Desmosterol and Membrane Fluidity

Previous spin-label and electromyographic experiments with rats fed 20,25-diazacholesterol, an inhibitor of the biosynthet ic conversion of desmostero[ to cholesterol, demonstrated an increased e ry th rocy te membrane f luidi ty and myotonia, a prolonged muscle contraction upon stimulation. The current studies with rats showed normal erythrocyte f luidi ty in animals fed 20,25-diazacholesterol but maintained on a high-cholesterol diet and no myotonia. Studies of model membrane systems c o m p o s e d of phospho l i p id ves ic les c o n t a i n i n g desmosterol, cholesterol, or both demonstrated that desmosterol increased membrane lipid f luidi ty relative to c h o l e s t e r o l , sugges t ing tha t in 20,25-diazacholesterol induced myotonia, in which desmosterot accounts for g5% of the plasma sterol, the increased membrane f luidi ty previously observed in erythrocytes and sarcolemma m this animal model of human congenital myotonia may be due to desmosterol.