[Biology of malignant hyperthermia: a disease of the calcium channels of the skeletal muscle].
Malignant hyperthermia susceptibility (MHS), a skeletal muscle disorder, is mostly inherited as an autosomal dominant trait. Exposure of susceptible individuals to volatile halogenated anaesthetics can lead to a MH episode resulting in irreversible tissue damages or to the patient's death if not immediately reversed by dantrolene treatment. A MH episode is characterised by a combination of hyperthermia, skeletal muscle rigidity and hypermetabolism. Porcine stress syndrome has proved to be a valuable model for physiopathological studies of MHS. Malignant hyperthermia syndrome is associated with a failure of the calcium homeostasis in muscular fibres. Dysfunction of the calcium channels: the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR), which are involved in the release of the Ca2+ stored in sarcoplasmic reticulum has been clearly demonstrated. A biochemical test based on the analysis of the in vitro contracture response of muscular fibres to caffeine and halothane was developed to define the MHS status of patients. Although the genetic analysis of MHS has beneficiated from recent progresses, genetic testing is still far to answer to all testing situations. If in swine, hyperthermia syndrome was always associated with a unique mutation of the RyR1 gene, genetic analysis is far more complicated in human: i) more than 20 different MHS mutations in the RyR1 gene have been described; ii) a mutation of the gene encoding the dihydropyridine receptor has been identified; iii) 4 other potential MHS loci have been reported.
Monnier
N
N
Laboratoire de biochimie de l'ADN, CHU, BP 217X, 38043 Grenoble, France.
Lunardi
J
J
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D006801:Humans; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel