Alteration of Synaptosomal Plasma Membrane Cholesterol Content: Membrane Physical Properties and Cation Transport Proteins

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Abstract
The level of nerve membrane cholesterol was altered by in vitro incubation of rat brain synaptosomal plasma membrane with liposomes having varying cholesterol contents. The normal plasma membrane cholesterol/phospholipid ratio of 0.3-0.4 (mol/mol) could be decreased by about 1/2 or increased more than 100%. Fluorescence polarization measurements were made using the probe 1,6-dip henyl-1,3,5-hexatrieine. At temperatures below 35.degree. C, lowering membrane cholesterol led to increased apparent microviscosity, while raising cholesterol content produced little change. At 45.degree. C a continuous direct relationship existed between experimental membrane cholesterol/phospholipid ratio (ranging 0.18-0.73) and apparent microviscosity. Under standard liposome-synaptosomal plasma membrane exchange conditions, 80% of the initial specific [3H]saxitoxin binding activity to the voltage-dependent Na channel and at least 95% of the (Mg2+, K+)-p-nitrophenylphosphatase activity were preserved. Neither the characteristics of toxin binding nor the kinetics of this enzyme activity is dependent upon membrane cholesterol content.