title: Nortriptyline, a tricyclic antidepressant, inhibits voltage-dependent K+channels in coronary arterial smooth muscle cells.
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 IC50value 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.
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Shin
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Han Sol
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Seo
authors.affiliation: Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Pulmonary, Critical Care and Sleep Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA90033, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Firth
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan 48516, Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Physiology, Konkuk University School of Medicine, Chungju 27478, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Bae
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
keywords: Coronary artery; Nortriptyline; Voltage-dependent K+ channel