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 (> 1 x 1-0 M) decreased the amplitude of spontaneous rhythmic contractions and also the acetylcholine-enhanced spontaneous contractions. Cromakalim was less effective against the 25.9mm and 35.9 mm K+-induced tonic contractions. 3 Glibenclamide (1 x 10-6M) 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 10-8M) increased the amplitude of spontaneous contractions but failed to affect the actions of cromakalim. 4 Cromakalim (>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 10-6M 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.

Effects of cromakalim on the electrical slow wave in the circular muscle of guinea‐pig gastric antrum

“…It has been reported that cromakalim blocks spontaneous spike activity during hyperpolarization in guinea-pig taenia caeci Den Hertog et al, 1989) and rat portal vein (Hamilton et al, 1986) or slow rhythmic electrical activity in guinea-pig trachealis (Allen et al, 1986). On the other hand, the frequency of slow waves in the guinea-pig gastric antrum is not significantly affected by the hyperpolarization caused by cromakalim (Ito et al, 1992;present study). Such results are consistent with those of previous studies obtained with the sucrose-gap method that slow wave frequency is only weakly voltage-dependent (Tomita, 1981).…”

“…The frequency of slow waves was found to be either decreased (Post et al, 1991) or remained constant (Farraway & Huizinga, 1991), during hyperpolarization caused by these K+ channel openers. On the other hand, a marked decrease of amplitude in the slow wave of guinea-pig gastric muscle, was observed in the presence of 1 tiM cromakalim, although the frequency was not significantly altered (Ito et al, 1992). In the present experiments, we studied the effects of cromakalim on the electrical and mechanical activities in the circular muscle of guinea-pig gastric antrum to determine any correlation between mechanical inhibition and the amplitude of the slow wave.…”

Modification by charybdotoxin and apamin of spontaneous electrical and mechanical activity of the circular smooth muscle of the guinea‐pig stomach

“…Cromakalim inhibited the spontaneous contraction in the absence of either toxin with a pD2 of 6.65 ± 0.06 (n = 9, Ito et al, 1992).…”

“…The pD2 value was calculated as described by Ito et al (1992). The statistical significance was tested by Student's t test for paired or unpaired observations at the level of P <0.05.…”

“…The blocking action of CTX on Ca`-activated K+ channels in smooth muscles has been demonstrated in myocytes from the rabbit aorta (Talvenheimo et al, 1988) and from the canine colon and stomach (Carl et al, 1990a). CTX caused or potentiated contractions in many types of smooth muscles (Murray et al, 1991;Suarez-Kurtz et al, 1991;Ito et al, 1992). Apamin is a bee venom polypeptide of 18 amino acids with two disulphide bridges (Romey et al, 1984), which has been shown to block a Ca2'-activated K+ channel of small conductance (SK chan-nel) in skeletal muscle (Blatz & Magleby, 1986).…”