Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons

Cation-selective P2X receptor channels were first described in sensory neurons^1-4 where they are important for primary afferent neurotransmission and nociception^5,6. Here we report the cloning of a complementary DNA (P2X₃) from rat dorsal root ganglia that had properties dissimilar to those of sensory neurons. We also found RNA for (P2X₁) (ref. 7), (P2X₂) (ref. 8) and P2X₄ (ref. 9) in sensory neurons; channels expressed from individual cDNAs did not reproduce those of sensory ganglia. Coexpression of P2X₃ with P2X₂, but not other combinations, yielded ATP-activated currents that closely resembled those in sensory neurons. These properties could not be accounted for by addition of the two sets of channels, indicating that a new channel had formed by subunit heteropoly-merization. Although in some tissues responses to ATP can be accounted for by homomeric channels^1,7-10, our results indicate that ATP-gated channels of sensory neurons may form by a specific heteropolymerization of P2X receptor subunits.