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大鼠孤束核中的兴奋性氨基酸转运体1(EAAC1):亚细胞定位表明其在谷氨酸清除中无主要作用。

The excitatory amino acid carrier 1 (EAAC1) in the rat nucleus of the solitary tract: subcellular localization suggests no major role in glutamate clearance.

作者信息

Chounlamountry Keodavanh, Castets Francis, Tell Fabien, Kessler Jean-Pierre

机构信息

Aix Marseille Université, CNRS, CRN2M UMR 7286, 51 Bd Pierre Dramard, CS80011, 13344, Marseille Cedex 15, France.

出版信息

Brain Struct Funct. 2016 Mar;221(2):1113-24. doi: 10.1007/s00429-014-0958-7. Epub 2014 Dec 11.

DOI:10.1007/s00429-014-0958-7
PMID:25515313
Abstract

The excitatory amino acid carrier 1 (EAAC1) is a sodium-dependent glutamate transporter widely found in the mammalian brain and mainly localized in the somatodendritic compartment of neurons. The present study was performed to determine whether EAAC1 is present in the rat nucleus of the solitary tract (NST, a sensory brainstem nucleus involved in visceroception) and to document its subcellular localization. Using fluorescent immunolabeling, peroxidase immunostaining and quantitative immunogold labeling, we showed that both intracellular and plasma membrane-associated pools of EAAC1 transporters existed in dendrites of NST neurons. Although plasma membrane-associated transporters were more concentrated in the vicinity of synapses, no labeling was found at the axon-dendrite interface, suggesting that EAAC1 was not (or barely) expressed in this portion of dendritic membrane. Using computer simulation, we next showed that the ability of EAAC1 to efficiently take up synaptically released glutamate was very low outside the axon-dendrite interface. These data suggest that EAAC1 transporters present on NST dendrites may play a minor role if any in glutamate clearance.

摘要

兴奋性氨基酸转运体1(EAAC1)是一种依赖于钠的谷氨酸转运体,广泛存在于哺乳动物大脑中,主要定位于神经元的树突-胞体部分。本研究旨在确定EAAC1是否存在于大鼠孤束核(NST,参与内脏感觉的感觉性脑干核)中,并记录其亚细胞定位。通过荧光免疫标记、过氧化物酶免疫染色和定量免疫金标记,我们发现NST神经元树突中存在细胞内和与质膜相关的EAAC1转运体池。虽然质膜相关转运体在突触附近更为集中,但在轴突-树突界面未发现标记,这表明EAAC1在树突膜的这一部分未(或几乎未)表达。通过计算机模拟,我们接下来表明,在轴突-树突界面之外,EAAC1有效摄取突触释放的谷氨酸的能力非常低。这些数据表明,NST树突上存在的EAAC1转运体即使有作用,在谷氨酸清除中也可能起次要作用。

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引用本文的文献

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Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate.孤束核中胶质细胞谷氨酸转运体GLT1的抑制作用减弱了压力反射对交感神经活动和心率的控制。
Physiol Rep. 2018 Sep;6(18):e13877. doi: 10.14814/phy2.13877.
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Glial EAAT2 regulation of extracellular nTS glutamate critically controls neuronal activity and cardiorespiratory reflexes.
神经胶质细胞EAAT2对细胞外孤束核谷氨酸的调节严格控制神经元活动和心肺反射。
J Physiol. 2017 Sep 1;595(17):6045-6063. doi: 10.1113/JP274620. Epub 2017 Aug 2.
4
Reduced responses to glutamate receptor agonists follow loss of astrocytes and astroglial glutamate markers in the nucleus tractus solitarii.孤束核中星形胶质细胞和星形胶质细胞谷氨酸标志物缺失后,对谷氨酸受体激动剂的反应减弱。
Physiol Rep. 2017 Mar;5(5). doi: 10.14814/phy2.13158.
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Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function.兴奋性氨基酸转运体持续抑制孤束核突触和神经元活动,以调节心肺功能。
J Neurophysiol. 2016 Mar;115(3):1691-702. doi: 10.1152/jn.01054.2015. Epub 2015 Dec 30.