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A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP

Abstract

EXTRACELLULAR ATP exerts its effects through P2 purino-ceptors1: these are ligand-gated ion channels (P2x)2,3 or G-protein-coupled receptors (Piv, Piu)4- ATP at P2X receptors mediates synaptic transmission between neurons5–7 and from neurons to smooth muscle1, being responsible, for example, for sympathetic vasoconstriction in small arteries and arterioles8,9. We have now cloned a complementary DNA encoding the P2x receptor from rat vas deferens and expressed it in Xenopus oocytes and mammalian cells. ATP activates a cation-selective ion channel with relatively high calcium permeability. Structural predictions suggest that the protein (399 amino acids long) is mostly extracellular and contains only two transmembrane domains plus a pore-forming motif which resembles that of potassium channels. The P2x receptor thus defines a new family of ligand-gated ion channels.

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References

  1. Burnstock, G. Ann. N. Y. Acad. Sci. 603, 1–17 (1990).

    Article  ADS  CAS  Google Scholar 

  2. Bean, B. P. Trends pharmac. Sci. 13, 87–90 (1992).

    Article  CAS  Google Scholar 

  3. Bean, B. P. & Friel, D. D. Ion Channels 2, 169–203 (1990).

    Article  CAS  Google Scholar 

  4. Barnard, E. A., Burnstock, G. & Webb, T. E. Trends pharmac. Sci. 15, 67–71 (1994).

    Article  CAS  Google Scholar 

  5. Evans, R. J., Derkach, V. & Surprenant, A. Nature 357, 503–505 (1992).

    Article  ADS  CAS  Google Scholar 

  6. Edwards, F. A., Gibb, A. J. & Colquhoun, D. Nature 359, 144–147 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Silinsky, E. M., Gerzanich, V. & Vanner, S. M. Br. J. Pharmac. 106, 762–763 (1994).

    Article  Google Scholar 

  8. Burnstock, G. Trends pharmac. Sci. 9, 116–117 (1988).

    Article  CAS  Google Scholar 

  9. Evans, R. J. & Surprenant, A. Br. J. Pharmac. 106, 242–249 (1992).

    Article  CAS  Google Scholar 

  10. Benham, C. D. & Tsien, R. W. Nature 328, 275–278 (1987).

    Article  ADS  CAS  Google Scholar 

  11. Ziganshin, A. U. et al. Br. J. Pharmac. 111, 923–929 (1994).

    Article  CAS  Google Scholar 

  12. Abbrachio, M. P. & Burnstock, G. Pharmac. Therap. (in tne press).

  13. Bo, X., Simon, J., Burnstock, G. & Barnard, E. A. J. biol. Chem. 267, 17581–17587 (1992).

    CAS  PubMed  Google Scholar 

  14. Walker, J., Saraste, M., Runswick, M. & Gay, N. EMBO J. 1, 945–951 (1982).

    Article  CAS  Google Scholar 

  15. North, R. A. (ed.) Handbook of Receptors and Channels Vol. 2 (CRC Press, Toca Baton, Florida, USA, in the press).

  16. Ashford, M. L. J., Bond, C. T., Blair, T. A. & Adelman, J. P. Nature 370, 456–459 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Durell, S. R. & Guy, H. R. Biophys. J. 62, 238–250 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Barnard, E. A. Trends biochem. Sci. 17, 368–374 (1992).

    Article  CAS  Google Scholar 

  19. Chalfie, M., Driscoll, M. & Huang, M. Nature 361, 504 (1993).

    Article  ADS  CAS  Google Scholar 

  20. Canessa, C. M. et al. Nature 367, 463–467 (1994).

    Article  ADS  CAS  Google Scholar 

  21. Owens, G. P., Hahn, W. E. & Cohen, J. J. Molec. cell. Biol. 11, 4177–4188 (1991).

    Article  CAS  Google Scholar 

  22. Zheng, L. M., Zychlinsky, A., Liu, C.-C., Ojcius, D. M. & Young, J. D.-E. J. cell. Biol. 112, 279–288 (1991).

    Article  CAS  Google Scholar 

  23. Zoeteweij, J. P., van de Water, B., de Bont, H. J. G. M., Mudler, G. J. & Nagelkerke, J. F. Biochem. J. 288, 207–213 (1992).

    Article  CAS  Google Scholar 

  24. Spranzi, E., Djeu, J. Y., Hoffman, S. L., Epling-Burnette, P. K. & Blanchard, D. K. Blood 82, 1578–1585 (1993).

    CAS  PubMed  Google Scholar 

  25. Felgner, P. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 7413–7417 (1987).

    Article  ADS  CAS  Google Scholar 

  26. Adams, D. J., Dwyer, T. M. & Hille, B. J. gen. Physiol. 75, 493–510 (1980).

    Article  CAS  Google Scholar 

  27. Kubo, Y., Baldwin, T. J., Jan, Y. N. & Jan, L. Y. Nature 362, 127–133 (1993).

    Article  ADS  CAS  Google Scholar 

  28. Kubo, Y., Reuveny, E., Slesinger, P. A., Jan, Y. N. & Jan, L. Y. Nature 364, 802–806 (1993).

    Article  ADS  CAS  Google Scholar 

  29. Henikoff, S. Meth. Enzym. 155, 156–165 (1987).

    Article  CAS  Google Scholar 

  30. Schaeren-Weimers, N. & Gerfin-Moser, A. Histochemistry 100, 431–440 (1993).

    Article  Google Scholar 

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Valera, S., Hussy, N., Evans, R. et al. A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP. Nature 371, 516–519 (1994). https://doi.org/10.1038/371516a0

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