Abstract
The ionic mechanism underlying the chronotropic effect of epinephrine on the rabbit sinoatrial (S-A) node has been studied. Epinephrine (5.5×10−6 M) increased the spontaneous rate from 206±25 min−1 to 242±39 min−1. The effect of epinephrine was reproducible on repetitive applications.
Voltage clamp experiments using the two microelectrode technique revealed the following changes in the membrane current: epinephrine (5.5×10−7 M) increased the limiting conductance for the slow inward current (i s ) by approximately 30% and the potassium current (i k ) by about 10%, keeping the kinetics ofi s andi k constant. From the holding potential of −70 mV the activation ofi s was observed on step depolarization positive to −60 or −55 mV in both control and epinephrine solution. The hyperpolarization-activated current (i h ) was also increased by about 20% at −70 mV, and its time course was slightly accelerated.
Participation ofi s for the chronotropic effect of epinephrine was strongly suggested by the findings thati s was partially available positive to −60 mV and that epinephrine could not increase the slope of diastolic depolarization wheni s was blocked by D 600.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Beeler GW, Reuter H (1977) Reconstruction of the action potential of ventricular myocardial fibres. J Physiol (Lond) 268:177–210
Brown HF, Noble SJ (1974) Effects of adrenaline on membrane currents underlying pacemaker activity in frog atrial muscle. J Physiol (Lond) 238:51–53p
Brown HF, McNaughton PA, Noble D, Noble SJ (1975) Adrenergic control of cardiac pacemaker currents. Phil Trans R Soc B 270:527–537
Brown HF, Di Francesco D, Noble SJ (1979) How does adrenaline accelerate the heart? Nature 280:235–236
Di Francesco D, Noma A, Trautwein W (1979) Kinetics and magnitude of the time-dependent potassium current in the rabbit sinoatrial node: Effect of external potassium. Pflügers Arch 381:271–279
Hauswirth O, Noble D, Tsien RW (1968) Adrenaline: Mechanism of action on the pacemaker potential in cardiac Purkinje fibers. Science 162:916–917
Hutter OF, Trautwein W (1956) Vagal and sympathetic effects on the pacemaker fibers in the sinus venosus of the heart. J Gen Physiol 39:715–733
Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (Lond) 117:500–544
McDonald TF, Trautwein W (1978) Membrane currents in cat hyocardium: Separation of inward and outward components. J Physiol (Lond) 274:193–216
New W, Trautwein W (1972) Inward membrane currents in mammalian myocardium. Pflügers Arch Ges Physiol 334:1–23
Noble D (1975) The Initiation of the Heartbeat. Clarendon Press Oxford
Noma A, Irisawa H (1976a) Membrane currents in the rabbit sinoatrial node cell as studied by the double microelectrode method. Pflügers Arch 364:45–52
Noma A, Irisawa H (1976b) A time- and voltage-dependent potassium current in the rabbit sinoatrial node cell. Pflügers Arch 366:251–258
Noma A, Yanagihara K, Irisawa H (1977) Inward current of the rabbit sinoatrial node cell. Pflügers Arch 372:43–51
Noma A, Trautwein W (1978) Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell. Pflügers Arch 377:193–200
Noma A, Peper K, Trautwein W (1979) Acetylcholine-induced potassium current fluctuations in the rabbit sino-atrial node. Pflügers Arch 381:255–262
Noma A, Osterrieder W, Trautwein W (1979) The effect of external potassium on the elementary conductance of the ACh-induced potassium channel in the sino-atrial node. Pflügers Arch 381:263–269
Reuter H (1974) Localization of beta adrenergic receptors and effects of noradrenaline and cyclic nucleotides on action potentials. ionic currents and tension in mammalian cardiac muscle. J Physiol (Lond) 242:429–451
Reuter H (1976) The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol (Lond) 192:479–492
Reuter H, Scholz H (1977) The regulation of the Ca conductance of cardiac muscle by adrenaline. J Physiol (Lond) 264:49–62
Tsien RW (1974) Effects of epinephrine on the pacemaker potassium current of cardiac Purkinje fibers. J Gen Physiol 64:293–319
Vassort G, Rougier O, Garnier D, Sauviat MP, Coraboeuf E, Gargouil YM (1969) Effects of adrenaline on membrane inward currents during the cardiac action potential. Pflügers Arch Ges Physiol 309:70–81
West TC (1955) Ultramicroelectrode recording from the cardiac pacemaker. J Pharmacol Exp Ther 115:283–290
West TC, Falk G, Cervoni P (1956) Drug alteration of transmembrane potentials in atrial pacemaker cells. J Pharmacol Exp Ther 117:245–252
Yanagihara K, Irisawa H (1980) Inward current activated during hyperpolarization in the rabbit sinoatrial node cell. Pflügers Arch 385:11–19
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Noma, A., Kotake, H. & Irisawa, H. Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrfal node. Pflugers Arch. 388, 1–9 (1980). https://doi.org/10.1007/BF00582621
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00582621