DOCSLIB.ORG

THE ROLE of CARBON DIOXIDE (AND INTRACELLULAR Ph) IN

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
THE ROLE of CARBON DIOXIDE (AND INTRACELLULAR Ph) IN THEORETICAL ARTICLE—ELMÉLETI ÖSSZEFOGLALÁS THE ROLE OF CARBON DIOXIDE (AND INTRACELLULAR pH) IN THE PATHOMECHANISM OF SEVERAL MENTAL DISORDERS ARE THE DISEASES OF CIVILIZATION CAUSED BY LEARNT BEHAVIOUR, NOT THE STRESS ITSELF? ANDRÁS SIKTER , GÁBOR FALUDI , ZOLTÁN RIHMER 1 Municipal Clinic of Szentendre, Section of Internal Medicine 2 Dept of Clinical and Theoretical Mental Health, Kutvolgyi Clinical Center, Semmelweis University, Budapest ELMÉLETI ÖSSZEFOGLALÁS Neuropsychopharmacologia Hungarica 2009, XI/3, 161-173 A SZÉNDIOXID (ÉS AZ INTRACELLULÁRIS matikus betegségek patomechanizmusában. Fel- pH) SZEREPE NÉHÁNY MENTÁLIS tételezik, hogy a civilizációs betegségeket nem BETEGSÉG PATOMECHANIZMUSÁBAN maga a stressz, hanem annak le nem reagálása Nem maga a stressz, hanem tanult okozza azáltal, hogy a CO2 szint tartósan eltér a viselkedési formák okoznák a civilizációs fiziológiástól. A növekvõ agyi pCO2, acidotikus betegségeket? citoszol pH, és/vagy emelkedett bazális citoszol A széndioxid szerepe alábecsült a neuropszichi- Ca2+ koncentráció csökkenti a citoszolba történõ átriai betegségek patomechanizmusában, ugyan- Ca2+ beáramlást és az arousalt – dysthymiát, de- akkor fontos kapocs a lélek és a test között. A pressziót okozhatnak. Ez többnyire ATP hiány- mindenkori lelki állapot többnyire a légzést is nyal és a citoszol Mg2+ tartalmának csökkenésé- befolyásolja (lassítja, gyorsítja, irregulárissá te- vel is jár. Ez az energetikai és ionkonstelláció jel- szi), ezért változik a pH. Másrészt a neuronok lemzõ az életkor emelkedésével korrelációt mu- citoszoljának aktuális pH-ja a Ca2+ konduktivitás tató krónikus szervi betegségekre is, és a legfon- egyik legfontosabb modifikátora, ezért a légzés a tosabb kapcsolat az organikus betegségekkel, Ca2+-on keresztül közvetlenül, gyorsan, hatéko- például az iszkémiás szívbetegséggel. A felvá- nyan befolyásolja a “second messenger” rend- zolt modellbe beleillik, hogy egyes farmakológi- szert. (A csökkenõ CO2 koncentráció mindig al- ai szerek (katecholaminok, szerotonin, litium, kalózis, az emelkedõ pedig acidózis irányában triacetiluridin, tiroxin), valamint az alvásmegvo- viszi el a pH-t, íly módon az elõbbi gyorsít, növe- nás okozta H+ és/vagy Ca2+ metabolizmus válto- li az arousalt, míg az utóbbi lassít, csökkenti az zás szintén a logikailag kívánt irányban hat. + arousalt.) A H ion koncentráció állandóságának KULCSSZAVAK: arousal, bipoláris betegség, megõrzése, helyreállítása az egyik legfontosabb civilizációs betegségek, delírium, depresszió, homeosztatikus funkció, ezért a széndioxid szint GAD, hyperventilációs szindróma, locus mino- megváltozása az ellenregulációs változások ris resistentiae, milieu interieur, pánikbetegség, egész sorozatát indítja el. Mindazonáltal bizo- stressz, széndioxid, viselkedés nyítható, hogy nincs tökéletes kompenzáció, ezért a kompenzáló mechanizmusok pszichoszo- SUMMARY matikus betegségeket generálhatnak, minthogy The role of carbon dioxide (CO2) is underesti- másodlagos eltéréseket okoznak a “milieu in- mated in the pathomechanism of neuropsychiat- terieur”-ban. A szerzõk tárgyalják a CO2 rendha- ric disorders, though it is an important link be- gyó fizikókémiai tulajdonságait, a CO2 és a kate- tween psyche and corpus. The actual spiritual sta- cholamin szintek összefonódó változásainak tör- tus also influences respiration (we start breathing vényszerûségeit (feedback), az akut és krónikus rarely, frequently, irregularly, etc.) causing pH hipokapnia szerepét néhány hyperarousal kór- alteration in the organism; on the other hand the képben (delirium, pánikbetegség, hiperventilá- actual cytosolic pH of neurons is one of the main ciós szindróma, GAD, bipoláris betegség), a “lo- modifiers of Ca2+-conductance, hence breathing cus minoris resistentiae” szerepét a pszichoszo- directly, quickly, and effectively influences the Neuropsychopharmacologia Hungarica 2009, XI/3, 161-173 161 ELMÉLETI ÖSSZEFOGLALÁS ANDRÁS SIKTER , GÁBOR FALUDI , ZOLTÁN RIHMER second messenger system through Ca2+-currents. man instinctive reaction to it, and this would (Decreasing pCO2 turns pH into alkalic direc- cause long-lasting CO2 alteration. Increased tion, augments psychic arousal, while increasing brain-pCO2, acidic cytosol pH and/or increased 2+ 2+ pCO2 turns pH acidic, diminishes arousal.) One basal cytosolic Ca level diminish inward Ca - of the most important homeostatic function is to current into cytosol, decrease arousal – they may maintain or restore the permanence of H+-con- cause dysthymia or depression. This state usu- centration, hence the alteration of CO2 level ally co-exists with ATP-deficiency and de- starts cascades of contraregulation. However it creased cytosolic Mg2+ content. This energetical- can be proved that there is no perfect compensa- and ion-constellation is also typical of ageing- tion, therefore compensational mechanisms may associated and chronic organic disorders. It is the generate psychosomatic disorders causing sec- most important link between depression and or- ondary alterations in the “milieu interieur”. Au- ganic disorders (e.g. coronary heart disease). The thors discuss the special physico-chemical fea- above-mentioned model is supported by the fact + 2+ tures of CO2, the laws of interweaving alterations that H and/or Ca metabolism is affected by of pCO2 and catecholamine levels (their feed- several drugs (catecholemines, serotonin, lith- back mechanism), the role of acute and chronic ium, triaecetyluridine, thyroxine) and sleep de- hypocapnia in several hyperarousal disorders privation, they act for the logically right direc- (delirium, panic disorder, hyperventilation syn- tion. drome, generalized anxiety disorder, bipolar dis- KEYWORDS: arousal, behaviour, bipolar disorder, order), the role of “locus minoris resistentiae” in carbon dioxide, delirium, depression, diseases of civi- the pathomechanism of psychosomatic disorders. lization, generalized anxiety disorder, hyperventila- It is supposed that the diseases of civilization are tion syndrome, locus minoris resistentiae, milieu caused not by the stress itself but the lack of hu- interieur, panic disorder, stress Introduction alkalic cytoplasm allowes Ca2+ to enter in the The role of carbon dioxide is underestimated not cytosol. If we keep on this kind of breathing for a only in the pathomechanism of somatic diseases long time, our pulse will slowly come back to the but of mental disorders too (Gardner). It is a fact incipient frequency because the organism com- pensates the alteration of pH in the cytosol. The that the intracellular pH is strictly regulated in + brain cells, and also marginal aberration of H+ lack of H in cytosol increases conductance of 2+ - concentration may cause big functional deviation Ca and some other ions (Harvey et al.), thus it in 2 - in neurons (Tombaugh & Somjen). The regulation creases contraction, metabolism and O require of intracellular pH is complex, there are several ment (Laffey et al.), and also increases excitability compensational mechanisms (Boron). Carbon di- of neurons in the peripherium (Macefield et al.) and in the brain (Stenkamp et al.). All these events oxide concentration is one of the most important + factor which influences the intra- and extracellular can be explained by the simple fact that lack of H (=alkalosis) increases transmembrane conduc- pH. Why? CO2 is extremely diffusible and in this way we can rapidly send or extract H+ ions to or tance of ions and (consequently) increases active - from all tissues, all cells (nearly the same time) ion-pumping mechanisms too (because the origi - drawing breath rarely or frequently. It is because nal ion-status has to be restored). By contrast, aci dosis decreases the transmembrane Ca2+-conduc- CO2 passes very quickly through the cellmemb- tance (Tombaugh & Somjen), decreases excitabil- ranes and it forms carbonic acid with H2O which 2+ + - gives H ions. On the other hand ions get slowly ity of neurons, and the decreased Ca -conduc + tance can dramatically affect neurotransmitter re- through membranes, even H -ion itself. That is 2+ because they have electric charge and become hy- lease (Dodge et al..). In some cells the Ca entry into cytosol itself increases cytosolic H+ concen- drated, and this multiplies their radius, but CO2 tration, which physiological acidosis then limits does not have either of them and it is soluble in 2+ lipids (Sikter, 2007a). If we take our breath deeply further Ca entry. (It is supposed to be a novel feedback mechanism:Tombaugh et al. 1998). or frequently our pulse speeds up proving that CO2 has left the pacemaker cells of heart, and the Alteration of carbon dioxide concentration can appear in the whole organism at the same time. If 162 Neuropsychopharmacologia Hungarica 2009, XI/3, 161-173 THE ROLE OF CARBON DIOXIDE IN THE PATHOMECHANISM… ELMÉLETI ÖSSZEFOGLALÁS it endures for a long time (several hours to one way they get a good chance to restore the de- week), the organism starts to “compensate”. Sta- creased carbon dioxide level. Contrarily human bility of extra- and intracellular pH is of high pri- acute stress response mostly differs from that be- ority. Renal function and tissular buffer mecha- cause of their learnt behaviour. They mostly re- nisms (mostly) restore the pH in the cytosol of the strain their temper, the physical activity will fail cells and in the extracellular space, but the con- and the hyperventilation/hypocapnia endures long centration of other ions is altered in the cytosol at causing a range of ion-movements through mem- the
Load more

Recommended publications
  • Assessing the Influence of Environmental Ph on Algal Physiology Using a Novel Culture System
    Assessing the influence of environmental pH on algal physiology using a novel culture system By Rachel L. Golda A DISSERTATION Presented to the Division of Environmental and Biomolecular Systems and the Oregon Health & Science University School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Environmental Science and Engineering August, 2017 i School of Medicine Oregon Health & Science University CERTIFICATE OF APPROVAL _________________________________ This is to certify that the PhD dissertation of Rachel L. Golda has been approved ________________________________________________ Mentor/Advisor: Tawnya Peterson (Oregon Health & Science University) ________________________________________________ Mentor/Advisor: Joseph Needoba (Oregon Health & Science University) ________________________________________________ Committee Chair: Paul Tratnyek (Oregon Health & Science University) ________________________________________________ Member: Anne Thompson (Portland State University) i TABLE OF CONTENTS CERTIFICATE OF APPROVAL ........................................................... Error! Bookmark not defined. TABLE OF CONTENTS ........................................................................................................................... ii LIST OF FIGURES .................................................................................................................................... v LIST OF EQUATIONS ...........................................................................................................................
    [Show full text]
  • Does Aerobic Respiration Produce Carbon Dioxide Or Hydrogen Ion and Bicarbonate?
    SPECIAL ARTICLE Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate? Erik R. Swenson, M.D. ABSTRACT Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/128/5/873/381029/20180500_0-00010.pdf by guest on 30 September 2021 cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long- abiding interest in acid–base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism. Dr. John Severinghaus has posited that hydrogen ion and bicarbon- ate are the direct end products in the Krebs cycle. In the late 1960s, he showed in brain and brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor, reduces intracellular pH. This led him to conclude that hydrogen ion and bicarbonate are the end products, and the role of intracellular carbonic anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis. Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs cycle, a more widely accepted view, and that acetazolamide prevents rapid intracellular bicarbonate formation, which can then codiffuse with carbon dioxide to the cell surface and there be reconverted for exit from the cell. Loss of this “facilitated diffusion of carbon dioxide” leads to intracellular acidosis as the still appreciable uncatalyzed rate of carbon dioxide hydration generates more protons.
    [Show full text]
  • Nanomaterials for Intracellular Ph Sensing and Imaging
    Nanomaterials for intracellular pH sensing and imaging Ying Lian, Wei Zhang, Longjiang Ding, Xiao-ai Zhang, Yinglu Zhang, Xu-dong Wang* Department of Chemistry, Fudan University, 200433, Shanghai, CHINA Western Chemistry bld. 114, Handan Road No. 220, Shanghai [email protected] Abstract: Intracellular pH is a vital parameter that precisely controls cell functionalities, activities and cellular events. Abnormal intracellular pH is always closely related to the healthy status of cells, which is further translated into pathological changes in a macro perspective. Because of the highly compartmentalized structure inside cells, the pH in each compartment can be precisely tuned to optimize certain cellular functionality, and biological reactions in these regions occur at optimum condition. Thus, it is important to design sensors that can precisely measure pH in these regions, and sensors must have good biocompatibility, physical stability, high sensitivity, wide measurement range, as well as fast response, to fulfill requirements for intracellular pH measurement. In this chapter, we will start from illustrating the importance of measuring intracellular pH, and further discuss how to design optical nanosensors for sensing and imaging intracellular pH. The state of the art technology in intracellular pH sensing and imaging will be reviewed, nanomaterials that are used for constructing intracellular pH sensors will be summarized and the perspective of nanomaterials for intracellular pH sensing and imaging will be given at the end. 1. Overview of the history of pH measurement pH is the abbreviation for Latin "Pondus hydrogenii", Pondus stands for power and hydrogenii stands for hydrogen. In chemistry, the pH scale is a numeric index used to specify acidity and alkalinity of aqueous solutions.
    [Show full text]
  • New Insights Into the Physiological Role of Carbonic Anhydrase IX in Tumour Ph Regulation
    Oncogene (2010) 29, 6509–6521 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW New insights into the physiological role of carbonic anhydrase IX in tumour pH regulation P Swietach1, A Hulikova1, RD Vaughan-Jones1,3 and AL Harris2,3 1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK and 2Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK In this review, we discuss the role of the tumour-associated acidity, commonly expressed using the pH scale. A carbonic anhydrase isoform IX (CAIX) in the context of particularly important class of pH-sensitive molecules is pH regulation. We summarise recent experimental find- protein because of the strong link between protonation ings on the effect of CAIX on cell growth and survival, and state, tertiary structure and functional output. The þ present a diffusion-reaction model to help in the assess- responsiveness to pH depends on H affinity (KH), ment of CAIX function under physiological conditions. bestowed on the protein by the chemistry of its amino CAIX emerges as an important facilitator of acid acid residues. For many proteins, KH is numerically diffusion and acid transport, helping to overcome large close to physiological [H þ ], thus even small displace- cell-to-capillary distances that are characteristic of solid ments from ‘normal’ intracellular pH (pHi) can sig- tumours. The source of substrate for CAIX catalysis is nificantly alter cellular biochemistry. H þ ions serve as likely to be CO2, generated by adequately oxygenated universal and potent modulators of virtually all aspects mitochondria or from the titration of metabolic acids with of life.
    [Show full text]
  • The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and Ph Homeostasis in Non-Secretory Organs
    International Journal of Molecular Sciences Review The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs Dongun Lee and Jeong Hee Hong * Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon 21999, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-32-899-6682; Fax: +82-32-899-6039 Received: 17 December 2019; Accepted: 3 January 2020; Published: 4 January 2020 Abstract: The bicarbonate ion has a fundamental role in vital systems. Impaired bicarbonate transport leads to various diseases, including immune disorders, cystic fibrosis, tumorigenesis, kidney diseases, brain dysfunction, tooth fracture, ischemic reperfusion injury, hypertension, impaired reproductive system, and systemic acidosis. Carbonic anhydrases are involved in the mechanism of bicarbonate movement and consist of complex of bicarbonate transport systems including bicarbonate transporters. This review focused on the convergent regulation of ion homeostasis through various ion transporters including bicarbonate transporters, their regulatory enzymes, such as carbonic anhydrases, pH regulatory role, and the expression pattern of ion transporters in non-secretory systems throughout the body. Understanding the correlation between these systems will be helpful in order to obtain new insights and design potential therapeutic strategies for the treatment of pH-related disorders. In this review, we have discussed the broad prospects and challenges that remain in elucidation of bicarbonate-transport-related biological and developmental systems. Keywords: bicarbonate; ion transporters; carbonic anhydrase; intracellular pH; maturation 1. Convergent Regulation of Ion Homeostasis Ion homeostasis is an important process involved in various organ functions, including modulation of sensitivity to blood pressure, immune cell differentiation, fluid secretion, and fertilization of reproductive cells such as sperm and eggs.
    [Show full text]
  • Sensors and Regulators of Intracellular Ph
    REVIEWS Sensors and regulators of intracellular pH Joseph R. Casey*, Sergio Grinstein‡ and John Orlowski§ Abstract | Protons dictate the charge and structure of macromolecules and are used as energy currency by eukaryotic cells. The unique function of individual organelles therefore depends on the establishment and stringent maintenance of a distinct pH. This, in turn, requires a means to sense the prevailing pH and to respond to deviations from the norm with effective mechanisms to transport, produce or consume proton equivalents. A dynamic, finely tuned balance between proton-extruding and proton-importing processes underlies pH homeostasis not only in the cytosol, but in other cellular compartments as well. Proton-motive force Eukaryotic cells are highly compartmentalized, seg- As a result, βintrinsic is comparatively low at physiological regating specific functions within membrane-bound pH (10–20 mM at pH 7.2), increasing at more extreme (ψH+). The driving force for proton (or equivalent) organelles. Compartmentalization probably evolved from values (for example, 40 mM at pH 6.4)3. This apparent movement, consisting of the the need to provide distinct environmental conditions shortcoming is alleviated by the second component of the proton concentration gradient for the optimal operation of individual metabolic pathways, total buffering capacity, β . Mammalian cells are con- and the transmembrane HCO3– electrical potential. and also to store energy as electrochemical gradients tinuously exposed to CO2, which is uncharged and readily across the membrane dielectric. Protons (and proton traverses most biological membranes4. The hydration of pH buffering capacity equivalents) have a crucial role in this context. Virtually CO2 and the subsequent deprotonation of carbonic acid A measure of the ability of a all proteins depend on pH to maintain their structure generate HCO –, an effective proton buffer (BOX 1).
    [Show full text]
  • Bicarbonate-Dependent and -Independent Intracellular Ph Regulatory Mechanisms in Rat Hepatocytes
    Bicarbonate-dependent and -independent intracellular pH regulatory mechanisms in rat hepatocytes. Evidence for Na+- HCO3- cotransport. D Gleeson, … , N D Smith, J L Boyer J Clin Invest. 1989;84(1):312-321. https://doi.org/10.1172/JCI114156. Research Article Using the pH-sensitive dye 2,7-bis(carboxyethyl)-5(6)-carboxy-fluorescein and a continuously perfused subconfluent hepatocyte monolayer cell culture system, we studied rat hepatocyte intracellular pH (pHi) regulation in the presence (+HCO3-) and absence (-HCO3-) of bicarbonate. Baseline pHi was higher (7.28 +/- 09) in +HCO3- than in -HCO3- (7.16 +/- 0.14). Blocking Na+/H+ exchange with amiloride had no effect on pHi in +HCO3- but caused reversible 0.1-0.2-U acidification in -HCO3- or in +HCO3- after preincubation in the anion transport inhibitor 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). Acute Na+ replacement in +HCO3- alos caused acidification which was amiloride independent but DIDS inhibitible. The recovery of pHi from an intracellular acid load (maximum H+ efflux rate) was 50% higher in +HCO3- than in -HCO3-. Amiloride inhibited H+ effluxmax by 75% in -HCO3- but by only 27% in +HCO3-. The amiloride- independent pHi recovery in +HCO3- was inhibited 50-63% by DIDS and 79% by Na+ replacement but was unaffected by depletion of intracellular Cl-, suggesting that Cl-/HCO3- exchange is not involved. Depolarization of hepatocytes (raising external K+ from 5 to 25 mM) caused reversible 0.05-0.1-U alkalinization, which, however, was neither Na+ nor HCO3- dependent, nor DIDS inhibitible, findings consistent with electroneutral HCO3- transport. We conclude that Na+-HCO3- cotransport, in addition to Na+/H+ exchange, is an important regulator of pHi in rat hepatocytes.
    [Show full text]
  • Smad5 Acts As an Intracellular Ph Messenger and Maintains Bioenergetic Homeostasis
    Cell Research (2017) 27:1083-1099. ORIGINAL ARTICLE www.nature.com/cr Smad5 acts as an intracellular pH messenger and maintains bioenergetic homeostasis Yujiang Fang1, Zhongliang Liu1, Zhenyu Chen1, Xiangjie Xu1, Mengtao Xiao4, Yanyan Yu4, Yuanyuan Zhang1, Xiaobai Zhang3, Yanhua Du3, Cizhong Jiang3, Yuzheng Zhao5, Yiran Wang1, Beibei Fan1, Daniel Terheyden-Keighley1, Yang Liu1, Lei Shi1, Yi Hui2, Xin Zhang2, Bowen Zhang1, Hexi Feng1, Lin Ma1, Quanbin Zhang1, Guohua Jin2, Yi Yang5, Bin Xiang4, Ling Liu1, 6, Xiaoqing Zhang1, 6, 7 1Shanghai Tenth People’s Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China; 2Department of Anatomy and Neurobiology, the Jiangsu Key Laboratory of Neuroregen- eration, Nantong University, Nantong, Jiangsu 226001, China; 3The School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; 4China Novartis Institutes for BioMedical Research, Shanghai 201203, China; 5Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Bio- manufacturing Technology, East China University of Science and Technology, Shanghai 200237, China; 6Tongji University Ad- vanced Institute of Translational Medicine, Shanghai 200092, China; 7The Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China Both environmental cues and intracellular bioenergetic states profoundly affect intracellular pH (pHi). How a cell responds to pHi changes to maintain bioenergetic homeostasis remains elusive. Here we show that Smad5, a well-characterized downstream component of bone morphogenetic protein (BMP) signaling responds to pHi changes. Cold, basic or hypertonic conditions increase pHi, which in turn dissociates protons from the charged amino acid clusters within the MH1 domain of Smad5, prompting its relocation from the nucleus to the cytoplasm.
    [Show full text]
  • ADRENERGIC CONTROL of RED CELL Ph in SALMONID FISH: ROLES of the SODIUM/PROTON EXCHANGE, JACOBS-STEWART CYCLE and MEMBRANE POTENTIAL
    J. exp. Biol. 154, 257-271 (1990) 257 Printed in Great Britain © The Company of Biologists Limited 1990 ADRENERGIC CONTROL OF RED CELL pH IN SALMONID FISH: ROLES OF THE SODIUM/PROTON EXCHANGE, JACOBS-STEWART CYCLE AND MEMBRANE POTENTIAL BY MIKKO NIKINMAA, KIRSTI TIIHONEN AND MARITA PAAJASTE Division of Physiology, Department of Zoology, University of Helsinki, Arkadiankatu 7, SF-00100 Helsinki, Finland Accepted 11 June 1990 Summary We investigated the mechanisms by which adrenergic activation of sodium/pro- ton exchange reduces the pH gradient across the membrane of rainbow trout red cells. In untreated cells, adrenergic stimulation caused a significant increase in the + + proton distribution ratio ([H ]e/[H ]i) across the red cell membrane. The increase in the proton distribution ratio caused by adrenergic stimulation was inhibited by the protonophore 2,4-dinitrophenol (2,4-DNP). Thus, sodium/pro- ton exchange displaces protons from electrochemical equilibrium. Active regu- lation of intracellular pH by sodium/proton exchange is possible, because the extracellular dehydration of carbonic acid to carbon dioxide is uncatalyzed. The increase in proton distribution ratio caused by adrenergic stimulation was inhibited in red cell suspensions to which extracellular carbonic anhydrase had been added before stimulation. In contrast, inhibition of intracellular carbonic anhydrase markedly increased the pH changes induced by adrenergic stimulation, suggesting that the net direction of the intracellular hydration/dehydration reaction may markedly affect the intracellular pH changes. Membrane potential changes are not a necessary component of the adrenergic response. The increases in red cell volume and sodium and chloride concentrations induced by adrenergic stimulation were unaffected in cells 'voltage-clamped' by valinomycin.
    [Show full text]
  • CALCULATION of INTRACELLULAR Ph from the DISTRIBUTION of 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE (DMO)
    CALCULATION OF INTRACELLULAR pH FROM THE DISTRIBUTION OF 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE (DMO). APPLICATION TO SKELETAL MUSCLE OF THE DOG William J. Waddell, Thomas C. Butler J Clin Invest. 1959;38(5):720-729. https://doi.org/10.1172/JCI103852. Research Article Find the latest version: https://jci.me/103852/pdf CALCULATION OF INTRACELLULAR PH FROM THE DISTRIBUTION OF 5,5-DIMETHYL-2,A-OXAZOLIDINEDIONE (DMO). APPLICA- TION TO SKELETAL MUSCLE OF THE DOG* By WILLIAM J. WADDELL AND THOMAS C. BUTLER (From the Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, N. C.) (Submitted for publication October 6, 1958; accepted January 2, 1959) Estimations of hydrogen ion activities in the that the undissociated form of an acid or base is in interior of cells have been attempted through a equal concentration on the two sides of the cellu- number of different experimental approaches. lar membrane permits the calculation of intracel- The methods that have been employed are of sev- lular pH from measurements of extracellular pH eral general types: measurements on preparations and the extracellular and intracellular concentra- of broken cells, measurements on fluid with- tions of the acid or base. In most of the work that drawn from cells, observations with visible in- has hitherto been done based on this principle, dicators, measurements with micro-electrodes carbon dioxide has been the compound used as the introduced into cells, measurements of the intra- indicator. It is assumed that the cellular mem- cellular and extracellular concentrations of weak brane is permeable to carbon dioxide and that the organic acids and bases, and calculation of the tension of carbon dioxide inside the cell is equal balance of ionic charges.
    [Show full text]
  • Intracellular Ph Regulation and the Acid Delusion
    Canadian Journal of Physiology and Pharmacology Intracellular pH Regulation and the Acid Delusion Journal: Canadian Journal of Physiology and Pharmacology Manuscript ID cjpp-2020-0631 Manuscript Type: Review Date Submitted by the 29-Oct-2020 Author: Complete List of Authors: Magder, Sheldon; Mcgill University Health Centre Magder, Alexandr; Royal College of Surgeons in Ireland Samoukovic, Gordan; McGill University Faculty of Medicine, critical care Is the invited manuscript for consideration in a Special Not applicable (regular submission) Issue: Draft Keyword: strong ion, acid base, stewart, buffer, sodium hydrogen exchanger © The Author(s) or their Institution(s) Page 1 of 67 Canadian Journal of Physiology and Pharmacology 1 1 2 3 4 Intracellular pH Regulation and the Acid Delusion 5 Sheldon Magder, Alexandr Magder, Gordan Samoukovic 6 McGill University Health Centre 7 Department of Critical Care 8 687 Pine Av W 9 Montreal, Quebec 10 H3A 1A1 11 12 13 14 15 Address correspondence to: 16 Draft 17 S Magder 18 Royal Victoria Hospital 19 687 Pine Av W 20 Montreal, Quebec 21 H3A 1A1 22 [email protected] 23 24 25 26 27 Dec 14 edits © The Author(s) or their Institution(s) Canadian Journal of Physiology and Pharmacology Page 2 of 67 2 29 Abstract 30 The concentration H+ ([H+]) in intracellular fluid (ICF) must be maintained in a narrow range in 31 all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental 32 biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH 33 notation, failure to consider the roles played by differences in the concentration of strong ions ( + - 34 SID), the conservation of mass, the principle of electrical neutrality and that [H ] and [HCO3 ] 35 are dependent variables.
    [Show full text]
  • Elevated Carbon Dioxide Exposure Alters Intracellular Ph and Energy Charge in Avocado Fruit Tissue Diana L
    J. Amer. Soc. hort. Sci. 122(2):253-257. 1997. Elevated Carbon Dioxide Exposure Alters Intracellular pH and Energy Charge in Avocado Fruit Tissue Diana L. Lange1 and Adel A. Kader Department of Pomology, University of California, Davis, CA 95616 31 ADDITIONAL INDEX WORDS. Nuclear magnetic resonance spectroscopy, ATP, ADP, P- NMR ABSTRACT. Changes in cytosolic and vacuolar pH, ATP, ADP, and the ATP:ADP ratio were measured in whole fruit or mesocarp disks of avocado [Persea americana (Mill.) cv. Hass] during brief exposures to elevated CO2. Intact climacteric fruit exposed to air (21 % O2), 20% CO2 (17% O2, balance N2), or 40% CO2 (13% O2, balance N2) had cytosolic pH values of 7.0, 6.6, and 6.4, respectively, while mesocarp disks had cytosolic pH values of 6.9, 6.7, and 6.4, respectively. The ß-ATP levels of intact climacteric fruit exposed to 20% CO2 or 40% CO2 for 2 h were reduced by 25% or 43%, respectively, relative to air-exposed fruit. HPLC analysis of nucleotide phosphates from preclimacteric avocados revealed that ATP levels and the ATP:ADP ratio increased in 40% compared to the air-stored fruit. However, 1 day after transfer to air, the effects of elevated CO2 had dissipated. These modifications in cellular state could alter the activity of respiratory enzymes in fruit exposed to elevated CO2 atmospheres. Short postharvest exposures of fruit to CO2 levels >15% have many potential uses, such as alleviation of decay and reduction of insect infestation and certain physiological disorders in fruit (Ke and Kader, 1992; Truter and Eksteen, 1987).
    [Show full text]