DISSOCIATION OF EXCITATION AND CONTRACTION IN SKELETAL MUSCLE INDUCED BY DEUTERIUM OXIDE AND DANTROLENE-SODIUM

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The effect of D₂0 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 D₂0.
These results suggest that there is a Ca²⁺-mediated trigger mechanism for the rapid release of activator Ca²⁺from internal storage (SR). DAN and D₂0 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.