Dual effect of membrane cholesterol on simple and mediated transport processes in human erythrocytes

The influence of cholesterol on simple and facilitated transport processes across the membrane of intact human erythrocytes was studied after graded depletion or enrichment of membrane cholesterol by incubation of the cells in phospholipid or phospholipid/cholesterol suspensions. 1. The carrier-mediated transfer of L-lactate and of L-arabinose proved to be enhanced in this effect. In contrast, the self-exchange of SO4(2-), mediated by the inorganic anion-exchange system, and the simple diffusion of erythritol via the lipid phase of the membrane are inhibited by cholesterol. 2. Reversibility of these two opposite effects of cholesterol was demonstrated by measurements on cells depleted again after cholesterol enrichment and enriched again after previous depletion. 3. Certain phospholipids used for preparing the lipid dispersions that are required for cholesterol variation have effects on permeability of their own, due, for example, to traces of contaminants. A discrimination of such artifacts due, for example, to traces of contaminants. A discrimination of such artifacts from the effects of cholesterol is only possible by demonstrating reversibility. 4. The opposite effects of cholesterol on various facilitated transfer processes, which have a correlation in the opposite effects of other modifications of the membrane lipid phase (Deuticke, B., Grunze, M. and Haest, C.W.M. (1979) Alfred Benzon Symposium 14, Munksgaard, Copenhagen, in the press), are indicative of different types of lipid-protein interaction in the erythrocyte membrane.