Lack of ATP-evoked GABA and glutamate release in the hippocampus of P2X7 receptor−/− mice

Abstract

In this study we revealed the participation of P2X(7) receptors in the modulation of electrical stimulation and ATP-evoked GABA and glutamate release from mouse hippocampal slices. Whereas the uptake of radioactivity was not changed, the electrical stimulation-induced release of both [(3)H]glutamate and [(3)H]GABA was decreased in the hippocampus of P2X(7) receptor-deficient mice. ATP (10 mM) elicited [(3)H]glutamate and [(3)H]GABA efflux in wild-type mice, which was inhibited by the non-selective P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (30 microM) and the P2X(7)-selective antagonist Brilliant Blue G (1 microM). The ATP-evoked release of both GABA and glutamate was virtually absent in the knockout mice. These results indicate that ATP facilitates GABA and glutamate release in the hippocampus by a mechanism involving P2X(7)R.