PIP₂ activates the BK channel by amplifying Ca²⁺-driven gating, resulting in modifications of both open and closed times. (A) PIP₂ activation of cbv1 is negligible at zero nominal Ca²⁺_i and reaches a maximum at 10 μM Ca²⁺_i; (a) zero Ca²⁺_i vs. 0.3 μM Ca²⁺_i: P < 0.001; (b) zero Ca²⁺_i vs. 10 μM Ca²⁺_i: P < 0.001; (c) zero Ca²⁺_i vs. 100 μM Ca²⁺_i: P < 0.001; (d) 0.3 μM Ca²⁺_i vs. 10 μM Ca²⁺_i: P < 0.001; (e) 0.3 μM Ca²⁺_i vs. 100 μM Ca²⁺_i: P < 0.001; n = 3–12. (B) Single channel records in the absence (top) and presence (bottom) of 10 μM PIP₂ show that the lipid increases P_o from 0.06 to 0.43 (616% of control). Records were low-passed at 7 kHz and digitized at 35 kHz. Upward deflections: channel openings. (C) Open and (D) closed time distributions in control (top) and PIP₂ (bottom) from records shown in B. Each life time constant (τ) is shown in milliseconds, with its contribution to the total fit in parentheses. Each component of a fit is shown with a dotted line, and the composite fit is shown with a solid line; 40 mV; Ca²⁺_i = 0.3 μM.