Possible regulation of the myometrial Na+/K+-ATPase activity by Ca2+ and cAMP-dependent protein kinase.

We have previously reported an inhibition of the rat myometrial Na+/K+-ATPase by micromolar Ca2+ concentrations which was abolished by SDS treatment of the microsomal preparation. Application of dimethyl sulphoxide (DMSO) prevented this effect of SDS. In this report, we present our investigation into the mechanism of the inhibitory effect of Ca2+ on the myometrial Na+/K+-ATPase. We observed that, in parallel with inhibition by Ca2+, phosphorylation of a number of membrane components was abolished by SDS treatment of the microsome fraction. Exogenously added calmodulin had no effect. However, the catalytic subunit of cAMP-dependent protein kinase restored Ca2+ sensitivity of the Na+/K+-ATPase and phosphorylation of the other components. Furthermore, addition of the heat-stable protein kinase inhibitor reduced drastically the Ca2+ sensitivity of the Na+/K+-ATPase, as well as the phosphorylation of a number of proteins in the myometrial microsome fraction. It is concluded that the cAMP-dependent protein kinase may be involved in the modulation of Na+/K+-ATPase activity by Ca2+ in the myometrial plasma membrane.