Skeletal muscle sarcolemma (SL), transverse tubule (TT) and heavy sarcoplasmic reticulum (HSR) membranes were isolated from malignant hyperthermia susceptible (MHS) and normal pigs, and the rotational dynamics of lipid hydrocarbon chain motion was examined by electron paramagnetic resonance (EPR) spectroscopy. The stearic acid spin probe 16-SASL was incorporated into MHS and normal membranes and both the order parameter (S) and effective correlation time (τr) of probe motion were calculated from spectra recorded over the temperature range of 2 to 40°C. At any given temperature, TT membranes exhibited significantly greater values for both the S and τr of probe motion than did SL, which exhibited significantly greater values than did HSR membranes. The order of decreasing S and τr values for 16-SASL mobility correlated with the decreasing cholesterol content of these membranes (TT>SL>HSR), however there was no difference in the S or τr values for a given membrane fraction isolated from both MHS and normal muscle. Arrhenius plots of 16-SASL mobility in SL, TT and HSR were linear from 2 to 40°C, indicating no abrupt thermotropic change in the lipid hydrocarbon phase of any of the membrane types studied. Apparent activation energies (Ea), calculated from the Arrhenius plots, were similar for MHS and normal membranes derived from a given cellular location. However, the Ea of probe motion for TT membranes (2.3 ± 0.1 and 2.4 ± 0.1 kcal/mol/degree for MHS and normal, respectively) was significantly less than for SL (3.4 ± 0.4 and 2.9 ± 0.1 kcal/mol/degree for MHS and normal, respectively) which, in turn, was significantly less than the Ea for HSR (3.7 ± 0.1 and 3.7 ± 0.1 kcal/mol/degree for MHS and normal, respectively). Since 16-SASL motion was similar in MHS and normal membranes, we conclude that there is no evidence for a generalized membrane defect affecting lipid mobility in these MHS muscle membranes.
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plasmic reticulum (SR) is thought to play a major role in this syndrome \[2-8\].T his conclusion is supported by reports of abnormal calcium release \[4-7\] and ryanodine binding \[8\]a ctivities of heavy SR (HSR) isolated from MH susceptible (MHS) pig muscle. A number of studies, however, have indicated that there may be a generalized membrane defect in all tissues of MHS individuals. We have recently reported altered \[3H\]nitrendipine and (-)\[~H\]desmethoxyverapamil binding to the dihydropyridine receptor of isolated MHS transverse tubules (TT) \[9\], as well as diminished calcium-accumulating activity in both isolated MHS TT \[10\]a nd sarcolemma (SL) \[11\].F urthermore, red blood cells (RBC) from MHS pigs have been shown to have increased osmotic fragility relative to normal pig RBC \[12\], while both MHS RBC ghosts \[13\] and isolated MHS SR \[14\]h ave been reported to exhibit lower than normal lipid mobility. A possible explanation for these
- Malignant hyperthermia
- Membrane fluidity