Glycine regulation of synaptic NMDA receptors in hippocampal neurons.

Glycine regulation of synaptic NMDA receptors in hippocampal neurons.
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海马神经元突触 NMDA 受体的甘氨酸调节。

DOI:
10.1152/jn.1996.76.5.3415
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发表时间:
1996
期刊:
Journal of neurophysiology.
影响因子:
--
通讯作者:
Dichter,MA
Dichter,MA
中科院分区:
--
文献类型:
--
作者:
Wilcox,KS;Fitzsimonds,RM;Johnson,B;Dichter,MA

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1.虽然甘氨酸已被确定为N-甲基-D-天冬氨酸(NMDA)受体上谷氨酸的必需促凝剂,但对甘氨酸在兴奋性突触神经传递中的作用的理解非常有限。在本研究中,我们使用全细胞膜片钳技术研究甘氨酸调节电流通过突触NMDA受体在兴奋性突触培养的海马神经元之间的能力,在急性分离的海马脑片。2.这些研究表明,在基线条件下,突触NMDA受体上的甘氨酸调节位点是不饱和的,并且在分离的细胞培养物和切片中,增加甘氨酸浓度可以显著增加海马神经元中NMDA受体介导的兴奋性突触后电流(EPSC)。饱和的甘氨酸的最大作用发生在不同浓度的不同细胞在文化中,表明存在的异质性NMDA受体亚基组合物。3.在脑切片或培养物中,连续施用的甘氨酸对EPSC的时间过程没有影响,表明在EPSC的时间过程中,甘氨酸不能阻止NMDA受体的脱敏。4.当细胞外甘氨酸浓度高时,在培养的海马神经元中记录的所有微型EPSC都含有NMDA成分,这表明在单个突触终扣处不发生非NMDA受体的分离。
1. Although glycine has been identified as a required coagonist with glutamate at N-methyl-D-aspartate (NMDA) receptors, the understanding of glycine's role in excitatory synaptic neurotransmission is quite limited. In the present study, we used the whole cell patch-clamp technique to examine the ability of glycine to regulate current flow through synaptic NMDA receptors at excitatory synapses between cultured hippocampal neurons and in acutely isolated hippocampal slices. 2. These studies demonstrate that the glycine modulatory site on the synaptic NMDA receptor is not saturated under baseline conditions and that increased glycine concentrations can markedly increased NMDA-receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal neurons in both dissociated cell culture and in slice. Saturation of the maximal effect of glycine takes place at different concentrations for different cells in culture, suggesting the presence of heterogenous NMDA receptor subunit compositions. 3. Bath-applied glycine had no effect on the time course of EPSCs in either brain slice or culture, indicating that desensitization of the NMDA receptor is not prevented by glycine over the time course of an EPSC. 4. When extracellular glycine concentration is high, all miniature EPSCs recorded in the cultured hippocampal neurons contained NMDA components, indicating that segregation of non-NMDA receptors at individual synaptic boutons does not occur.