Biochemical basis of malignant hyperpyrexia.
Pharmacologically-induced muscle contracture in vitro has been used as a model to study the biochemical basis of malignant hyperpyrexia. In 15 susceptible subjects halothane, succinylcholine, and potassium chloride all produced an abnormal muscle contracture, and the caffeine-induced contracture was greater than normal. The contractures were reproducible only in the presence of extracellular calcium ions. The fact that such dissimilar pharmacological stimuli all induced contracture in the affected muscle suggests that the essential abnormality in the muscle cell in malignant hyperpyrexia is an impaired binding of calcium ions to the membranes of the sarcoplasmic reticulum and the sarcolemma. Exposure of these membranes to halothane, succinylcholine, and other anaesthetic agents then leads to a rapid and abnormally large release of calcium into the myoplasm, which in turn gives rise to all the clinical features of the syndrome.
D001706:Biopsy; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D005110:Extracellular Space / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000378:metabolism*; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013390:Succinylcholine / Q000494:pharmacology; D013696:Temperature
D002110:Caffeine; D011343:Procaine; D011189:Potassium Chloride; D003402:Creatine Kinase; D013390:Succinylcholine; D002118:Calcium; D006221:Halothane