Hg2+ and Cu+ are ionophores, mediating Cl-/OH- exchange in liposomes and rabbit renal brush border membranes.

Organometals, including organomercurials, are capable of mediating Cl-/OH- exchange across lipid membranes by forming neutral ion pairs. In this study, the ability of inorganic metals to catalyze Cl-/OH- exchange was examined. In the presence of an inwardly directed chloride gradient, HgCl2 at concentrations as low as 30 nM resulted in quenching of acridine orange fluorescence in liposomes, indicating liposomal acidification. In the presence of the reducing agent, ascorbate, CuSO4 at concentrations as low as 0.6 microM also mediated chloride-dependent liposomal acidification. Copper in the absence of ascorbate, iron (with or without ascorbate), cobalt, cadmium, zinc, nickel, and lead were without an effect. 36Cl efflux from rabbit renal brush border membrane vesicles was also markedly stimulated by micromolar concentrations of mercury or copper plus ascorbate. Vesicle integrity was not altered by the concentrations of mercury or copper employed in these studies. In the absence of ascorbate, CuCl stimulated chloride efflux only under anaerobic conditions, confirming that it is the reduced form of copper (Cu+) that mediates chloride transport across the membrane. In the presence of mercury or reduced copper, an inside alkaline pH gradient stimulated the uphill accumulation of 36Cl and 82Br, respectively, confirming Cl-/OH- exchange. Studies in liposomes and brush border membranes demonstrate that this is an electroneutral process. These results show that Hg2+ and Cu+ are capable of acting as ionophores, mediating electroneutral Cl-/OH- exchange in liposomes and brush border membrane vesicles. This effect could contribute to the toxicity of these two metals.