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

• Published in: Anesthesiology (Philadelphia) Vol. 75; no. 3; pp. 413 - 419
• Main Authors: Adnet, P J, Krivosic-Horber, R M, Adamantidis, M M, Reyford, H, Cordonnier, C, Haudecoeur, G
• Format: Journal Article
• Language: English
• Published: United States 01-09-1991
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Biopsy; Calcium Channel Blockers - metabolism; Calcium Channels; Disease Susceptibility; Halothane - pharmacology; Humans; In Vitro Techniques; Isotonic Solutions - pharmacology; Malignant Hyperthermia - physiopathology; Muscle Contraction - drug effects; Muscles - chemistry; Nifedipine - pharmacology; Receptors, Nicotinic - metabolism; Verapamil - pharmacology
• ISSN: 0003-3022
• DOI: 10.1097/00000542-199109000-00006

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.