Blocking actions of glibenclamide on ATP-sensitive K+ channels in pig urethral myocytes.

The inhibitory effects of glibenclamide on the levcromakalim-induced ATP-sensitive K+ (K(ATP)) channels were investigated with cell-attached configuration in pig proximal urethra. Application of 10 microM glibenclamide reversibly inhibited the activity of the 100 microM levcromakalim-induced K(ATP) channel, decreasing not only the channel open probability but also the amplitude of unitary current. The inhibitory concentration-response curve of the glibenclamide-induced sublevel conductance of K(ATP) channel was shifted to the right (IC50 = 4.7 microM), compared with the levcromakalim-induced K(ATP) channel (full conductance, IC50 = 0.5 microM). Glibenclamide is the first reported sulphonylurea to selectively block K(ATP) channel, not only by decreasing the channel activity but also by reducing the unitary amplitude in smooth muscle.