Summary
Effects of adenosine (30 to 200 μmol/l) on the spontaneous action potentials and the membrane currents in rabbit sino-atrial node (SA) preparations were examined. Adenosine (30 μmol/l) lengthened the action potential duration and the cycle length. At 100 μmol/l, adenosine also hyperpolarized the maximum diastolic potential. However, the action potential amplitude and the maximum rate of depolarization \(\dot V\) max) were unaffected. In the presence of adenosine (200 μmol/l) addition of aminophylline (an antagonist) (23–46 μmol/l) shortened the cycle length and depolarized the maximum diastolic potential to the contrary. Aminophylline did not antagonize the prolongation of the action potential. Aminophylline (46 μmol/l) alone decreased the cycle length and the maximum diastolic potential, but did not affect the action potential amplitude, the action potential duration and the \(\dot V\) max. In the presence of aminophylline (46 μmol/l). addition of adenosine (200 μmol/l) increased the cycle length and the action potential duration, and decreased \(\dot V\) max. In voltage-clamp experiments, adenosine greatly shifted the background current in the outward direction. Holding potential was −40 mV. Adenosine reduced a slow inward and a time-dependent outward current, in a concentration-dependent manner. Adenosine did not affect the time constant of inactivation phase and the voltages of the half-maximum activation and inactivation for the slow inward current. The activation curve for the outward current was also unaffected. A hyperpolarization-activated inward current was decreased. In the presence of aminophylline (46 μmol/l), adenosine (200 μmol/l) decreased the slow inward current, the time-dependent outward current and the hyperpolarization-activated inward current. These results suggest that adenosine produces its actions on the heart by inhibition of ionic currents and activation of the outward background current.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baumann G, Schrader J, Gerlach E (1981) Inhibitory action of adenosine on histamine- and dopamine-stimulated cardiac contractility and adenylate cyclase in guinea-pigs. Circ Res 48:259–266
Belardinelli L, Isenberg G (1983) Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes. Circ Res 53:287–297
Belardinelli L, Rubio R, Berne RM (1979) Blockade of Ca2+ dependent rat atrial slow action potentials by adenosine and lanthanum. Pflügers Arch 280:19–27
Belardinelli L, Belloni FL, Rubio R, Berne RM (1980) Atrioventricular conduction disturbances during hypoxia: Possible role of adenosine in rabbit and guinea pig heart. Am J Physiol 61:H684-H691
Belardinelli L, Fenton AR, West A, Linden J, Althaus JS, Berne M (1982) Extracellular action of adenosine and the antagonism by aminophylline on the atrioventricular conduction of isolated perfused guinea pig and rat hearts. Circ Res 51:569–579
Belardinelli L, West GA, Crampton R, Berne RM (1983) Chronotropic and dromotropic actions of adenosine. In: Berne RM, Rall TW, Rubio R (eds) The regulatory function of adenosine. Nijhoff, The Hague, Netherlands, pp 378–398
Belardinelli L, Giles WR, West A (1988) Ionic mechanisms of adenosine actions in pacemaker cells from rabbit heart. J Physiol (Lond) 405:615–633
Berne RM (1963) Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol 204:317–322
Böhm M, Brückner R, Hackbarth I, Haubitz B, Linhart R, Meyer W, Schmidt B, Schmitz W, Scholz H (1984) Adenosine inhibition of catecholamine-induced increase in force of contraction in guinea-pig atrial and ventricular heart preparations. Evidence against a cyclic AMP- and cyclic GMP-dependent effect. J Pharmacol Exp Ther 230:483–492
Brown HIT (1982) Electrophysiology of the sinoatrial node. Physiol Rev 62:505–530
Camm AJ, Garratt CJ (1991) Adenosine and supraventricular tachycardia. N Engl J Med 325:1621–1629
De Gubareff T, Sleator W (1965) Effects of caffeine on mammalian atrial muscle, and its interaction with adenosine and calcium. J Pharmacol Exp Ther 148:202–214
DiMarco JP, Sellers TD, Berne RM, West GA, Belardinelli L (1983) Adenosine: Electrophysiological effects and therapeutic use for terminating paroxysmal supraventricular tachycardia. Circulation 68:1254–1263
Dobson JG (1978) Reduction by adenosine of the isoproterenol-induced increase in cyclic adenosine 3′, 5′monophosphate formation and glycogen phosphorylase activity in rat heart muscle. Circ Res 43:785–792
Dole WP, Yamada N, Bishop VS, Olsson RA (1985) Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure. Circ Res 56:517–524
Endoh M, Maruyama M, Taira N (1983) Adenosine-induced changes in rate of beating and cyclic nucleotide levels in rat atria: Modification by islet-activating protein. In: Daly JM, Kuroda Y, Phillis JW, Shimizu H, Ui M (eds) Physiology and pharmacology of adenosine derivatives. Raven Press, New York, pp 127–141
Hartzell HC (1979) Adenosine receptors in frog sinus venosus: Slow inhibitory potentials produced by adenosine compounds and acetylcholine. J Physiol (Lond) 293:23–49
Heller LJ, Olsson RA (1985) Inhibition of rat ventricular automaticity by adenosine. Am J Physiol 248:H907-H913
James TN (1965) The chronotropic action of ATP and related compounds studied by direct perfusion of the sinus node. J Pharmacol Exp Ther 149:233–247
Kolossa N, Pfleger K, Rummel W (1970) Specificity of adenosine uptake into the heart and inhibition by dipyridamole. Eur J Pharmacol 9:265–268
Linden J, Hollen CE, Patel A (1985) The mechanism by which adenosine and cholinergic agents reduce contractility in rat myocardium: Correlation with cyclic adenosine monophosphate and receptor densities. Circ Res 56:728–735
Maylie J, Morad M, Weiss J (1981) A study of pace-maker potential in the rabbit sino-atrial note. Measurement of potassium activity under voltage-clamp conditions. J Physiol (Lond) 311:161–178
McDonald TF, Trautwein W (1978) Membrane currents in cat myocardium. Separation of inward and outward components. J Physiol (Lond) 274:193–216
Noble D (1984) The surprising heart: A review of recent progess 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
Osterrieder W, Noma A, Trautwein W (1980) On the kinetics on the potassium channel activated acetylcholine in the S-A node of the rabbit heart. Pflügers Arch 386:101–109
Rockoff JB, Dobson JG (1980) Inhibition by adenosine of catecholamine-induced increase in rat atrial contractility. Am J Physiol 239:H365-H370
Satoh H, Hashimoto K (1984a) Effect of lidocaine on membrane currents in rabbit sino-atrial node cells. Arch Int Pharmacodyn 270:241–254
Satoh H, Hashimoto K (1984b) Effect of propafenone on the membrane currents of rabbit sino-atrial node cells. Eur J Pharmacol 99:185–191
Satoh H, Hashimoto K (1984c) Effects of nicorandil on the membrane currents of rabbit sino-atrial node cells. Jpn J Pharmacol 34:411–415
Satoh H, Hashimoto K (1991) Comparative effects of a new calcium channel antagonist, mepirodipine, on rabbit spontaneously beating sino-atrial node cells. Eur J Pharmacol 193:9–13
Schrader J, Rubio R, Berne RM (1975) Inhibition of slow action potentials of guinea pig atrial muscle by adenosine. A possible effect of Ca2+ influx. J Mol Cell Cardiol 7:427–433
Schrader J, Baumann G, Gerlach E (1977) Adenosine as inhibitor of myocardial effects of catecholamines. Pflügers Arch 372:29–35
Shibata EF, Giles WR (1983) Ionic currents in isolated cardiac pacemaker cells from bullfrog sinus venosus. Proc Int Union Physiol Sci 15:76
Szentmiklosi AJ, Nemeth M, Szegi J, Papp JG, Szekeres L (1980) Effect of adenosine on sinoatrial and ventricular automaticity of the guinea pig. Naunyn-Schmiedeberg's Arch Pharmacol 311:147–149
Tuganowski W, Tarnowski W, Gorzyca J, Slabun J (1980) Effect of adenosine on electrical activity in guinea pig atrium. Pol J Pharmacol Pharm 32:725–729
West GA, Belardinelli L (1985a) Sinus slowing and pacemaker shift caused by adenosine in rabbit SA node. Pflügers Arch 403:1–9
West GA, Belardinelli L (1985b) Correlation of sinus slowing and hyperpolarization caused by adenosine in sinus node. Pflügers Arch 403:75–81
Yanagihara K, Noma A, Irisawa H (1980) Reconstruction of sino-atrial node pacemaker potential based on the voltage clamp experiments. Jpn J Physiol 30:841–857
Author information
Authors and Affiliations
Additional information
Correspondence to H. Satoh at the above address
Rights and permissions
About this article
Cite this article
Satoh, H. Electrophysiological actions of adenosine and aminophylline in spontaneously beating and voltage-clamped rabbit sino-atrial node preparations. Naunyn-Schmiedeberg's Arch Pharmacol 347, 197–204 (1993). https://doi.org/10.1007/BF00169267
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169267