title: The class III anti-arrhythmic agent, amiodarone, inhibits voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells.
abstract: We examined the inhibitory effect of amiodarone, a class III anti-arrhythmic agent, on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. Amiodarone inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 3.9 ± 1.44 μM and a Hill coefficient of 0.45 ± 0.14. Amiodarone did not have a significant effect on the steady-state activation of Kv channels, but shifted the inactivation current toward a more negative potential. Application of consecutive pulses progressively augmented the amiodarone-induced Kv channel inhibition. Another class III anti-arrhythmic agent, dofetilide, did not inhibit the Kv current or change the inhibitory effect of amiodarone on Kv channels. Therefore, these results strongly suggest that amiodarone inhibits Kv currents in a concentration- and state-dependent manner.
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, 1 Kangwondaehak-gil, Chuncheon, 200-701, 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, 1 Kangwondaehak-gil, Chuncheon, 200-701, 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, 1 Kangwondaehak-gil, Chuncheon, 200-701, 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, 1 Kangwondaehak-gil, Chuncheon, 200-701, 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, 608-737, 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, 200-701, 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, 200-701, 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, 200-701, South 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, CA, 90033, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Firth
authors.affiliation: Department of Physiology, Konkuk University School of Medicine, Chungju, 380-701, South Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Bae
authors.affiliation: Department of Microbiology, Inje University College of Medicine, Busan, 614-735, South Korea. cihima@inje.ac.kr.
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, 1 Kangwondaehak-gil, Chuncheon, 200-701, South Korea. parkws@kangwon.ac.kr.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D000638:Amiodarone
keywords: Amiodarone; Coronary artery; Voltage-dependent K+ channel