The calcium dependence of the biphasic inotropic response to ouabain in the isolated rat heart.

From the results of this study the following significant conclusions can be drawn. First, there are two separate inotropic responses to ouabain in the rat ventricle and the isolated rat heart resulting in a biphasic dose-response curve. Second, both the "low dose" and "high dose" inotropic responses of ouabain in the rat heart result from the inhibition of NKA, i.e., NKA is the binding site of ouabain for both "low" and "high" dose effects. Third, biphasic inotropic effects (rat ventricle) go together with alpha + and alpha (high and low affinity) isoforms of NKA, monophasic (rat atrium) with the alpha isoform (low affinity). Fourth, high extracellular calcium concentrations inhibit NKA and mask the full expression of the "low-dos" effect.