functional insights into modulation of bk_ca channel activity to alter myometrial contractility

The large-conductance voltage- and Ca²⁺-activated K⁺ channel (BK_Ca) is an important regulator of membrane excitability in a wide variety of cells and tissues. In myometrial smooth muscle, activation of BK_Ca plays essential roles in buffering contractility to maintain uterine quiescence during pregnancy and in the transition to a more contractile state at the onset of labor. Multiple mechanisms of modulation have been described to alter BK_Ca channel activity, expression, and cellular localization. In the myometrium, BK_Ca is regulated by alternative splicing, protein targeting to the plasma membrane, compartmentation in membrane microdomains, and posttranslational modifications. In addition, interaction with auxiliary proteins (i.e., β1- and β2-subunits), association with G-protein coupled receptor signaling pathways, such as those activated by adrenergic and oxytocin receptors, and hormonal regulation provide further mechanisms of variable modulation of BK_Ca channel function in myometrial smooth muscle. Here, we provide an overview of these mechanisms of BK_Ca channel modulation and provide a context for them in relation to myometrial function.