The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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A Carbohydrate Fraction, AIP1, from Artemisia Iwayomogi Reduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier $K^+$ Channels in Rabbit Ventricular Myocytes

  • Park, Won-Sun (Department of Physiology, Institute of Medical Science, Kangwon National University School of Medicine) ;
  • Son, Youn-Kyoung (Department of Physiology, Institute of Medical Science, Kangwon National University School of Medicine) ;
  • Ko, Eun-A (National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University) ;
  • Choi, Seong-Woo (National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University) ;
  • Kim, Na-Ri (National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University) ;
  • Choi, Tae-Hoon (Department of Sport and Leisure Studies, Andong Science College) ;
  • Youn, Hyun-Joo (Department of Microbiology and School of Biotechnology & Biomedical Science, Inje University) ;
  • Jo, Su-Hyun (Department of Physiology, Institute of Medical Science, Kangwon National University School of Medicine) ;
  • Hong, Da-Hye (National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University) ;
  • Han, Jin (National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University)
  • Received : 2010.03.17
  • Accepted : 2010.05.10
  • Published : 2010.06.30
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Abstract

We investigated the effects of a hot-water extract of Artemisia iwayomogi, a plant belonging to family Compositae, on cardiac ventricular delayed rectifier $K^+$ current ($I_K$) using the patch clamp technique. The carbohydrate fraction AIP1 dose-dependently increased the heart rate with an apparent $EC_{50}$ value of $56.1{\pm}5.5\;{\mu}g/ml$. Application of AIP1 reduced the action potential duration (APD) in concentration-dependent fashion by activating $I_K$ without significantly altering the resting membrane potential ($IC_{50}$ value of $APD_{50}$: $54.80{\pm}2.24$, $IC_{50}$ value of $APD_{90}$: $57.45{\pm}3.47\;{\mu}g/ml$). Based on the results, all experiments were performed with $50\;{\mu}g/ml$ of AIP1. Pre-treatment with the rapidly activating delayed rectifier $K^+$ current ($I_{Kr}$) inhibitor, E-4031 prolonged APD. However, additional application of AIP1 did not reduce APD. The inhibition of slowly activating delayed rectifier $K^+$ current ($I_{Ks}$) by chromanol 293B did not change the effect of AIP1. AIP1 did not significantly affect coronary arterial tone or ion channels, even at the highest concentration of AIP1. In summary, AIP1 reduces APD by activating $I_{Kr}$ but not $I_{Ks}$. These results suggest that the natural product AIP1 may provide an adjunctive therapy of long QT syndrome.

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References

  1. Sanguinetti MC, Jurkiewicz NK. Two components of cardiac delayed rectifier $K^{+}$ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol. 1990;96:195-215. https://doi.org/10.1085/jgp.96.1.195
  2. Zeng J, Laurita KR, Rosenbaum DS, Rudy Y. Two components of the delayed rectifier $K^{+}$ current in ventricular myocytes of the guinea pig type. Theoretical formation and their role in repolarization. Circ Res. 1995;77:140-152. https://doi.org/10.1161/01.RES.77.1.140
  3. delayed rectifier potassium current using selective blockers of $I_{Kr}$ and $I_{Ks}$ in guinea-pig isolated ventricular myocytes. Exp Physiol. 1996a;81:587-603. https://doi.org/10.1113/expphysiol.1996.sp003961
  4. Heath BM, Terrar DA. The deactivation kinetics of the delayed rectifier components $I_{Kr}$ and $I_{Ks}$ in guinea-pig isolated ventricular myocytes. Exp Physiol. 1996b;81:605-621. https://doi.org/10.1113/expphysiol.1996.sp003962
  5. Chiang CE, Roden DM. The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol. 2000;36:1-12. https://doi.org/10.1016/S0735-1097(00)00716-6
  6. Salata JJ, Jurkiewicz NK, Wang J, Evans BE, Orme HT, Sanguinetti MC. A novel benzodiazepine that activates cardiac slow delayed rectifier $K^{+}$ currents. Mol Pharmacol. 1998;53: 220-230.
  7. Keating MT, Sanguinetti MC. Molecular and cellular mechanisms of cardiac arrhythmias. Cell. 2001;104:569-580. https://doi.org/10.1016/S0092-8674(01)00243-4
  8. Lee KR, Zee OP, Kwak JH, Kim YS, Park HK, Koo KA, Youn HJ. The polysaccharide fractions of Artemisia species. Korean J Pharmacogn. 1993;24:289-295.
  9. Park EJ, Nan JX, Kim JY, Kang HC, Choi JH, Lee SJ, Lee BH, Lee JH, Kim YC, Sohn DW. The ethanol-soluble part of a hot-water extract from Artemisia iwayomogi inhibits liver fibrosis induced by carbon tetrachloride in rats. J Pharm Pharmacol. 2000;52:875-881. https://doi.org/10.1211/0022357001774561
  10. Koo KA, Kwak JW, Lee KR, Zee OP, Woo ER, Park HK, Youn HJ. Antitumor and immuno-modulating activities of the polysaccharide fractions from Artemisia selengenesis and Artemisia iwayomogi. Arch Pharm Res. 1994;17:371-374. https://doi.org/10.1007/BF02974179
  11. Hwang JS, Chung HK, Bae EK, Lee AY, Ji HJ, Park DW, Jung HJ, Cho CW, Choi HJ, Lee DS, Lee KR, Youn HJ. The polysaccharide fraction AIP1 from Artemisia iwayomogi suppresses apoptotic death of the mouse spleen cells in culture. Arch Pharm Res. 2003;26:294-300. https://doi.org/10.1007/BF02976958
  12. Hwang JS, Ji HJ, Koo KA, Lee NH, Yeo HK, Cheong SW, Park JH, Oh GS, Yoon CS, Youn HJ. AIP1, a water-soluble fraction from Artemisia iwayomogi, suppresses thymocyte apoptosis in Vitro and down-regulates the expression of Fas gene. Biol Pharm Bull. 2005;28:921-924. https://doi.org/10.1248/bpb.28.921
  13. Ji HJ, Yeo HK, Lee NH, Hwang JS, Koo KA, Cheong SW, Park JH, Oh GS, Yoon CS, Youn HJ. A carbohydrate graction, AIP1, from Artemisia iwayomogi down-regulated Fas gene expression and suppresses apoptotic death of the thymocytes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biotechnol Lett. 2005;27:253-257. https://doi.org/10.1007/s10529-004-8294-2
  14. Kim NR, Youm JB, Joo H, Kim EY, Han J. Protein kinase C activates ATP-sensitive potassium channels in rabbit ventricular myocytes. Korean J Physiol Pharmacol. 2005;9:187-193.
  15. Park WS, Ko JH, Kim NR, Son YK, Kang SH, Warda M, Jung ID, Park YM, Han J. Increased inhibition of inward rectifier $K^{+}$ channels by angiotensin II in small-diameter coronary artery of isoproterenol-induced hypertrophied model. Arterioscler Thromb Vasc Biol. 2007;27:1768-1775. https://doi.org/10.1161/ATVBAHA.107.143339
  16. Lengyel C, Iost N, Virag L, Varro A, Lathrop DA, Papp JG. Pharmacological block of the slow component of the outward delayed rectifier current ($I_{Ks}$) fails to lengthen rabbit ventricular muscle QTc and action potential duration. Br J Pharmacol. 2001;132:101-110. https://doi.org/10.1038/sj.bjp.0703777
  17. Volders PG, Stengl M, van Opstal JM, Gerlach U, Spatjens RL, Beekman JD, Sipido KR, Vos MA. Probing the contribution of IKs to canine ventricular repolarization: Key role for betaadrenergic receptor stimulation. Circulation. 2003;107:2753-2760. https://doi.org/10.1161/01.CIR.0000068344.54010.B3
  18. Guerard NC, Traebert M, Suter W, Dumotier BM. Selective block of $I_{Ks}$ plays a significant role in MAP triangulation induced by $I_{Kr}$ block in isolated rabbit heart. J Pharmacol Toxicol Methods. 2008;58:32-40. https://doi.org/10.1016/j.vascn.2008.05.129
  19. Chung HK, Bae EK, Ji HJ, Hwang JS, Park DW, Kim EJ, Jung HJ, Choi HJ, Lee DS, Youn HJ. An oligosaccharide fraction from Korean mugwort herb suppresses death of the mouse thymocytes in culture by down-regulating the Fas death receptor gene. Biotechnol Lett. 2003;25:1549-1553. https://doi.org/10.1023/A:1025482516404
  20. Kim SH, Choi CH, Kim SY, Eun JS, Shin TY. Anti-allergic effects of Artemisia iwayomogi on mast cell-mediated allegy model. Exp Biol Med. 2005;230:82-88. https://doi.org/10.1177/153537020523000111
  21. Lee JA, Sung HN, Jeon CH, Gill BC, Oh GS, Youn HJ, Park JH. A carbohydrate fraction, AIP1 from Artemisia iwayomogi suppresses pulmonary eosinophilia and Th2-type cytokine production in an ovalbumin-induced allergic asthma. Down- regulation of TNF-$\alpha$ expression in the lung. Int Immunopharmacol. 2008;8:117-125. https://doi.org/10.1016/j.intimp.2007.10.022
  22. Ahn H, Kim JY, Lee HJ, Kim YK, Ryu JH. Inhibitors of inducible nitric oxide synthase expression from Artemisia iwayomogi. Arch Pharm Res. 2003;26:301-305. https://doi.org/10.1007/BF02976959
  23. Kim AR, Zou YN, Park TH, Shim KH, Kim MS, Kim ND, Kim JD, Bae SJ, Choi JS, Chung HY. Active components from Artemisia iwayomogi displaying ONOO- scavenging activity. Phytother Res. 2004;18:1-7. https://doi.org/10.1002/ptr.1358
  24. Takumi T, Ohkubo H, Nakanishi S. Cloning of a membrane protein that induced a slow voltage-gated potassium current. Science. 1988;242:1042-1045. https://doi.org/10.1126/science.3194754
  25. Folaander K, Smith JS, Antanavage J, Bennett C, Stein RB, Swanson R. Cloning and expression of the delayed rectifier $I_{Ks}$channel from neonatal rat heart and diethylstilbestrol-primed rat uterus. Proc Natl Acad Sci USA. 1990;87:2975-2979. https://doi.org/10.1073/pnas.87.8.2975
  26. Freeman LS, Kass RS. Expression of a minimal $K^{+}$ channel protein in mammalian cells and immunolocalization in guinea pig heart. Circ Res. 1993;73:968-973. https://doi.org/10.1161/01.RES.73.5.968
  27. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between and inherited and an acquired cardiac arrhythmia: HERG encodes the $I_{Kr}$ potassium channel. Cell. 1995;81:299-307. https://doi.org/10.1016/0092-8674(95)90340-2
  28. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT. Coassembly of KvLQT1 and mink ($I_{Ks}$) proteins to form cardiac $I_{Ks}$ potassium channel. Nature. 1996;384:80-83. https://doi.org/10.1038/384080a0
  29. Wang L, Feng Z, Kondo CS, Sheldon RS, Duff HJ. Developmental changes in the delayed rectifier $K^{+}$ channels in mouse heart. Circ Res. 1996;79:79-85. https://doi.org/10.1161/01.RES.79.1.79
  30. Hansen RS, Olesen SP, Ronn LC, Grunnet M. In vivo effects of the $I_{Kr}$ agonist NS 3623 on cardiac electrophysiology of the guinea pig. J Cardiovasc Pharmacol. 2008;52:35-41. https://doi.org/10.1097/FJC.0b013e31817dd013
  31. Heath BM, Terrar DA. Protein kinase C enhances the rapidly activating delayed rectifier potassium current, $I_{Kr}$, through a reduction in C-type inactivation in guinea-pig ventricular myocytes. J Physiol. 2000;522:391-402. https://doi.org/10.1111/j.1469-7793.2000.t01-2-00391.x
  32. Yuan XJ, Wang J, Juhaszova M, Golovina VA, Rubin LJ. Molecular basis and function of voltage-gated $K^{+}$ channels in pulmonary arterial smooth muscle cells. Am J Physiol. 1998;274:L621-635.
  33. Platoshyn O, Yu Y, Golovina VA, McDaniel SS, Krick S, Li L, Wang JY, Rubin LJ, Yuan JX. Chronic hypoxia decrease K(V) channel expression and function in pulmonary artery myocytes. Am J Physiol. 2001;280:L801-812.
  34. Ko EA, Han J, Jung ID, Park WS. Physiological roles of $K^{+}$ channels in vascular smooth muscle cells. J Smooth Muscle Res. 2008;44:65-81. https://doi.org/10.1540/jsmr.44.65

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