P2X(4) - AN ATP-ACTIVATED IONOTROPIC RECEPTOR CLONED FROM RAT-BRAIN

Extracellular ATP exerts pronounced biological actions in virtually ev ery organ or tissue that has been studied, In the central and peripher al nervous system, ATP acts as a fast excitatory transmitter in certai n synaptic pathways [Evans, R. J., Derkach, V. & Surprenant, A. (1992) Nature (London) 357, 503-505; Edwards, F. A., Gigg, A. J. & Colquhoun , D. (1992) Nature (London) 359, 144-147], Here, we report the cloning and characterization of complementary DNA from rat brain, encoding an additional member (P2X(4)) of the emerging multigenic family of ligan d-gated ATP channels, the P2X receptors. Expression in Xenopus oocytes gives an ATP activated cation-selective channel that is highly permea ble to Ca2+ and whose sensitivity is modulated by extracellular Zn2+, Surprisingly, the current elicited by ATP is almost insensitive to the common P2X antagonist suramin, In situ hybridization reveals the expr ession of P2X(4) mRNA in central nervous system neurons, Northern blot and reverse transcription-PCR (RT-PCR) analysis demonstrate a wide di stribution of P2X(4) transcripts in various tissues, including blood v essels and leukocytes. This suggests that the P2X(4) receptor might me diate not only ATP-dependent synaptic transmission in the central nerv ous system but also a wide repertoire of biological responses in diver se tissues.