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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  );
  • 초록

    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.


  • 참고문헌 (21)

    1. Carneiro, L. V., Ferreira, S. R., Chen, C. L., and Andreu, G. L., Psoralen derivatives and longwave ultraviolet irradiation are activie in vitro against human melanoma cell line. J. Photochem. Photobiol. B, 76, 49-53 (2004) 
    2. Colatsky, T. J., Follmer, C. H., and Starmer, C. F., Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. Circulation, 82, 2235-2242 (1990) 
    3. Damjanovich, S., Gaspar, R., and Panyi, G., An alternative to conventional immunosuppression: small- molecule inhibitors of Kv1.3 channels. Mol. Interv., 4, 250-254 (2004) 
    4. Fedida, D., Chen, F. S., and Zhang, X., The 1997 Stevenson Award Lecture, Cardiac $K^+$ channel gating: cloned delayed rectifier mechanisms and drug modulation. Can. J. Physiol. Pharmacol., 76, 77-89 (1998) 
    5. Kostovic, K., Nola, I., Bucan, Z., and Situm, M., Treatment of vitiligo: current methods and new approaches. Acta. Dermatovenerol Croat., 11, 163-170 (2003) 
    6. Nakano, Y., Matsunaga, H., Saita, T., Mori, M., Katano, M., and Okabe, H., Anitproliferative constituents in Umbelliferae plants II. Screening for polyacetylenes in some Umbelliferae plants, and isolation of panaxynol and falcarindiol from the root of Heracleum moellendorffii. Biol. Pharm. Bull., 21, 257- 261 (1998) 
    7. Roden, D. M. and George, A. J. Jr., The cardiac ion channel: relevance to management of arrhythmias. Annu. Rev. Med., 47, 138-148 (1999) 
    8. Vaughan-Williams, E. M., Classification of antiarrhythmic actions. In: Vaughan-Willims EM, ed. Handbook of Experimental Pharmacology, 89, 45-62 (1989) 
    9. Wang, Z., Fermini, B., and Nattel, S., Sustained depolarizationinduced outward current in human atrial myocytes. Evidence for a novel delayed rectifier $K^+$ current similar to Kv1.5 cloned channel currents. Circ. Res., 73, 1061-1076 (1993) 
    10. Snyders, D. J., Tamkun, M. M., and Bennett, P. B., A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J. Gen. Physiol., 101, 513-543 (1993) 
    11. Mariano, T. M., Vetrano, A. M., Gentile, S. L., Heck, D. E., Whittemore, M. S., and Guillon, C. D., Cell-impermeant pyridinium derivatives of psoralens as inhibitors keratinocyte growth. Biochem. Pharmacol., 3, 31-39 (2002) 
    12. Roden, D. M., Current status of class III antiarrhythmic drug therapy. Am. J. Cardiol., 72, 44B-49B (1993) 
    13. Sanguinetti, M. C. and Keating, M. T., Role of delayed rectifier potassium channels in cardiac repolarization and arrhythmias. News Physiol. Sci., 12, 152-157 (1997) 
    14. Zhang, H. Q., Studies on the coumarin of root of Heracleum moellendorffii Hance. Zhong Yao Tong Bao., 6, 27-29 (1981) 
    15. Roden, D. M., Mechanism and management of proarrhythmia. Am. J. Cardiol., 82, 491-571 (1998) 
    16. Snyders, D. J., Knoth, K. M., Roberts, S. L., and Tamkun, M. M., Time-, voltage, and state-dependent block by quinidine of a cloned human cardiac potassium channel. Mol. Pharmacol., 41, 322-330 (1992) 
    17. Wu, S. J., Li, D. Y., Zhang, L., Du, X. D., and Zhang, Y. K., Studies on the coumarins from the zou-ma-qin (Heracleum moellendorffii Hance var. Paucivitatum). Yao Xue Xue Bao., 21, 599-604 (1986) 
    18. Wang, Z., Fermini, B., and Nattel, S., Rapid and slow components of delayed rectifier current in human atrial myocytes. Cardiovasc. Res., 28, 1540-1546 (1994) 
    19. Smith, M. L., Gregory, P., Bafi-Yeboa, N. F., and Arnason, J. T., Inhibition of DNA polymerization and antifungal specificity of furanocoumarins present in traditional medicines. Photochem. Photobiol., 79, 506-509 (2004) 
    20. Matsumoto, H. and Ohkura, Y., Studies of the absorption spectra of some psoralens. Chem. Pharm. Bull., 26, 3433- 3437 (1978) 
    21. Kwak, Y. G., Navarro-Polanco, R. A., Grobaski, T., Gallagher, D. J., and Tamkun, M. M., Phosphorylation is required for alteration of Kv1.5 $K^+$ channel function by the Kvbeta 1.3 subunit. J. Biol. Chem., 274, 25355-25361 (1999) 
  • 이 논문을 인용한 문헌 (4)

    1. 2006. "" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, 29(10): 834~839     
    2. 2006. "" The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology, 14(2): 102~105     
    3. 2007. "" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, 30(2): 155~160     
    4. 2011. "" Biomolecules & therapeutics, 19(1): 33~37     

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