PMID- 23233222 OWN - NLM STAT- MEDLINE DCOM- 20130517 LR - 20131121 IS - 1869-1889 (Electronic) IS - 1674-7305 (Linking) VI - 55 IP - 12 DP - 2012 Dec TI - Zinc reverses glycine-dependent inactivation of NMDARs in cultured rat hippocampal neurons. PG - 1075-81 LID - 10.1007/s11427-012-4421-9 [doi] AB - 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, however, 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 mumol L(-1)) in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mumol 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. FAU - Li, Xia AU - Li X AD - Institute of Nautical Medicine, Nantong University, Nantong 226001, China. FAU - Chen, Zhaoqin AU - Chen Z FAU - Jiang, Zhenglin AU - Jiang Z FAU - Li, Yefei AU - Li Y FAU - Zhang, Yunfeng AU - Zhang Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121212 PL - China TA - Sci China Life Sci JT - Science China. Life sciences JID - 101529880 RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - J41CSQ7QDS (Zinc) RN - SY7Q814VUP (Calcium) RN - TE7660XO1C (Glycine) SB - IM MH - Animals MH - Calcium/metabolism MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Glycine/*pharmacology MH - Hippocampus/cytology/*drug effects/metabolism MH - Neurons/*drug effects/metabolism MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors MH - Zinc/*pharmacology EDAT- 2012/12/13 06:00 MHDA- 2013/05/18 06:00 CRDT- 2012/12/13 06:00 PHST- 2012/11/16 00:00 [received] PHST- 2012/11/26 00:00 [accepted] PHST- 2012/12/13 06:00 [entrez] PHST- 2012/12/13 06:00 [pubmed] PHST- 2013/05/18 06:00 [medline] AID - 10.1007/s11427-012-4421-9 [doi] PST - ppublish SO - Sci China Life Sci. 2012 Dec;55(12):1075-81. doi: 10.1007/s11427-012-4421-9. Epub 2012 Dec 12.