Functional roles of post-synaptic ATP P2X receptors in spinal deep dorsal horn neurons

Abstract

ATP P2X receptor, a family of non-selective cation channels gated by extracellular ATP, may play an important role on synaptic transmission in CNS. It has been demonstrated that the activation of spinal P2X receptors results in thermal hyperalgesia and allodynia. Multiple subtypes of P2X receptors are expressed at the central terminals of primary afferents as well as postsynaptic dorsal horn neurons inthe spinal cord. Our recent findings have shown that presynaptic P2X receptors enhance glutamaterelease at central terminals in dorsal horn. Although P2X receptors are also expressed at a subpopulation of dorsal horn neurons, it is still unknown which subtype of P2X receptors can functionally activate postsynaptic dorsal horn neurons. In this study, we demonstrate the distinct subtypes of P2X receptors are expressed at the postsynaptic sites of deep dorsal horn neurons using patch-clamp recordings in spinal cord slices. Bath application of ATPγS (100 µM), broad ATP analog induced inward currents in about 40% of deep dorsal horn neurons examined and significantly increased mEPSC frequency inalmost all deep dorsal horn neurons. ATPγS-induced inward currents were not inhibited by addingGDP-β-S into patch-pipette solution, which indicate that the ATPγS-induced inward currents are notmediated by spinal P2Y receptors. Bath application of α, β-methylene ATP (100 µM) did not induce any inward current, but increased mEPSC frequency in almost all deep dorsal horn neurons tested. In addition, these ATPγS-induced inward currents were completely blocked by PPADS (10 µM), but notby TNP-ATP (20 µM). These results suggested that distinct subtypes of P2X receptors are expressed atboth pre- and post-synaptic sites and that their activations enhance the excitability of spinal deep dorsalhorn neurons in different manners.