Abstract
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 65Zn 2+ resulted in a rapid accumulation of 65Zn 2+. Hill plot analysis demonstrated a lack of cooperativity in zinc activation of 65Zn 2+ uptake. Zinc uptake was inhibited in the presence of 1 mM Ni 2+, Cd 2+, or Co 2+. Calcium (1 mM) was less effective at inhibiting 65Zn 2+ uptake and Mg 2+ and Mn 2+ had no effect. The initial rate of vesicular 65Zn 2+ uptake was inhibited by increasing extravesicular H + concentration. Vesicles preloaded with 65Zn 2+ could be induced to release 65Zn 2+ by increasing extravesicular H + or addition of 1 mM nonradioactive Zn 2+. Hill plot analysis showed a lack of cooperativity in H + activation of 65Zn 2+ release. Based on the Hill analyses, the stoichiometry of transport may include Zn 2+/Zn 2+ exchange and Zn 2+/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.
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