Open AccessModulation of N -methyl- d -aspartate receptor function by glycine transport
Author(s) -
Richard Bergeron,
Torsten Meyer,
Joseph T. Coyle,
Robert Greene
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.26.15730
Subject(s) - glycine , nmda receptor , glycine receptor , kynurenic acid , strychnine , 2 amino 5 phosphonovalerate , biochemistry , chemistry , excitatory postsynaptic potential , glutamatergic , biophysics , amino acid , biology , receptor , glutamate receptor , excitatory amino acid antagonists
The recent discovery of glycine transporters in both the central nervous system and the periphery suggests that glycine transport may be critical toN -methyl-d -aspartate receptor (NMDAR) function by controlling glycine concentration at the NMDAR modulatory glycine site. Data obtained from whole-cell patch–clamp recordings of hippocampal pyramidal neurons,in vitro , demonstrated that exogenous glycine and glycine transporter type 1 (GLYT1) antagonist selectively enhanced the amplitude of the NMDA component of a glutamatergic excitatory postsynaptic current. The effect was blocked by 2-amino-5-phosphonovaleric acid and 7-chloro-kynurenic acid but not by strychnine. Thus, the glycine-binding site was not saturated under the control conditions. Furthermore, GLYT1 antagonist enhanced NMDAR function during perfusion with medium containing 10 μM glycine, a concentration similar to that in the cerebrospinal fluidin vivo , thereby supporting the hypothesis that the GLYT1 maintains subsaturating concentration of glycine at synaptically activated NMDAR. The enhancement of NMDAR function by specific GLYT1 antagonism may be a feasible target for therapeutic agents directed toward diseases related to hypofunction of NMDAR.