Sarcolemmal cation channels and exchangers modify the increase in intracellular calcium in cardiomyocytes on inhibiting Na-K-ATPase

Although inhibition of the sarcolemmal (SL) Na+-K+-ATPase is known to cause an increase in the intracellular concentration of Ca2+ ([Ca2+]i) by stimulating the SL Na+/Ca2+ exchanger (NCX), the involvement of other SL sites in inducing this increase in [Ca2+]i is not fully understood. Isolated rat cardiomyocytes were treated with or without different agents that modify Ca2+ movements by affecting various SL sites and were then exposed to ouabain. Ouabain was observed to increase the basal levels of both [Ca2+]i and intracellular Na+ concentration ([Na+]i) as well as to augment the KCl-induced increases in both [Ca2+]i and [Na+]i in a concentration-dependent manner. The ouabain-induced changes in [Na+]i and [Ca2+]i were attenuated by treatment with inhibitors of SL Na+/H+ exchanger and SL Na+ channels. Both the ouabain-induced increase in basal [Ca2+]i and augmentation of the KCl response were markedly decreased when cardiomyocytes were exposed to 0–10 mM Na+. Inhibitors of SL NCX depressed but decreasing e...