Effects of oxypeucedanin on hKv1.5 and action potential duration.
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.
Eun
Jae Soon
JS
College of Pharmacy, Woosuk University, Samrye, Korea.
Park
Jung Ah
JA
Choi
Bok Hee
BH
Cho
Sun Kyung
SK
Kim
Dae Keun
DK
Kwak
Yong Geun
YG
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
D011564:Furocoumarins; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; C031535:oxypeucadanin