Evidence for a zinc/proton antiporter in rat brain

The data presented in this paper are consistent with the existence of a pla sma membrane zinc/proton antiport activity in rat brain. Experiments were p erformed using purified plasma membrane vesicles isolated from whole rat br ain. Incubating vesicles in the presence of various concentrations of Zn-65 (2+) resulted in a rapid accumulation of Zn-65(2+). Hill plot analysis demo nstrated a lack of cooperativity in zinc activation of Zn-65(2+) uptake. Zi nc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or Co2+. Calciu m (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 inhibit ed by increasing extravesicular H+ concentration. Vesicles preloaded with Z n-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 la ck of cooperativity in H+ activation of Zn-65(2+) release. Based on the Hil l analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange a nd Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribu te to the reuptake of zinc to replenish presynaptic vesicle stores after st imulation. (C) 2000 Elsevier Science Ltd. All rights reserved.