title: The selective serotonin reuptake inhibitor dapoxetine inhibits voltage-dependent K+channels in rabbit coronary arterial smooth muscle cells.
abstract: We investigated the inhibitory effect of dapoxetine, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K+(Kv) channels using native smooth muscle cells from rabbit coronary arteries. Dapoxetine inhibited Kv channel currents in a concentration-dependent manner, with an IC50value of 2.68±0.94 μmol/L and a slope value (Hill coefficient) of 0.63±0.11. Application of 10 μmol/L dapoxetine accelerated the rate of inactivation of Kv currents. Although dapoxetine did not modify current activation kinetics, it caused a significant negative shift in the inactivation curves. Application of train step (1 or 2 Hz) progressively increased the inhibitory effect of dapoxetine on Kv channels. In addition, the recovery time constant was extended in its presence, suggesting that the longer recovery time constant from inactivation underlies a use-dependent inhibition of the channel. From these results, we conclude that dapoxetine inhibits Kv channels in a dose-, time-, use-, and state (open)-dependent manner, independent of serotonin reuptake inhibition.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: Han Sol
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Shin
authors.affiliation: Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, South Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.affiliation: Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, South 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, South Korea.
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
authors.affiliation: Institute of Medical Sciences, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Firth
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan, South Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, South Korea.
authors.forename: Won Sun
authors.identifier: http://orcid.org/0000-0001-5868-3797
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D003331:Coronary Vessels / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001596:Benzylamines; D009281:Naphthalenes; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D017367:Selective Serotonin Reuptake Inhibitors; C080598:dapoxetine
keywords: coronary artery; dapoxetine; serotonin reuptake inhibitor; smooth muscle; voltage-dependent K+ channel