Alteration of synaptic membrane cholesterol/phospholipid ratio using a lipid transfer protein. Effect on gamma-aminobutyric acid uptake.

摘要: A procedure was developed to vary the cholesterol-to-phospholipid (Ch/PL) ratio of synaptic plasma membranes and synaptosomes using a nonspecific lipid transfer protein so that membrane composition could be correlated with presynaptic function. In membranes, Ch/PL molar ratios from 0.21 1.19 were produced normal value 0.52 +/- 0.01 by incubation an excess either phosphatidylcholine or cholesterol/phosphatidylcholine liposomes for 60 min at 32 degrees C. synaptosomes, 0.16 0.81 similarly 0.38 0.04. Cholesterol loading depletion accompanied decrease increase, respectively in phospholipid-to-protein ratio. The fluidity membrane, as estimated 1,6-diphenylhexatriene anisotropy measurements, increased lowering decreased raising Decreasing vesicles resulted loss sodium-dependent gamma-aminobutyric acid (GABA) uptake (70-100% 40% normal) reduction number accessible GABA-binding sites. Choline not affected these same preparations. GABA restored reinserting cholesterol into membrane. Synaptosomal potential sodium permeability changing Increase above had no effect on choline uptake. Both increase lipid-to-protein "fluidity," which may modulate vertical displacement motional characteristics transporter.