ATP-gated P2X receptors on excitatory nerve terminals onto interneurons initiate a form of asynchronous glutamate release

Previous work has shown that ATP-gated P2X2 receptors are expressed in excitatory nerve terminals onto stratum radiatum interneurons in the mouse hippocampal CA1 region. At these synapses receptor activation results in calcium-dependent facilitation of miniature and spontaneous EPSC frequency. In this study I determined if activation of presynaptic P2X receptors produces these effects by utilizing the vesicles underlying action potential dependent release. Brief trains of electrical stimuli caused short-term synaptic depression of excitatory synapses onto interneurons, in a manner consistent with depletion of the readily releasable pool of vesicles. P2X receptor activation increased the frequency of spontaneous EPSCs, but unexpectedly evoked little effect on synaptic depression. This suggests that P2X receptor activation does not markedly draw on the vesicles underlying action potential dependent glutamate release. However asynchronous EPSCs were increased following synaptic depression and a component of these appeared to be initiated by endogenously released ATP acting on presynaptic P2X receptors. Unexpectedly, the data suggest P2X receptor activation initiates a form of asynchronous glutamate release, rather than detectably affecting the vesicles underlying action potential evoked release. (C) 2008 Elsevier Ltd. All rights reserved.