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 mum glibenclamide reversibly inhibited the activity of the 100 mum levcromakalim-induced KATP channel, decreasing not only the channel open probability but also the amplitude of unitary current. The inhibitory concentration-response curve of the glibenciamide-induced sublevel conductance of K-ATP channel was shifted to the right (IC50 = 4.7 mum), compared with the levcromakalim-incluced K-ATP channel (full conductance, IC50 = 0.5 mum). 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.