Inhibitory action of dantrolene on Ca-induced Ca2+ release from sarcoplasmic reticulum in guinea pig skeletal muscle.

The effects of dantrolene on the sarcoplasmic reticulum and contractile machinery were examined in skinned skeletal muscles of guinea pigs. Dantrolene inhibited Ca-induced Ca2+ release at 38 degrees C. The inhibitory effect of dantrolene on Ca2+ release was greater in the presence of caffeine or adenine nucleotide than in their absence at low Ca2+ concentrations. Dantrolene suppressed the maximum rate of Ca-induced Ca2+ release but did not affect the sensitivity to Ca2+. At 20 degrees C, however, dantrolene did not inhibit Ca2+ release induced by any Ca2+ concentration, regardless of the presence and absence of caffeine, adenine nucleotide or Mg2+. Ca2+ uptake into the sarcoplasmic reticulum and the Ca2+ sensitivity of the contractile machinery were not affected by dantrolene at 38 degrees C and 20 degrees C. These results suggest that dantrolene is a selective inhibitor of the Ca-induced Ca2+ release mechanism at physiological temperatures without having an effect on the Ca2+ pump of the sarcoplasmic reticulum or on the contractile machinery of skeletal muscle.