A minK–HERG complex regulates the cardiac potassium current IKr (original) (raw)

Nature volume 388, pages 289–292 (1997)Cite this article

Abstract

MinK is a widely expressed protein of relative molecular mass ∼15K that forms potassium channels by aggregation with other membrane proteins1,2,3. MinK governs ion channel activation4, regulation by second messengers5,6, and the function and structure of the ion conduction pathway7,8. Association of minK with a channel protein known as KvLQT1 produces a voltage-gated outward K+ current (_I_sK) resembling the slow cardiac repolarization current (_I_Ks)9,10. HERG, a human homologue of the ether-a-go-go gene of the fruitfly Drosophila melanogaster, encodes a protein that produces the rapidly activating cardiac delayed rectifier (_I_Kr)11,12. These two potassium currents, _I_Ks and _I_Kr, provide the principal repolarizing currents in cardiac myocytes for the termination of action potentials13,14. Although heterologously expressed HERG channels are largely indistinguishable from native cardiac _I_Kr, a role for minK in this current is suggested by the diminished _I_Kr in an atrial tumour line subjected to minK antisense suppression15. Here we show that HERG and minK form a stable complex, and that this heteromultimerization regulates _I_Kr activity. MinK, through the formation of heteromeric channel complexes, is thus central to the control of the heart rate and rhythm.

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Acknowledgements

We thank G. Robertson for HERG cDNA, J. Nerbonne and A. Pond for HERG antisera, K. Sawada for E4031, and V. S. Srinivas for technical assistance. This work was supported by funds from the AECOM Molecular Cardiology Endowment to T.V.M., M.B.M. and G.I.F., and by grants to G.I.F. from the American Heart Association (Established Investigator) and the Council for Tobacco Research and to S.A.N.G. from the NIH-NIGMS and Donaghue Foundation.

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Authors and Affiliations

  1. Section of Molecular Cardiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, 10461, New York, USA
    Thomas V. McDonald, Zhihui Yu, Zhen Ming, Eugen Palma, Marian B. Meyers & Glenn I. Fishman
  2. *Departments of Pediatrics and Cellular and Molecular Physiology, The Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, 06536, Connecticut, USA
    Ke-Wei Wang & Steve A. N. Goldstein

Authors

  1. Thomas V. McDonald
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  2. Zhihui Yu
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  3. Zhen Ming
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  4. Eugen Palma
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  5. Marian B. Meyers
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  6. Ke-Wei Wang
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  7. Steve A. N. Goldstein
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  8. Glenn I. Fishman
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Correspondence toThomas V. McDonald.

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McDonald, T., Yu, Z., Ming, Z. et al. A minK–HERG complex regulates the cardiac potassium current _I_Kr.Nature 388, 289–292 (1997). https://doi.org/10.1038/40882

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