ZINC INHIBITS CA2-BRAIN NA+( TRANSPORT BY RAT)CA2+ EXCHANGER/

CALCIUM transport by the Na+/Ca2+ exchanger was measured in plasma mem branes vesicles purified from rat brain and in primary rat cortical ce ll culture. Sodium-loaded vesicles rapidly accumulate Ca2+ via Na+/Ca2 + exchange (Na-i(+)-dependent Ca2+ uptake). Extravesicular zinc inhibi ted Na+/Ca2+ exchange as evidenced by a reduction of the initial veloc ity of Ca2+ uptake. Significant inhibition of Ca2+ uptake was seen at concentrations of zinc as low as 3 mu M. Lineweaver-Burk analysis of t he data was consistent with noncompetitive inhibition with respect to extravesicular Ca2+ concentration. The K-i for zinc inhibition of Ca2 uptake determined from a Dixon plot was 14.5 mu M. This is within the range of zinc concentrations thought to be obtained extracellularly a fter excitation. When vesicles were preloaded with Ca2+, extravesicula r zinc also inhibited reversal of Na+/Ca2+ exchange (Na-o(+)-dependent Ca2+ release) although its potency was much less: concentrations of g reater than or equal to 30 mu M zinc were required. Zinc inhibition of Ca2+ release was not Na+ dependent. Na-i(+)-dependent calcium uptake by rat cortical cells in primary culture also was inhibited by zinc. T he extent of inhibition was similar to that seen for inhibition of Na- i(+)-dependent Ca2+ uptake in membrane vesicles, but the potency was l ess. The results suggest that Ca2+ transport by the Na+/Ca2+ exchanger is inhibited by concentrations of zinc thought to be attained extrace llularly after excitation. NeuroReport 9: 3091-3096 (C) 1998 Lippincot t Williams & Wilkins.