Two binding sites for ouabain in cardiac cell membranes.

Cardiac glycoside receptors were defined by simultaneous measurement of 3H-ouabain binding and its effects on cardiac cell membranes, contracting cardiac muscle and cultured cardiac cells. These measurements show that: Rat and guinea pig cardiac cell membranes have two specific ouabain binding sites. In both species, ouabain binding to the high affinity site on cell membranes correlates with the positive inotropic effect in contracting cardiac muscle. Inhibition of (Na+ + K+)-ATPase activity corresponds to binding to the low affinity site. This questions the hypothesis that (Na+ + K+)-ATPase inhibition is necessary for ouabain-induced positive inotropy. K+ may induce an heterogeneity in the ouabain binding sites of the digitalis-sensitive cat and human heart.