Skip to main content
Log in

Alinidine modifies the pacemaker current in sheep Purkinje fibers

  • Excitable Tissues and Central Nervous Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

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

    Google Scholar 

  • 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

    Google Scholar 

  • Brown HF (1982) Electrophysiology of the sinoatrial node. Physiol Rev 62:505–530

    Google Scholar 

  • 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

    Google Scholar 

  • Carmeliet EE (1961) Chloride and the membrane potential of Purkinje fibres. J Physiol (Lond) 156:375–388

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • De Mello WC (1982) Cell-to-cell communication in heart and other tissues. Prog Biophys Mol Biol 39:147–182

    Google Scholar 

  • DiFrancesco D (1981a) A new interpretation of the cardiac pacemaker current in calf Purkinje fibers. J Physiol (Lond) 314: 359–376

    Google Scholar 

  • DiFrancesco D (1981b) A study of the ionic nature of the pacemaker current in calf Purkinje fibers. J Physiol (Lond) 314:377–393

    Google Scholar 

  • DiFrancesco D (1984) Characterization of the pacemaker current kinetics in calf Purkinje fibres. J Physiol (Lond) 348:341–367

    Google Scholar 

  • DiFrancesco D (1985) The cardiac hyperpolarizing-activated current,i f. Origins and developments. Prog Biophys Mol Biol 46:163–183

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • DiFrancesco D, Ferroni A, Visentin S (1984) Barium-induced blockade of the inward rectifier in calf Purkinje fibres. Pflügers Arch 402:446–453

    Google Scholar 

  • 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

    Google Scholar 

  • Hauswirth O, Noble D, Tsien RW (1968) Adrenaline: mechanisms of action on the pacemaker potential in cardiac Purkinje fibers. Science 162:916

    Google Scholar 

  • 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

    Google Scholar 

  • Hutter OP, Noble D (1961) Anion conductance of cardiac muscle. J Physiol (Lond) 157:335–350

    Google Scholar 

  • Isenberg G (1976) Cardiac Purkinje fibers: cesium as a tool to block inward rectifying potassium currents. Pflügers Arch 365:99–106

    Google Scholar 

  • Kenyon JL, Gibbons WR (1977) Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers. J Gen Physiol 70:635–660

    Google Scholar 

  • Kobinger W (1985) Specific bradycardic agent, a new approach to therapy in angina pectoris? Progress in Pharmacology, Fischer, Stuttgart, New York, pp 89–100

    Google Scholar 

  • 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

    Google Scholar 

  • Kobinger W, Lillie C (1984) Alonidine. In: Scriabine A (ed) New drug annual cardiovascular drugs. Raven Press, New York, pp 193–210

    Google Scholar 

  • McAllister RE, Noble D, Tsien RW (1975) Reconstruction of the electrical activity of cardiac Purkinje fibers. J Physiol (Lond) 251:1–59

    Google Scholar 

  • 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

    Google Scholar 

  • Noble D (1984) The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol (Lond) 353:1–50

    Google Scholar 

  • 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

    Google Scholar 

  • Roos A, Boron WF (1981) Intracellular pH. Physiol Rev 61:296–434

    Google Scholar 

  • Satoh H, Hashimoto K (1986) Electrophysiological study of alinidine in voltage clamped rabbit sino-atrial node cells. Eur J Pharmacol 121:211–219

    Google Scholar 

  • Seyama I (1979) Characteristics of the anion channel in the sinoatrial node cell of the rabbit. J Physiol (Lond) 294:447–460

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Tsien RW (1974a) Effects of epinephrine on the pacemaker potassium current of cardiac Purkinje fibers. J Gen Physiol 64:293–319

    Google Scholar 

  • 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

    Google Scholar 

  • Van Bogaert PP (1985) Pacemaker current changes during intracellular pH transients in sheep cardiac Purkinje fibers. Pflügers Arch 404:29–40

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Vereecke J, Isenberg G, Carmeliet EE (1980) K-efflux through inward rectifying K-channels in voltage clamped Purkinje fibres. Pflügers Arch 384:207–217

    Google Scholar 

  • Yanagihara K, Irisawa H (1980) Inward current activated during hyperpolarization in the rabbit sinoatrial node cell. Pflügers Arch 385:11–19

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00581900

Key words

Navigation