Dantrolene inhibits excitation-contraction coupling in skeletal muscle by acting on the transverse tubular membrane to decrease activator calcium release, without directly affecting contractile proteins or sarcoplasmic reticulum.
Dantrolene's T-tubule action on skeletal EC coupling may guide targeted therapies; leaves open human translation from animal data alone.
The effect of dantrolene sodium, 1-(5-(p-nitrophenyl)furfuryli-deneamino)hydantoin sodium hydrate, on electrical and mechanical response in frog skeltal muscles (whole muscles or single fibers) and on the biochemical properties of contractile proteins and fragmented sarcoplasmic reticulum isolated from frog or rabbit skeletal muscle was investigated. The peak tensions of twitch, tetanus and potassium contracture were significantly inhibited by dantrolene, without affecting the magnitude of resting potential, the amplitude and duration of action potential and the negative afterpotential. On the other hand, ATP-INDUCED SHORTENING OF GLYCEROL-EXTRACTED RABBIT PSOAS MUSCLE FIBERS, ATPase activity of frog myofibrils and Ca release induced by caffeine, Ca uptake and ATPase activity of fragmented sarcoplasmic reticulum of frog or rabbit muscle were not affected by dantrolene. Caffeine contracture was partially inhibited by dantrolene and was almost unchanged by it in potassium-depolarized muscele fiber. Nitrate ions and low concentration of caffeine rapidly recovered the twitch inhibition induced by dantrolene. These results suggested that dantrolene acts on the membrane of transverse tubules and possibly the triadic junction and that it inhibits the inward movement of Ca and subsequently decreases the release of activator Ca from sarcoplasmic reticulum.
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Takauji et al. (1975) studied this question.
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