Skip to main content
SpringerLink
Log in

Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+channel

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

INWARD-RECTIFIER potassium channels conduct K+across the cell membrane more efficiently in the inward than outward direction. This unusual conduction property is directly related to the biological action of these channels1–6. One basis for inward rectification is voltage-dependent blockade by intracellular Mg2+ (refs 1, 7–9): strong inward-rectifier channels are so sensitive to intracellular Mg2+ that no outward K+ current is measurable under physiological conditions; weak inward rectifiers are less sensitive and allow some K+ to flow outwards. Background Kl channels and acetylcholine-regulated K+ channels from the heart are examples of strong inward rectifiers and ATP-sensitive K+ channels are weak rectifiers1,7a–10. Here we show that mutations at one position in the second transmembrane segment can alter the Mg2+affinity and convert a weakly rectifying channel (ROMK1) into a strong rectifier. The amino acid at this position exposes its side chain to the aqueous pore and affects Mg2+ blockade as well as K+ conduction through an electrostatic mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hille, B. Ionic Channels of Excitable Membranes (Sinauer, Sunderland, MA, 1991).

    Google Scholar 

  2. Trautwein, W. & Dudel, J. Pflügers Arch. 266, 324–334 (1958).

    Article  CAS  Google Scholar 

  3. Noma, A., Peper, K. & Trautwein, W. Pflügers Arch. 400, 424–431 (1983).

    Google Scholar 

  4. Sakmann, B., Noma, A. & Trautwein, W. Nature 303, 250–253 (1983).

    Article  ADS  CAS  Google Scholar 

  5. Seojima, M. & Noma, A. Pflügers Arch. 400, 424–431 (1984).

    Article  Google Scholar 

  6. Ashcroft, F. M. & Rorsman, P. Biochem. Soc. Trans. 18, 109–111 (1990).

    Article  CAS  Google Scholar 

  7. Horie, M., Isisawa, H. & Noma, A. J. Physiol. 387, 251–272 (1987).

    Article  CAS  Google Scholar 

  8. Matsuda, H., Saigusa, A. & Isisawa, H. Nature 325, 156–159 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Vandenberg, C. A. Proc. natn. Acad. Sci. U.S.A. 84, 2560–2564 (1987).

    Article  ADS  CAS  Google Scholar 

  10. Matsuda, H. J. Physiol. 435, 83–99 (1991).

    Article  CAS  Google Scholar 

  11. Ho, K. et al. Nature 362, 31–38 (1993).

    Article  ADS  CAS  Google Scholar 

  12. Nichols, C. G., Ho, K. & Hebert, S. J. Physiol. 476, 399–409 (1994).

    Article  CAS  Google Scholar 

  13. Kubo, Y., Baldwin, T. J., Yan, Y. N. & Jan, L. Y. Nature 362, 127–132 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Miller, C. Science 252, 1092–1096 (1991).

    Article  ADS  CAS  Google Scholar 

  15. Choi, K. L., Mossman, C., Aube, J. & Yellen, G. Neuron 10, 533–541 (1993).

    Article  CAS  Google Scholar 

  16. Kirsch, G. E., Shieh, C. C., Drewe, J. A., Vener, D. F. & Brown, A. M. Neuron 11, 503–512 (1993).

    Article  CAS  Google Scholar 

  17. Slesinger, P. A., Jan, Y. N. & Jan, L. Y. Neuron 11, 739–749 (1993).

    Article  CAS  Google Scholar 

  18. Lopez, G. A., Jan, Y. N. & Jan, L. Y. Nature 367, 179–182 (1994).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  20. Dascal, N. et al. Proc. natn. Acad. Sci. U.S.A. 90, 10235–10239 (1993).

    Article  ADS  CAS  Google Scholar 

  21. Stanfield, P. R. et al. J. Physiol. 475, 1–7 (1994).

    Article  CAS  Google Scholar 

  22. Kurachi, Y. J. Physiol. 366, 365–385 (1985).

    Article  CAS  Google Scholar 

  23. Ishihara, K., Mitsuiye, T., Noma, A. & Takano, T. J. Physiol. 419, 297–320 (1989).

    Article  CAS  Google Scholar 

  24. Silver, M. R. & DeCoursey, T. E. J. gen. Physiol. 96, 109–133 (1990).

    Article  CAS  Google Scholar 

  25. Taglialatela, M., Wibb, B. A., Caporaso, R. & Brown, A. M. Science 264, 844–847 (1994).

    Article  ADS  CAS  Google Scholar 

  26. Creighton, T. E. Proteins: Structures and Molecular Properties 2nd edn (Freeman, New York, 1993).

    Google Scholar 

  27. MacKinnon, R., Reinhart, P. H. & White, M. M. Neuron 1, 997–1001 (1988).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Grahame, D. Chem. Rev. 41, 441–501 (1947).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Zhe Lu & Roderick MacKinnon

Authors
  1. Zhe Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roderick MacKinnon
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, Z., MacKinnon, R. Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+channel. Nature 371, 243–246 (1994). https://doi.org/10.1038/371243a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/371243a0

  • Springer Nature Limited

This article is cited by

Search

Navigation