UNUSUAL LOW PROTON PERMEABILITY OF LIPOSOMES PREPARED FROM THE ENDOGENOUS MYELIN LIPIDS

In contrast with most other lipid substrates, in this article we show that liposomes prepared from the total myelin lipids exhibited a negli gible proton permeability. Neither the generation of valinomycin-induc ed potassium diffusion potentials as high as -177 mV nor the impositio n of large pH gradients (up to three units) was able to produce a subs tantial flux of protons through liposomal membranes, as determined by the distribution of [C-14]-methylamine, or the changes in the fluoresc ence of the probes 9-aminoacridine, acridine orange, and pyranine. The presence of cations (Na+, K+, Ca2+) did not alter this behavior. Volt age clamping did not increase the transmembrane Delta pH-driven proton permeability. However, liposome diameter was found to be critical bec ause small unilamellar vesicles displayed a much higher proton permeab ility than large unilamellar or multilamellar vesicles. This abnormall y low proton permeability is interpreted by virtue of the characterist ic biochemical composition of myelin lipid matrix, with a high content of cholesterol and sphingolipids and a very low level of free fatty a cids. These results could be important for elucidating the role of mye lin in the regulation of pH in the brain. In addition, the myelin lipi d extract could be useful for reconstituting proteins that participate in the transport of H+ through the membrane.