Abstract
-
1.
In 1.35 mM [K+]o, sheep cardiac Purkinje fibers depolarized to about −40 mV. Whereas some fibers oscillated spontaneously at plateau potentials, others could be made to oscillate when polarized by intracellular currents. Pacemaker activity at plateau potentials (−50 to 0 mV) was distinct from that caused by the\(i_{{\text{K}}_2 }\) pacemaker at more negative potentials (−60 to −100 mV).
-
2.
Epinephrine induced spontaneously occurring action potentials and increased pacemaker activity in depolarized Purkinje fibers. The ED50 for the positive chronotropic effect of epinephrine was about 5×10−7 M. This concentration is similar to that reported for the effect of epinephrine on plateau amplitude (Carmeliet and Vereecke, 1969) and the slow inward current (i si , Reuter, 1974).
-
3.
In voltage clamp experiments, epinephrine increased the magnitude ofi si and of an outward plateau current,i xi . It is concluded that epinephrine effects pacemaking at plateau potentials by increasingi si and without shifting the voltage dependence of these currents. The onset of pacemaker activity by epinephrine was preceded by membrane depolarization that results from an inward shift of the steady-state current-voltage relation. This current may flow throughi si channels that are activated but not completely inactivated.
Similar content being viewed by others
References
Aronson, R. S., Cranefield, P. F.: The electrical activity of canine cardiac Purkinje fibers in sodium-free, calcium-rich solutions. J. Gen. Physiol.61, 786–808 (1973)
Aronson, R. S., Gelles, J. M., Hoffman B. F.: A new method for producing short cardiac Purkinje fibers suitable for voltage clamp. J. Appl. Physiol.34, 527–530 (1973)
Beeler, G. W., Jr., Reuter, H.: Reconstruction of the action potential of ventricular myocardial fibres. J. Physiol. (Lond.)268, 177–210 (1977)
Brown, H. F., Noble, S. J.: Effects of adrenaline on membrane currents underlying pacemaker activity in frog atrial muscle. J. Physiol. (Lond.)238, 51P-53P (1974)
Brown, H. F., McNaughton, P. A., Noble, D., Noble, S. J.: Adrenergic control of cardiac pacemaker currents. Philos. Trans. R. Soc. Lond. (Biol.)270, 527–537 (1975)
Carmeliet, E. E.: Chloride and potassium permeability in cardiac Purkinje fibres. Thesis. Bruxelles: Presses Academiques Europeennes, S. C. 1961a
Carmeliet, E. E.: Chloride ions and the membrane potential of Purkinje fibres. J. Physiol. (Lond.)156, 375–388 (1961b)
Carmeliet, E., Vereecke, J.: Adrenaline and the plateau phase of the cardiac action potential. Pflügers Arch.313, 300–315 (1969)
Cranefield, P. F.: The conduction of the cardiac impulse. Mount Kisco, N. Y.: Futura Publishing Company 1975
Deck, K. A., Kern, R., Trautwein, W.: Voltage clamp technique in mammalian myocardial fibers. Pflügers Arch. ges. Physiol.280 50–62 (1964)
Dudel, J., Peper, K., Rüdel, R., Trautwein, W.: The potassium component of membrane current in Purkinje fibers. Pflügers Arch. ges. Physiol.296, 308–327 (1967)
Fozzard, H. A., Hiraoka, M.: The positive dynamic current and its inactivation properties in cardiac Purkinje fibres. J. Physiol. (Lond.)234, 569–586 (1973)
Gadsby, D. C., Cranefield, P.: Two levels of resting potential in cardiac Purkinje fibers. J. Gen. Physiol.70, 725–746 (1977)
Gelles, J. M., Aronson, R. S.: Voltage clamp analysis of the effects of dopamine on the transmembrane ionic currents underlying the action potential of sheep cardiac Purkinje fibers. Circ. Res.40, 561–566 (1977)
Gibbons, W. R., Fozzard, H. A.: Slow inward current and contraction of sheep cardiac Purkinje fibers. J. Gen. Physiol.65, 367–384 (1975)
Grabowski, W., Lüttgau, H. Ch., Schulze, J. J.: The effects of isoprenaline and a new β-sympathomimetic amine upon spontaneous activity, diastolic depolarization and plateau height in cardiac Purkinje fibres. Br. J. Pharmacol.63, 427–434 (1978)
Hauswirth, O., Noble, D., Tsien, R. W.: The mechanism of oscillatory activity at low membrane potentials in cardiac Purkinje fibres. J. Physiol. (Lond.)200, 255–265 (1969)
Hutter, O. F., Noble, D.: Anion conductance of cardiac muscle. J. Physiol. (Lond.)157, 335–350 (1961)
Imanishi, S.: Calcium-sensitive discharges in canine Purkinje fibers. Jap. J. Physiol.21, 443–463 (1971)
Imanishi, S., Surawicz, B.: Automatic activity in depolarized guinea pig ventricular myocardium. Circ. Res.39, 751–759 (1976)
Irisawa, H.: Comparative physiology of the cardiac pacemaker mechanism. Physiol. Rev.58, 461–498 (1978)
Isenberg, G.: Cardiac Purkinje fibers: [Ca2+]i controls the potassium permeability via the conductance componentsg k 1 andg k 2. Pflügers Arch.371, 77–85 (1977)
Kass, R. S., Siegelbaum, S., Tsien, R. W.: Incomplete inactivation of the slow inward current in cardiac Purkinje fibers. J. Physiol. (Lond.)263, 127P-128P (1976)
Katzung, B. G., Morgenstern, J. A.: Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium. Circ. Res.40, 105–111 (1977)
McAllister, R. E., Noble, D., Tsien, R. W.: Reconstruction of the electrical activity of cardiac Purkinje fibres. J. Physiol. (Lond.)251, 1–59 (1975)
Noble, D.: The initiation of the heartbeat. Oxford: Clarendon Press 1975
Noble, D., Tsien, R. W.: The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres. J. Physiol. (Lond.)195, 185–214 (1968)
Pappano, A., Vereecke, J. Carmeliet, E.: Epinephrine and pacemaker activity at plateau potentials in cardiac Purkinje fibers. Proc. Int. Union Physiol. Sci. XIII, Abstracts of volunteer papers, p. 577 (1977)
Reuter, H.: Localization of beta adrenergic receptors, and the effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J. Physiol. (Lond.)242, 429–451 (1974)
Reuter, H., Scholz, H.: The regulation of the calcium conductance of cardiac muscle by adrenaline. J. Physiol. (Lond.)264, 49–62 (1977)
Rougier, O., Vassort, G., Garnier, D., Gargouïl, Y.-M., Coraboeuf, E.: Existence and role of a slow inward current during the frog atrial action potential. Pflügers Arch.308, 91–110 (1969)
Siegelbaum, S. A., Tsien, R., Kass, R. S.: Role of intracellular calcium in the transient outward current of calf Purkinje fibres. Nature269, 611–613 (1977)
Tsien, R. W.: Effects of epinephrine on the pacemaker potassium current of cardiac Purkinje fibers. J. Gen. Physiol.64, 293–319 (1974a)
Tsien, R. W.: 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 (1974b)
Tsien, R. W., Giles, W., Greengard, P.: Cyclic AMP mediates the effects of adrenaline on cardiac Purkinje fibres. Nature New Biol.240, 181–183 (1972)
Weidmann, S.: The effect of the cardiac membrane potential on the rapid availability of the sodium-carrying system. J. Physiol. (Lond.)127, 213–224 (1955)
Author information
Authors and Affiliations
Additional information
This research was supported by grants from the U.S. Public Health Service (HLBI-13339) and from the Fonds voor Geneeskundig Wetenschappelijk Onderzoek (nr. 20.487), Belgium. A. J. Pappano is the recipient of Research Career Development Award (HL-00027)
Rights and permissions
About this article
Cite this article
Pappano, A.J., Carmeliet, E.E. Epinephrine and the pacemaking mechanisms at plateau potentials in sheep cardiac Purkinje fibers. Pflugers Arch. 382, 17–26 (1979). https://doi.org/10.1007/BF00585899
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00585899