Skip to main content

Advertisement

Log in

The inward rectification mechanism of the HERG cardiac potassium channel

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

A HUMAN genetic defect associated with 'long Q–T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel1. The HERG K+ channel is unusual in that it seems to have the architectural plan of the depolarization-activated K+ channel family (six putative trans-membrane segments), yet it exhibits rectification like that of the inward-rectifying K+ channels, a family with different molecular structure (two transmembrane segments)2–4. We have studied HERG channels expressed in mammalian cells and find that this inward rectification arises from a rapid and voltage-dependent inactivation process that reduces conductance at positive voltages. The inactivation gating mechanism resembles that of C-type inactivation, often considered to be the Slow inactivation' mechanism of other K+ channels. The characteristics of this gating suggest a specific role for this channel in the normal suppression of arrhythmias.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Curran, M. E. et al. Cell 80, 795–803 (1995).

    Article  CAS  Google Scholar 

  2. Warmke, J. W. & Ganetzky, B. Proc. natn. Acad. Sci. U.S.A. 91, 3438–3442 (1994).

    Article  ADS  CAS  Google Scholar 

  3. Sanguinetti, M. C., Jiang, C., Curran, M. E. & Keating, M. T. Cell 81, 299–307 (1995).

    Article  CAS  Google Scholar 

  4. Trudeau, M. C., Warmke, J. W., Ganetzky, B. & Robertson, G. A. Science 269, 92–95 (1995).

    Article  ADS  CAS  Google Scholar 

  5. Sanguinetti, M. C. & Jurkiewicz, N. K. J. gen. Physiol. 96, 195–215 (1990).

    Article  CAS  Google Scholar 

  6. Shibasaki, T. J. Physiol., Lond. 387, 227–250 (1987).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  8. Lu, Z. & MacKinnon, R. Nature 371, 243–246 (1994).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  13. Demo, S. D. & Yellen, G. Neuron 7, 743–753 (1991).

    Article  CAS  Google Scholar 

  14. Hoshi, T., Zagotta, W. N. & Aldrich, R. W. Neuron 7, 547–556 (1991).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  16. Yellen, G., Sodickson, D., Chen, T.-Y. & Jurman, M. E. Biophys. J. 66, 1068–1075 (1994).

    Article  CAS  Google Scholar 

  17. Anderson, J. A., Huprikar, S. S., Kochian, L. V., Lucas, W. J. & Gaber, R. F. Proc. natn. Acad. Sci. U.S.A. 89, 3736–3740 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Cao, Y., Crawford, N. M. & Schroeder, J. I. J. biol. Chem. 270, 17697–17701 (1995).

    Article  CAS  Google Scholar 

  19. Hoshi, T. J. gen. Physiol. 105, 309–328 (1995).

    Article  CAS  Google Scholar 

  20. Löpez-Barneo, J., Hoshi, T., Heinemann, S. H. & Aldrich, R. W. Recept. Chan. 1, 61–71 (1993).

    Google Scholar 

  21. Heginbotham, L., Lu, Z., Abramson, T. & MacKinnon, R. Biophys. J 66, 1061–1067 (1994).

    Article  CAS  Google Scholar 

  22. Baukrowitz, T. & Yellen, G. Neuron 15, 951–960 (1995).

    Article  CAS  Google Scholar 

  23. Baukrowitz, T. & Yellen, G. Science 271, 653–656 (1996).

    Article  ADS  CAS  Google Scholar 

  24. Jurman, M. E., Boland, L. M., Liu, Y. & Yellen, G. BioTechniques 17, 876–881 (1994).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, P., Baukrowitz, T. & Yellen, G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 379, 833–836 (1996). https://doi.org/10.1038/379833a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/379833a0

  • Springer Nature Limited

This article is cited by

Navigation