Dissociation of excitation and contraction in skeletal muscle induced by deuterium oxide and dantrolene-sodium

Abstract

The effect of D2O and dantrolene-Na (DAN) on the electrical and mechanical responses of single muscle fiber (mouse EDL and frog semitendinosus), Ca2+ uptake and release of sarcoplasmic reticulum (SR) and contractile proteins was investigated to elucidate the coupling mechanism between depolarization and contraction. Both agents inhibited tension development induced by depolarization and caffeine, especially the initial phase of contraction (more pronounced in fast muscle) without affecting excitation of membrane and contractile machinery. The effect of DAN can be antagonized by increasing Ca2+ concentration and lowering the temperature of the medium. Ca2+ uptake and release abilities of isolated SR were not altered significantly in DAN, but were reduced considerably in D2O. These results suggest than there is a Ca2+-mediated trigger mechanism for the rapid release of activator Ca2+ from internal storage (SR). DAN and D2O interfere predominantly the action of the site(s) of this mechanism, probably on the T-tubules. In addition, D2O decelerates Ca2+ release from SR per se.