Class III antiarrhythmic drug dronedarone inhibits cardiac inwardly rectifying Kir2.1 channels through binding at residue E224
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- 作者：Panagiotis Xynogalos (1)
Claudia Seyler (1)
Daniel Scherer (1)
Christoph Koepple (1)
Eberhard P. Scholz (1)
Dierk Thomas (1) (2)
Hugo A. Katus (1) (2)
Edgar Zitron (1) (2) - 关键词：Class III antiarrhythmic drug ; Dronedarone ; Cardiac inwardly rectifying Kir2.x channels ; Residue E224 ; IK1
- 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：387
- 期：12
- 页码：1153-1161
- 全文大小：587 KB
- 参考文献：1. Amoros I et al (2013) Propafenone blocks human cardiac Kir2.x channels by decreasing the negative electrostatic charge in the cytoplasmic pore. Biochem Pharmacol 86:267鈥?78 CrossRef
2. Bosch RF, Li GR, Gaspo R, Nattel S (1999a) Electrophysiologic effects of chronic amiodarone therapy and hypothyroidism, alone and in combination, on guinea pig ventricular myocytes. J Pharmacol Exp Ther 289:156鈥?65
3. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, K眉hlkamp V (1999b) Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 44:121鈥?31 CrossRef
4. Connolly SJ et al (2011) Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 365:2268鈥?276. doi:10.1056/NEJMoa1109867 CrossRef
5. Danelich IM, Reed BN, Hollis IB, Cook AM, Rodgers JE (2013) Clinical update on the management of atrial fibrillation. Pharmacotherapy 33:422鈥?46. doi:10.1002/phar.1217 CrossRef
6. de Boer TP et al (2010) The anti-protozoal drug pentamidine blocks KIR2.x-mediated inward rectifier current by entering the cytoplasmic pore region of the channel. Br J Pharmacol 159:1532鈥?541 CrossRef
7. Dhamoon AS, Jalife J (2005) The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis. Heart Rhythm 2:316鈥?24. doi:10.1016/j.hrthm.2004.11.012 CrossRef
8. Dobrev D, Graf E, Wettwer E, Himmel HM, H谩la O, Doerfel C, Christ T, Sch眉ler S, Ravens U (2001) Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K, ACh) in chronic human atrial fibrillation: decrease in GIRK4 mRNA correlates with reduced I(K, ACh) and muscarinic receptor-mediated shortening of action potentials. Circulation 104:2551鈥?557 CrossRef
9. Du X, Zhang H, Lopes C, Mirshahi T, Rohacs T, Logothetis DE (2004) Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of Kir channels by diverse modulators. J Biol Chem 279:37271鈥?7281. doi:10.1074/jbc.M403413200 CrossRef
10. Ferrer T, Ponce-Balbuena D, Lopez-Izquierdo A, Arechiga-Figueroa IA, de Boer TP, van der Heyden MA, Sanchez-Chapula JA (2011) Carvedilol inhibits Kir2.3 channels by interference with PIP(2)鈥揷hannel interaction. Eur J Pharmacol 668:72鈥?7 CrossRef
11. Gautier P, Guillemare E, Marion A, Bertrand JP, Tourneur Y, Nisato D (2003) Electrophysiologic characterization of dronedarone in guinea pig ventricular cells. J Cardiovasc Pharmacol 41:191鈥?02 CrossRef
12. Girmatsion Z, Biliczki P, Bonauer A, Wimmer-Greinecker G, Scherer M, Moritz A, Bukowska A, Goette A, Nattel S, Hohnloser SH, Ehrlich JR (2009) Changes in microRNA-1 expression and IK1 up-regulation in human atrial fibrillation. Heart Rhythm 6:1802鈥?809 CrossRef
13. Hilgemann DW (1997) Cytoplasmic ATP-dependent regulation of ion transporters and channels: mechanisms and messengers. Annu Rev Physiol 59:193鈥?20. doi:10.1146/annurev.physiol.59.1.193 CrossRef
14. Hohnloser SH et al (2009) Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 360:668鈥?78. doi:10.1056/NEJMoa0803778 CrossRef
15. Logothetis DE, Lupyan D, Rosenhouse-Dantsker A (2007) Diverse Kir modulators act in close proximity to residues implicated in phosphoinositide binding. J Physiol 582:953鈥?65. doi:10.1113/jphysiol.2007.133157 CrossRef
16. Lopes CM, Zhang H, Rohacs T, Jin T, Yang J, Logothetis DE (2002) Alterations in conserved Kir channel鈥揚IP2 interactions underlie channelopathies. Neuron 34:933鈥?44 CrossRef
17. Lopez-Izquierdo A (2011a) Mechanisms for Kir channel inhibition by quinacrine: acute pore block of Kir2.x channels and interference in PIP2 interaction with Kir2.x and Kir6.2 channels. Pflugers Arch 462:505鈥?17. doi:10.1007/s00424-011-0995-5 CrossRef
18. Lopez-Izquierdo A et al (2011b) The antimalarial drug mefloquine inhibits cardiac inward rectifier K鈥?鈥塩hannels: evidence for interference in PIP2鈥揷hannel interaction. J Cardiovasc Pharmacol 57:407鈥?15 CrossRef
19. Madeja M, Musshoff U, Speckmann EJ (1997) Follicular tissues reduce drug effects on ion channels in oocytes of / Xenopus laevis. Eur J Neurosci 9:599鈥?04 CrossRef
20. Melnyk P, Zhang L, Shrier A, Nattel S (2002) Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle. Am J Physiol Heart Circ Physiol 283:H1123鈥揌1133
21. Noujaim SF et al (2007) Up-regulation of the inward rectifier K鈥?鈥塩urrent (I K1) in the mouse heart accelerates and stabilizes rotors. J Physiol 578:315鈥?26 CrossRef
22. Noujaim SF et al (2010) Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets. FASEB J 24:4302鈥?312. doi:10.1096/fj.10-163246 CrossRef
23. Noujaim SF, Stuckey JA, Ponce-Balbuena D, Ferrer-Villada T, L贸pez-Izquierdo A, Pandit SV, S谩nchez-Chapula JA, Jalife J (2011) Structural bases for the different anti-fibrillatory effects of chloroquine and quinidine. Cardiovasc Res 89:862鈥?69. doi:10.1093/cvr/cvr008 CrossRef
24. Ponce-Balbuena D, Lopez-Izquierdo A, Ferrer T, Rodriguez-Menchaca AA, Arechiga-Figueroa IA, Sanchez-Chapula JA (2009) Tamoxifen inhibits inward rectifier K鈥?鈥?.x family of inward rectifier channels by interfering with phosphatidylinositol 4,5-bisphosphate鈥揷hannel interactions. J Pharmacol Exp Ther 331:563鈥?73 CrossRef
25. Preisig-Muller R (2002) Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen鈥檚 syndrome. Proc Natl Acad Sci U S A 99:7774鈥?779. doi:10.1073/pnas.102609499 CrossRef
26. Rodriguez-Menchaca AA, Navarro-Polanco RA, Ferrer-Villada T, Rupp J, Sachse FB, Tristani-Firouzi M, Sanchez-Chapula JA (2008) The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel. Proc Natl Acad Sci U S A 105:1364鈥?368. doi:10.1073/pnas.0708153105 CrossRef
27. Rohacs T, Lopes CM, Jin T, Ramdya PP, Molnar Z, Logothetis DE (2003) Specificity of activation by phosphoinositides determines lipid regulation of Kir channels. Proc Natl Acad Sci U S A 100:745鈥?50. doi:10.1073/pnas.0236364100 CrossRef
28. Sato R, Koumi S, Singer DH, Hisatome I, Jia H, Eager S, Wasserstrom JA (1994) Amiodarone blocks the inward rectifier potassium channel in isolated guinea pig ventricular cells. J Pharmacol Exp Ther 269:1213鈥?219
29. Schimpf R, Bauersfeld U, Gaita F, Wolpert C (2005a) Short QT syndrome: successful prevention of sudden cardiac death in an adolescent by implantable cardioverter鈥揹efibrillator treatment for primary prophylaxis. Heart Rhythm 2:416鈥?17. doi:10.1016/j.hrthm.2004.11.026 CrossRef
30. Schimpf R, Wolpert C, Gaita F, Giustetto C, Borggrefe M (2005b) Short QT syndrome. Cardiovasc Res 67:357鈥?66. doi:10.1016/j.cardiores.2005.03.026 CrossRef
31. Schram G, Pourrier M, Wang Z, White M, Nattel S (2003) Barium block of Kir2 and human cardiac inward rectifier currents: evidence for subunit-heteromeric contribution to native currents. Cardiovasc Res 59:328鈥?38 CrossRef
32. Singh BN et al (2007) Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N England J Med 357:987鈥?99. doi:10.1056/NEJMoa054686 CrossRef
33. Thomas D et al (2003) Acute effects of dronedarone on both components of the cardiac delayed rectifier K鈥?鈥塩urrent, HERG and KvLQT1/minK potassium channels. Br J Pharmacol 140:996鈥?002 CrossRef
34. Tristani-Firouzi M, Etheridge SP (2010) Kir2.1 channelopathies: the Andersen鈥揟awil syndrome. Pflugers Arch 460:289鈥?94 CrossRef
35. Tristani-Firouzi M et al (2002) Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Investig 110:381鈥?88 CrossRef
36. Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, Nerbonne JM (1997) Outward K鈥?鈥塩urrent densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res 80:772鈥?81 CrossRef
37. Varro A et al (2001) Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone. Br J Pharmacol 133:625鈥?34 CrossRef
38. Voigt N, Trausch A, Knaut M, Matschke K, Varr贸 A, Van Wagoner DR, Nattel S, Ravens U, Dobrev D (2010) Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation. Circ Arrhythm Electrophysiol 3:472鈥?80. doi:10.1161/CIRCEP.110.954636 CrossRef
39. Wang Z, Yue L, White M, Pelletier G, Nattel S (1998) Differential distribution of inward rectifier potassium channel transcripts in human atrium versus ventricle. Circulation 98:2422鈥?428 CrossRef
40. Xia M et al (2005) A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem Biophys Res Commun 332:1012鈥?019 CrossRef
41. Xie LH, John SA, Ribalet B, Weiss JN (2008) Phosphatidylinositol-4,5-bisphosphate (PIP2) regulation of strong inward rectifier Kir2.1 channels: multilevel positive cooperativity. J Physiol 586:1833鈥?848 CrossRef
42. Zaritsky JJ, Eckman DM, Wellman GC, Nelson MT, Schwarz TL (2000) Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation. Circ Res 87:160鈥?66 CrossRef
43. Zobel C, Cho HC, Nguyen TT, Pekhletski R, Diaz RJ, Wilson GJ, Backx PH (2003) Molecular dissection of the inward rectifier potassium current (IK1) in rabbit cardiomyocytes: evidence for heteromeric co-assembly of Kir2.1 and Kir2.2. J Physiol 550:365鈥?72 CrossRef - 作者单位：Panagiotis Xynogalos (1)
Claudia Seyler (1)
Daniel Scherer (1)
Christoph Koepple (1)
Eberhard P. Scholz (1)
Dierk Thomas (1) (2)
Hugo A. Katus (1) (2)
Edgar Zitron (1) (2)
1. Department of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
2. DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany - ISSN：1432-1912
文摘
Dronedarone is a novel class III antiarrhythmic drug that is widely used in atrial fibrillation. It has been shown in native cardiomyocytes that dronedarone inhibits cardiac inwardly rectifying current IK1 at high concentrations, which may contribute both its antifibrillatory efficacy and its potential proarrhythmic side effects. However, the underlying mechanism has not been studied in further detail to date. In the mammalian heart, heterotetrameric assembly of Kir2.x channels is the molecular basis of IK1 current. Therefore, we studied the effects of dronedarone on wild-type and mutant Kir2.x channels in the Xenopus oocyte expression system. Dronedarone inhibited Kir2.1 currents but had no effect on Kir2.2 or Kir2.3 currents. Onset of block was slow but completely reversible upon washout. Blockade of Kir2.1 channels did not exhibit strong voltage dependence or frequency dependence. In a screening with different Kir2.1 mutants lacking specific binding sites within the cytoplasmic pore region, we found that residue E224 is essential for binding of dronedarone to Kir2.1 channels. In conclusion, direct block of Kir2.1 channel subunits by dronedarone through binding at E224 may underlie its inhibitory effects on cardiac IK1 current.