Interactions of Fatty Acids with the Calcium Release Channel in Malignant Hyperthermia
The anesthesia-induced malignant hyperthermia (MH) syndrome has been suggested to be a consequence of a halothane-sensitive defect in Ca2+ regulation, based on muscle rigidity during the syndrome and the increase in Ca2+ in isolated fiber bundles exposed to halothane. Additionally, the threshold of Ca2+-induced Ca2+ release (TCICR) is lower than normal in isolated fractions of heavy sarcoplasmic reticulum (HSR) from porcine MH muscle.1,2 However, the defect need not reside in the Ca2+-release channel protein, as there are reports of nonrigid MH in humans3 and loss of Ca2+ regulation could be the result of a disturbance in fatty acid metabolism.4 The present study examines fatty acid metabolism and the influence of fatty acids on various aspects of Ca2+ regulation and on caffeine, halothane and succinylcholine action in normal and MH muscle. Additionally, since phenytoin has been suggested to antagonize MH,5 its effects on Ca2+ regulation and fatty acid metabolism have been examined.
KeywordsFatty Acid Metabolism Malignant Hyperthermia Malignant Hyperthermia Muscle Strip Porcine Muscle
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