Open channel block of hKv1.5 by psoralen from Heracleum moellendorffii Hance

• Published in: Archives of pharmacal research Vol. 28; no. 3; pp. 269 - 273
• Main Authors: Eun, Jae Soon, Choi, Bok Hee, Park, Jeong Ah, Lee, Ggot Im, Lee, Taek Yul, Kim, Dae Keun, Jung, Young Hoon, Yoo, Dong Jin, Kwak, Yong Geun
• Format: Journal Article
• Language: English
• Published: Korea (South) 01.03.2005
• Subjects: Action Potentials; Animals; Calcium Channel Blockers - pharmacology; Cell Line; Dose-Response Relationship, Drug; Furocoumarins - pharmacology; Heart - drug effects; Heart - physiology; Heracleum; Humans; In Vitro Techniques; Kv1.5 Potassium Channel; Mice; Patch-Clamp Techniques; Plant Extracts - chemistry; Potassium Channels, Voltage-Gated - antagonists & inhibitors; Potassium Channels, Voltage-Gated - physiology; Rats
• ISSN: 0253-6269
• DOI: 10.1007/bf02977790

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.