Estrous Cycle-Mediated Regional Diversity in BK Channel Expression and Function in Arterial Myocytes: 2219 Board #55 June 1 11 00 AM - 12 30 PM

Large-conductance calcium (Ca2+)-activated potassium (BK) channels are significant regulators of arterial smooth muscle cell (myocyte) membrane potential and arterial contractility. The expression and function of BK channels in ovary-intact female resistance arteries are poorly understood. Moreover, the effects of endogenous steroid levels associated with the estrous cycle on arterial BK channels are unclear. PURPOSE: To investigate estrous cycle effects on BK channel expression and function in uterine and cerebral arterial smooth muscle. RESULTS: Western blotting and biotinylation of whole uterine arteries revealed an increase in total (~39%, n=7) and plasma membrane- localized (~64%, n=4-5) β1 subunits during proestrus as compared to diestrus. Patch-clamp electrophysiology demonstrated that BK channel activation (open probability [PO]) was enhanced ~ 5-fold during proestrus in uterine arterial myocytes (diestrus: PO =0.09±0.05 (n=4), proestrus: PO =0.55±0.10 (n=5); 10μM free Ca2+). In contrast, BK channel expression and activation were unchanged during proestrus in cerebral arterial myocytes (diestrus: PO =0.48±0.08 (n=11), proestrus: PO =0.56±0.09 (n=4); 10μM free Ca2+). CONCLUSION: These data suggest that endogenous steroids associated with the estrous cycle can alter BK channel expression and function in female resistance arteries. However, the estrous cycle effects on arterial BK channels are region-specific.