SITE OF ACTION OF DANTROLENE IN FROG SARTORIUS MUSCLE

¹ Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Dantrolene, 1-[5-(p-nitrophenyl)furfurylideneamino]hydantoin, is known to inhibit contraction in skeletal muscle without affecting the electrical properties of the surface or transverse tubular membranes. When added to frog sartorius muscle preparations (3 µg/ml) the drug had no effect on tissue cation or water content or contractures elicited by 10 mM caffeine. Twitch tensions, twitch/tetanus ratios and potassium contractures were significantly inhibited. The kinetics of twitch depression and the sensitivity of dantrolenetreated muscles to ethylene glycol bis(aminoethyl ether)-N, N'-tetraacetic acid suggested a superficial site of action. Whereas resting ⁴⁵Ca influx was not affected by dantrolene, the drug significantly decreased the ⁴⁵Ca influx per twitch and the ⁴⁵Ca influx associated with K⁺ depolarization. These data suggest that dantrolene owes its effect, at least in part, to an inhibition of the "triggering" step in excitation-contraction coupling.