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.
LI XiaCHEN ZhaoQinJIANG ZhengLI YeFeiZHANG YunFeng
