Stimulatory effect of vanadate on (Na⁺ + K⁺)-ATPase activity and on ³H-ouabain-binding in a cat heart cell membrane preparation

Abstract

VANADATE has been reported to inhibit (Na⁺ + K⁺)-ATPase activity in membrane preparations from dog kidney¹ and in red cells². This inhibition, which occurs in the nanomolar concentration range in the presence of high Mg²⁺ concentrations and in the micromolar range at physiological Mg²⁺ concentrations^2,3 is specific as other ATPase enzymes are not affected in these conditions¹. Therefore vanadate has been suggested to be ‘an ideal specific regulator’ of (Na⁺ + K⁺)-ATPase¹. We have shown⁴ that vanadate has a distinct positive inotropic effect in cat papillary muscle. It has been claimed that the positive inotropic action of cardiac glycosides, which are specific inhibitors of (Na⁺ + K⁺)-ATPase activity^5,6, is associated with the inhibition of that enzyme. If that is so, vanadate would be expected to inhibit (Na⁺ + K⁺)-ATPase, in a concentration-dependent manner, in parallel with its effect on force of contraction. To test this hypothesis, we measured the effect of vanadate on (Na⁺ + K⁺)-ATPase activities and on ³H-ouabain-binding in identical conditions in a membrane preparation taken from cat hearts that were also used for experiments on contraction. We report here, however, that vanadate may stimulate (Na⁺ + K⁺)-ATPase activity transiently and ³H-ouabain-binding permanently in these conditions.