Maxi-anion channels play a key role in glutamate-induced ATP release from mouse astrocytes in primary culture
Maxi-anion channels play a key role in glutamate-induced ATP release from mouse astrocytes in primary culture
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Maxi 阴离子通道在原代培养中谷氨酸诱导的小鼠星形胶质细胞 ATP 释放中发挥关键作用
DOI：
10.1097/wnr.0000000000000759
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发表时间：
2017-05
期刊：
影响因子：
1.7
通讯作者：
Hongtao Liu
中科院分区：
文献类型：
--
作者：
Bin Zhao;Hongtao Liu
星形胶质细胞是ATP的丰富来源，在各种情况下，ATP可能从细胞质中释放到细胞外空间，甚至在某些情况下影响细胞的命运。在本研究中，我们旨在评估谷氨酸诱导的小鼠星形胶质细胞释放ATP的途径。首先，我们对培养的星形胶质细胞的研究显示，不同浓度（0.1-1 mM）谷氨酸刺激下ATP释放明显，且在时间过程上呈有趣的双峰分布。ATP释放的潜在途径如胞外囊泡释放、间隙连接半通道、P2X7受体和体积敏感的外整流氯离子通道的抑制剂或阻滞剂对观察到的ATP释放没有显著影响。相反，谷氨酸诱导的星形胶质细胞ATP释放被gadolinium（50µM）显著抑制，gadolinium是一种最大阴离子通道抑制剂；同时，钆对谷氨酸诱导的细胞损伤有明显的缓解作用。因此，我们认为最大阴离子通道可能在谷氨酸诱导的小鼠星形胶质细胞ATP释放中发挥重要作用，抑制最大阴离子通道活性以减少ATP释放可以在谷氨酸刺激下产生保护作用。
Astrocytes are an abundant source of ATP, which might be released from the cytosol into extracellular spaces under various conditions and even affect cell fate under some circumstances. In the present study, we aimed to evaluate the pathway(s) contributing toward glutamate-induced ATP release from mouse astrocytes. Firstly, our study of cultured astrocytes showed marked ATP release in response to stimuli of glutamate at different concentrations (0.1–1 mM), with an interesting bimodal distribution in time course. Inhibitors or blockers of potential pathways for ATP release such as exocytotic vesicular release, gap junction hemichannels, P2X7 receptors, and volume-sensitive outwardly rectifying chloride channels had no significant effects on the observed ATP release. In contrast, glutamate-induced ATP release from astrocytes was significantly inhibited by gadolinium (50 µM), an inhibitor of a maxi-anion channel; meanwhile, the application of gadolinium can allay glutamate-induced cell injury significantly. Thus, we propose that the maxi-anion channel might play an important role in glutamate-induced ATP release from mouse astrocytes and inhibition of maxi-anion channel activities to reduce ATP release can produce protective effects in the case of glutamate stimuli.
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ATP通过阴离子通道释放。
影响因子：
3.5
作者：
Sabirov, Ravshan Z;Okada, Yasunobu
通讯作者：
Okada, Yasunobu
影响因子：
6.2
作者：
Shinozaki, Y;Koizumi, S;Inoue, K
通讯作者：
Inoue, K
DOI：
10.1073/pnas.95.26.15735
发表时间：
1998-12-22
影响因子：
11.1
作者：
Cotrina, ML;Lin, JHC;Nedergaard, M
通讯作者：
Nedergaard, M
DOI：
10.1085/jgp.118.3.251
发表时间：
2001-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Sabirov RZ;Dutta AK;Okada Y
通讯作者：
Okada Y
影响因子：
4.8
作者：
Coco, S;Calegari, F;Verderio, C
通讯作者：
Verderio, C