title: Effects of oxypeucedanin on hKv1.5 and action potential duration.
abstract: A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC(50) value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between -40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.
authors.affiliation: College of Pharmacy, Woosuk University, Samrye, Korea.
authors.forename: Jae Soon
authors.initials: JS
authors.lastname: Eun
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Park
authors.forename: Bok Hee
authors.initials: BH
authors.lastname: Choi
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Cho
authors.forename: Dae Keun
authors.initials: DK
authors.lastname: Kim
authors.forename: Yong Geun
authors.initials: YG
authors.lastname: Kwak
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D029969:Angelica; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects* / Q000502:physiology; D051381:Rats
chemical_list: D011564:Furocoumarins; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C031535:oxypeucadanin