D-Serine-induced Inactivation of NMDA Receptors in Cultured Rat Hippocampal Neurons Expressing NR2A Subunits is Ca2+-Dependent
D-Serine-induced Inactivation of NMDA Receptors in Cultured Rat Hippocampal Neurons Expressing NR2A Subunits is Ca2+-Dependent
复制标题
D-丝氨酸诱导表达 NR2A 亚基的培养大鼠海马神经元 NMDA 受体失活是 Ca2+ 依赖性的
DOI：
10.1111/cns.12308
复制
发表时间：
2014-11-01
影响因子：
5.5
通讯作者：
Zhang, Yun-Feng
中科院分区：
文献类型：
--
作者：
Li, Xia;Zhang, Yuan-Yuan;Zhang, Yun-Feng
AimsOur 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 NMDARs in cultured rat hippocampal neurons and to investigate the underlying mechanisms of this effect.MethodsCell culture, whole-cell patch-clamp electrophysiology, Ca2+ imaging, immunohistochemistry, and Western blot analysis were used.ResultsWe found that the peak current and Ca2+ influx evoked by 30M NMDA were increased by co-application of D-serine, but those evoked by 300M NMDA were reduced dose-dependently by co-application of D-serine. However, the inhibitory effect of D-serine on NMDAR responses was reversed by ZnCl2 (30nM), an inhibitor of the NR2A subunit, but was less influenced by ifenprodil (10M), 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 10mM BAPTA.ConclusionsD-Serine can also induce inactivation of NMDARs, the NR2A subunit is required for the induction of this effect, and this inactivation is Ca2+-dependent in nature. This action of D-serine is hypothesized to play a neuroprotective role upon a sustained large glutamate insult to the brain.
