IP₃R1 mediates IP₃-induced BK_Ca channel activation. (A) Mean data illustrating that heparin reverses IP₃-induced BK_Ca channel activation (n: control (10 µM Ca²⁺), 5; 30 µM IP₃, 5; 30 µM IP₃ plus 1 mg/ml heparin, 5). (B) Original recording from the same inside-out patch illustrating control BK_Ca channel activity (i), IP₃ (30 µM)-induced channel activation (ii), reversal by monoclonal IP₃R1 antibody (iii, 1:100; clone L24/18; NeuroMab), and no further effect of heparin applied in the continued presence of IP₃R1 antibody (iv). (C) Mean data illustrating that monoclonal IP₃R1 antibody inhibits IP₃-induced BK_Ca channel activation, and that the addition of heparin leads to no further change in activity (control (10 µM Ca²⁺), n = 4; 30 µM IP₃, n = 4; 30 µM IP₃ plus IP₃R1 antibody (1:100), n = 4; 30 µM IP₃ plus IP₃R1 antibody (1:100), n = 4; 30 µM IP₃ plus IP₃R1 antibody (1:100) plus heparin, n = 4; IP₃ plus boiled IP₃R1 antibody, n = 4). (D) Mean data illustrating that adenophostin A activates BK_Ca channels (n: control (10 µM Ca²⁺), 4; 1 µM adenophostin A, 4). *, P < 0.05.