title: Inhibitory effects of a bisbenzylisoquinline alkaloid dauricine on HERG potassium channels.
abstract: BACKGROUND
  The roots of Menispermum dauricum have been widely used for the treatment of inflammation, allergy and arrhythmia in China for a long time. Dauricine (Dau), a bisbenzylisoquinline alkaloid from Menispermum dauricum, mainly contributes to the anti-arrhythmic effect and has received pharmacological attention. Dau can prolong the action potential duration (APD), which has been attributed to its ability to modulate Ca(2+) and several K(+) channels. However, its effects on human-ether-a-go-go-related gene (HERG) channels are unknown.
  
  
  OBJECTIVE
  The effects of Dau on HERG channels were investigated.
  
  
  METHODS
  Whole-cell patch-clamp technique was used to record HERG current (I(HERG)) carried by recombinant HERG channels expressed in HEK293 cells.
  
  
  RESULTS
  Dau inhibited I(HERG) in a concentration-dependent manner with an IC(50) of 3.5 μM. Development of block and washout were fast. The inhibitory action of Dau was contingent on channel gating, showing significant voltage and time dependence. Dau inhibited I(HERG) in the open and inactivated states, but not in the closed states. The activation curve was shifted in a negative direction.
  
  
  CONCLUSIONS
  Dau inhibits HERG encoded potassium channels and this action might be a molecular mechanism for the previously reported APD prolongation with this drug.
authors.affiliation: Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Fengtai District, Beijing, PR China. zhaojing106@163.com
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Lian
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.forename: Haitao
authors.initials: H
authors.lastname: Yuan
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Peng
mesh_terms: D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008516:Medicine, Chinese Traditional; D008564:Membrane Potentials; D031603:Menispermum / Q000737:chemistry; D018408:Patch-Clamp Techniques; D018517:Plant Roots; D010946:Plants, Medicinal; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
chemical_list: D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers; D011994:Recombinant Proteins; D044005:Tetrahydroisoquinolines; C035934:dauricine