THALLIUM MEDIATES A RAPID CHLORIDE HYDROXYL ION-EXCHANGE THROUGH MYELIN LIPID BILAYERS

We have investigated the effects of several heavy metal cations on the proton and chloride permeabilities of liposomes prepared with endogen ous lipids from brain myelin, by monitoring the fluorescence emitted b y acridine orange and N-(6-methoxyquinolyl)acetoethyl ester. In additi on to Hg2+ and Cu+, nanomolar concentrations of Tl3+, but not Tl+, wer e able to generate a pH gradient (internally acidic) when an inwardly directed chloride gradient was established. No effect was observed eit her in the absence of Tl3+ or when Tl3+ was added (a) in the presence of chelating agents, reducing chemicals, or thiol compounds, (b) with identical intra- and extravesicular chloride concentrations, or (c) in the absence of chloride. Furthermore, Tl3+ was able to dissipate a pH gradient across the membrane for identical intra-and extravesicular c hloride concentrations and to increase the chloride permeability in re sponse to a pH gradient. All of these results suggest that Tl3+ behave s as a Cl-/OH- exchanger ionophore. Because the kinetics of the proces s did not vary with alterations of the membrane potential of the lipos omes, it was concluded that the reaction is electroneutral, with a Cl- /OH- stoichiometry of 1:1. The results presented could explain some of the toxicological effects, largely unknown to date, of this extremely neurotoxic heavy metal and raise the possibility that thallium could have one of its main neurotoxicological targets in myelin.