Effect of cyanide and verapamil on sodium-free contractures in the frog heart.
Sodium-free contractures were studied in myocardial strips from R. pipiens with extracellular sodium (Na0+) replaced by choline chloride and extracellular calcium (Ca20+) varied with EGTA buffer. At calculated Ca02+ below 2.8 X 10(-7) mol/l, no contracture occurred in most of the experiments, even in the presence of cyanide. When Ca02+ was above 2.8 X 10(-7) mol/l, relatively short tension transients of up to 80 sec duration could be avoided if the myocardial strip was previously equilibrated for 20 min in a Na+-Ca2+-free solution. Instead, contractures developed slowly within one to several hours. The maximum contracture was dependent on Ca02+ in a dose-response-like pattern. The time-course of contracture development was not affected by verapamil, but KCN significantly increased the rate of resting tension increase. In solutions with normal Na+-Ca2+ content and even in a Na+-Ca2+-free milieu, the cellular ultrastructure was normal. Development of contracture after addition of Ca2+ to the Na+-free solution was combined with ultrastructural damage of the ventricular strip. It is concluded that Na+-free contractures depend on transsarcolemmal net-Ca2+ uptake as a sum of Na-Ca-exchange-dependent Ca2+ uptake and active sequestering of intracellular free calcium Ca2+ mediated by sarcolemmal and probably intracellular Ca2+-ATPases. The negative inotropic effect of the Ca blocker verapamil seems not to be mediated by the Na-Ca exchange.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000648:ultrastructure; D011190:Potassium Cyanide / Q000494:pharmacology*; D011894:Rana pipiens; D012964:Sodium / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D003486:Cyanides; D004533:Egtazic Acid; D012964:Sodium; D014700:Verapamil; D011190:Potassium Cyanide; D002118:Calcium