RELAXATION IN FERRET VENTRICULAR MYOCYTES - ROLE OF THE SARCOLEMMAL CA ATPASE

In ferret ventricular myocytes the rate of intracellular Ca concentration [Ca](i) decline and relaxation is remarkably fast (compared with rabbit and rat) under conditions where both the sarcoplasmic reticulum Ca uptake and Na/Ca exchange are inhibited. Here we explore the possibility that this rapid [Ca](i) decline in ferret cells is attributable to the sarcolemmal Ca ATPase by using carboxyeosin (a potent inhibitor of the sarcolemmal Ca-ATPase). We compare the effects of carboxyeosin with those of elevated extracellular [Ca] ([Ca](o)) (a thermodynamic approach to limit Ca transport by the sarcolemmal Ca ATPase). In rabbit cells, carboxyeosin and high [Ca](o) slowed [Ca](i) decline similarly and both virtually abolished [Ca](i) decline when mitochondrial Ca uptake was also inhibited. In ferret cells, carboxyeosin treatment produced these same effects on [Ca](i) decline, but high [Ca](o) did not mimic them. Moreover, only in carboxyeosin-treated ferret cells did additional inhibition of mitochondrial Ca uptake nearly abolish [Ca](i) decline. We conclude that,carboxyeosin loading can inhibit colemmal Ca-ATPase in intact myocytes; that this pump seems likely to be responsible for the much faster relaxation observed in ferret cells after block of SR Ca accumulation and Na/Ca exchange transport and that the sarcolemmal Ca pump apparently has different characteristics in rabbit and ferret ventricular myocytes.