STIMULATION AND INHIBITION OF THE SODIUM PUMP BY CARDIOACTIVE STEROIDS IN RELATION TO THEIR BINDING SITES AND THEIR INOTROPIC EFFECT ON GUINEA‐PIG ISOLATED ATRIA

Abstract

1 The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea-pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined. 2 The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Na_i whereas high doses produced an increase. Dihydroouabain evoked only a Na_i gain. 3 The increase of KCl concentration from 2.7 to 12 mm decreased Na_i in untreated atria and displaced ouabain dose-effect curves to the right. 4 ED₅₀ values for the positive inotropic effect were lower than ED₅₀ values for the inhibition of the pump and were not similarly affected by an increase in KCl concentration. 5 The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively. 6 The increase in KCl reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high-affinity sites whereas the capacity of the other sites remained unchanged. 7 The results confirm the existence of two specific binding sites for ouabain in guinea-pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.