ANALYSIS OF LIPID-COMPOSITION OF SARCOPLASMIC-RETICULUM MEMBRANES FROM NORMAL AND MALIGNANT HYPERTHERMIC PIG SKELETAL-MUSCLE

In search of a general membrane defect hypothesis for malignant hypert hermia syndrome, we analysed the lipid profiles of heavy sarcoplasmic reticulum membranes isolated from normal and malignant hyperthermia lo ngissimus dorsi pig muscle. Malignant hyperthermia susceptibility was assessed by halothane challenge of pigs. Sarcoplasmic reticulum membra nes from malignant hyperthermia susceptible pigs differed significantl y from control ones in the cholesterol content and phosphatidylethanol amine/phosphatidylcholine ratio; both were higher in former membranes. These latter lipid modifications were in agreement with the significa nt increase of their bulk lipid viscosity, as evidenced by an increase of diphenyl hexatriene fluorescence anisotropy. The increased level o f phosphatidylethanolamine associated with the decreased content of ph osphatidylcholine in malignant hyperthermic membranes was shown to be a potential consequence of depressed activities of both phospholipid N -methyltransferase I and II activities. Finally, the distribution of f atty acids in these particular phospholipids showed no change in phosp hatidylcholine molecules, whereas the percentage of arachidonate and s tearate in the phosphatidylethanolamine species were respectively high er and lower in malignant hyperthermic membranes. These differences in major phospholipids content and the enrichment of a metabolically imp ortant fatty acyl chains in malignant hyperthermia sarcoplasmic reticu lum membranes strongly suggest that the lipid metabolism may contribut e to the molecular mechanism of malignant hyperthermia syndrome.