Nortriptyline, a tricyclic antidepressant, inhibits voltagedependent K+ channels in coronary arterial smooth muscle cells

• Published in: The Korean journal of physiology & pharmacology pp. 225 - 232
• Main Authors: 신성은, Hongliang Li, 김한솔, 김혜원, 서미선, 하권수, 한은택, 홍석호, Amy L. Firth, 최일환, 배영민, 박원선
• Format: Journal Article
• Language: English
• Published: 대한약리학회 01.03.2017
• Subjects: 약리학
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2017.21.2.225

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 usedependent. 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 concentrationdependent and state-independent manner independently of serotonin reuptake. KCI Citation Count: 7