Ethanol effect on BK macroscopic currents is Ca²⁺_i dependent. 50 mM ethanol activates homomeric cbv1 channels at submicromolar (0.3 µM) Ca²⁺_i while causing mild inhibition at higher Ca²⁺_i (100 µM). (A) Macroscopic current recordings evoked from I/O patches at 0.3 and 100 µM Ca²⁺_i in the absence or presence of 50 mM ethanol after cbv1 expression in Xenopus oocytes. (B) At 0.3 µM Ca²⁺_i, ethanol shifts the G/G_max-V plot to the left, indicating channel activation. (C) At 100 µM Ca²⁺_i, ethanol shifts the G/G_max-V plot to the right, indicating inhibition of channel activity. (D) At nominal zero Ca²⁺_i, ethanol does not shift the G/G_max-V plot, indicating ethanol fails to modulate cbv1 channel activity at nominal zero Ca²⁺_i. (E) V_0.5 versus [Ca²⁺]_i plot showing that the activation to inhibition crossover for ethanol effect on cbv1 currents occurs at ≈20 µM Ca²⁺_i. (F) Bar graph showing ethanol-induced change in V_0.5 from control obtained at nominal zero, 0.3, and 100 µM Ca²⁺_i. n = 5–8; each patch was excised from a different cell. *, different from control (P < 0.05); **, different from control (P < 0.01). Data are expressed as mean ± SEM.