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.

  • Letter
  • Published:

Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel

Abstract

INACTIVATION of ion channels is important in the control of membrane excitability. For example, delayed-rectifier K+ channels, which regulate action potential repolarization, are inactivated only slowly, whereas A-type K+ channels, which affect action potential duration and firing frequency, have both fast and slow inactivation1. Fast inactivation of Na+ and K+ channels may result from the blocking of the permeation pathway by a positively charged cytoplasmic gate2 such as the one encoded by the first 20 amino acids of the Shaker B (ShB) K+ channel3, 4. We report here that mutation of five highly conserved residues between the proposed membrane-spanning segments S4 and S5 (also termed H4)5 of ShB affects the stability of the inactivated state and alters channel conductance. One such mutation stabilizes the inactivated state of ShB as well as the inactivated state induced in the delayed-rectifier type K+ channel drkl (ref. 6) by the cytoplasmic application of the ShB N-terminal peptide. The S4–S5 loop, therefore, probably forms part of a receptor for the inactivation gate and lies near the channel's permeation pathway.

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

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

Similar content being viewed by others

References

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

    Google Scholar 

  2. Armstrong, C. M. & Bezanilla, C. F. J. gen. Physiol. 70, 567–590 (1977).

    Article  CAS  Google Scholar 

  3. Hoshi, T., Zagotta, W. N. & Aldrich, R. W. Science 250, 533–538 (1990).

    Article  ADS  CAS  Google Scholar 

  4. Zagotta, W. N., Hosbi, T. & Aldrich, R. W. Science 250, 568–571 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Schwarz, T. L., Tempel, B. L., Papazian, D. M., Jan, Y. N. & Jan, L. Y. Nature 331, 137–142 (1988).

    Article  ADS  CAS  Google Scholar 

  6. Freeh, G. C., Van Dongen, A. M. J., Schuster, G., Brown, A. M. & Joho, R. H. Nature 340, 642–645 (1989).

    Article  ADS  Google Scholar 

  7. Zagotta, W. N., Hoshi, T. & Aldrich, R. W. Proc natn. Acad. Sci. U.S.A. 86, 7243–7243 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Isacoff, E. Y., Papazian, D. M., Timpe, L. C., Jan, Y. N. & Jan, L. Y. Cold Spring Harb. Symp. quant. Biol. 55, 9–17 (1990).

    Article  CAS  Google Scholar 

  9. Greenblatt, R. E., Blatt, Y. & Montal, M. FEBS Lett. 193, 125–134 (1985).

    Article  CAS  Google Scholar 

  10. Guy, H. R. & Seetharamulu, P. Proc. natn. Acad. Sci. U.S.A. 83, 508–521 (1986).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  12. Catterall, W. A. A. Rev. Biochem. 55, 953–985 (1986).

    Article  CAS  Google Scholar 

  13. Stuhmer, W. et al. Nature 339, 597–603 (1989).

    Article  ADS  CAS  Google Scholar 

  14. Papazian, D. M., Timpe, L. C., Jan, Y. N. & Jan, L. Y. Nature 349, 305–310 (1991).

    Article  ADS  CAS  Google Scholar 

  15. Baumann, A., Grupe, A., Ackermann, A. & Pongs, O. EMB0 J. 7, 2457–2467 (1988).

    Article  CAS  Google Scholar 

  16. Jan, L. Y. & Jan, Y. N. Trends Neurosci. 13, 415–419 (1990).

    Article  CAS  Google Scholar 

  17. Armstrong, C. M. J. gen. Physiol. 54, 553–575 (1969).

    Article  CAS  Google Scholar 

  18. Armstrong, C. M. J. gen. Physiol. 58, 413–437 (1971).

    Article  CAS  Google Scholar 

  19. Choi, K. L., Aldrich, R. W. & Yellen, G. Proc. natn. Acad. Sic. U.S.A. 88, 5092–5095 (1991).

    Article  ADS  CAS  Google Scholar 

  20. Isacoff, E. Y., Jan, Y. N. & Jan, L. Y. Nature 345, 530–534 (1990).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  22. Hartmann, H. A. et al. Science 251, 942–945 (1991).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  25. Zagotta, W. N. & Aldrich, R. W. J. gen. Physiol. 95, 29–60 (1990).

    Article  CAS  Google Scholar 

  26. Pfaffinger, P. J., Furukawa, Y., Zhao, B., Dugan, D. & Kandel, E. R. J. Neurosci. 11, 918–927 (1991).

    Article  CAS  Google Scholar 

  27. Ribera, A. B. Neuron 5, 691–701 (1990).

    Article  CAS  Google Scholar 

  28. McCormack, T., Vega-Saenz de Miera, C. & Rudy, B. Proc. natn. Acad. Sci. U.S.A. 87, 5227–5231 (1990).

    Article  ADS  CAS  Google Scholar 

  29. Roberds, S. L. & Tamkun, M. M. Proc. natn. Acad. Sci. U.S.A. 88, 1798–1802 (1991).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isacoff, E., Jan, Y. & Jan, L. Putative receptor for the cytoplasmic inactivation gate in the Shaker K+ channel. Nature 353, 86–90 (1991). https://doi.org/10.1038/353086a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/353086a0

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