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 glyci...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.展开更多
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)
文摘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.
