TNP-ATP-resistant P2X ionic current on the central terminals and somata of rat primary sensory neurons

P2X receptors have been suggested to be expressed on the central terminals of Aδ-afferent fibers innervating dorsal horn lamina V and play a role in modulating sensory synaptic transmission. These P2X receptors have been widely thought to be P2X₂₊₃ receptors. However, we have recently found that P2X receptor-mediated modulation of sensory transmission in lamina V is not inhibited by trinitrophenyl-adenosine triphosphate (TNP-ATP), a potent antagonist of P2X₁, P2X₃ homomers, and P2X₂₊₃ heteromers. To provide direct evidence for the presence of TNP-ATP-resistant P2X receptors on primary afferent fibers, we examined α,β-methylene-ATP (αβmeATP)-evoked currents and their sensitivity to TNP-ATP in rat dorsal root ganglion (DRG) neurons, αβmeATP evoked fast currents, slow currents, and mixed currents that contained both fast and slow current-components. Fast currents and fast current components in the mixed currents were both completely inhibited by 0.1 μM TNP-ATP (n = 14). Both slow currents and slow-current components in the mixed currents showed broad spectrum of sensitivity to 1 μM TNP-ATP, ranging from complete block (TNP-ATP-sensitive) to little block (TNP-ATP-resistant). TNP-ATP-resistant currents evoked by 10 μM αβmeATP could be largely inhibited by 10 μM iso-pyridox-alphosphate-6-azophenyl-2′,4′-disulphonic acid. Cells with P2X currents that were highly resistant to TNP-ATP were found to be insensitive to capsaicin. These results suggest that TNP-ATP-resistant P2X receptor subtypes are expressed on capsaicin-insensitive Aδ-afferent fibers and play a role in modulating sensory transmission to lamina V neurons.