Abstract
Recent studies have shown that permeability of some chloride channels to organic anions, such as glutamate and ATP, is involved in cell-to-cell communication mediated by released organic anions. Previous our studies demonstrated that a maxi-anion channel serves as a conductive pathway for ATP release in a mouse mammary cell line (Sabirov et al., 2001), rabbit kidney macula densa cells (Bell et al., 2003) and rat cardiomyocytes (Dutta et al, 2004). In the present study, the possible relation between expression of maxi-anion channel and ATP release was tested in mouse astrocytes in primary culture. In response to hypoxia stress, astrocytes exhibited both activation of maxi-anion channel and massive release of ATP. Hypoxia-induced ATP release was inhibited by blockers of maxi-anion channel, but not by those of other candidate pathways for ATP release, such as gap junction hemi-channel, CFTR channel, exocytosis and volume-sensitive outwardly rectifying (VSOR) anion channel. Using a biosensor technique based on ATP responses of P2X2 receptors expressed in HEK293 cells, the local ATP concentration on a single astrocyte surface was found to increase to about 5 μM during hypoxia. Therefore, it is concluded that the maxi-anion channel serves as a major pathway for ATP release from astrocytes under hypoxia. [J Physiol Sci. 2006;56 Suppl:S115]
