the devolved administrations, the focus shifts to the role of the Academy in addressing these challenges in research and development, education and training, and in practice - whether laboratory, clinical or public-health. Year on year, we are strengthened by an infusion of fresh blood and, as we warmly welcome our newly elected Fellows, we are encouraged to realise that we are increasingly well placed not only to represent the best of the medical scientific (or is it the scientific medical) community but to make crucial contributions to this task.
    [Show full text]