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The Pharmaceutical Society of Korea (대한약학회)
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Open Channel Block of hKv1.5 by Psoralen from Heracleum moellendorffii Hance

  • Eun Jae Soon (College of Pharmacy, Woosuk University) ;
  • Cho Bok Hee (Department of Pharmacology, Chonbuk National University Medical School) ;
  • Park Jeong Ah (Department of Pharmacology, Chonbuk National University Medical School) ;
  • Lee Ggot Im (Department of Pharmacology, Chonbuk National University Medical School) ;
  • Lee Taek Yul (College of Pharmacy, Woosuk University) ;
  • Kim Dae Keun (College of Pharmacy, Woosuk University) ;
  • Jung Young Hoon (College of Pharmacy, Woosuk University) ;
  • Yoo Dong Jin (Department of Chemistry, Seonam University) ;
  • Kwak Yong Geun (Department of Pharmacology, Chonbuk National University Medical School)
  • Published : 2005.03.01
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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 psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 180 $\pm$ 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.

Keywords

References

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