DIFFERENTIAL MODULATION OF LARGE-CONDUCTANCE K-CA CHANNELS BY PKA IN PREGNANT AND NONPREGNANT MYOMETRIUM

Uterine excitability depends on ion channel activity, the expression of which is regulated by sexual hormones (6, 16, 20, 22). We show now that the action of protein kinase A (PKA) on large-conductance calcium-activated K+ (K-Ca) channel activity also depends on the hormonal status. PKA-dependent phosphorylation of reconstituted K-Ca channels from midpregnant rats usually stimulated channel activity; in contrast, K-Ca channels from nonpregnant rat and human myometrium were primarily inhibited by this mechanism. Both effects were reversible by phosphatase treatment. These results suggest that one important factor modulating uterine contractility during pregnancy or the regular cycle may be the differential response of K-Ca channels toward PKA-induced phosphorylation.