Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Expression of functional sodium channels from cloned cDNA

Abstract

The voltage-gated sodium channel is a transmembrane protein essential for the generation of action potentials in excitable cells1. It has been reported that sodium channels purified from the electric organ of the electric eel, Electrophorus electricus2,3, and from chick cardiac muscle4 consist of a single polypeptide of relative molecular mass (Mr) 260,000, whereas those purified from rat brain5 and from rat6,7 and rabbit skeletal muscle7 contain, in addition to the large polypeptide, one or two smaller polypeptides of Mr33,000–43,000. The primary structures of the Electrophorus sodium channel8 and two distinct sodium channel large polypeptides9 (designated as sodium channels I and II) from rat brain have been elucidated by cloning and sequencing the complementary DNAs. The purified sodium channel preparations from Electrophorus electroplax10 and from mammalian muscle11,12 and brain13–15, when reconstituted into lipid vesicles or planar lipid bilayers, exhibit some functional activities. The successful reconstitution with the Electrophoruspreparation would imply that the large polypeptide alone is sufficient to form functional sodium channels. However, studies with the rat brain preparation suggest that the smaller polypeptide of Mr36,000 is also required for the integrity of the saxitoxin (STX) or tetrodotoxin (TTX) binding site of the sodium channel16. Here we report that the messenger RNAs generated by transcription of the cloned cDNAs encoding the rat brain sodium channel large polypeptides, when injected into Xenopus oocytes, can direct the formation of functional sodium channels.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Hille, B. Ionic Channels of Excitable Membranes (Sinauer Associates Inc., Sunderland, Massachusetts, 1984).

    Google Scholar 

  2. Agnew, W. S., Levinson, S. R., Brabson, J. S. & Raftery, M. A. Proc. natn. Acad. Sci. U.S.A. 75, 2606–2610 (1978).

    Article  ADS  CAS  Google Scholar 

  3. Miller, J. A., Agnew, W. S. & Levinson, S. R. Biochemistry 22, 462–470 (1983).

    Article  CAS  Google Scholar 

  4. Lombet, A. & Lazdunski, M. Eur. J. Biochem. 141, 651–660 (1984).

    Article  CAS  Google Scholar 

  5. Messner, D. J. & Catterall, W. A. J. biol. Chem. 260, 10597–10604 (1985).

    CAS  PubMed  Google Scholar 

  6. Barchi, R. L. J. Neurochem. 40, 1377–1385 (1983).

    Article  CAS  Google Scholar 

  7. Barchi, R. L., Tanaka, J. C. & Furman, R. E. J. cell. Biochem. 26, 135–146 (1984).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  10. Rosenberg, R. L., Tomiko, S. A. & Agnew, W. S. Proc. natn. Acad. Sci. U.S.A. 81, 1239–1243 (1984).

    Article  ADS  CAS  Google Scholar 

  11. Tanaka, J. C., Eccleston, J. F. & Barchi, R. L. J. biol. Chem. 258, 7519–7526 (1983).

    CAS  PubMed  Google Scholar 

  12. Kraner, S. D., Tanaka, J. C. & Barchi, R. L. J. biol. Chem. 260, 6341–6347 (1985).

    CAS  PubMed  Google Scholar 

  13. Hanke, W., Boheim, G., Barhanin, J., Pauron, D. & Lazdunski, M. EMBO J. 3, 509–515 (1984).

    Article  CAS  Google Scholar 

  14. Hartshorne, R. P., Keller, B. U., Talvenheimo, J. A., Catterall, W. A. & Montal, M. Proc. natn. Acad. Sci. U.S.A. 82, 240–244 (1985).

    Article  ADS  CAS  Google Scholar 

  15. Feller, D. J., Talvenheimo, J. A. & Catterall, W. A. J. biol. Chem. 260, 11542–11547 (1985).

    CAS  PubMed  Google Scholar 

  16. Messner, D. J. & Catterall, W. A. J. biol. Chem. 261, 211–215 (1986).

    CAS  PubMed  Google Scholar 

  17. Green, M. R., Maniatis, T. & Melton, D. A. Cell 32, 681–694 (1983).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Gundersen, C. B., Miledi, R. & Parker, I. Proc. R. Soc. B220, 131–140 (1983).

    ADS  CAS  Google Scholar 

  20. Gundersen, C. B., Miledi, R. & Parker, I. Nature 308, 421–424 (1984).

    Article  ADS  CAS  Google Scholar 

  21. Baud, C., Kado, R. T. & Marcher, K. Proc. natn. Acad. Sci. U.S.A. 79, 3188–3192 (1982).

    Article  ADS  CAS  Google Scholar 

  22. Baud, C. & Kado, R. T. J. Physiol., Lond. 356, 275–289 (1984).

    Article  CAS  Google Scholar 

  23. Kusano, K., Miledi, R. & Stinnakre, J. J. Physiol., Lond. 328, 143–170 (1982).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  25. Leonard, J., Snutch, T., Lubbert, H., Davidson, N. & Lester, H. A. Biophys. J. 49, 386a (1986).

    Google Scholar 

  26. Methfessel, C. et al. Pflügers Arch. ges. Physiol. (in the press).

  27. Hodgkin, A. L. & Huxley, A. F. J. Physiol., Lond. 117, 500–544 (1952).

    Article  CAS  Google Scholar 

  28. Sumikawa, K., Parker, I. & Miledi, R. Proc. natn. Acad. Sci. U.S.A. 81, 7994–7998 (1984).

    Article  ADS  CAS  Google Scholar 

  29. Hirono, C. et al. Brain Res. 359, 57–64 (1985).

    Article  CAS  Google Scholar 

  30. Yanisch-Perron, C., Vieira, J. & Messing, J. Gene 33, 103–119 (1985).

    Article  CAS  Google Scholar 

  31. Messing, J. Meth. Enzym. 101, 20–78 (1983).

    Article  CAS  Google Scholar 

  32. Konarska, M. M., Padgett, R. A. & Sharp, P. A. Cell 38, 731–736 (1984).

    Article  CAS  Google Scholar 

  33. McMaster, G. K. & Carmichael, G. G. Proc. natn. Acad. Sci. U.S.A. 74, 4835–4838 (1977).

    Article  ADS  CAS  Google Scholar 

  34. Miledi, R. & Sumikawa, K. Biomed. Res. 3, 390–399 (1982).

    Article  CAS  Google Scholar 

  35. Aviv, H. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 69, 1408–1412 (1972).

    Article  ADS  CAS  Google Scholar 

  36. Houghton, M. et al. Nucleic Acids Res. 8, 1913–1931 (1980).

    Article  CAS  Google Scholar 

  37. Gurdon, J. B. The Control of Gene Expression in Animal Development (Clarendon, Oxford, 1974).

    Google Scholar 

  38. Sakmann, B. et al. Nature 318, 538–543 (1985).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Noda, M., Ikeda, T., Suzuki, H. et al. Expression of functional sodium channels from cloned cDNA. Nature 322, 826–828 (1986). https://doi.org/10.1038/322826a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/322826a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing