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A cellular test system expressing hERG K+ channels for assaying drug cardiotoxicity: Elaboration and analysis

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Many drugs are cardiotoxic because they inhibit hERG K+ channels, thus prolonging the repolarization phase of the cardiomyocyte action potential giving rise to cardiac arrhythmias. Early detection of inhibiting effects of candidate drugs on the activity of K+ channels in cardiomyocytes is one of the main challenges in preclinical drug screening. The aim of this study was to obtain a cell line expressing recombinant hERG channels at a stable and reproducible level as a prerequisite to its further application as a test system.

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References

  1. Brown, A.M., Drugs, hERG and Sudden Death, Cell Calcium, 2004, vol. 35, pp. 543–547.

    Article  PubMed  CAS  Google Scholar 

  2. Nattel, S., Maguy, A., Le Bouter, S., and Yeh, Y.-H., Arrhythmogenic Ion-Channel Modeling in the Heart: Heart Failure, Myocardial Infarction, and Atrial Fibrillation, Physiol. Rev., 2007, vol. 87, pp. 425–456.

    Article  PubMed  CAS  Google Scholar 

  3. Sanguinetti, M.C. and Tristani-Firouz, M., hERG Potassium Channels and Cardiac Arrhythmia, Nature, 2006, vol. 440, pp. 463–469.

    Article  PubMed  CAS  Google Scholar 

  4. Lankipalli, R.S., Zhu, T., Guo, D., and Yan, G.-X., Mechanisms Uderlying Arrhythmogenesis in Long QT Syndrome, J. Electrocardiol., 2005, vol. 38, pp. 69–73.

    Article  PubMed  Google Scholar 

  5. Marban, E., Cardiac Channelopathies, Nature, 2002, vol. 415, pp. 213–218.

    Article  PubMed  CAS  Google Scholar 

  6. Sanguinetti, M.C., Jiang, C., Curran, M.E., and Keating, M.T., A Mechanistic Link between an Inherited and an Acquired Cardiac Arrhythmia: HERG Encodes the IKr Potassium Channel, Cell, 1995, vol. 81, pp. 299–307.

    Article  PubMed  CAS  Google Scholar 

  7. Trudeau, M.C., Warmke, J.W., Ganetzky, B., and Robertson, G.A., hERG a Human Inward Rectifier in the Voltage-Gated Potassium Channel Family, Science, 1995, vol. 269, pp. 92–95.

    Article  PubMed  CAS  Google Scholar 

  8. Snyders, D.J. and Chaudhary, A., High Affinity Open Channel Block by Dofetilide of HERG Expressed in a Human Cell Line, Mol. Pharmacol., 1996, vol. 49, pp. 949–955.

    PubMed  CAS  Google Scholar 

  9. Spector, P.S., Curran, M.E., Keating, M.T., and Sanguinetti, M.C., Class III Antiarrhythmic Drugs Block HERG, a Human Cardiac Delayed Rectifier K+ Channel. Open-Channel Block by Methanesulfonanilides, Circ. Res., 1996, vol. 78, pp. 499–503.

    PubMed  CAS  Google Scholar 

  10. Mohammad, S., Zhou, Z., Gong, Q., and January, C.T., Blockage of the HERG Human Cardiac K+ Channel by the Gastrointestinal Prokinetic Agent Cisapride, Am. J. Physiol. Heart. Circ. Physiol., 1997, vol. 273, pp. 2534–2538.

    Google Scholar 

  11. Simons, F.E., Kesselman, M.S., Giddings, N.G., Pelech, A.N., and Simons, K.J., Astemizole-Induced Torsades De Pointes, Lancet, 1988, vol. 2, p. 624.

    Article  PubMed  CAS  Google Scholar 

  12. Woosley, R.L., Chen, Y., Freiman, J.P., and Gilles, R.A., Mechanism of the Cardiotoxic Actions Terfenadine, JAMA, 1993, vol. 269, pp. 1532–1536.

    Article  PubMed  CAS  Google Scholar 

  13. Ball, P., Mandell, L., Niki, Y., and Tillotson, G., Comparative Tolerability of the Newer Fluoroquinolone Antibacterials, Drug. Saf., 1999, vol. 21, pp. 407–421.

    Article  PubMed  CAS  Google Scholar 

  14. Iannini, P., Doddamani, S., Byazrova, E., Curciumaru, I., and Kramer, H., Risk of Torsades De Pointes with Non-Cardiac Drugs. Prolongation of QT Interval Is Probably a Class Effect of Fluoroquinolones, BMJ, 2001, vol. 322, pp. 46–47.

    Article  PubMed  CAS  Google Scholar 

  15. Ball, H.L, Myers, J.S., and Cortez, D., ATRIP Binding to Replication Protein A-Single-Stranded DNA Promotes ATR-ATRIP Localization but Is Dispensable for Chk1 Phosphorylation, Mol. Biol. Cell, 2005, vol. 16, pp. 2372–2381.

    Article  PubMed  CAS  Google Scholar 

  16. Kolesnikov, S.S. and Margolskee, R.F., Extracellular K+ Activates a K+-and H+-Permeable Conductance in Frog Taste Cells, J. Physiol., 1998, vol. 507, pp. 415–432.

    Article  PubMed  CAS  Google Scholar 

  17. Vandenberg, J.I., Torres, A.M., Campbell, T.J., and Kuchel, P.W., The HERG K+ Channel: Progress in Understanding the Molecular Basis of Its Unusual Gating Kinetics, Eur. Biophys. J., 2004, vol. 33, pp. 89–97.

    Article  PubMed  CAS  Google Scholar 

  18. Lin, G.X., Zhou, J., Nattek, S., and Koren, G., Single-Channel Recording of a Rapid Delayed Rectifier Current in Adult Mouse Ventricular Myocytes: Basic Properties and Effects of Divalent Cations, J. Physiol., 2004, vol. 556, pp. 401–413.

    Article  Google Scholar 

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Authors and Affiliations

  1. Bioscreening Laboratory Ltd., ul. Gabrichevskogo 5, bld. 8, Moscow, 125367, Russia

    A. A. Shutov, O. V. Lebedeva & E. R. Safarova

  2. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, 142290, Moscow oblast, Russia

    R. A. Romanov, O. A. Rogachevskaya, N. V. Kabanova & S. S. Kolesnikov

Authors
  1. A. A. Shutov
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  2. O. V. Lebedeva
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  3. R. A. Romanov
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  4. O. A. Rogachevskaya
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  5. N. V. Kabanova
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  6. S. S. Kolesnikov
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  7. E. R. Safarova
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Correspondence to R. A. Romanov.

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Original Russian Text © A.A. Shutov, O.V. Lebedeva, R.A. Romanov, O.A. Rogachevskaya, N.V. Kabanova, S.S. Kolesnikov, E.R. Safarova, 2008, published in Biologicheskie Membrany, 2008, Vol. 25, No. 4, pp. 301–307.

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Shutov, A.A., Lebedeva, O.V., Romanov, R.A. et al. A cellular test system expressing hERG K+ channels for assaying drug cardiotoxicity: Elaboration and analysis. Biochem. Moscow Suppl. Ser. A 2, 253–258 (2008). https://doi.org/10.1134/S1990747808030094

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  • DOI: https://doi.org/10.1134/S1990747808030094

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