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

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Abstract
Cation-selective P2X receptor channels were first described in sensory neurons1-4 where they are important for primary afferent neurotransmission and nociception5,6. 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 channels1,7-10, our results indicate that ATP-gated channels of sensory neurons may form by a specific heteropolymerization of P2X receptor subunits.