title: Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia.
abstract: The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors.
authors.affiliation: Department of Anesthesia, Faculty of Medicine, Lille, France.
authors.forename: P J
authors.initials: PJ
authors.lastname: Adnet
authors.forename: R M
authors.initials: RM
authors.lastname: Krivosic-Horber
authors.forename: M M
authors.initials: MM
authors.lastname: Adamantidis
authors.forename: H
authors.initials: H
authors.lastname: Reyford
authors.forename: C
authors.initials: C
authors.lastname: Cordonnier
authors.forename: G
authors.initials: G
authors.lastname: Haudecoeur
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D001706:Biopsy; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels; D004198:Disease Susceptibility; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000737:chemistry; D009543:Nifedipine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D011978:Receptors, Nicotinic; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D006221:Halothane