Department of Cell Physiology, National Institute for Physiological Sciences, Myodaiji-cho, Okazaki, 444-8585, Japan.
Purinergic Signal. 2008 Jun;4(2):147-54. doi: 10.1007/s11302-007-9077-8. Epub 2007 Sep 12.
ATP represents a major gliotransmitter that serves as a signaling molecule for the cross talk between glial and neuronal cells. ATP has been shown to be released by astrocytes in response to a number of stimuli under nonischemic conditions. In this study, using a luciferin-luciferase assay, we found that mouse astrocytes in primary culture also exhibit massive release of ATP in response to ischemic stress mimicked by oxygen-glucose deprivation (OGD). Using a biosensor technique, the local ATP concentration at the surface of single astrocytes was found to increase to around 4 muM. The OGD-induced ATP release was inhibited by Gd(3+) and arachidonic acid but not by blockers of volume-sensitive outwardly rectifying Cl(-) channels, cystic fibrosis transmembrane conductance regulator (CFTR), multidrug resistance-related protein (MRP), connexin or pannexin hemichannels, P2X(7) receptors, and exocytotic vesicular transport. In cell-attached patches on single astrocytes, OGD caused activation of maxi-anion channels that were sensitive to Gd(3+) and arachidonic acid. The channel was found to be permeable to ATP(4-) with a permeability ratio of P(ATP)/P(Cl) = 0.11. Thus, it is concluded that ischemic stress induces ATP release from astrocytes and that the maxi-anion channel may serve as a major ATP-releasing pathway under ischemic conditions.
三磷酸腺苷（ATP）是一种重要的神经递质，作为神经胶质细胞和神经元细胞之间相互交流的信号分子。已有研究表明，在非缺血条件下，多种刺激均可导致星形胶质细胞释放 ATP。本研究采用荧光素酶法发现，在氧葡萄糖剥夺（OGD）模拟的缺血应激下，原代培养的小鼠星形胶质细胞也会大量释放 ATP。利用生物传感器技术发现，单个星形胶质细胞表面的局部 ATP 浓度增加到约 4 μM。Gd(3+)和花生四烯酸可抑制 OGD 诱导的 ATP 释放，但容积敏感性外向整流氯离子通道、囊性纤维化跨膜电导调节因子（CFTR）、多药耐药相关蛋白（MRP）、连接蛋白或缝隙连接蛋白半通道、P2X(7)受体和胞吐囊泡转运的阻断剂对此无影响。在单个星形胶质细胞的细胞贴附式膜片上，OGD 可激活对 Gd(3+)和花生四烯酸敏感的大阴离子通道。该通道对 ATP(4-)具有通透性，P(ATP)/P(Cl)为 0.11。因此，结论是缺血应激可诱导星形胶质细胞释放 ATP，而在缺血条件下，大阴离子通道可能作为主要的 ATP 释放途径。
