Down-Regulation of the (alpha)- and (beta)-Subunits of the Calcium-Activated Potassium Channel in Human Myometrium with Parturition

Large-conductance, calcium-dependent potassium (BKCa) channels are implicated in maintaining uterine quiescence during pregnancy. The mechanisms whereby calcium sensitivity of the BKCa channel is dramatically removed at parturition remain unknown. The aim of the present study was to investigate whether this loss of calcium sensitivity of the BKCa channel with the onset of labor is associated with changes in the protein expression of the (alpha)- and/or (beta)-subunit or arises from a physical dissociation of the -subunit from the (beta)-subunit. The (beta)-subunit is a key determinant of BKCa-channel Ca^2+ sensitivity. Western blot ana(alpha)lysis, using (alpha)- and (beta)-subunit-specific antibodies, detected bands of 110–125 and 36 kDa, respectively. Protein expression levels of the (alpha)-subunit in term labor myometrium were significantly reduced compared with term pregnancy without labor. Furthermore, (alpha)-subunit levels at term pregnancy were significantly increased relative to the nonpregnant state, whereas levels at preterm gestations were unchanged. Densitometric analysis demonstrated significantly decreased (beta)-subunit levels in term and preterm labor samples compared with term nonlabor samples. Immunoprecipitation studies revealed the presence of both the (alpha)- and (beta)-subunits in samples taken before or after the onset of labor. We conclude that during labor, the (alpha)-subunit is not physically uncoupled from the (beta)subunit, but a decline occurs in the level of (beta)-subunit protein, which may underlie the loss of calcium and voltage sensitivity of the BKCa channel with labor. Furthermore, reduced (beta)-subunit protein in preterm labor myometrium implies that ion channels may also contribute to pathophysiological labor.