Zinc reverses glycine-dependent inactivation of NMDARs in cultured rat hippocampal neurons  

作　　者：LI Xia CHEN ZhaoQin JIANG Zheng LI YeFei ZHANG YunFeng 

机构地区：[1]Institute of Nautical Medicine, Nantong University, Nantong 226001, China [2]Zhejiang University School of Medicine, Hangzhou 310058, China [3]Affiliated Hospital of Nantong University, Nantong 226007, China

出　　处：《Science China(Life Sciences)》2012年第12期1075-1081,共7页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China (Grant No. J20110170);the National Natural Science Foundation of China (Grant Nos. 81000497 and 81071614)

摘　　要：In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor （NMDAR） plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glycine could inhibit NMDAR respons- es induced by high concentration of NMDA in hippocampal neurons. The mechanism underlying this inhibitory impact, how- ever, has been unclear. In this study, the whole-cell patch-clamp recording and Ca2＋ imaging with Fluo-3/AM under laser scanning confocal microscope were used to analyze the possible involvement of NMDAR subnnits in this effect. We found that the peak current of NMDARs and Ca2＋ influx induced by high concentration of NMDA were reduced by treatment of gly- cine （0.03-10 I.tmol L-1） in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mol L-1 NMDA, was reversed by ZnCI2 through the blocking of the NR2A subunit of NMDARs, but was less influenced by ifenprodil, a NR2B inhibitor. Our results suggest that the glycine-dependent inactivation of NMDARs is potentially modulated by the regulatory subunit NR2A.In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor (NMDAR) plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glycine could inhibit NMDAR responses induced by high concentration of NMDA in hippocampal neurons. The mechanism underlying this inhibitory impact, how- ever, has been unclear. In this study, the whole-cell patch-clamp recording and Ca 2+ imaging with Fluo-3/AM under laser scanning confocal microscope were used to analyze the possible involvement of NMDAR subunits in this effect. We found that the peak current of NMDARs and Ca 2+ influx induced by high concentration of NMDA were reduced by treatment of glycine (0.03-10 mol L 1 ) in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mol L 1 NMDA, was reversed by ZnCl 2 through the blocking of the NR2A subunit of NMDARs, but was less influenced by ifenprodil, a NR2B inhibitor. Our results suggest that the glycine-dependent inactivation of NMDARs is potentially modulated by the regulatory subunit NR2A.

关 键 词：N-methyI-D-aspartate （NMDA） NMDARs （NMDARs） GLYCINE ZINC INACTIVATION hippocampal neurons 

分 类 号：Q426[生物学—神经生物学] TQ226.36[生物学—生理学]