Effects of calcium flux inhibitors on contracture and calcium content during inhibition of high energy phosphate production in cultured heart cells.
The effects of inhibition of oxidative phosphorylation by 1 mM cyanide (CN) and of glycolysis by 20 mM 2-deoxyglucose (2DG) on contraction and relaxation of cultured monolayers of chick embryo heart cells were determined. Exposure to these agents first induced a gradual decline in contractility and a transient impairment of relaxation. Spontaneous beating then ceased, associated with increased relaxation, followed by a marked and prolonged contracture. This contracture was completely reversible after washout of metabolic inhibitors. The effects of calcium flux inhibitors on the time course of development of contracture were studied. Verapamil, which inhibits Ca influx via the slow Ca channel, delayed the onset of contracture when used in pretreatment, but had no effect if added to cultures after exposure to CN + 2DG. Lanthanum, which inhibits Ca influx both via the slow Ca channel and via Na-Ca exchange, delayed onset of contracture if added after exposure to CN and 2DG, but accelerated contracture if added prior to treatment with CN + 2DG. Cellular exchangeable calcium content, measured after exposure to CN and 2DG for the same time period that produced contracture, was reduced compared to the control level while unidirectional Ca influx rate was not measurably altered. Exchangeable Ca content was unaffected by pretreatment with verapamil and La, but was reduced if cells were exposed to La after metabolic inhibition. These findings suggest that after metabolic inhibition intracellular storage capacity for Ca+ is reduced in cultured heart cells. Ca influx via the slow Ca channel after metabolic inhibition does not appear to contribute to development of contracture in this model system. However, Ca entry via Na-Ca exchange may accelerate cellular contracture developing after metabolic inhibition of ATP production.
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D007811:Lanthanum / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007811:Lanthanum; D000255:Adenosine Triphosphate; D014700:Verapamil; D002118:Calcium