2. Academic Validation
  3. The anticholinergic drug oxybutynin inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells

The anticholinergic drug oxybutynin inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells

  • Clin Exp Pharmacol Physiol. 2019 Nov;46(11):1030-1036. doi: 10.1111/1440-1681.13138.
Hongliang Li 1,  Mi Seon Seo 2,  Jin Ryeol An 2,  Hee Seok Jung 2,  Kwon-Soo Ha 3,  Eun-Taek Han 4,  Seok-Ho Hong 5,  Young Min Bae 6,  Dong Ryeol Ryu 7,  Won Sun Park 2
Affiliations

Affiliations

  • 1 Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment for Senile Diseases, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
  • 2 Department of Physiology, Institute of Medical Sciences, Kangwon National University, School of Medicine, Chuncheon, South Korea.
  • 3 Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, South Korea.
  • 4 Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea.
  • 5 Department of Internal Medicine, Institute of Medical Sciences, Kangwon National University School of Medicine, Chuncheon, South Korea.
  • 6 Department of Physiology, Konkuk University School of Medicine, Chungju, South Korea.
  • 7 Division of Cardiology, Department of Internal Medicine, Institute of Medical Sciences, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea.
PMID: 31330060 DOI: 10.1111/1440-1681.13138
Abstract

This study demonstrates the inhibitory effect of anticholinergic drug oxybutynin on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Oxybutynin inhibited vascular Kv channels in a concentration-dependent manner, with an IC50 value of 11.51 ± 0.38 μmol/L and a Hill coefficient (n) of 2.25 ± 0.12. Application of oxybutynin shifted the activation curve to the right and the inactivation curve to the left. Pretreatment with the Kv1.5 subtype inhibitor DPO-1 and the Kv2.1 subtype inhibitor guangxitoxin suppressed the oxybutynin-induced inhibition of the Kv current. However, application of the Kv7 subtype inhibitor linopirdine did not affect the inhibition by oxybutynin of the Kv current. The anticholinergic drug atropine did not inhibit the Kv current nor influence oxybutynin-induced inhibition of the Kv current. From these results, we concluded that oxybutynin inhibited the vascular Kv current in a concentration-dependent manner by influencing the steady-state activation and inactivation curves independent of its anticholinergic effect.

Keywords

coronary artery; oxybutynin; voltage-dependent K+ channels.

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