A defect in the sarcolemma has been proposed as a cause of malignant hyperthermia. Halothane has been shown to cause depolarization of the sarcolemma in pigs susceptible to malignant hyperthermia and may enhance its permeability to calcium more than in normal muscle. Dantrolene, which is the only specific therapy for treating malignant hyperthermia but whose site of action is unknown, has been shown to reduce significantly the muscle contractures caused by K + which result in progressive depolarization of the sarcolemma and subsequent influx of extracellular Ca 2+. It has little effect on contractures caused by caffeine, which acts on the sarcoplasmic reticulum, or by dinitrophenol, which causes uncoupling of oxidative phosphorylation in the mitochondria.

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