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Calcium channel characteristics conferred on the sodium channel by single mutations

Nature volume 356, pages 441–443 (1992)Cite this article

Abstract

THE sodium channel, one of the family of structurally homologous voltage-gated ion channels1, differs from other members, such as the calcium and the potassium channels, in its high selectivity for Na+. This selectivity presumably reflects a distinct structure of its ion-conducting pore. We have recently identified two clusters of predominantly negatively charged amino-acid residues, located at equivalent positions in the four internal repeats of the sodium channel as the main determinants of sensitivity to the blockers tetrodotoxin and saxitoxin2. All site-directed mutations reducing net negative charge at these positions also caused a marked decrease in single-channel conductance2. Thus these two amino-acid clusters probably form part of the extracellular mouth and/or the pore wall of the sodium channel. We report here the effects on ion selectivity of replacing lysine at position 1,422 in repeat III and/or alanine at position 1,714 in repeat IV of rat sodium channel II (ref. 3), each located in one of the two clusters, by glutamic acid, which ccurs at the equivalent positions in calcium channels. These amino-acid substitutions, unlike other substitutions in the adjacent regions, alter ion-selection properties of the sodium channel to resemble those of calcium channels. This result indicates that lysine 1,422 and alanine 1,714 are critical in deter mining the ion selectivity of the sodium channel, suggesting that these residues constitute part of the selectivity filter of the channel.

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References

  1. Numa, S. Harvey Lect 83, 121–165 (1989).

    Google Scholar 

  2. Terlau, H. et al. FEBS Lett. 293, 93–96 (1991).

    Article  CAS  Google Scholar 

  3. Noda, M. et al. Nature 320, 188–192 (1986).

    Article  ADS  CAS  Google Scholar 

  4. Noda, M. et al. Nature 312, 121–127 (1984).

    Article  ADS  CAS  Google Scholar 

  5. Kayano, I., Noda, M., Flockerzi, V., Takahashi, H. & Numa, S. FEBS Lett. 228, 187–194 (1988).

    Article  CAS  Google Scholar 

  6. Trimmer, J. S. et al. Neuron 3, 33–49 (1989).

    Article  CAS  Google Scholar 

  7. Rogart, R. B., Cribbs, L. L., Muglia, L. K., Kephart, D. D. & Kaiser, M. W. Proc. natn. Acad Sci. U.S.A. 86, 8170–8174 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Tanabe, T. et al. Nature 328, 313–318 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Mikami, A. et al. Nature 340, 230–233 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Mori, Y., et al. Nature 350, 398–402 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Noda, M., Suzuki, H., Numa, S. & Stühmer, W. FEBS Lett. 259, 213–216 (1989).

    Article  CAS  Google Scholar 

  12. Pusch, M., Noda, M., Stühmer, W., Numa, S. & Conti, F. Eur. Biophys. J. 20, 127–133 (1991).

    Article  CAS  Google Scholar 

  13. MacKinnon, R. & Yellen, G. Science 250, 276–279 (1990).

    Article  ADS  CAS  Google Scholar 

  14. Yellen, G., Jurman, M. E., Abramson, T. & MacKinnon, R. Science 251, 939–942 (1991).

    Article  ADS  CAS  Google Scholar 

  15. Yool, A. J. & Schwarz, T. L. Nature 349, 700–704 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Hartmann, H. A. et al Science 251, 942–944 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Guy, H. R. & Conti, F. Trends Neurosci. 13, 201–206 (1990).

    Article  CAS  Google Scholar 

  18. Stühmer, W., Methfessel, C., Sakmann, B., Noda, M. & Numa, S. Eur. Biophys. J. 14, 131–138 (1987).

    Article  Google Scholar 

  19. Yamamoto, D., Yen, J. Z. & Narahashi, T. Biophys. J. 45, 337–344 (1984).

    Article  ADS  CAS  Google Scholar 

  20. Pusch, M. Eur. Biophys. J. 18, 327–333 (1990).

    CAS  PubMed  Google Scholar 

  21. Kostyuk, P. G., Mironov, S. L. & Shuba, Y. M. J. Membrane Biol. 76, 83–93 (1983).

    Article  Google Scholar 

  22. Almers, W. & McCleskey, E. W. J. Physlol., Lond. 353, 585–608 (1984).

    Article  CAS  Google Scholar 

  23. Hess, P. & Tsien, R. W. Nature 309, 453–456 (1984).

    Article  ADS  CAS  Google Scholar 

  24. Salkoff, L. et al. Science 237, 744–749 (1987).

    Article  ADS  CAS  Google Scholar 

  25. Stühmer, W. et al. Nature 339, 597–603 (1989).

    Article  ADS  Google Scholar 

  26. Melton, D. A. et al. Nucleic Acids Res. 12, 7035–7056 (1984).

    Article  CAS  Google Scholar 

  27. Methfessel, C. et al. Pflügers Arch. 407, 577–588 (1986).

    Article  CAS  Google Scholar 

  28. Goldman, D. E. J. gen. Physiol. 27, 37–60 (1943).

    Article  CAS  Google Scholar 

  29. Hodgkin, A. L. & Katz, B. J. Physiol., Lond. 108, 37–77 (1949).

    Article  CAS  Google Scholar 

  30. Miledi, R. Proc. R. Soc. B 215, 491–497 (1982).

    ADS  CAS  Google Scholar 

  31. Barish, M. E. J. Physiol, Lond. 342, 309–325 (1983).

    Article  ADS  CAS  Google Scholar 

  32. White, M. M. & Aylwin, M. Molec. Pharmac. 37, 720–724 (1990).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Max-Planck-lnstitut für biophysikalische Chemie, Abteilung Membranbiophysik, Göttingen, D-3400, Germany

    Stefan H. Heinemann, Heinrich Terlau & Walter Stühmer

  2. Departments of Medical Chemistry and Molecular Genetics, Kyoto University Faculty of Medicine, Kyoto, 606, Japan

    Keiji Imoto & Shosaku Numa

Authors
  1. Stefan H. Heinemann
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  2. Heinrich Terlau
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  3. Walter Stühmer
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  4. Keiji Imoto
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  5. Shosaku Numa
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Heinemann, S., Terlau, H., Stühmer, W. et al. Calcium channel characteristics conferred on the sodium channel by single mutations. Nature 356, 441–443 (1992). https://doi.org/10.1038/356441a0

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