Abstract
THE N-methyl-D-aspartate (NMDA) receptor channel is highly permeable to Ca2+ but is blocked by Mg2+ in a voltage-dependent manner1–4. These characteristics are essential for the NMDA receptor channel to mediate the induction of long-term potentiation of synaptic efficacy, a form of activity-dependent synaptic plasticity thought to underlie memory, learning and development5–8. Recent studies have revealed the molecular and functional diversity of the NMDA receptor channel subunits, which are classified into the ɛ and ζ families according to the amino-acid sequence homology9–12. Here we report that replacement by glutamine of asparagine 598 in putative transmembrane segment M2 of the ζ1 subunit, strongly reduces the sensitivity of the heteromeric ɛ 2/ζ1 NMDA receptor channel to Mg2+ block. The corresponding mutation of the ɛ2 subunit has a similar effect. Furthermore, the heteromeric ɛ 2/ζl NMDA receptor channel with the mutation on both subunits shows greatly reduced sensitivity to MK-801, a channel blocker of the NMDA receptor channel13,14, but is still susceptible to inhibition by Zn2+15,16. These findings suggest that the conserved asparagine residue in segment M2 constitutes a Mg2+-block site of the NMDA receptor channel, and that the MK-801 site overlaps the Mg2+ site.
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Mori, H., Masaki, H., Yamakura, T. et al. Identification by mutagenesis of a Mg2+ -block site of the NMDA receptor channel. Nature 358, 673–675 (1992). https://doi.org/10.1038/358673a0
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DOI: https://doi.org/10.1038/358673a0
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