Partial inhibition of skeletal muscle contraction by dantrolene sodium and its modification with perchlorate and Bay K 8644

Abstract

The effects of dantrolene sodium (DAN) on the dihydropyridine receptor (DHPR) of the transverse (T) tubule voltage sensor (Ca2+ channel) was studied with single fibers from bullfrog toe muscle. Perchlorate [Formula: see text], which acts selectively on the DHPR, overcame DAN-induced inhibition of twitch tension. Bay K 8644, a DHPR agonist, slowed the rate of twitch inhibition by DAN. DAN inhibited twitch tension to a greater extent in Ca2+-free solution than in Ringer solution or solution containing Zn2+, whereas twitch inhibition by DAN was less in caffeine-containing solution than in the control. The effects of DAN on Zn2+- and caffeine-treated fibers and on fibers in Ca2+-free solution suggest that DAN must act near the voltage sensor of the T tubule. However, differences in net twitch inhibition by DAN between control fibers and fibers potentiated by [Formula: see text] or Bay K 8644 suggest that DAN does not bind to the same site as these potentiating agents do. The role of myoplasmic Ca2+ in DAN-induced inhibition of twitch and the effects of DAN on the mechanical threshold and membrane potential in skeletal muscle are discussed.Key words: dantrolene sodium, perchlorate, Bay K 8644, twitch tension.