Electrophysiological classification of P2X7 receptors in rat cultured neocortical astroglia

Background and purpose: P2X7 receptors are ATP-gated cation channels mediating important functions in microglial cells, such as the release of cytokines and phagocytosis. Electrophysiological evidence that these receptors also occur in CNS astroglia is rare and rather incomplete. Experimental approach: We used whole-cell patch-clamp recordings to search for P2X7 receptors in astroglial-neuronal co-cultures prepared from the cerebral cortex of rats. Key results: All the astroglial cells investigated responded to ATP with membrane currents, reversing around 0 mV. These currents could be also detected in isolated outside-out patch vesicles. The results of the experiments with the P2X [alpha,beta-methylene ATP and 2'-3'-O-(4-benzoyl) ATP] and P2Y receptor agonists [adenosine 5'-O-(2-thiodiphosphate), uridine 5'-diphosphate, uridine 5'-triphosphate (UTP) and UDP-glucose] suggested the involvement of P2X receptors in this response. The potentiation of ATP responses in a low divalent cation or alkaline bath, but not by ivermectin, made it likely that a P2X7 receptor is operational. Blockade of the ATP effect by the P2X7 antagonists Brilliant Blue G, calmidazolium and oxidized ATP corroborated this assumption. Conclusions and implications: Rat cultured cortical astroglia possesses functional P2X7 receptors. It is suggested that astrocytic P2X7 receptors respond to high local ATP concentrations during neuronal injury.