Inhibitory effect of cromakalim in human detrusor muscle is mediated by glibenclamide-sensitive potassium channels.

Abstract

The effects of cromakalim, a potassium channel activating drug, and glibenclamide, a relatively selective antagonist of ATP-sensitive potassium channels, have been investigated on isolated detrusor muscle from human bladder. Specimens of human bladder were cut into strips and suspended in an organ bath filled with modified Tyrode solution for measurement of isometric contractile force. Concentration-response curves to acetylcholine were constructed before and after pretreatment with cromakalim and cromakalim plus glibenclamide. The concentration-response curves to acetylcholine were displaced to the right, and the maximal response to acetylcholine was significantly inhibited by cromakalim in a concentration-dependent manner. The inhibitory effect of cromakalim on acetylcholine-induced contraction was significantly reduced by glibenclamide. Following sustained contraction induced by 20 mM. KCl, the cumulative addition of cromakalim to the organ bath produced a concentration-dependent relaxation. However, in strips precontracted with 60 mM. KCl, the addition of cromakalim in concentrations as high as 10(-5) M. did not induce relaxation. The relaxation induced by cromakalim in strips precontracted with 20 mM. KCl was significantly inhibited by glibenclamide. These results suggest that the inhibitory effect of cromakalim in human bladder involves activation of glibenclamide-sensitive potassium channels.