Open channel block of hKv1.5 by psoralen from Heracleum moellendorffii Hance.
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.
Eun
Jae Soon
JS
College of Pharmacy, Woosuk University, Samrye 565-701, Korea.
Choi
Bok Hee
BH
Park
Jeong Ah
JA
Lee
Ggot Im
GI
Lee
Taek Yul
TY
Kim
Dae Keun
DK
Jung
Young Hoon
YH
Yoo
Dong Jin
DJ
Kwak
Yong Geun
YG
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
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