Down-regulation of the α- and β-subunits of the calcium-activated potassium channel in human myometrium with parturition

Large-conductance, calcium-dependent potassium (BK_Ca) channels are implicated in maintaining uterine quiescence during pregnancy. The mechanisms whereby calcium sensitivity of the BK_Ca 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 BK_Ca channel with the onset of labor is associated with changes in the protein expression of the a- and/or ß-subunit or arises from a physical dissociation of the a-subunit from the ß-subunit. The ß-subunit is a key determinant of BK_Ca-channel Ca²⁺ sensitivity. Western blot analysis, using a- and ß-subunit-specific antibodies, detected bands of 110-125 and 36 kDa, respectively. Protein expression levels of the a-subunit in term labor myometrium were significantly reduced compared with term pregnancy without labor. Furthermore, a-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 ß-subunit levels in term and preterm labor samples compared with term nonlabor samples. Immunoprecipitation studies revealed the presence of both the a- and ß-subunits in samples taken before or after the onset of labor. We conclude that during labor, the a-subunit is not physically uncoupled from the ß-subunit, but a decline occurs in the level of ß-subunit protein, which may underlie the loss of calcium and voltage sensitivity of the BK_Ca channel with labor. Furthermore, reduced ß-subunit protein in preterm labor myometrium implies that ion channels may also contribute to pathophysiological labor.