title: Effects of the natural flavone trimethylapigenin on cardiac potassium currents.
abstract: The natural flavones and polymethylflavone have been reported to have cardiovascular protective effects. In the present study, we determined whether quecertin, apigenin and their methylated compounds (3,7,3',4'-tetramethylquecertin, 3,5,7,3',4'-pentamethylquecertin, 7,4'-dimethylapigenin, and 5,7,4'-trimethylapigenin) would block the atrial specific potassium channel hKv1.5 using a whole-cell patch voltage-clamp technique. We found that only trimethylapigenin showed a strong inhibitory effect on hKv1.5 channel current. This compound suppressed hKv1.5 current in HEK 293 cell line (IC₅₀=6.4 μM), and the ultra-rapid delayed rectify K⁺ current I(Kur) in human atrial myocytes (IC₅₀=8.0 μM) by binding to the open channels and showed a use- and frequency-dependent manner. In addition, trimethylapigenin decreased transient outward potassium current (I(to)) in human atrial myocytes, inhibited acetylcholine-activated K⁺ current (IC₅₀=6.8μM) in rat atrial myocytes. Interestingly, trimethylapigenin had a weak inhibition of hERG channel current. Our results indicate that trimethyapigenin significantly inhibits the atrial potassium currents hKv1.5/I(Kur) and I(KACh), which suggests that trimethylapigenin may be a potential candidate for anti-atrial fibrillation.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Xin-Ling
authors.initials: XL
authors.lastname: Du
authors.forename: Kui-Hao
authors.initials: KH
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Xin
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Jin
authors.forename: Ji-Zhong
authors.initials: JZ
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
authors.forename: Man-Wen
authors.initials: MW
authors.lastname: Jin
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D005260:Female; D057809:HEK293 Cells; D006325:Heart Atria / Q000166:cytology; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C548139:3,3',4',5,7-pentamethylquercetin; C544737:3,7,3',4'-O-tetramethylquercetin; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C103112:5,7,4'-trimethylapigenin; D047310:Apigenin; D011794:Quercetin