Open AccessD‐Serine‐induced Inactivation of NMDA Receptors in Cultured Rat Hippocampal Neurons Expressing NR 2A Subunits is Ca 2+ ‐Dependent
Author(s) -
Li Xia,
Zhang YuanYuan,
Chen ZhaoQin,
Jiang ZhengLin,
Sun Li,
Xu LiHua,
Yang Yao,
Zhang YunFeng
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12308
Subject(s) - nmda receptor , ifenprodil , hippocampal formation , serine , glutamate receptor , bapta , chemistry , excitatory postsynaptic potential , neuroprotection , glycine , neuroscience , protein subunit , inhibitory postsynaptic potential , microbiology and biotechnology , receptor , patch clamp , biology , biochemistry , phosphorylation , amino acid , gene
Summary Aims Our previous studies indicate that glycine can inhibit N‐methyl‐D‐aspartate receptor ( NMDAR ) responses induced by high concentrations of NMDA in rat hippocampal neurons. The present study was designed to observe whether D‐serine induces inactivation of NMDAR s in cultured rat hippocampal neurons and to investigate the underlying mechanisms of this effect. Methods Cell culture, whole‐cell patch‐clamp electrophysiology, Ca 2+ imaging, immunohistochemistry, and Western blot analysis were used. Results We found that the peak current and Ca 2+ influx evoked by 30 μ M NMDA were increased by co‐application of D‐serine, but those evoked by 300 μ M NMDA were reduced dose‐dependently by co‐application of D‐serine. However, the inhibitory effect of D‐serine on NMDAR responses was reversed by ZnCl 2 (30 nM), an inhibitor of the NR2A subunit, but was less influenced by ifenprodil (10 μ M), an NR2B inhibitor. In addition, the inhibitory effect of D‐serine was not detected in young hippocampal neurons that expressed less of the NR2A subunits and reversed in the presence of 10 mM BAPTA. Conclusions D‐Serine can also induce inactivation of NMDAR s, the NR 2A subunit is required for the induction of this effect, and this inactivation is Ca 2+ ‐dependent in nature. This action of D‐serine is hypothesized to play a neuroprotective role upon a sustained large glutamate insult to the brain.