Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses
Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses
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DOI：
10.1152/jn.1998.80.6.3336
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发表时间：
1998-12-01
影响因子：
2.5
通讯作者：
Ascher, P
中科院分区：
文献类型：
--
作者：
Berger, AJ;Dieudonné, S;Ascher, P
在中枢突触中，N-甲基-D-天冬氨酸受体（NMDA-Rs）的甘氨酸结合位点的占据是兴奋性神经递质谷氨酸激活这些受体的必要前提。关于甘氨酸结合位点是否通常是饱和的，存在相互矛盾的证据。如果它们不是，那么局部甘氨酸浓度的改变可以调节兴奋性突触传递。通过使用在体外脑干切片制备，我们调查了甘氨酸网站是否饱和的突触激活NMDA-Rs在新生大鼠舌下神经运动神经元。我们发现，NMDA-R介导的自发性微型兴奋性突触后电流的组成部分可以增强外源性应用甘氨酸以及D-丝氨酸。甘氨酸的影响，观察到只有在浓度（100 μ M或以上）两个数量级以上的表观解离常数的甘氨酸从NMDA受体。相反，D-丝氨酸，一种非转运的NMDA-R甘氨酸位点激动剂，在低微摩尔范围内有效，即，其浓度类似于对分离的细胞或外向贴片有效的浓度。我们的结论是，在这些突触周围的突触NMDA-R的甘氨酸浓度设置低于饱和其甘氨酸位点所需的浓度，很可能是稳定的一个强大的甘氨酸转运机制。
At central synapses occupation of glycine binding sites of N-methyl-D-aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites normally are saturated. If they are not, then alterations in local glycine concentration could modulate excitatory synaptic transmission. By using an in vitro brain stem slice preparation we investigated whether the glycine site is saturated for synaptically activated NMDA-Rs in neonatal rat hypoglossal motoneurons. We found that the NMDA-R-mediated component of spontaneous miniature excitatory postsynaptic currents could be potentiated by exogenously applied glycine as well as by D-serine. The effects of glycine were observed only at concentrations (100 mu M or more) two orders of magnitude above the apparent dissociation constant of glycine from NMDA receptors. In contrast, D-serine, a nontransported NMDA-R glycine site agonist, was effective in the low micromolar range, i.e., at concentrations similar to those found to be effective on isolated cells or on outside-out patches. We conclude that at these synapses the glycine concentration around synaptic NMDA-Rs is set below the concentration required to saturate their glycine site and is Likely to be stabilized by a powerful glycine transport mechanism.