Large conductance, Ca2+-activated K+ channels (BKCa) and arteriolar myogenic signaling

Myogenic, or pressure-induced, vasoconstriction is critical for local blood flow autoregulation. Underlying this vascular smooth muscle (VSM) response are events including membrane depolarization, Ca2+ entry and mobilization, and activation of contractile proteins. Large conductance, Ca2+-activated K+ channel (BKCa) has been implicated in several of these steps including, (1) channel closure causing membrane depolarization, and (2) channel opening causing hyperpolarization to oppose excessive pressure-induced vasoconstriction. As multiple mechanisms regulate BKCa activity (subunit composition, membrane potential (Em) and Ca2+ levels, post-translational modification) tissue level diversity is predicted. Importantly, heterogeneity in BKCa channel activity may contribute to tissue-specific differences in regulation of myogenic vasoconstriction, allowing local hemodynamics to be matched to metabolic requirements. Knowledge of such variability will be important to exploiting the BKCa channel as a therapeutic target and understanding systemic effects of its pharmacological manipulation.