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Effect of matrine on human ether à go-go related gene (HERG) channels expressed in Chinese hamster ovary cells

  • Experimental Research
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Abstract

Objective

To observe the effect of matrine on human ether à go-go related gene (HERG) potassium channels expressed in Chinese hamster ovary (CHO) cells and investigate whether HERG channel is a new target of the pharmacological effect of matrine on arrhythmia and tumor

Methods

HERG channel potassium current in CHO cell was recorded using whole-cell patch-clamp technique, and the influence of matrine on the current was explored.

Results

Matrine inhibited HERG potassium current in a dose-dependent manner, and the 50% inhibitory concentration (IC IC50) was 411±23 μmol/L. Matrine had no significant effect on the activation kinetics, and mainly blocked HERG channels in their closed state.

Conclusions

The blocking effect of matrine on HERG channels might be one of the mechanisms against arrythmias and tumors. Unlike most other blockers exerting blocking effect at the intracellular sites by entering the cell with the opening of HERG channel, matrine blocked HERG channels at the extracellular sites.

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References

  1. Shah RR. Drugs, QT interval prolongation and ICH E14: the need to get it right. Drug Saf 2005; 28: 115–125.

    Article  PubMed  Google Scholar 

  2. Lastraioli E, Guasti L, Crociani O, Polvani S, Hofmann G, Witchel H, et al. herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells. Cancer Res 2004;64:606–611.

    Article  CAS  PubMed  Google Scholar 

  3. Sanguinetti MC, Tristani-Firouzi M. HERG potassium channels and cardiac arrhythmia. Nature 2006;440:463–469.

    Article  CAS  PubMed  Google Scholar 

  4. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995;81:299–307.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang Y, Du J, Zhang Y, Sun HL, Pan ZW, Lu YJ, et al. Effects of matrine, oxymatrine and resveratrol on HERG channel expression. Acta Pharm Sin 2007;42:139–144.

    Article  CAS  Google Scholar 

  6. Yatani A, Wakamori M, Mikala G, Bahinski A. Block of transient outward-type cloned cardiac K+ channel currents by quinidine. Circ Res 1993;73:351–359.

    CAS  PubMed  Google Scholar 

  7. Deal KK, England SK, Tamkun MM. Molecular physiology of cardiac potassium channels. Physiol Rev 1996;76:49–67.

    CAS  PubMed  Google Scholar 

  8. Amos GJ, Jacobson I, Duker G, Carlsson L. Block of HERG-carried K+ currents by the new repolarization delaying agent H345/52. J Cardiovas Electrophysiol 2003;14:651–658.

    Article  Google Scholar 

  9. Sanchez-Chapula JA, Ferer T, Navaro-Polanco RA, Sanguinetti MC. Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain. Mol Pharmacol 2003; 63: 1051–1058.

    Article  CAS  PubMed  Google Scholar 

  10. Tu DN, Liao YH, Zou AR, Du YM, Run Q, Wang XP, et al. Electropharmacological properties of telmisartan in blocking hKv1.5 and HERG potassium channels expressed on Xenopus laevis oocytes. Acta Pharmacol Sin 2008;29:913–922.

    Article  CAS  PubMed  Google Scholar 

  11. Su Z, Chen J, Martin RL, McDermott JS, Cox BF, Gopalakrishnan M, et al. Block of hERG channel by ziprasidone: biophysical properties and molecular determinants. Biochem Pharmacol 2006; 7l: 278–286.

    Article  Google Scholar 

  12. Milnes JT, Dempsey CE, Ridley JM, Crociani O, Arcangeli A, Hancox JC, et al. Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm-1 scorpion toxin. FEBS Letters 2003; 547: 20–26.

    Article  CAS  PubMed  Google Scholar 

  13. Vandenberg JI, Torres AM, Campbell TJ, Kuchel PW. The HERG K+ channel: progress in understanding the molecular basis of its unusual gating kinetics. Eur Biophys J 2004;33:89–97.

    Article  CAS  PubMed  Google Scholar 

  14. Shan HL, Yang BF, Zhou YH, Wang H, Li BX. Effects of matrine on aconitine-induced electrophysiological changes in rat ventricular myocytes. J Chin Pharm Sci 2004;13:193–198.

    CAS  Google Scholar 

  15. Yang BF, Li BX, Zhou YH, Dong DL, Shan HL, Wang L. Inhibitory effects of matrine, E-4031, dofetilide and RP58866 on inward rectifier potassium current in rabbit ventricular myocytes. Chin Pharm Toxicol 2004;18:407–414.

    CAS  Google Scholar 

  16. Zhang W, Pan ZW, Feng TM, Lu YJ, Dong DL, Yang BF. Effects of matrine on the rapid component of delayed rectifier potassium current in ischemic ventricular myocytes. Chin Pharmacol Bull 2008;24:322–326.

    CAS  Google Scholar 

  17. Zhao J, Zheng JQ. HERG gene and tumor. Tumour J World 2005;4:148–151.

    Google Scholar 

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Authors and Affiliations

  1. Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, 100039, China

    Hong-jin Wu  (吴红金), Fang Xie  (谢 芳), Yu Cao  (曹 于), Yu-na Liu  (刘宇娜), Ji-yuan Yang  (杨继媛) & Xin-min Li  (李新民)

  2. Ion Channelopathy Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    An-ruo Zou  (邹安若) & Yi-mei Du  (杜以梅)

Authors
  1. Hong-jin Wu  (吴红金)
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  2. An-ruo Zou  (邹安若)
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  3. Fang Xie  (谢 芳)
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  4. Yi-mei Du  (杜以梅)
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  5. Yu Cao  (曹 于)
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  6. Yu-na Liu  (刘宇娜)
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  7. Ji-yuan Yang  (杨继媛)
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  8. Xin-min Li  (李新民)
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Corresponding author

Correspondence to Hong-jin Wu  (吴红金).

Additional information

Supported by Beijing Administration Bureau of Traditional Chinese Medicine (No. JZZ-312)

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Wu, Hj., Zou, Ar., Xie, F. et al. Effect of matrine on human ether à go-go related gene (HERG) channels expressed in Chinese hamster ovary cells. Chin. J. Integr. Med. 16, 430–434 (2010). https://doi.org/10.1007/s11655-010-9997-y

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  • DOI: https://doi.org/10.1007/s11655-010-9997-y

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