Ouabain blockade of inward slow current in cardiac muscle

Abstract

Myocardial cells rendered inexcitable by tetrodotoxin (TTX) or by partial depolarization with elevated K + (25 m m ) are a useful preparation on which to study the properties of slow channels. Utilizing this preparation, we previously demonstrated that certain positive inotropic agents, such as catecholamines, methylxanthines, histamine or F − ion, act to rapidly increase the number of available slow Ca 2+ −Na + channels, thus permitting the appearance of slowly-rising overshooting electrical responses which resemble the plateau component of the cardiac action potential. Hence, we examined the possibility that a cardiac glycoside might exert its positive inotropic action through a similar mechanism. Two preparations of 16-to 20-day-old embryonic chick myocardial cells were studied: (a) intact perfused hearts, and (b) spherical reaggregate cultures of trypsin-dispersed cells. Ouabain (10 −8 to 10 −4 m ) did not induce the slow response in either preparation. In contrast, high concentrations (10 −6 to 10 −4 m ) of ouabain depressed and blocked the isoproterenol- or caffeine-induced slow responses. These findings indicate that the positive inotropic effects of ouabain are not mediated by an increased electrogenic transmembrane Ca 2+ inward current during the cardiac action potential.