Biphasic positive inotropic actions of ouabain on rat, guinea-pig and cat heart: a mathematical description

The inotropic action of ouabain on isolated perfused hearts of rat, guinea-pig, and cat was studied over a wide concentration range (10(-12)-5 X 10(-3) M). In all three species used, the positive inotropic effect (PIE) of ouabain appeared to be biphasic in character. However, there was a remarkable difference in the course of the logdose-response curves of ouabain on guinea-pig and cat heart as compared with than on rat heart. The first two species showed, at very low concentrations of ouabain (guinea-pig heart: 10(-9) M and cat heart: 10(-10) M), a typical bell-shaped increase in cardiac contractile activity, while at higher concentrations (10(-8)-10(-6) M and 10(-9)-10(-7) M, respectively) the normally observed S-shaped increase in contractile activity occurred. On the contrary, rat hearts showed a flat S-curve between 10(-8) and 10(-6) M and a steep one between 10(-6) and 10(-4) M of ouabain. In order to explain the biphasic action of ouabain a hypothetical model for the mechanism(s) of action of ouabain is discussed. Mathematical description of this model is based on the existence of two different receptor-types for ouabain. It is suggested that sarcolemma-bound calcium may play an important role in both mechanisms of inotropic action of ouabain.