Effects of cromakalim on the contraction and the membrane potential of the circular smooth muscle of guinea-pig stomach.

Abstract

1. The effects of cromakalim on mechanical and electrical activities of the circular smooth muscles of guinea-pig stomach antrum were observed. 2. Cromakalim (greater than 1 x 10(-7) M) decreased the amplitude of spontaneous rhythmic contractions and also the acetylcholine-enhanced spontaneous contractions. Cromakalim was less effective against the 25.9 mM and 35.9 mM K(+)-induced tonic contractions. 3. Glibenclamide (1 x 10(-6) M) itself caused no detectable change in the spontaneous contractions, those potentiated by acetylcholine or tonic contractions induced by high K+ solutions, but attenuated the actions of cromakalim. On the other hand, charybdotoxin (3 x 10(-8) M) increased the amplitude of spontaneous contractions but failed to affect the actions of cromakalim. 4. Cromakalim (greater than 1 x 10(-6) M) decreased the amplitude and duration of slow waves, and hyperpolarized the membrane. These actions of cromakalim were completely antagonized by 1 x 10(-6) M glibenclamide, whereas part of the effects of cromakalim on mechanical activity was resistant to glibenclamide. 5. The results suggest that the inhibition by cromakalim of the electrical activity and the hyperpolarization, which may be associated with the opening of glibenclamide-sensitive K+ channel, are responsible for its inhibitory action on circular smooth muscle of guinea-pig stomach. Further, some effects independent of glibenclamide-sensitive K+ channel may also be responsible for the mechanical effect.