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The class III anti-arrhythmic agent, amiodarone, inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

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Abstract

We examined the inhibitory effect of amiodarone, a class III anti-arrhythmic agent, on voltage-dependent K+ (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. Amiodarone inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 3.9 ± 1.44 μM and a Hill coefficient of 0.45 ± 0.14. Amiodarone did not have a significant effect on the steady-state activation of Kv channels, but shifted the inactivation current toward a more negative potential. Application of consecutive pulses progressively augmented the amiodarone-induced Kv channel inhibition. Another class III anti-arrhythmic agent, dofetilide, did not inhibit the Kv current or change the inhibitory effect of amiodarone on Kv channels. Therefore, these results strongly suggest that amiodarone inhibits Kv currents in a concentration- and state-dependent manner.

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Acknowledgments

This work was supported by the National Research Foundation (NRF) of Korea grant funded by the Korean government (Ministry of Education: 2014-R1A1A4A01003840) (Ministry of Science, ICT and Future Planning: 2012-M3A9C7050184, 2015-R1A4A1038666).

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Authors and Affiliations

  1. Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, 1 Kangwondaehak-gil, Chuncheon, 200-701, South Korea

    Hongliang Li, Han Sol Kim, Hye Won Kim, Sung Eun Shin & Won Sun Park

  2. Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, 608-737, South Korea

    Won-Kyo Jung

  3. Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Kwon-Soo Ha

  4. Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Eun-Taek Han

  5. Institute of Medical Sciences, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, 200-701, South Korea

    Seok-Ho Hong

  6. Department of Pulmonary, Critical Care and Sleep Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, 90033, USA

    Amy L. Firth

  7. Department of Physiology, Konkuk University School of Medicine, Chungju, 380-701, South Korea

    Young Min Bae

  8. Department of Microbiology, Inje University College of Medicine, Busan, 614-735, South Korea

    Il-Whan Choi

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  1. Hongliang Li
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  2. Han Sol Kim
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Correspondence to Il-Whan Choi or Won Sun Park.

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All experimental procedures performed in studies involving animals were approved by the Committee for Animal Experiments of Kangwon National University.

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Li, H., Kim, H.S., Kim, H.W. et al. The class III anti-arrhythmic agent, amiodarone, inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. Naunyn-Schmiedeberg's Arch Pharmacol 389, 713–721 (2016). https://doi.org/10.1007/s00210-016-1232-8

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  • DOI: https://doi.org/10.1007/s00210-016-1232-8

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