Ionic dependence of a P2-purinoceptor mediated depolarization of cultured astrocytes

The membrane potential of cultured mouse astrocytes was recorded to assess the effects of extracellular adenosine 5'-triphosphate (ATP) and related H purines on astrocyte electrophysiology. The purines were applied with or without the presence of barium, which blocks the high resting K+ conductance in astrocytes. The response to ATP alone was a moderate depolarization; however, the response to ATP in the presence of barium was a large, dose dependent depolarization. The ED50 was approximately 10 microM. The effect of adenosine 5'-diphosphate (ADP) or adenosine 5'-monophosphate (AMP), in the presence of barium, on membrane potential was less than that of ATP. Adenosine, with or without barium, had no effect on membrane potential; furthermore, adenosine agonists in barium produced no response. The results of applying various ATP analogues indicate that the response is mediated via a P2-purinoceptor. Ion replacement studies reveal a complicated response to ATP that has several components and involves Na+ and K+. These results show that astrocytes respond with ionic changes to very small, physiological concentrations of extracellular ATP. We suggest that ATP plays a role in interactions between neurons/endothelial cells and glial cells.