Positive inotropic effect of acetylcholine in canine cardiac Purkinje fibers.
The purpose of this study was to investigate possible mechanisms to explain the positive inotropic effects of acetylcholine in canine cardiac Purkinje fibers. Action potentials and tension were recorded from Purkinje fibers in vitro using microelectrodes and a force transducer. Acetylcholine (10(-9) to 10(-4) M) produced a dose-dependent increase in tension that was blocked by atropine but not by propranolol, phentolamine, hexamethonium, or verapamil. At 10(-5) and 10(-4) M, acetylcholine increased action potential duration at 50% of repolarization (APD50) but did not affect resting membrane potential, action potential amplitude, Vmax, or action potential duration at 90% of repolarization (APD90). Isoproterenol (10(-7) M) shortened APD50 and APD90 and increased developed tension. Subsequent addition of acetylcholine (10(-5) M) prolonged APD50 and APD90 and decreased tension. Increasing extracellular Ca2+ concentration [( Ca2+]o) from 2.0 to 3.0 mM increased tension and shortened APD50. Addition of acetylcholine (10(-5) M) increased tension further and prolonged APD50. In K+-depolarized fibers high concentrations of acetylcholine (10(-4) M) restored excitability, but lower concentrations (10(-6) M) suppressed slow responses induced by isoproterenol. Thus acetylcholine alone or with elevated [Ca2+]o increased APD50 and tension and facilitated the induction of slow responses, yet in the presence of isoproterenol acetylcholine increased APD50, decreased tension, and suppressed slow responses. These effects were mediated by muscarinic receptors and were independent of catecholamine release.
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D011976:Receptors, Muscarinic; D009599:Nitroprusside; D001285:Atropine; D014700:Verapamil; D006152:Cyclic GMP; D007545:Isoproterenol; D000109:Acetylcholine; D002118:Calcium