Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor

K. Sakurada, M. Masu, S. Nakanishi

研究成果: Article査読

139 被引用数 (Scopus)

抄録

The N-methyl-D-aspartate (NMDA) receptor plays an important role in glutamate-mediated neuronal plasticity and neurotoxicity in the central nervous system. This receptor is composed of a fundamental subunit (NMDAR1) and its potentiating subunits (NMDAR2A-NMDAR2D). The NMDA receptor is distinct from other glutamate receptor channels because of its high Ca2+ permeability and inhibition by selective cationic channel blockers such as Mg2+, Zn2+, and MK-801. In this study, we investigated the structural features that control Ca2+ permeation and channel blockade of the NMDA receptor by in vitro mutagenesis and expression in Xenopus oocytes. We constructed a series of mutations with single amino acid substitutions in the second transmembrane segment of NMDAR1 and examined channel properties of the resultant mutants in combined expression with the NMDAR2A subunit. Substitution of the asparagine with either glutamine or arginine altered both the Ca2+ permeability and the sensitivity to blockades by Mg2+ and MK- 801. These mutations also reduced the inhibitory effects of Zn2+ and an antidepressant, desipramine. Based on these results, we concluded that an asparagine ring formed in the central part of the channel-forming second transmembrane segments plays a critical role in determining the Ca2+ permeability and the inhibition of open channel blockers.

本文言語English
ページ(範囲)410-415
ページ数6
ジャーナルJournal of Biological Chemistry
268
1
出版ステータスPublished - 1993
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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