title: Inhibitory action of dantrolene on Ca-induced Ca2+ release from sarcoplasmic reticulum in guinea pig skeletal muscle.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: A
authors.initials: A
authors.lastname: Ohga
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D003080:Cold Temperature; D003620:Dantrolene / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000227:Adenine Nucleotides; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D002110:Caffeine; D000255:Adenosine Triphosphate; D003620:Dantrolene; D008274:Magnesium; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium