New Ca2+ agonist (Bay K 8644) enhances and induces cardiac slow action potentials

G. M. Wahler and N. Sperelakis Bay K 8644 is an analogue of nifedipine that has positive inotropic and vasoconstricting actions and was postulated to be a Ca agonist (i.e., a Ca2+-channel activator). To test this hypothesis, we examined the electrophysiological effects of this compound in isolated guinea pig papillary muscles. Bay K 8644 (10(-6) M) had little effect on the normal fast action potentials, although it did increase contractility. Bay K 8644 did, however, induce Ca2+-dependent slow action potentials (fast Na+ channels inactivated by 25 mM K+). When slow action potentials had been previously induced by tetraethylammonium chloride (10 mM) plus Ca2+ (4.0 mM) or isoproterenol (2 X 10(-7) M), 10(-6) M Bay K 8644 potentiated the slow action potentials, i.e., increased their maximal rate of rise (Vmax), concomitant with its positive inotropic effect. All effects of Bay K 8644 could be reversed by 10(-6) M nifedipine. Thus it appears that Bay K 8644 enhances Ca2+ influx through the myocardial slow channels, consistent with the concept that Bay K 8644 is a Ca2+-channel stimulator.