ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in dorsal horn neurons of the rat spinal cord

Presynaptic ATP P2X receptors have been proposed to play a role in modulati ng glutamate release from the first sensory synapse in the spinal cord. Usi ng spinal cord slice preparations and patch-clamp recordings from dorsal ho rn neurons in lamina V of the rat spinal cord, we showed that the activatio n of P2X receptors by alpha,beta -methylene- ATP (alpha betam-ATP) resulted in a large increase in the frequency of spontaneous EPSCs (sEPSCs) and min iature EPSCs (mEPSCs). The increases in mEPSC frequency by alpha betam-ATP were not blocked by the Ca2+ channel blocker, 30 muM La3+, but were abolish ed in a bath solution when Ca2+ was omitted. The increases in mEPSC frequen cy by alpha betam-ATP were blocked completely by the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) at 10 muM. Fu rthermore, the EPSCs evoked by dorsal root stimulation were potentiated by alpha betam-ATP as well as by the ecto-ATPase inhibitor ARL67156 and were d epressed in the presence of P2 receptor antagonists PPADS (10 muM) and sura min (5 muM). The effects of these compounds on the evoked EPSCs were associ ated with the changes in glutamate release probability of primary afferent central terminals. Our results indicate that alpha betam-ATP-sensitive P2X receptors play a significant role in modulating excitatory sensory synaptic transmission in the spinal cord, and the potential role of endogenous ATP is suggested.