Abstract
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1.
Intracellular acidosis, at constant extracellular pH, hyperpolarizes the resting potential and reduces the diastolic depolarization rate of cardiac Purkinje fibres. With alkaline pHi, the fibre depolarizes and spontaneous firing is observed.
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2.
Intracellular pH transients induced either by superfusion with Tyrode buffered with 5% CO2/23 mM HCO −3 or 16% CO2/61 mM HCO −3 , or with solutions containing weak undissociated acids, transiently shifted the half-maximum activation potentialE 0.5 of the pace-maker current. Similar transients were observed when NH4Cl was added and subsequently withdrawn from the solution.
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3.
Simultaneous pHi measurements demonstrate a close relation between the time course of the pHi andE 0.5 variations. Acid pHi shiftsE 0.5 to more negative and alkaline pHi's to less negative potentials.
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4.
These pace-maker current activation voltage shifts are interpreted as the direct consequence of fixed charges titration at the inside of the sarcolemma. Other effects, like the slowing-down and reduction of the pace-maker current by acid pHi, presumably result from other interactions of protons with the pace-maker channel.
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References
Aickin, CC, Thomas RC (1977a) Microelectrode measurements of the intracellular pH and buffering power of mouse soleus muscle fibres. J Physiol (Lond) 267:791–810
Aickin CC, Thomas RC (1977b) An investigation of the ionic mechanism of intracellular pH regulation in mouse soleus muscle fibres. J Physiol (Lond) 273:295–316
Allen D, Orchard CH (1983) The effects of pH on intracellular calcium transients in mammalian cardiac muscle. J Physiol (Lond) 335:555–567
Bers DM, Ellis D (1982) Intracellular calcium and sodium activity in sheep heart Purkinje fibres. Effects of changes of external sodium and intracellular pH. Pflügers Arch 393:171–178
Boron WF (1983) Transport of H+ and ionic weak acids and bases. Membr Biol 72:1–16
Boron WF, De Weer P (1976) Intracellular pH transients in squid giant axons caused by CO2, NH3 and metabolic inhibitors. J Gen Physiol 67:91–112
Brown RH, Noble D (1978) Displacement of activation thresholds in cardiac muscle by protons and calcium. J Physiol (Lond) 282:333–343
Burton RF (1975) Ringer solutions and physiological salines. Bristol Wright-Scientechnica
Callewaert G, Carmeliet E, Vereecke J (1984 (1984) Single cardiac Purkinje cells: general electrophysiology and voltage-clamp analysis of the pace-maker current. J Physiol (Lond) 349:643–661
Carbone E, Testa PL, Wanke E (1981) Intracellular pH and ionic channels in the Loligo vulgaris giant axon. Biophys J 35:393–414
Cobbe SM, Poole-Wilson PA (1980) The time of onset and severity of acidosis in myocardial ischemia. J Mol Cel Cardiol 12:745–760
Cohen I, Noble D, Ohba M, Ojeda C (1979) Actions of salicylate ions on the electrical properties of sheep cardiac Purkinje fibres. J Physiol (Lond) 297:163–185
Cohen I, Falk RT, Mulrine NK (1983) Actions of barium and rubidium on membrane currents in canine Purkinje fibres. J Physiol (Lond) 338:589–612
Dani JA, Sanchez JA, Hille B (1983) Lyotropic actions: Na channel gating and Ca electrode response. J Gen Physiol 81:255–281
Deitmer JW, Ellis D (1980) Interactions between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres. J Physiol (Lond) 304:471–488
De Hemptine A, Marrannes R, Vanheel B (1983) Influence of organic acids on intracellular pH. Am J Physiol 245:C178-C183
De Mello WC (1983) The influence of pH on the healing-over of mammalian cardiac muscle. J Physiol (Lond) 339:299–307
Di Francesco D (1981a) A new interpretation of the cardiac pace-maker current in calf Purkinje fibres. J Physiol (Lond) 314:359–376
Di Francesco D (1981b) A study of the ionic nature of the pace-maker current in calf Purkinje fibres. J Physiol (Lond) 314:377–393
Di Francesco D, McNaughton PA (1979) The effect of calcium on outward membrane currents in the cardiac Purkinje fibre. J Physiol (Lond) 289:333–347
Di Francesco D, Ohba M, Ojeda C (1979) Measurement and significance of the reversal potential for the pace-maker current (i k2 in sheep Purkinje fibres. J Physiol (Lond) 297:135–162
Ellis D, Thomas RC (1976a) Micro-electrode measurement of the intracellular pH of mammalian heart cells. Nature 262:224–225
Ellis D, Thomas RC (1976b) Direct measurement of the intracellular pH of iammalian cardiac muscle. J Physiol (Lond) 262:755–771
Eisner DA, Lederer WJ, Vaughan-Jones AJ (1981) The dependence of sodium pumping and tension on intracellular sodium activity in voltage-clamped sheep Purkinje fibres. J Physiol (Lond) 317:163–187
Eisner DA, Lederer WJ, Sheu SS (1983) The role of intracellular sodium activity in the anti-arrhytmic action of local anaesthetics in sheep Purkinje fibres. J Physiol (Lond) 340:239–257
Frankenhaeuser B, Hodgkin AL (1957) The action of calcium on the electrical properties of squid axons. J Physiol (Lond) 137:218–244
Gilbert DL, Ehrenstein G (1969) Effect of divalent cations on potassium conductance of squid axons: determinations of surface charge. Biophys J 9:447–464
Goldberg G, Yoram L (1983) Evidence for acetylcholine receptor blockade by intracelluar hydrogen ions in cultured chick myoballs. J Physiol (Lond) 343:429–437
Gutknecht J, Tosteson DC (1973) Diffusion of weak acids across lipid blayer membranes: effects of chemical reactions in the unstirred layers. Science 182:1258–1261
Hanke W, Miller C (1983) Single chloride channels from Torpedo electroplax. J Gen Physiol 82:25–45
Hart G (1983) The kinetics and temperature dependence of the pace-maker currenti f in sheep Purkinje fibres. J Physiol (Lond) 337:401–416
Hart G, Noble D, Shimoni Y (1980) Adrenaline shifts the voltage dependence of the Na and K components ofi f in sheep Purkinje fibres. J Physiol 308:34P
Hille B, Woodhull A, Shapiro BI (1975) Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Phil Trans R Soc Lond B 270:301–318
Isenberg G (1977a) Cardiac Purkinje fibres. Resting, action and pace-maker potential under the influence of [Ca2+]i as modified by intracellular injection technique. Pflügers Arch 371:51–59
Isenberg G (1977b) Cardiac Purkinje fibres. [Ca2+]i controls the potassium permeability via the conductance componentsg k1 andg k2. Pflügers Arch 371:77–85
Kass RS, Tsien RW (1975) Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers. J Gen Physiol 66:169–192
Kenyon JL, Gibbons WR (1977) Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers. J Gen Physiol 70:635–660
Kurachi Y (1982) The effects of intracellular protons on the electrical activity of single ventricular cells. Pflügers Arch 394:264–270
Lea TJ (1983) CO2/HCO −3 induced Ca2+ release from frog sacroplasmic reticulum and the effects of weak bases. J Physiol (Lond) 334:39–40P
Lea TJ, Ashley CC (1981) Carbon dioxide or bicarbonate ions release Ca from internal stores in crustacean myofibrillar bundles. J Membr Biol 61:115–125
Loewenstein WR (1981) Junctional intercellular communication: the cell-to-cell membrane channel. Physiol Rev 61:829–913
McLaughlin SGA, Dilger JP (1980) Trasport of protons across membranes by weak acids. Physiol Rev 60:825–863
Marrannes R, de Hemptine A, Leusen I (1981) pH aspects of transient changes in conduction velocity in isolated heart fibers after partial replacement of chloride with organic anions. Pflügers Arch 389:199–209
Matsuda H, Noma A, Kurachi Y, Irisawa H (1982) Transient depolarization and spontaneous voltage fluctuations in isolated single cell from guinea-pig ventricles. Calcium-mediated membrane potential fluctuations. Circ Res 51:142–151
Meech RW, Thomas RC (1977) The effect of calcium injection on the intracellular sodium and pH of snail. neurones. J Physiol (Lond) 265:867–879
Miller C, White MM (1980) A voltage dependent chloride channel from Torpedo electroplax membrane. Ann NY Acad Sci 341:534–551
Moody WJ (1980) Appearance of calcium action potentials in crayfish slow muscle fibres under conditions of low intracellular pH. J Physiol (Lond) 302:335–346
Moody WJ, Hagiwara S (1982) Block of inward rectification by intracellular H+ in immature oocytes of the starfish Mediaster aequalis. J Gen Physiol 79:115–130
Noble D (1974) Cardiac action potentials and pace-maker activity. In: Linden RJ (ed) Recent advances in physiology, pp 1–50
Noble D, Tsien RW (1968) The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibers. J Physiol (Lond) 195:185–214
Nuccitelli R, Deamer DW (1982) Intracellular pH: its measurement, regulation and utilization in cellular functions. Alan R Liss, Inc, New York
Obaid AL, Socolar SJ, Rose B (1983) Cell-to-cell channels with two independently regulated gates in series: analyses of junctional conductance modulation by membrane potential, calcium and pH. J Membr Biol 73:69–89
Poole-Wilson PA (1978) Measurement of myocardial intracellular pH in pathological states. J Mol Cell Cardiol 10:511–526
Reber WR, Weingart R (1982) Ungulate cardiac Purkinje fibres: the influence of intracellular pH on the electrical cell-to-cell coupling. J Physiol (Lond) 328:87–104
Roos A, Boron WF (1981) Intracellular pH. Physiol Rev 61:296–434
Sharp AP, Thomas RC (1981) The effects of chloride substitution on intracellular pH in crab muscle. J Physiol (Lond) 312:71–80
Shrager P (1974) Ionic conductance changes in voltage clamped crayfish axons at low pH. J Gen Physiol 64:666–690
Spitzer KW, Hogan PM (1979) The effects and bicarbonate on action potential repolarization in canine cardiac Purkinje fibres. J Gen Physiol 73:199–218
Thomas RC (1974) Intracellular pH of snail neurones measured with a new pH-sensitive glas microelectrode. J Physiol (Lond) 238:159–180
Thomas RC (1976) The effect of carbon dioxide on the intracellular pH and buffering power of snail neurones. J Physiol (Lond) 255:715–735
Thomas RC (1978) Ion-sensitive intracellular microelectrodes. How to make them and use them. Academic Press, London
Tsien RW (1974a) Effects of epinephrine on the pacemaker potassium current of cardiac Purkinje fibers. J Gen Physiol 64:293–319
Tsien RW (1974b) Mode of action of chronotropic agents in cardiac Purkinje fibers. J Gen Physiol 64:320–342
Van Bogaert PP (1980) Modification of cardiac pacemaker currents by intracellular pH changes. Proc Int Un Physiol Sci Intern Congress Budapest 1980, vol XIV, p 762
Van Bogaert PP (1983) Time course of pacemaker current changes during intracellular pH transients. Arch Int Physiol Biochem 91:60–61
Van Bogaert PP, Snyders DJ (1979) Intracellular pH transient induced by chloride substitution in cardiac Purkinje fibres. Arch Int Physiol Biochem 87:341–342
Van Bogaert PP, Snyders DJ (1982) Effects of 4-Aminopyridine on inward rectifying and pacemaker currents of cardiac Purkinje fibres. Pflügers Arch 394:230–238
Van Bogaert PP, Vereecke JS, Carmeliet EE (1978) The effect of raised pH on pacemaker activity and ionic currents in cardiac Purkinje fibres. Pflügers Arch 375:45–52
Vaughan-Jones RD (1979a) Non-pasive chloride distribution in mammalian heart muscle: micro-electrode measurement of the intracellular chloride activity. J Physiol (Lond) 295:83–109
Vaughan-Jones RD (1979b) Regulation of chloride in quiescent sheep-heart Purkinje fibers studied using intracellular chloride and pH-sensitive micro-electrodes. J Physiol 295:111–137
Vaughan-Jones RD, Lederer WJ, Eisner DA (1983) Ca2+ ions affect intracellular pH in mammalian cardiac muscle. Nature 301:522–524
Wanke E, Carbone E, Testa PL (1980) The sodium channel and intracellular H+ blockage in squid axon. Nature 287:62–63
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Van Bogaert, P.P. Pace-maker current changes during intracellular pH transients in sheep cardiac Purkinje fibres. Pflugers Arch. 404, 29–40 (1985). https://doi.org/10.1007/BF00581487
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DOI: https://doi.org/10.1007/BF00581487