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

Abstract

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