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星形胶质细胞系 GL261 通过细胞内离子环境的改变释放谷氨酸。

Glutamate release from astrocyte cell-line GL261 via alterations in the intracellular ion environment.

机构信息

Department of Brain Function, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan.

出版信息

J Neural Transm (Vienna). 2014;121(3):245-57. doi: 10.1007/s00702-013-1096-8. Epub 2013 Oct 8.

DOI:10.1007/s00702-013-1096-8
PMID:24100416
Abstract

Astrocytes modify and maintain neural activity and functions via gliotransmitter release such as, glutamate. They also change their properties and functions in response to alterations of ion environment resulting from neurotransmission; however, the direct evidence for whether intracellular ion alteration in astrocytes triggers gliotransmitter release is not indicated. Recent studies have reported that channelrhodopsin-2 (ChR2) is useful for alteration of intracellular ion environment in several types of cells with blue light exposure. Here, we show that ChR2-expressing GL261 (GLChR2) cells, clonal astrocytes, change their properties by photo-activation. Increased intracellular sodium and calcium ion concentrations and an altered membrane potential were observed in GLChR2 cells with blue light exposure. Alterations in the intracellular ion environment caused intracellular acidification and the inhibition of proliferation. In addition, it triggered glutamate release from GLChR2 cells. Glutamate from GLChR2 cells acted on N18 cells, clonal neuronal cells, as both a transmitter and neurotoxin depending on photo-activation. Our results show that the properties of ChR2-expressing astrocytes can be controlled by blue light exposure, and cation influx through photo-activated ChR2 might trigger functional cation influx via endogenous channels and result in the increase of glutamate release. Further, our results suggest that ChR2-expressing glial cells could become a useful tool in understanding the roles of glial cell activation and neural communication in the regulation of brain functions.

摘要

星形胶质细胞通过神经递质释放(如谷氨酸)来调节和维持神经活动和功能。它们还会根据神经传递引起的离子环境变化改变自身特性和功能;然而,目前尚无直接证据表明星形胶质细胞内离子变化是否会触发神经递质释放。最近的研究报告称,通道视紫红质 2(ChR2)在暴露于蓝光时可用于改变多种类型细胞的细胞内离子环境。在这里,我们展示了表达 ChR2 的 GL261(GLChR2)细胞,克隆星形胶质细胞,通过光激活改变其特性。在 GLChR2 细胞暴露于蓝光时,观察到细胞内钠离子和钙离子浓度增加以及膜电位改变。细胞内离子环境的改变导致细胞内酸化和增殖抑制。此外,它还触发了 GLChR2 细胞的谷氨酸释放。来自 GLChR2 细胞的谷氨酸作用于 N18 细胞,克隆神经元细胞,根据光激活,谷氨酸既是递质又是神经毒素。我们的结果表明,表达 ChR2 的星形胶质细胞的特性可以通过暴露于蓝光来控制,并且通过光激活的 ChR2 内流的阳离子可能会通过内源性通道触发功能性阳离子内流,从而增加谷氨酸释放。此外,我们的结果表明,表达 ChR2 的神经胶质细胞可能成为理解神经胶质细胞激活和神经通讯在大脑功能调节中的作用的有用工具。

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