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2-adrenoreceptor and the BKCa channel to uterine quiescence
* To whom correspondence should be addressed. E-mail: raheela.khan{at}nottingham.ac.uk.
The 
2 adrenergic receptor (2-AR) and the large conductance calcium-activated potassium (BKCa channel have been shown, separately, to be involved in mediating uterine relaxation. Our recent studies reveal that the levels of both 2 AR and BKCa channel proteins in pregnant human myometrium decrease by approximately 50% after the onset of labor. We present direct evidence in support of a structural and functional association between the 2 AR and the BKCa channel in pregnant human myometrium. Localization of both proteins is predominantly plasmalemmal with sixty percent of 2 AR colocalizing with the BKCa channel. Co-immunoprecipitation studies indicate that BKCa and 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 the2 AR agonist, ritodrine. These novel findings provide an insight into the coupling between the 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.
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