Comparison of the Effects of Ouabain and High Tissue Sodium on the Calcium Pools Involved in Excitation-Contraction Coupling

Abstract

According to one hypothesis for the mechanism of action of cardiac glycosides, inhibition of cardiac Na,K-ATPase elevates [Na]i and by increasing Na:Ca exchange, increases [Ca]i to ultimately produce the positive inotropic effect (PIE). Therapeutic concentrations of ouabain specifically increase the Ca content of a superficial pool involved in excitation-contraction coupling. Thus, for this hypothesis to be correct, equivalent increases in total Na by means other than Na,K-ATPase inhibition must also specifically increase the Ca content of this pool and produce a PIE. However, unlike the effects produced by ouabain, contracture, an elevation of tissue K and a nonspecific increase in Ca uptake occurred in Na-loaded hearts. Although Na loading and ouabain treatment increased total tissue Na to the same extent, the results suggest that (a) the increased tissue Na may not reflect an equivalent increase in [Na]i; (b) the Na-loading procedure was not a valid model for Na,K-ATPase inhibition, or (c) the hypothesis for cardiac glycoside action is incorrect.