PMID: 9187268Jun 1, 1997Paper

Differential sensitivity of recombinant N-methyl-D-aspartate receptor subtypes to zinc inhibition

Molecular Pharmacology
N ChenL A Raymond

Abstract

Zinc has been shown to be present in synaptic vesicles of a subset of glutamatergic boutons and is believed to be core-leased with glutamate at these synapses. A variety of studies have suggested that zinc might play a role in modulation of excitatory transmission, as well as excitotoxicity, by inhibiting N-methyl-D-aspartate (NMDA)-type glutamate receptors. To further investigate the modulatory effects of zinc on NMDA receptors of different subunit compositions, we coexpressed the recombinant subunit NR1 with NR2A and/or NR2B in HEK 293 cells. In whole-cell patch-clamp recordings from these transfected cells, zinc inhibited peak glutamate-evoked current responses in a noncompetitive manner, but there were significant differences between the receptor subtypes in sensitivity to zinc inhibition. For NR1/NR2A, approximately 40% of the peak current was inhibited by zinc in a voltage-independent manner with an IC50 value of 5.0 +/- 1.6 nM and at a V(H) value of -60 mV; the remainder was blocked at a second, voltage-dependent site with an IC50 value of 79 +/- 18 microM. In contrast, NR1/NR2B currents showed nearly complete inhibition at a voltage-independent site with an IC50 value of 9.5 +/- 3.3 microM. Cells cotransfected with NR1,...Continue Reading

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Citations

May 10, 2000·The Journal of Nutrition·R A ColvinP A Carter
Dec 26, 2001·Molecular Pharmacology·Gayathri SwaminathTae Weon Lee
Jan 15, 2004·Molecular Pharmacology·Nansheng ChenLynn A Raymond
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