Abstract
The effects of Zn 2+ on recombinant N-methyl- d-aspartate (NMDA) receptors expressed in Xenopus oocytes were examined. Zn 2+ inhibited macroscopic currents induced by NMDA at both NR1/NR2B and NR1/NR2A receptors. At NR1/NR2B receptors the Zn 2+ concentration-inhibition curve was monophasic, with an apparent affinity for Zn 2+ of 1.6 μM, and inhibition by Zn 2+ was not voltage-dependent. In contrast, the Zn 2+ concentration-inhibition curve at NR1/NR2A receptors was biphasic, with high ( K i=0.08 μM) and low ( K i=30 μM) affinity components. The high affinity component produced a maximal inhibition of 45% of macroscopic NMDA currents and was not voltage-dependent. Thus, Zn 2+ is more potent in producing voltage-independent block at NR1/NR2A than at NR1/NR2B receptors, but the maximal effect of Zn 2+ is smaller at NR1/NR2A than at NR1/NR2B receptors. The low affinity component of Zn 2+ inhibition at NR1/NR2A receptors was voltage-dependent and may represent an open-channel blocking effect of Zn 2+. Differential effects of Zn 2+ at recombinant NMDA receptors containing different NR2 subunits provide a potential marker for distinguishing subtypes of native NMDA receptors and for dissecting the site and mechanism of action of Zn 2+ at these receptors.
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