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首页> 外文期刊>The European Journal of Neuroscience >Functional evidence for D-serine inhibition of non-N-methyl-D-aspartate ionotropic glutamate receptors in retinal neurons.
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Functional evidence for D-serine inhibition of non-N-methyl-D-aspartate ionotropic glutamate receptors in retinal neurons.

机译：D-丝氨酸抑制视网膜神经元中非N-甲基-D-天冬氨酸离子型谷氨酸受体的功能证据。

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摘要

D-Serine is an important signaling molecule throughout the central nervous system, acting as an N-methyl-D-aspartate (NMDA) receptor coagonist. This study investigated the D-serine modulation of non-NMDA ionotropic glutamate receptors expressed by inner retinal neurons. We first identified that the degradation of endogenous retinal D-serine, by application of D-amino acid oxidase, caused an enhancement of kainate- and α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor-mediated calcium responses from the ganglion cell layer of the isolated rat retina and light-evoked responses obtained by multi-electrode array recordings from the guinea pig retina. Approximately 30-45% of cells were endogenously inhibited by D-serine, as suggested by the effect of D-amino acid oxidase. Conversely, bath application of D-serine caused a reduction in multi-electrode array recorded responses and decreased kainate, but not potassium-induced calcium responses, in a concentration-dependent manner (IC(50), 280 μm). Using cultured retinal ganglion cells to reduce network influences, D-serine reduced kainate-induced calcium responses and AMPA induced whole-cell currents. Finally, the inhibitory effect of D-serine on the kainate-induced calcium response was abolished by IEM 1460, thereby identifying calcium-permeable AMPA receptors as a potential target for D-serine. To our knowledge, this is the first study to address specifically the effect of D-serine on AMPA/kainate receptors in intact central nervous system tissue, to identify its effect on calcium permeable AMPA receptors and to report the endogenous inhibition of AMPA/kainate receptors.
机译：D-丝氨酸是整个中枢神经系统的重要信号分子，充当N-甲基-D-天冬氨酸（NMDA）受体的激动剂。这项研究调查了由内视网膜神经元表达的非NMDA离子型谷氨酸受体的D-丝氨酸调节。我们首先发现，通过应用D-氨基酸氧化酶降解内源性视网膜D-丝氨酸，可增强红藻氨酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体-介导的来自离体大鼠视网膜神经节细胞层的钙反应，以及通过豚鼠视网膜多电极阵列记录获得的光诱发反应。如D-氨基酸氧化酶的作用所暗示，约30-45％的细胞被D-丝氨酸内源性抑制。相反，D-丝氨酸的浴应用以浓度依赖的方式（IC（50），280μm）导致多电极阵列记录的响应减少，而红藻氨酸减少，而不是钾诱导的钙响应减少。使用培养的视网膜神经节细胞减少网络影响，D-丝氨酸可减少红藻氨酸诱导的钙反应和AMPA诱导的全细胞电流。最后，IEM 1460取消了D-丝氨酸对海藻酸盐诱导的钙反应的抑制作用，从而确定了钙可渗透的AMPA受体是D-丝氨酸的潜在靶标。据我们所知，这是第一个专门研究D-丝氨酸对完整的中枢神经系统组织中AMPA /红藻氨酸受体的作用，鉴定其对钙可渗透AMPA受体的作用并报告AMPA /红藻氨酸受体的内源性抑制的研究。 。

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