Zhang Long-Hua, Gong Neng, Fei Da, Xu Lin, Xu Tian-Le
Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Neuropsychopharmacology. 2008 Feb;33(3):701-11. doi: 10.1038/sj.npp.1301449. Epub 2007 May 23.
Functional glycine receptors (GlyRs) are enriched in the hippocampus, but their role in hippocampal function remains unclear. Since the concentration of ambient glycine is determined by the presence of powerful glycine transporter (GlyT), we blocked the reuptake of glycine in hippocampal slices to examine the role of GlyRs. Antagonists of GlyT type 1 (GlyT1) but not that of GlyT type 2 (GlyT2) induced excitatory postsynaptic potential (EPSP)-spike depression, which was reversed by the specific GlyR antagonist strychnine. Moreover, endogenously elevating the glycine concentration with the GlyT1 antagonists facilitated NMDA receptor-dependent long-term potentiation induction, and elicited a strychnine-sensitive chloride current. In addition, impairment of glial function with fluoroacetate blocked the effect of GlyT1 antagonists on the EPSP-spike curve. Furthermore, pretreatment with sarcosine was effective in controlling pentylenetetrazol-induced seizures. These results indicate an essential role of GlyTs in fine-tuning tonic activation of GlyRs and suggest a potential role of GlyR-dependent EPSP-spike depression in hippocampal network stability.
功能性甘氨酸受体（GlyRs）在海马体中含量丰富，但其在海马体功能中的作用仍不清楚。由于细胞外甘氨酸的浓度由强大的甘氨酸转运体（GlyT）决定，我们阻断了海马体切片中甘氨酸的再摄取，以研究GlyRs的作用。1型甘氨酸转运体（GlyT1）的拮抗剂而非2型甘氨酸转运体（GlyT2）的拮抗剂可诱导兴奋性突触后电位（EPSP）-峰电位抑制，该抑制可被特异性GlyR拮抗剂士的宁逆转。此外，用GlyT1拮抗剂内源性提高甘氨酸浓度可促进N-甲基-D-天冬氨酸受体（NMDA受体）依赖性的长时程增强诱导，并引发士的宁敏感的氯离子电流。此外，用氟乙酸损害胶质细胞功能可阻断GlyT1拮抗剂对EPSP-峰电位曲线的影响。此外，用肌氨酸预处理可有效控制戊四氮诱导的癫痫发作。这些结果表明GlyT在微调GlyRs的强直激活中起重要作用，并提示GlyR依赖性EPSP-峰电位抑制在海马体网络稳定性中具有潜在作用。
