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首页> 外文期刊>The European Journal of Neuroscience >Transporter-mediated replacement of extracellular glutamate for GABA in the developing murine neocortex
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Transporter-mediated replacement of extracellular glutamate for GABA in the developing murine neocortex

机译：转运蛋白介导的新生小鼠新皮层中GABA的细胞外谷氨酸替代

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During early development, cortical neurons migrate from their places of origin to their final destinations where they differentiate and establish synaptic connections. During corticogenesis, radially migrating cells move from deeper zone to the marginal zone, but they do not invade the latter. This "stop" function of the marginal zone is mediated by a number of factors, including glutamate and gamma-aminobutyric acid (GABA), two main neurotransmitters in the central nervous system. In the marginal zone, GABA has been shown to be released via GABA transporters (GAT)-2/3, whereas glutamate transporters (EAATs) operate in the uptake mode. In this study, GABAergic postsynaptic currents (GPSCs) were recorded from Cajal-Retzius cells in the marginal zone of murine neonatal neocortex using a whole-cell patch-clamp technique. Minimal electrical stimulation was applied to elicit evoked GPSCs using a paired-pulse protocol. EAAT blockade with DL-threo-b-benzyloxyaspartic acid (dl-TBOA), a specific non-transportable EAAT antagonist, abolishes constitutive GAT-2/3-mediated GABA release. In contrast to dl-TBOA, D-aspartate, an EAAT substrate, fails to block GAT-2/3-mediated GABA release. SNAP-5114, a specific GAT-2/3 antagonist, induced an elevation of intracellular sodium concentration ([Na~+]_i) under resting conditions and in the presence of D-aspartate, indicating that GAT-2/3 operates in reverse mode. In the presence of dl-TBOA, however, SNAP-5114 elicited a [Na~+]_j decrease, demonstrating that GAT-2/3 operates in uptake mode. We conclude that EAATs via intracellular Na~+ signaling and/or cell depolarization can govern the strength/direction of GAT-mediated GABA transport.
机译：在早期发育中，皮层神经元从其起源位置迁移到最终目的地，在那里它们分化并建立突触连接。在皮质发生过程中，径向迁移的细胞从更深的区域移动到边缘区域，但它们并未侵入边缘区域。边缘区的“停止”功能由多种因素介导，包括谷氨酸和γ-氨基丁酸（GABA），它们是中枢神经系统中的两种主要神经递质。在边缘地带，已证明GABA是通过GABA转运蛋白（GAT）-2/3释放的，而谷氨酸转运蛋白（EAAT）则以吸收模式运行。在这项研究中，使用全细胞膜片钳技术从鼠新生新生儿皮层边缘区域的Cajal-Retzius细胞记录了GABA能突触后电流（GPSC）。使用成对脉冲协议，将最小的电刺激应用于诱发诱发的GPSC。用DL-苏-b-苄氧基天冬氨酸（dl-TBOA）（一种特定的不可运输的EAAT拮抗剂）进行EAAT阻断，可消除GAT-2 / 3介导的GABA组成型释放。与dl-TBOA不同，D-天冬氨酸（一种EAAT底物）不能阻止GAT-2 / 3介导的GABA释放。 SNAP-5114，一种特定的GAT-2 / 3拮抗剂，在静止条件下和D-天冬氨酸的存在下诱导细胞内钠浓度（[Na〜+] _ i）升高，表明GAT-2 / 3反向运行模式。但是，在存在dl-TBOA的情况下，SNAP-5114引起[Na〜+] _ j的降低，表明GAT-2 / 3以吸收模式运行。我们得出结论，通过细胞内Na +信号传导和/或细胞去极化的EAAT可以控制GAT介导的GABA转运的强度/方向。

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