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Evidence for cooperative interactions in potassium channel gating

Abstract

CLONING and expression of voltage-activated potassium ion-channel complementary DNAs1–4 has confirmed that these channels are composed of four identical subunits5, each containing a voltage sensor. It has been generally accepted that the voltage sensors must reach a permissive state through one or more confor-mational ('gating') transitions before the channel can open6,7. To test whether each subunit gates independently, we have constructed cDNAs encoding four subunits on a single polypeptide chain, enabling us to specify the subunit stoichiometry. The gating of heterotetramers made up from combinations of subunits with different gating phenotypes strongly suggests that individual sub-units gate cooperatively, rather than independently8. Nonindependent subunit gating is consistent with measurements of the kinetics of K+-channel gating currents9–13 and in line with the widespread subunit cooperativity observed in other multisubunit proteins14.

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References

  1. Papazian, D., Schwarz, T. L., Tempel, B. L., Jan, Y. N. & Jan, L. Y. Science 237, 749–753 (1987).

    Article  ADS  CAS  Google Scholar 

  2. Timpe, L. C. et al. Nature 331, 143–145 (1988).

    Article  ADS  CAS  Google Scholar 

  3. Pongs, O. et al. EMBO J. 7, 1087–1096 (1988).

    Article  CAS  Google Scholar 

  4. Iverson, L. E., Tanouye, M. A., Lester, H. A., Davidson, N. & Rudy, B. Proc. natn. Acad. Sci. U.S.A. 85, 5723–5727 (1988).

    Article  ADS  CAS  Google Scholar 

  5. MacKinnon, R. Nature 350, 232–235 (1991).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Koren, G., Liman, E. R., Logothetis, D. E., Nadal-Ginard, B. & Hess, P. Neuron 2, 39–51 (1991).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Stuehmer, W., Conti, F., Stocker, M., Pongs, O. & Heinemann, S. H. Pfluegers Arch. 418, 423–429 (1991).

    Article  Google Scholar 

  10. Bezanilla, F., Perozo, E., Papazian, D. M. & Stefani, E. Science 254, 679–683 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Gilly, W. F. & Armstrong, C. M. J. gen. Physiol. 79, 965–996 (1982).

    Article  CAS  Google Scholar 

  12. Vandenberg, C. A. & Bezanilla, F. Biophys. J. 60, 1511–1533 (1991).

    Article  CAS  Google Scholar 

  13. Schoppa, N. E., McCormack, K., Tanouye, M. A. & Sigworth, F. J. Science 255, 1712–1715 (1992).

    Article  ADS  CAS  Google Scholar 

  14. Monod, J., Wyman, J. & Changeux, J.-P. J. molec. Biol. 12, 88–118 (1965).

    Article  CAS  Google Scholar 

  15. Baumann, A., Grupe, A., Ackermann, A. & Pongs, O. EMBO J. 7, 2457–2463 (1988).

    Article  CAS  Google Scholar 

  16. Christie, M. J., Adelman, J. P., Douglass, J. & North, R. A. Science 244, 221–224 (1989).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  18. Heginbotham, L. & MacKinnon, R. Neuron 8, 483–491 (1992).

    Article  CAS  Google Scholar 

  19. Kavanaugh, M. P. et al. Neuron 8, 493–497 (1992).

    Article  CAS  Google Scholar 

  20. Hurst, R. S., Kavanaugh, M. P., North, R. A. & Adelman, J. P. Biophys. J. 61, A425 (1992).

    Google Scholar 

  21. Tytgat, J. & Hess, P. Biophys. J. 61, A426 (1992).

    Google Scholar 

  22. Liman, E. R., Hess, P., Weaver, F. & Koren, G. Nature 353, 752–756 (1991).

    Article  ADS  CAS  Google Scholar 

  23. Kreig, P. A. & Melton, D. A. Nucleic Acids Res. 12, 7057–7070 (1984).

    Article  Google Scholar 

  24. Hille, B. Ionic Channels of Excitable Membranes 1–607 (Sinauer, Sunderland, 1992).

    Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  26. Stuehmer, W. et al. Nature 339, 597–603 (1989).

    Article  ADS  CAS  Google Scholar 

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Tytgat, J., Hess, P. Evidence for cooperative interactions in potassium channel gating. Nature 359, 420–423 (1992). https://doi.org/10.1038/359420a0

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