Summary
Effects of methoxamine and phenylephrine on the action potential and the membrane currents in spontaneously beating rabbit sino-atrial node cells were examined by means of a two-microelectrode voltageclamp technique. Both methoxamine and phenylephrine (10−4 mol/l) prolonged the cycle length (CL) and the action potential duration (APD), significantly. At concentrations higher than 3 × 10−4 mol/l, phenylephrine increased the maximum rate of rise of action potential (NONETH) but methoxamine reduced it. Both agents depolarized the maximum diastolic potential (MDP). These changes in the action potential parameters occurred in a concentration-dependent manner. In the presence of phentolamine (10−5 mol/l), methoxamine (3 × 10−4 mol/l) did not modify the action potential parameters. Also, phenylephrine did not affect them during exposure to phentolamine (10−5 mol/l) and pindolol (10−7 mol/1). In voltage-clamp experiments, at 10−3 mol/l both methoxamine and phenylephrine slightly increased the slow inward current (I is), but decreased the time-dependent outward current (I k). The steady-state activation variable of I k (p ∞.) was unaffected by these agents. The hyperpolarization-activated current (I b) was suppressed in the presence of methoxamine, but enhanced in the presence of phenylephrine. An additional application of pindolol (10−7 mol/l) during exposure to phenylephrine (10−3 mol/l) depressed the action potential amplitude (APA) and NONETH and prologed CL slightly. Under the same condition, all the membrane currents (I is, I k and I b) were decreased. In addition, the time courses of decay for I is were not modified in the absence and the presence of phenylephrine (10−3 mol/l) and phenylephrine plus pindolol (10−7 mol/l). These results suggest that the negative chronotropic effect induced by methoxamine and phenylephrine through α1-adrenoceptors is mainly due to decreases in I k and I b resulting from decreases in these channel conductances. Also, the prolongation of the action potential due to decrease in I k may in part contribute to the negative chronotropic effect.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Benfey BG (1980) Cardiac α-adrenoceptors. Can J Physiol Pharmacol 58:1145–1157
Berridge MJ, Irvine RF (1984) Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321
Brückner R, Scholz H (1984) Effects of α-adrenoceptor stimulation with phenylephrine in the presence of propranolol on force of contraction, slow inward current and cyclic AMP content in the bovine heart. Br J Pharmacol 82:223–232
Endoh M (1982) Adrenoceptors and the myocardial inotropic response: do alpha and beta receptor sites functionally coexist? In: Kalsner S (ed) Trends in autonomic pharmacology, vol 2. Urban and Schwarzenberg, Baltimore Munich, pp 303–322
Endoh M, Brodde O-E, Schumann HJ (1976) Relationship between the level of cAMP and the contractile force under stimulation of α− and β-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 295:109–115
Fabiato A (1986) Inositol (1,4,5)-tripphosphate-induced release of Ca2+ from the sarcoplasmic reticulum of skinned cardiac cells. Biophys J 49:190a
Farese RV (1984) Phospholipids as intermediates in hormone action. Mol Cell Endocrinol 35:1–14
Handa Y, Wagner J, Inui J, Averesch H, Schumann HJ (1982) Effect of α− and β-sympathomimetic agonists on calcium-dependent slow action potential and force of contraction in the rabbit papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 318:330–335
Hirata M, Suematsu E, Hashimoto T, Hamachi T, Koga T (1984) Release of Ca2+ from a non-mitochondrial store site in peritoneal macrophages treated with saponin by inositol 1,4,5-triphosphate. Biochem J 223:229–236
Imai S, Shigei T, Hashimoto K (1961) Cardiac actions of methoxamine: With special reference to its antagonistic action to epinephrine. Circ Res 9:552–560
Ledda F, Marchetti P, Manni A (1971) Influence of phenylephrine on transmembrane potentials and effective refractory period of single Purkinje fibers of sheep heart. Pharmacol Res Commun 3:195–206
Ledda F, Mantelli L, Mugelli A (1980) α-Sympathomimetic amines and calcium-mediated action potentials in guinea-pig ventricular muscle. Br J Pharmacol 69:565–571
McAllister RE, Noble D, Tsien RW (1975) Reconstruction of the electrical activity of cardiac Purkinje fibres. J Physiol (Lond) 251:1–59
McDonald TF, Trautwein W (1978) Membrane currents in cat myocardium: separation of inward and outward components. J Physiol (Lond) 274:193–216
Michell RH (1983) Polyphosphoinositide breakdown as the initiating reaction in receptor-stimulated inositol phospholipid metabolism. Life Sci 32:2083–2085
Miura Y, Inui J, Imamura H (1978) α-Adrenoceptor-mediated restoration of calcium-dependent potential in the partially depolarized rabbit papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 301:201–205
Molyvdas P-A, Sperelakis N (1986) Effects of calcium antagonistic drugs on the electrical activity of rabbit sino-atrial node. Br J Pharmacol 88:249–258
Nakayama T, Kurachi Y, Noma A, Irisawa H (1984) Action potential and membrane currents of single pacemaker cells of the rabbit heart. Pflügers Arch 402:248–257
Nishizuka Y (1983) Phospholipid degradation and signal translation for protein phosphorylation. Trends Biochem Sci 8:13–16
Noble D (1984) The surprising heart: A review of recent progress in cardiac electrophysiology. J Physiol (Lond) 353:1–50
Noma A, Irisawa H (1976) Membrane currents in the rabbit sinoatrial node cell as studied by the double microelectrode method. Pflügers Arch 364:45–52
Nosek TM, Williams MF, Zeigler ST, Godt RE (1986) Inositol triphosphate enhances calcium release in skinned cardiac and skeletal muscle. Am J Physiol 250:C807-C811
Poggioli J, Sulpice JC, Vassort G (1986) Inositol phosphate production following alpha 1-adrenergic, muscarinic or electrical stimulation in isolated rat heart. FEBS Lett 206:292:298
Sanchez-Chapula J (1981) Multiple effects of putative α-adrenoceptor agonists on the electrical and mechanical activity of guinea-pig papillary muscle. Naunyn-Schmiedeberg's Arch Pharmacol 316:108–111
Satoh H, Hashimoto K (1984) Effect of lidocaine on membrane currents in rabbit sino-atrial node cells. Arch Int Pharmacodyn 270:241–254
Satoh H, Hashimoto K (1986) An clectrophysiological study of amiloride on sino-atrial node cells and ventricular muscle of rabbit and dog. Naunyn-Schmiedeberg's Arch Pharmacol 333:83–90
Satoh H, Seyama I (1986) On the mechanism by which changes in extracellular pH affect the electrical activity of the rabbit sinoatrial node. J Physiol (Lond) 381:181–191
Schmitz W, Scholz H, Scholz J, Steinfath M (1987) Increase in IP3 precedes α-adrenoceptor-induced increase in force of contraction in cardiac muscle. Eur J Pharmacol 140:109–111
Scholz H (1980) Effects of beta- and alpha-adrenoceptor activators and adrenergic transmitter releasing agents on the mechanical activity of the heart. In: Szekeres L (ed) Adrenergic activators and inhibitors. Handbuch experimentelle Pharmakologie, vol 54/I. Springer, Berlin Heidelberg New York, pp 651–733
Schümann HJ (1980) Are there α-adrenoceptors in the mammalian heart? Trends Pharmacol Sci 1:195–197
Streb H, Irvine RF, Berridge MJ, Scholz I (1983) Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-triphosphate. Nature 306:67–69
Author information
Authors and Affiliations
Additional information
Send offprint requests to H. Satoh
Rights and permissions
About this article
Cite this article
Satoh, H., Hashimoto, K. Effect of α1-adrenoceptor stimulation with methoxamine and phenylephrine on spontaneously beating rabbit sino-atrial node cells. Naunyn-Schmiedeberg's Arch Pharmacol 337, 415–422 (1988). https://doi.org/10.1007/BF00169533
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169533