title: Inhibitory effects of imperatorin on voltage-gated K(+) channels and ATP-sensitive K(+) channels.
abstract: BACKGROUND
  Imperatorin is a furocoumarin isolated from Angelica archangelica and Cnidium monnieri. It has multiple neuromodulatory actions such as anticonvulsant effects, anxiolytic effects and anti-nociceptive effects. Although there have been reports demonstrating its effects on voltage-gated Na(+) channels (VGSC) and transient reversal potential (TRP) V1 channels in neurons, there is hitherto no work showing whether this compound affects voltage-gated K(+) (Kv) channels and ATP-sensitive K(+) (KATP) channels.
  
  
  METHODS
  We investigated the effects of imperatorin on K(+) channels using whole-cell configuration voltage-clamp technique.
  
  
  RESULTS
  Imperatorin inhibited Kv channels in differentiated neuronal NG108-15 cells, and caused a left shift in the steady-state inactivation curve without affecting activation gating. Imperatorin also inhibited heterologously expressed wild type Kv1.2 and Kv2.1 channels, but became much less potent in inhibiting Kv1.2 V370G, a mutant defective in C-type inactivation, implying that drug inhibition depends on C-type inactivation. At a high concentration (100μM), imperatorin also suppressed KATP channels.
  
  
  CONCLUSIONS
  Our results suggest that imperatorin inhibited both Kv and KATP channels.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Lan Yang Institute of Technology, Yilan, Taiwan.
authors.forename: Chin-Tsang
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Gong
authors.affiliation: Department of Pharmacology, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan; Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan. Electronic address: ymleung@mail.cmu.edu.tw.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D054086:KATP Channels / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D016296:Mutagenesis; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000235:genetics; D014162:Transfection
chemical_list: D011564:Furocoumarins; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C031534:imperatorin
keywords: ATP-sensitive K(+) channels; Imperatorin; NG108-15 cells; Neurons; Voltage-gated K(+) channels