Evaluation of agonist selectivity for the NMDA receptor ion channel in bilayer lipid membranes based on integrated single-channel currents

Ayumi Hirano, Masao Sugawara, Yoshio Umezawa, Shigeo Uchino, Sadayo Nakajima-Iijima

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A new method for evaluating chemical selectivity of agonists to activate the N-methyl-D-aspartate (NMDA) receptor was presented by using typical agonists NMDA, L-glutamate and (2S, 3R, 4S)-2-(carboxycyclopropyl)glycine (L-CCG-IV) and the mouse ε1/ζ1 NMDA receptor incorporated in bilayer lipid membranes (BLMs) as an illustrative example. The method was based on the magnitude of an agonist-induced integrated single-channel current corresponding to the number of total ions passed through the open channel. The very magnitudes of the integrated single-channel currents were compared with the different BLMs as a new measure of agonist selectivity. The ε1/ζ1 NMDA receptor was partially purified from Chinese hamster ovary (CHO) cells expressing the ε1/ζ1 NMDA receptor and incorporated in BLMs formed by the tip-dip method. The agonist-induced integrated single-channel currents were obtained at 50 μM agonist concentration, where the integrated current for NMDA was shown to reach its saturated value. The obtained integrated currents were found to be (4.5±0.55)x10-13 C/s for NMDA, (5.8±0.72)x10-13 C/s for L-glutamate and (6.6±0.61)x10-13 C/s for L-CCG-IV, respectively. These results suggest that the agonist selectivity in terms of the total ion flux through the single ε1/ζ1 NMDA receptor is in the order of L-CCG-IV~L-glutamate>NMDA. Copyright (C) 2000 Elsevier Science S.A.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalBiosensors and Bioelectronics
Volume15
Issue number3-4
DOIs
Publication statusPublished - 2000 Jun 1
Externally publishedYes

Keywords

  • (2S, 3R, 4S)-2-(carboxycyclopropyl)glycine
  • Agonist selectivity
  • L-Glutamate
  • N-Methyl-D-aspartate
  • Tip-dip method
  • ε1/ζ1 N-Methyl-D-aspartate receptor channel

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biomedical Engineering
  • Electrochemistry

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