Contribution of coupling between human myometrial β2-adrenoreceptor and the BKCa channel to uterine quiescence

The beta(2)-adrenergic receptor (beta(2)-AR) and the large-conductance Ca2+-activated K+ (BKCa) channel have been shown, separately, to be involved in mediating uterine relaxation. Our recent studies reveal that the levels of both beta(2)-AR and BKCa channel proteins in pregnant human myometrium decrease by similar to50% after the onset of labor. We present direct evidence in support of a structural and functional association between the beta(2)-AR and the BKCa channel in pregnant human myometrium. Localization of both proteins is predominantly plasmalemmal, with 60% of beta(2)-AR colocalizing with the BKCa channel. Coimmunoprecipitation studies indicate that BKCa and beta(2)-AR are structurally linked by direct protein-protein interactions. Functional correlation was confirmed by experiments of human myometrial contractility in which the BKCa channel blocker, paxilline, significantly antagonized the relaxant effect of the beta(2)-AR agonist ritodrine. These novel findings provide an insight into the coupling between the beta(2)-AR and BKCa channel and may have utility in the application of this signaling cascade for therapeutic potential in the management of preterm labor.