Studies on the contracture of the mouse diaphragm induced by sodium selenite
Journal
European Journal of Pharmacology
Journal Volume
167
Journal Issue
1
Pages
137-146
Date Issued
1989
Author(s)
Abstract
In this study, we found that sodium selenite was potent in inducing contracture of the mouse diaphragm. The possible mechanism of action of selenite was investigated. Contracture was induced by a direct action of selenite on the muscle membrane rather than that selenite enhanced transmitter release from the motor nerve terminals, since denervation, d-tubocurarine and tetrodotoxin did not inhibit the selenite-induced contracture. Although selenite decreased both the membrane potential and the amplitude of the muscle action potential, neither high K+ nor glycerol treatment, which closed the transverse tubule, reduced the selenite-induced contracture, suggesting that depolarization of the muscle membrane was not essential for the induction of the contracture. EGTA (1-50 mM) inhibited the selenite-induced contracture in a concentration-dependent manner. In contrast, varying the external Ca2+ concentrations from 10(-3) to 10 mM or raising Mg2+ concentration to 10 mM did not affect the contracture. Similarly, the contracture induced by caffeine was not affected by lowering the external Ca2+ concentration to 10(-3) mM but was completely inhibited by 30 mM EGTA. Selenite pretreatment markedly potentiated the caffeine contracture and prolonged treatment with caffeine inhibited the selenite contracture. All of these findings suggest that the selenite contracture was not dependent on external Ca2+ but was induced by the release of Ca2+ from internal membranes such as the sarcoplasmic reticulum. Pretreatment with trypsin, glutathione or cyanide blocked the selenite-evoked contracture. Therefore, we postulate that the selenite-induced contracture was induced by the initial binding of selenite to the sulfhydryl groups of the muscle membrane, which then triggered the release of Ca2+ from internal membranes such as the sarcoplasmic reticulum.
SDGs
Type
journal article