title: Open channel block of hKv1.5 by psoralen from Heracleum moellendorffii Hance.
abstract: A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psoralen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Ltk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC50 value of 180 +/- 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.
authors.affiliation: College of Pharmacy, Woosuk University, Samrye 565-701, Korea.
authors.forename: Jae Soon
authors.initials: JS
authors.lastname: Eun
authors.forename: Bok Hee
authors.initials: BH
authors.lastname: Choi
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Park
authors.forename: Ggot Im
authors.initials: GI
authors.lastname: Lee
authors.forename: Taek Yul
authors.initials: TY
authors.lastname: Lee
authors.forename: Dae Keun
authors.initials: DK
authors.lastname: Kim
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Jung
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Yoo
authors.forename: Yong Geun
authors.initials: YG
authors.lastname: Kwak
mesh_terms: D000200:Action Potentials; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D030002:Heracleum; D006801:Humans; D066298:In Vitro Techniques; D051666:Kv1.5 Potassium Channel; D051379:Mice; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000737:chemistry; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats
chemical_list: D002121:Calcium Channel Blockers; D011564:Furocoumarins; C496981:KCNA5 protein, human; C496982:Kcna5 protein, mouse; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D010936:Plant Extracts; D024642:Potassium Channels, Voltage-Gated