The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells

  • Shin, Sung Eun (Department of Physiology, Kangwon National University School of Medicine) ;
  • Li, Hongliang (Department of Physiology, Kangwon National University School of Medicine) ;
  • Kim, Han Sol (Department of Physiology, Kangwon National University School of Medicine) ;
  • Kim, Hye Won (Department of Physiology, Kangwon National University School of Medicine) ;
  • Seo, Mi Seon (Department of Physiology, Kangwon National University School of Medicine) ;
  • Ha, Kwon-Soo (Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine) ;
  • Han, Eun-Taek (Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine) ;
  • Hong, Seok-Ho (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Firth, Amy L. (Department of Pulmonary, Critical Care and Sleep Medicine, University of Southern California, Keck School of Medicine) ;
  • Choi, Il-Whan (Department of Microbiology, Inje University College of Medicine) ;
  • Bae, Young Min (Department of Physiology, Konkuk University School of Medicine) ;
  • Park, Won Sun (Department of Physiology, Kangwon National University School of Medicine)
  • Received : 2016.11.14
  • Accepted : 2016.12.07
  • Published : 2017.03.01
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Abstract

We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent $K^+$ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent $IC_{50}$ value of $2.86{\pm}0.52{\mu}M$ and a Hill coefficient of $0.77{\pm}0.1$. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential. Application of train pulses (1 or 2 Hz) did not change the nortriptyline-induced Kv channel inhibition, suggesting that the effects of nortiprtyline were not use-dependent. Preincubation with the Kv1.5 and Kv2.1/2.2 inhibitors, DPO-1 and guangxitoxin did not affect nortriptyline inhibition of Kv channels. From these results, we concluded that nortriptyline inhibited Kv channels in a concentration-dependent and state-independent manner independently of serotonin reuptake.

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