Maxi-anion channels play a key role in glutamate-induced ATP release from mouse astrocytes in primary culture

• Published in: Neuroreport Vol. 28; no. 7; p. 380
• Main Authors: Zhao, Bin, Gu, Li, Liu, Kaixi, Zhang, Mingming, Liu, Hongtao
• Format: Journal Article
• Language: English
• Published: England 03.05.2017
• Subjects: Adenosine Triphosphate - metabolism; Animals; Astrocytes - metabolism; Astrocytes - pathology; Cell Survival - physiology; Cells, Cultured; Dose-Response Relationship, Drug; Gadolinium - pharmacology; Glutamic Acid - metabolism; Glutamic Acid - pharmacology; Ion Channels - antagonists & inhibitors; Ion Channels - metabolism; Mice; Neurotransmitter Agents - pharmacology
• ISSN: 1473-558X
• 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.