Epiandrosterone activates BKCa channel in bovine coronary artery smooth muscle cells

Epiandrosterone (EPI), a metabolite of testosterone precursor dehydroepiandrosterone, causes relaxation of vascular smooth muscle (VSM) associated with inhibition of glucose‐6‐phosphate dehydrogenase (G6PD), which increases cellular reducing potential by converting NADP + to NADPH. BK Ca channel is a primary K + channels in VSM. We studied whether EPI regulates BK Ca channel and whether G6PD is involved in cultured bovine coronary artery smooth muscle cells (CASMC). Whole‐cell BK Ca current (I BK ) was recorded in the presence of 5.4 mM [K + ] o /30 mM [K + ] i and 0.1 or 1 μM [Ca 2+ ] i . I BK was predominant K + current in CASMC. I BK increased with moderate increase of depolarization, but large depolarizations caused inactivation presenting bell‐shaped I‐V relationship. The increase of [Ca 2+ ] i caused negative shift of maximal BK Ca conductance (G BKCa ). EPI (>3 μM) increased G BKCa and shifted voltage‐dependence of activation further to a negative direction; G BKCa increased by ∼50% at 10 μM and by ∼100% at 100 μM. EPI caused hyperpolarization that was reversed by TEA. Suppression of G6PD by siRNA did not affect G BKCa and EPI caused similar modulation of I BK in the G6PD KO myocytes. EPI is a novel activator of BK Ca channel and the activation is independent of its inhibitory action on G6PD. EPI‐induced increase in I BK may cause relaxation of CASMC via hyperpolarization.