title: Zinc reverses glycine-dependent inactivation of NMDARs in cultured rat hippocampal neurons.
abstract: 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 μmol L(-1)) in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 μmol 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.
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yefei
authors.initials: Y
authors.lastname: Li
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D015032:Zinc; D002118:Calcium; D005998:Glycine