Zinc inhibits Ca2+ transport by rat brain NA+/Ca2+ exchanger.
Calcium transport by the Na+/Ca2+ exchanger was measured in plasma membranes vesicles purified from rat brain and in primary rat cortical cell culture. Sodium-loaded vesicles rapidly accumulate Ca2+ via Na+/Ca2+ exchange (Na+(i)-dependent Ca2+ uptake). Extravesicular zinc inhibited Na+/Ca2+ exchange as evidenced by a reduction of the initial velocity of Ca2+ uptake. Significant inhibition of Ca2+ uptake was seen at concentrations of zinc as low as 3 microM. Lineweaver-Burk analysis of the data was consistent with noncompetitive inhibition with respect to extravesicular Ca2+ concentration. The Ki for zinc inhibition of Ca2+ uptake determined from a Dixon plot was 14.5 microM. This is within the range of zinc concentrations thought to be obtained extracellularly after excitation. When vesicles were preloaded with Ca2+, extravesicular zinc also inhibited reversal of Na+/Ca2+ exchange (Na+(i)-dependent Ca2+ release) although its potency was much less: concentrations of > or = 30 microM 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. The extent of inhibition was similar to that seen for inhibition of Na+(i)-dependent Ca2+ uptake in membrane vesicles, but the potency was less. The results suggest that Ca2+ transport by the Na+/Ca2+ exchanger is inhibited by concentrations of zinc thought to be attained extracellularly after excitation.
Colvin
R A
RA
Department of Biological Sciences, Ohio University, Athens, 45701, USA.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004622:Embryo, Mammalian; D051381:Rats; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology*
D019831:Sodium-Calcium Exchanger; D012964:Sodium; D015032:Zinc; D002118:Calcium