The importance of calcium ions for in vitro malignant hyperthermia testing

• Published in: Canadian journal of anesthesia Vol. 37; no. 6; pp. 695 - 698
• Main Authors: FLETCHER, J. E, HUGGINS, F. J, ROSENBERG, H
• Format: Journal Article
• Language: English
• Published: Toronto, ON Canadian Anesthesiologists' Society 01.09.1990
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Caffeine - adverse effects; Calcium - pharmacology; Contracture - physiopathology; Drug Interactions; General anesthesia. Technics. Complications. Neuromuscular blocking. Premedication. Surgical preparation. Sedation; Halothane - adverse effects; Humans; In Vitro Techniques; Malignant Hyperthermia - physiopathology; Medical sciences; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscles - drug effects; Muscles - physiopathology; Nifedipine - pharmacology; Quinacrine - pharmacology; Strontium - pharmacology; Succinylcholine - adverse effects; Verapamil - pharmacology; Human; Pharmacologic test; Anesthetic; Calcium; Malignant hyperthermia; General anesthesia; Complication; Extracellular; In vitro; Caffeine
• ISSN: 0832-610X; 1496-8975
• DOI: 10.1007/BF03006495

Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine.