Glycine transporter 1 modulates GABA release from amacrine cells by controlling occupancy of coagonist binding site of NMDA receptors.
Glycine transporter 1 modulates GABA release from amacrine cells by controlling occupancy of coagonist binding site of NMDA receptors.
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甘氨酸转运蛋白 1 通过控制 NMDA 受体共激动剂结合位点的占用来调节无长突细胞释放 GABA。
DOI：
10.1152/jn.00193.2013
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发表时间：
2013
影响因子：
2.5
通讯作者：
Vigh,Jozsef
中科院分区：
文献类型：
--
作者：
Rozsa,Eva;Vigh,Jozsef
甘氨酸或丝氨酸对NMDA受体（NMDAR）的促凝剂结合位点的占据被认为介导NMDAR依赖性兴奋性信号传导，因为谷氨酸和促凝剂的同时结合对于NMDAR活化是必需的。在金鱼视网膜中，无长突细胞（AC）介导混合双极细胞（Mbs）的GABA能反馈抑制已被证明表达NMDAR。在这里，我们研究了是否NMDAR介导的GABA能抑制电流（IGABA）记录从轴突末梢的MB的实验操作改变视网膜甘氨酸和d-丝氨酸水平的影响。Mb轴突终末的反馈IGABA由局灶性NMDA应用或由去极化Mb终末突触释放的谷氨酸触发。在这两种情况下，阻断NMDAR的促凝剂结合位点消除了NMDAR依赖性的GABA，表明促凝剂结合在介导NMDAR活性触发的GABA释放中至关重要。甘氨酸转运蛋白1（GLYT 1）抑制增加了IGABA，表明AC上NMDAR的凝血结合位点对Mb提供GABA能反馈抑制并不饱和。在离子型甘氨酸受体阻断剂士的宁的存在下，局灶性甘氨酸应用触发了AC中的GLYT 1依赖性电流，表明由推定的甘氨酸能AC表达的GLYT 1控制NMDAR的凝血受体位点的饱和水平。外部丝氨酸也增加了Mbs中NMDAR激活触发的IGABA，进一步证实了凝血活性位点是不饱和的。总之，我们的研究结果表明，通过NMDAR对GABA能AC的谷氨酸能输入的凝血调节剂调节强烈反映在AC神经元输出中（即，递质释放），因此在内层视网膜中的GABA能信号传递功能中是关键的。
The occupancy of coagonist binding sites of NMDA receptors (NMDARs) by glycine ord-serine has been thought to mediate NMDAR-dependent excitatory signaling, as simultaneous binding of glutamate and a coagonist is obligatory for NMDAR activation. Amacrine cells (ACs) mediating GABAergic feedback inhibition of mixed bipolar cells (Mbs) in the goldfish retina have been shown to express NMDARs. Here we studied whether NMDAR-mediated GABAergic inhibitory currents (IGABA) recorded from the axon terminals of Mbs are influenced by experimental manipulations altering retinal glycine andd-serine levels. FeedbackIGABAin Mb axon terminals was triggered by focal NMDA application or by synaptically released glutamate from depolarized Mb terminals. In both cases, blocking the coagonist binding sites of NMDARs eliminated the NMDAR-dependentIGABA, demonstrating that coagonist binding is critical in mediating NMDAR activity-triggered GABA release. Glycine transporter 1 (GLYT1) inhibition increasedIGABA, indicating that coagonist binding sites of NMDARs on ACs providing GABAergic feedback inhibition to Mbs were not saturated. Focal glycine application, in the presence of the ionotropic glycine receptor blocker strychnine, triggered a GLYT1-dependent current in ACs, suggesting that GLYT1 expressed by putative glycinergic ACs controls the saturation level of NMDARs' coagonist sites. Externald-serine also increased NMDAR activation-triggeredIGABAin Mbs, further substantiating that the coagonist sites were unsaturated. Together, our findings demonstrate that coagonist modulation of glutamatergic input to GABAergic ACs via NMDARs is strongly reflected in the AC neuronal output (i.e., transmitter release) and thus is critical in GABAergic signal transfer function in the inner retina.