Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+ channels in coronary arterial smooth muscle cells.
10.4196/kjpp.2017.21.2.225
- Author:
Sung Eun SHIN
1
;
Hongliang LI
;
Han Sol KIM
;
Hye Won KIM
;
Mi Seon SEO
;
Kwon Soo HA
;
Eun Taek HAN
;
Seok Ho HONG
;
Amy L FIRTH
;
Il Whan CHOI
;
Young Min BAE
;
Won Sun PARK
Author Information
1. Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea. parkws@kangwon.ac.kr
- Publication Type:Original Article
- Keywords:
Coronary artery;
Nortriptyline;
Voltage-dependent K⁺ channel
- MeSH:
Coronary Vessels;
Muscle, Smooth*;
Myocytes, Smooth Muscle*;
Nortriptyline*;
Serotonin
- From:The Korean Journal of Physiology and Pharmacology
2017;21(2):225-232
- CountryRepublic of Korea
- Language:English
-
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 IC₅₀ value of 2.86±0.52 µM and a Hill coefficient of 0.77±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.
