Zhao Bin, Gu Li, Liu Kaixi, Zhang Mingming, Liu Hongtao
aDepartment of Anesthesiology, Shengjing Hospital bDepartment of Brain Metabolic Disease, Institute of Metabolic Disease Research and Drug Development cDepartment of Anesthesiology, Hospital of Stomatology, China Medical University dDepartment of Anesthesiology, the People's Hospital of China Medical University, the People's Hospital of Liaoning Province, Shenyang eGrade 2012, Department of Anesthesiology, Dalian Medical University, Dalian, People's Republic of China.
Neuroreport. 2017 May 3;28(7):380-385. doi: 10.1097/WNR.0000000000000759.
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.
星形胶质细胞是ATP的丰富来源，在各种条件下，ATP可能从细胞质释放到细胞外空间，甚至在某些情况下影响细胞命运。在本研究中，我们旨在评估导致谷氨酸诱导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表明，在不同浓度（0.1 - 1 mM）的谷氨酸刺激下，ATP有明显释放，在时间进程上呈现出有趣的双峰分布。ATP释放潜在途径的抑制剂或阻滞剂，如胞吐小泡释放、间隙连接半通道、P2X7受体和容积敏感性外向整流氯通道，对观察到的ATP释放没有显著影响。相比之下，钆（50 µM），一种大阴离子通道抑制剂，可显著抑制谷氨酸诱导的星形胶质细胞ATP释放；同时，应用钆可显著减轻谷氨酸诱导的细胞损伤。因此，我们提出大阴离子通道可能在谷氨酸诱导的小鼠星形胶质细胞ATP释放中起重要作用，在谷氨酸刺激的情况下，抑制大阴离子通道活性以减少ATP释放可产生保护作用。
