Abstract
(1) The “specific bradycardic agent” alinidine reduces the slope of the diastolic depolarization in sinoatrial tissue and Purkinje fibers. In short Purkinje fibers of sheep, alinidine (28 μM) decreased the pacemaker current by a dual action. The voltage dependence ofi f activation was shifted in the hyperpolarizing direction by 7.8±0.6 mV (n=18,p<0.001) and the conductance of the fully activated\(\bar i_{\text{f}}\) current was reduced to 73±2% (n=18,p<0.001) of its control value. These effects were reversible and dose-dependent. (2) Ionophoretic injections of alinidine caused reversible reductions of the diastolic depolarization rate and simultaneous transient hyperpolarizing shifts of thei f activation range. (3) Some prolongation of the action potential duration was observed at 28 μM and more pronounced at higher concentration. This was presumably the consequence of a reduction by alinidine of outward repolarizing current carried by the background inward rectifier and plateau currenti x. (4) The action of alinidine oni f resulted in a slower activation of a reduced fraction of the pacemaker current at the maximal diastolic potential level. This explains the decrease of the diastolic depolarization rate observed in Purkinje fibers.
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References
Aronson RS, Gelles JM, Hoffman BF (1973) A new method for producing short cardiac Purkinje fibers suitable for voltage clamp. J Appl Physiol 34:527–530
Bouman LN, Duivenvoorden JJ, Opthof T, Treijtel BW (1984) Electrophysiological effects of alinidine on nodal and atrial fibers in the guinea pig heart. J Pharmacol Exp Ther 229:551–556
Brown HF (1982) Electrophysiology of the sinoatrial node. Physiol Rev 62:505–530
Callewaert G, Carmeliet E, Vereecke J (1984) Single cardiac Purkinje cells: general electrophysiology and voltage-clamp analysis of the pacemaker current. J Physiol (Lond) 349:643–661
Carmeliet EE (1961) Chloride and the membrane potential of Purkinje fibres. J Physiol (Lond) 156:375–388
Carmeliet EE, Vereecke J (1979) Electrogenesis of the action potential and automaticity. In: Berne RM (ed) Handbook of physiology. The cardiovascular system, vol I. American Physiological Society. Baltimore, pp 269–334
Cohen I, Noble D, Ohba M, Ojeda C (1979) Actions of salicylate ions on the electrical properties of sheep cardiac Purkinje fibers. J Physiol (Lond) 297:163–185
Deitmer JW, Ellis D (1980) Interaction between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres. J Physiol (Lond) 304:471–488
De Mello WC (1982) Cell-to-cell communication in heart and other tissues. Prog Biophys Mol Biol 39:147–182
DiFrancesco D (1981a) A new interpretation of the cardiac pacemaker current in calf Purkinje fibers. J Physiol (Lond) 314: 359–376
DiFrancesco D (1981b) A study of the ionic nature of the pacemaker current in calf Purkinje fibers. J Physiol (Lond) 314:377–393
DiFrancesco D (1984) Characterization of the pacemaker current kinetics in calf Purkinje fibres. J Physiol (Lond) 348:341–367
DiFrancesco D (1985) The cardiac hyperpolarizing-activated current,i f. Origins and developments. Prog Biophys Mol Biol 46:163–183
DiFrancesco D, Ojeda C (1980) Properties of the currenti f in the sinoatrial node of the rabbit compared with these of the current\(i_{{\text{k}}_{\text{2}} }\) in Purkinje fibers. J Physiol (Lond) 308:353–367
DiFrancesco D, Ohba M, Ojeda C (1979) Measurement and significance of the reversal potential for the pacemaker current (\(i_{{\text{k}}_{\text{2}} }\)) in sheep Purkinje fibers. J Physiol (Lond) 297:135–162
DiFrancesco D, Ferroni A, Visentin S (1984) Barium-induced blockade of the inward rectifier in calf Purkinje fibres. Pflügers Arch 402:446–453
Gliklich JI, Hoffman BF (1978) Sites of action and active forms of lidocaine and some derivatives on cardiac Purkinje fibers. Circ Res 43:638–651
Hauswirth O, Noble D, Tsien RW (1968) Adrenaline: mechanisms of action on the pacemaker potential in cardiac Purkinje fibers. Science 162:916
Hescheler J, Pelzer D, Trabe G, Trautwein W (1982) Does the organic calcium channel blocker D600 act from inside or outside on the cardiac cell membrane? Pflügers Arch 393:287–291
Hutter OP, Noble D (1961) Anion conductance of cardiac muscle. J Physiol (Lond) 157:335–350
Isenberg G (1976) Cardiac Purkinje fibers: cesium as a tool to block inward rectifying potassium currents. Pflügers Arch 365:99–106
Kenyon JL, Gibbons WR (1977) Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers. J Gen Physiol 70:635–660
Kobinger W (1985) Specific bradycardic agent, a new approach to therapy in angina pectoris? Progress in Pharmacology, Fischer, Stuttgart, New York, pp 89–100
Kobinger W, Lillie C, Pichler L (1979) Cardiovascular action of N-allyl-clonidine (ST 567), a substance with specific bradycardic action. Eur J Pharmacol 58:141–150
Kobinger W, Lillie C (1984) Alonidine. In: Scriabine A (ed) New drug annual cardiovascular drugs. Raven Press, New York, pp 193–210
McAllister RE, Noble D, Tsien RW (1975) Reconstruction of the electrical activity of cardiac Purkinje fibers. J Physiol (Lond) 251:1–59
Millar JS, Vaughan-Williams EM (1981) Pacemaker selectivity: influence on rabbit atria of ionic environment and of alinidine, a possible anion antagonist. Cardiovasc Res 15:335–350
Noble D (1984) The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol (Lond) 353:1–50
Noble D, Tsien RW (1968) The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres. J Physiol (Lond) 195:185–214
Roos A, Boron WF (1981) Intracellular pH. Physiol Rev 61:296–434
Satoh H, Hashimoto K (1986) Electrophysiological study of alinidine in voltage clamped rabbit sino-atrial node cells. Eur J Pharmacol 121:211–219
Seyama I (1979) Characteristics of the anion channel in the sinoatrial node cell of the rabbit. J Physiol (Lond) 294:447–460
Snyders DJ, Van Bogaert PP (1984) Alinidine modifies the pacemaker currenti f kinetics in sheep cardiac Purkinje fibers. Proc IIth Int Congr Electrocardiol: A 65
Snyders DJ, Van Bogaert PP (1985) Mode of action of alinidine, a new bradycardic agent: a voltage-clamp study. J Am Coll Cardiol 5:494
Tritthart HA, Windisch H, Heuberger S (1981) The effects of the bradycardia-producing compound alinidine on action potentials and tension development in cardiac fibers. Naunyn-Schmiedeberg's Arch Pharmacol 316:172–177
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: does epinephrine act by directly modifying the external surface charge? J Gen Physiol 64:320–342
Van Bogaert PP (1985) Pacemaker current changes during intracellular pH transients in sheep cardiac Purkinje fibers. Pflügers Arch 404:29–40
Van Bogaert PP, Carmeliet E (1985) Chloride sensitivity of thei f pacemaker current in Cardiac Purkinje fibers from sheep and atrial appendage fibres from human hearts. Arch Int Physiol Biochim 93:914
Vaughan-Jones RD (1979a) Non-passive 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-hart Purkinje fibers studied using intracellular chloride and pH-sensitive micro-electrodes. J Physiol (Lond) 295:111–137
Vereecke J, Isenberg G, Carmeliet EE (1980) K-efflux through inward rectifying K-channels in voltage clamped Purkinje fibres. Pflügers Arch 384:207–217
Yanagihara K, Irisawa H (1980) Inward current activated during hyperpolarization in the rabbit sinoatrial node cell. Pflügers Arch 385:11–19
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Snyders, D.J., Van Bogaert, PP. Alinidine modifies the pacemaker current in sheep Purkinje fibers. Pflugers Arch. 410, 83–91 (1987). https://doi.org/10.1007/BF00581900
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DOI: https://doi.org/10.1007/BF00581900