On the pharmacological and physiological role of glibenclamide-sensitive potassium channels in colonic smooth muscle.

Abstract

Actions of activators of glibenclamide sensitive K+ channels on canine colonic circular muscle were investigated. Cromakalim as well as its (-) enantiomer lemakalim caused inhibition of spontaneous phasic contractile activity (EC50's 4.4 +/- 0.1 x 10(-7) M and 2.3 +/- 0.4 x 10(-7) M, respectively) and of carbachol induced activity (EC50's: 9.4 +/- 5.1 x 10(-7) M and 4.3 +/- 1.4 x 10(-7) M, respectively). Cromakalim and lemakalim effects were completely inhibited by glibenclamide. Additive effects between K+ channel activators and other drugs relaxing colonic muscle (the L-type calcium channel blocker D600 and forskolin) were seen. A physiological role for specific glibenclamide sensitive K+ channels, if existing, remains unresolved. The present study indicates that the non-adrenergic inhibitory nerves do not act through these channels, neither does stimulation of muscarinic or beta-adrenergic receptors.