Stimulation of cardiac slow Ca++ current by high concentration of cimetidine.
Electrophysiological studies on the cardiac effects of a H2-antagonist, cimetidine, were examined in three kinds of preparations: guinea-pig papillary muscles, rat left atria and perfused chick hearts. Cimetidine (10(-5) to 10(-4) M) depressed or abolished the slow action potentials (APs) induced by histamine (10(-5) to 10(-4) M) in hearts whose fast Na+ channels had been inactivated by 25 mM K+. Higher concentrations of cimetidine (10(-3) to 5 X 10(-3) M) increased myocardial cyclic AMP level and allowed the generation of slow APs in such inexcitable tissues. These cimetidine-induced slow APs were not prevented by propranolol (10(-6) to 10(-5) M) or pretreatment with 6-hydroxydopamine (50 mg/kg). These results suggest that cimetidine, in doses higher than that required to block cardiac H2-receptors, may have a cardio-stimulating action mediated through increase of inward Ca++ current.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002927:Cimetidine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008785:Metiamide / Q000494:pharmacology; D009206:Myocardium / Q000032:analysis / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D008785:Metiamide; D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium