The Korean Journal of Physiology and Pharmacology

  • 제27권4호
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  • Pages.399-406
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  • 2023
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells

  • Hongliang Li (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Yue Zhou (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Yongqi Yang (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Yiwen Zha (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Bingqian Ye (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Seo-Yeong Mun (Department of Physiology, Kangwon National University School of Medicine) ;
  • Wenwen Zhuang (Department of Physiology, Kangwon National University School of Medicine) ;
  • Jingyan Liang (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Won Sun Park (Department of Physiology, Kangwon National University School of Medicine)
  • 투고 : 2023.03.23
  • 심사 : 2023.05.18
  • 발행 : 2023.07.01
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초록

Voltage-dependent K+ (Kv) channels are widely expressed on vascular smooth muscle cells and regulate vascular tone. Here, we explored the inhibitory effect of encainide, a class Ic anti-arrhythmic agent, on Kv channels of vascular smooth muscle from rabbit coronary arteries. Encainide inhibited Kv channels in a concentration-dependent manner with an IC50 value of 8.91 ± 1.75 μM and Hill coefficient of 0.72 ± 0.06. The application of encainide shifted the activation curve toward a more positive potential without modifying the inactivation curve, suggesting that encainide inhibited Kv channels by altering the gating property of channel activation. The inhibition by encainide was not significantly affected by train pulses (1 and 2 Hz), indicating that the inhibition is not use (state)-dependent. The inhibitory effect of encainide was reduced by pretreatment with the Kv1.5 subtype inhibitor. However, pretreatment with the Kv2.1 subtype inhibitor did not alter the inhibitory effects of encainide on Kv currents. Based on these results, encainide inhibits vascular Kv channels in a concentration-dependent and use (state)-independent manner by altering the voltage sensor of the channels. Furthermore, Kv1.5 is the main Kv subtype involved in the effect of encainide.

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과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2021-R1F1A1045544, 2021-R1A4A1031574) and The National Natural Science Foundation of China (No. 82100413).

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