PROTEIN-INDEPENDENT LEAD PERMEATION THROUGH MYELIN LIPID LIPOSOMES

We have investigated the permeability of protein-free myelin lipid lip osomes to inorganic lead by using the fluorescent probes fura-2, oxono l V, pyranine, and carboxyfluorescein. Inorganic lead readily crossed the lipid bilayer, as detected with fura-2, to an extent that depended on the external pH and the total nominal lead concentration in the as say medium. Lead entry generated an internally positive transmembrane potential, which could be detected by oxonol V fluorescence quenching, and dissipated a transmembrane pH gradient by alkalinization of the i ntravesicular space, as measured with pyranine. These results cannot b e explained by lead-mediated nonspecific damage to membrane lipids, ba sed on the following results: 1) lead exposure did not increase carbox yfluorescein leakage from liposomes, 2) it did not increase the permea bility of the lipid bilayer to glucose or KCl, 3) it did not generate peroxidation products in contact with myelin lipids, and 4) it did not induce chemical hydrolysis or modification of any myelin lipid class. We conclude that the principal molecular mechanism of lead permeation through a pure lipid bilayer is the passive diffusion of Pb(OH)(+). W e discuss the toxicological relevance of these findings for cells in g eneral and for myelin in particular and suggest that this mechanism mi ght contribute significantly to the total lead entry into the cells.