P2X7 receptors enhance glutamate release in hippocampal hilar neurons

We examined the effect of 2′-3′-O-(4-benzoylbenzoyl)-adenosine- 5′-triphosphate (Bz-ATP), a P2X7 receptor agonist, on action potential-independent glutamate release from nerve terminals attached to mechanically isolated immature hilar neurons. Bz-ATP increased spontaneous excitatory postsynaptic current (sEPSC) frequency, and this effect was blocked by Brilliant blue G, a P2X7 receptor antagonist, suggesting that P2X7 receptors mediate the facilitatory action of Bz-ATP on sEPSCs. In most of hilar neurons tested, the Bz-ATP-induced increase in sEPSC frequency was blocked by tetrodotoxin or Cd²⁺, suggesting that the activation of P2X7 receptors leads to a presynaptic depolarization. The P2X7 receptor-mediated facilitation of glutamate release would modulate the excitability of hilar neurons, and eventually have a broad impact on the pathophysiological functions mediated by the hippocampus.