Changes in cellular Na+, K+, and Ca2+ contents, monovalent cation transport rate, and contractile state during washout of cardiac glycosides from cultured chick heart cells.

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Abstract
To delineate more clearly the importance of altered monovalent cation transport rate in the mediation of the positive inotropic effects of cardiac glycosides, we studied changes in the contractile state and rate of uptake of K+ and Rb+ by monolayer cultures of chick embryo ventricular cells during exposure to and washout of ouabain and dihydro-ouabain. These cardiac glycosides produced a positive inotropic effect in this system, accompanied by a significant reduction in monovalent cation transport rate, by increases in cellular contents of Na+ and Ca2+, and by a decrease in cellular content of K+ as judged by radioisotopic tracer studies. Following removal of glycosides from media bathing the cultures, monovalent cation transport rate returned to normal within 1 minute, followed by a loss of inotropy which was complete by 7 minutes, a time at which cellular [Ca2+] had returned to normal. The bulk cellular concentration of Na+ remained increased, however, and that of K+ depressed for longer periods. Veratrine (1 microgram/ml) induced a positive inotropic effect, but caused a less marked increase in cellular [Na+] than did equipotent concentrations of ouabain and dihydroouabain. These results indicate that there is not a simple relationship between bulk cellular [Na+] and magnitude of inotropic effect in these cells, and are consistent with the proposal that there is a subsarcolemmal space in which [Na+] regulates Ca2+ fluxes and contractility, and in which [Na+] is regulated primarily by the balance between transsarcolemmal influx and Na+ pump rate and, to a lesser degree, by bulk [Na+].