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The inward rectification mechanism of the HERG cardiac potassium channel

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.

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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 

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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

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