CLONING OF P2X(5) AND P2X(6) RECEPTORS AND THE DISTRIBUTION AND PROPERTIES OF AN EXTENDED FAMILY OF ATP-GATED ION CHANNELS

Two new P2X receptor cDNAs (P2X(5) and P2X(6)) were isolated and expre ssed. All six proteins are 36-48% identical and seem to have two trans membrane segments with a large extracellular loop. Functionally, P2X(5 ) and P2X(6) receptors most resemble P2X(2) and P2X(4); they desensiti ze only slowly and do not respond to alpha beta methylene-ATP. P2X(6) receptors, like P2X(4) receptors, are not blocked by the antagonists s uramin and pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid. P2 X(6) and P2X(5) receptors express at lower levels than P2X(1)-P2X(4) r eceptors do, perhaps indicating that they do not normally form homomul timeric channels. P2X(6) and P2X(4) are the receptors expressed most h eavily in brain, where their RNAs have a widespread and extensively ov erlapping distribution. The spinal cord expresses all receptors except P2X(3). P2X(2), P2X(4), and P2X(6) are the most abundant in the dorsa l horn. Sensory neurons of the trigeminal, dorsal root, and nodose gan glia express all six RNAs; P2X(3) is found only there. The functional properties and tissue distribution of these six P2X receptors indicate new roles for ATP-gated ion channels.