Pregnancy

Down-Regulation of the - and -Subunit of the Calcium-Activated Potassium Channel in Human Myometrium with Parturition

Abstract

Large conductance calcium-dependent potassium (BK_Ca) channels are implicated in maintaining uterine quiescence during pregnancy. The mechanism(s) 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 either associated with changes in the protein expression of the and/or subunit or arises from a physical dissociation of the subunit from the subunit. The subunit is a key determinant of BK_Ca channel Ca²⁺ sensitivity. Western blot analysis, using and -subunit specific antibodies, detected bands of 110-125 and 36 kDa respectively. Protein expression levels of the -subunit in term labor myometrium were significantly reduced compared with term pregnancy. Furthermore, -subunit levels at term pregnancy were significantly increased relative to the non-pregnant state whereas levels at preterm gestations were unchanged. Densitometric analysis demonstrated significantly decreased -subunit levels in term and preterm labor samples compared with term non-labor. Immunoprecipitation studies revealed the presence of both the and subunit in samples taken before or after the onset of labor. We conclude that during labor, the subunit is not physically uncoupled from the -subunit but there is a decline in the level of -subunit protein which may underlie the loss of calcium and voltage sensitivity of the BK_Ca channel with labor. Furthermore, reduced -subunit protein in preterm labor myometrium implies that ion channels may also contribute to pathophysiological labor.