Partial inhibition of skeletal muscle contraction by dantrolene sodium and its modification with perchlorate and Bay K 8644.
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 (ClO4-), 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 Ca(2+)-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 Zn(2+)- and caffeine-treated fibers and on fibers in Ca(2+)-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 ClO4- 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.
Oba
T
T
Department of Physiology, Nagoya City University Medical School, Japan.
Aoki
T
T
Lu
A
A
Yamaguchi
M
M
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D003620:Dantrolene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D010472:Perchlorates / Q000494:pharmacology*; D011892:Rana catesbeiana; D011978:Receptors, Nicotinic / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
D015220:Calcium Channels; D010472:Perchlorates; D011978:Receptors, Nicotinic; D002110:Caffeine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003620:Dantrolene; D015032:Zinc