Sarcolemmal desmosterol accumulation and membrane physical properties in 20,25-diazacholesterol myotonia.
In rats treated biweekly with 20,25-diazacholesterol (200 mg/kg orally), the desmosterol level in skeletal muscle sarcolemma increased progressively to about 80% of membrane sterol while total sterol levels remained constant. Following a single oral dose of 20,25-D, the kinetics of desmosterol accumulation and subsequent loss in sarcolemma were more rapid than in whole muscle homogenates. The anisotropy of diphenylhexatriene fluorescence and the calculated microviscosity of the probe's microenvironment decreased significantly with increasing desmosterol levels in a temperature-dependent manner, although fluorescent lifetimes were not altered. Fluorescent probes which localize in more superficial regions of the membrane detected no change. Studies with erythrocyte ghost membranes yielded results comparable to sarcolemma. Replacement of membrane yielded results comparable to sarcolemma. Replacement of membrane cholesterol with desmosterol reduced the local microviscosity of membrane cholesterol with desmosterol reduced the local microviscosity of the membrane hydrophobic region associated with phospholipid acyl chains and sterol side chains, but had little apparent effect on more superficial, polar regions. These observations can be correlated with the membrane location of the unsaturated side chain in desmosterol.
D000818:Animals; D001373:Azacosterol; D002462:Cell Membrane / Q000032:analysis; D002784:Cholesterol / Q000031:analogs & derivatives; D003897:Desmosterol / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000032:analysis; D009132:Muscles / Q000378:metabolism*; D009222:Myotonia / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure; D014783:Viscosity
D008563:Membrane Lipids; D003897:Desmosterol; D002784:Cholesterol; D001373:Azacosterol