title: New Ca2+ agonist (Bay K 8644) enhances and induces cardiac slow action potentials.
abstract: 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.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D012964:Sodium; D009543:Nifedipine; D007545:Isoproterenol; D002118:Calcium