Glutamate uptake triggers transporter-mediated GABA release from astrocytes.
Glutamate uptake triggers transporter-mediated GABA release from astrocytes.
复制标题
谷氨酸摄取触发转运蛋白介导的GABA从星形胶质细胞释放。
DOI：
10.1371/journal.pone.0007153
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发表时间：
2009-09-24
期刊：
影响因子：
3.7
通讯作者：
Kardos J
中科院分区：
文献类型：
--
作者：
Héja L;Barabás P;Nyitrai G;Kékesi KA;Lasztóczi B;Toke O;Tárkányi G;Madsen K;Schousboe A;Dobolyi A;Palkovits M;Kardos J
谷氨酸（Glu）和γ-氨基丁酸（GABA）转运蛋白在调节神经元活动中发挥重要作用。谷氨酸主要通过神经胶质转运蛋白从细胞外空间去除。相比之下，GABA 主要被神经元吸收。然而，神经胶质GABA转运蛋白亚型与Glu转运蛋白具有相同的定位，并且它们的表达仅限于同一星形胶质细胞亚群，这提高了Glu和GABA转运过程之间合作的可能性。在这里，我们使用体外和体内的多种生物模型来探索这些过程之间的相互作用。我们发现星形胶质细胞转运蛋白去除 Glu 会引发细胞外 GABA 水平升高。研究发现，兴奋性和抑制性信号传导之间的这种耦合独立于 Glu 受体介导的去极化、Ca2+ 的外部存在和谷氨酸脱羧酶活性。当神经胶质 Glu 或 GABA 转运蛋白的非转运阻滞剂存在时，它被废除，这表明这些转运蛋白的协同作用是该过程的基础。我们的结果表明，Glu 转运蛋白的激活通过逆转胶质 GABA 转运蛋白导致 GABA 释放。这种转运蛋白介导的相互作用代表了抑制性和兴奋性神经传递之间的直接联系，并且可能作为负反馈来对抗癫痫或缺血等病理条件下的强烈兴奋。
Glutamate (Glu) and γ-aminobutyric acid (GABA) transporters play important roles in regulating neuronal activity. Glu is removed from the extracellular space dominantly by glial transporters. In contrast, GABA is mainly taken up by neurons. However, the glial GABA transporter subtypes share their localization with the Glu transporters and their expression is confined to the same subpopulation of astrocytes, raising the possibility of cooperation between Glu and GABA transport processes. Here we used diverse biological models both in vitro and in vivo to explore the interplay between these processes. We found that removal of Glu by astrocytic transporters triggers an elevation in the extracellular level of GABA. This coupling between excitatory and inhibitory signaling was found to be independent of Glu receptor-mediated depolarization, external presence of Ca2+ and glutamate decarboxylase activity. It was abolished in the presence of non-transportable blockers of glial Glu or GABA transporters, suggesting that the concerted action of these transporters underlies the process. Our results suggest that activation of Glu transporters results in GABA release through reversal of glial GABA transporters. This transporter-mediated interplay represents a direct link between inhibitory and excitatory neurotransmission and may function as a negative feedback combating intense excitation in pathological conditions such as epilepsy or ischemia.
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影响因子：
64.8
作者：
DURING, MJ;RYDER, KM;SPENCER, DD
通讯作者：
SPENCER, DD
影响因子：
2.5
作者：
Kinney, GA
通讯作者：
Kinney, GA
影响因子：
5.8
作者：
KARDOS, J;KOVACS, I;HAJOS, F
通讯作者：
HAJOS, F
影响因子：
4.2
作者：
Kékesi, KA;Szilágyi, N;Kardos, J
通讯作者：
Kardos, J
DOI：
10.1016/j.molbrainres.2005.09.010
发表时间：
2005-12-14
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Doi, T;Ueda, Y;Willmore, LJ
通讯作者：
Willmore, LJ