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Whole cell and single channel analysis of the kinetics of glycine‐sensitive N‐methyl‐D‐aspartate receptor desensitization
Author(s) -
Parsons Chris G.,
Zong Xiangang,
Lux Hans D.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13556.x
Subject(s) - desensitization (medicine) , nmda receptor , glycine , glycine receptor , 2 amino 5 phosphonovalerate , chemistry , strychnine , agonist , receptor , biophysics , amino acid , biology , biochemistry , excitatory amino acid antagonists
1 The kinetics of glycine‐sensitive, N‐methyl‐ d ‐aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2 The degree of fast NMDA‐receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 n m to 2.5 μ m potentiated desensitized NMDA responses (873% ± 101%) to a greater degree than peak responses (260% ± 27%). 3 The desensitization was due to a decrease in the affinity of glycine for the strychnine‐insensitive, glycine modulatory site (glycine B site) following activation of the NMDA‐receptor complex. Thus, the A 50 for glycine in potentiating peak responses (77 n m , 95% confidence limited 58–104 n m ) was five fold lower than that for plateau responses (399 n m , 340–468 n m ). 4 The rate of desensitization was related to glycine concentration such that a reciprocal plot of desensitization rate (1/τ S −1 ) against glycine concentration had a slope of 9.5* 10 6 M −1 S −1 . 5 Recovery from desensitization following step increases in glycine or l ‐alanine concentration in the continuous presence of NMDA (200 μ m ) reflected the association kinetics of the glycine B agonist used. 6 The rate and degree of NMDA receptor desensitization was independent of holding potential. 7 NMDA receptor desensitization was also evident at the single channel level. 8 The glycine B antagonist 7‐chlorokynurenic acid (7‐Chl‐Kyn 3 and 10 μ m ) concentration‐dependently induced an identical form of desensitization in the presence of 1 μ m glycine. 9 In contrast, the competitive NMDA antagonist (±)‐amino‐phosphonovaleric acid (APV 30 to 300 μ m ) concentration‐dependently antagonized and slowed the onset kinetics of NMDA responses.