Evidence for a zinc/proton antiporter in rat brain

The data presented in this paper are consistent with the existence of a plasma membrane zinc/proton antiport activity in rat brain. Experiments were performed using purified plasma membrane vesicles isolated from whole rat brain. Incubating vesicles in the presence of various concentrations of Zn-65(2+) resulted in a rapid accumulation of Zn-65(2+). Hill plot analysis demonstrated a lack of cooperativity in zinc activation of Zn-65(2+) uptake. Zinc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or Co2+. Calcium (1 mM) was less effective at inhibiting Zn-65(2+) uptake and Mg2+ and Mn2+ had no effect. The initial rate of vesicular Zn-65(2+) uptake was inhibited by increasing extravesicular H+ concentration. Vesicles preloaded with Zn-65(2+) could be induced to release Zn-65(2+) by increasing extravesicular HC or addition of 1 mM nonradioactive Zn2+. Hill plot analysis showed a lack of cooperativity in H+ activation of Zn-65(2+) release. Based on the Hill analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange and Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribute to the reuptake of zinc to replenish presynaptic vesicle stores after stimulation. (C) 2000 Elsevier Science Ltd. All rights reserved.