DOI QR코드

DOI QR Code

Remodeling of Ion Channel Expression in Patients with Chronic Atrial Fibrillation and Mitral Valvular Heart Disease

  • Oh, Se-Il (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Ki-Bong (Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine) ;
  • Ahn, Hyuk (Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine) ;
  • Cho, Hyun-Ju (Departments of Cardiovascular Center and Clinical Research Institute Cardiovascular Laboratory, Seoul National University Hospital) ;
  • Choi, Yun-Shik (Department of Internal Medicine, Seoul National University College of Medicine)
  • Received : 2009.11.23
  • Accepted : 2010.07.26
  • Published : 2010.12.01

Abstract

Background/Aims: Underlying cardiac pathology and atrial fibrillation (AF) affect the molecular remodeling of ion channels in the atria. Changes in the expression of these molecules have not been demonstrated in Korean patients with mitral valvular heart disease. Thus, the purpose of this study was to analyze ion channel expression in patients with chronic AF and mitral valvular heart disease. Methods: A total of 17 patients (eight males and nine females; mean age, $57{\pm}14$ years [range, 19 to 77]) undergoing open-heart surgery were included in the study. Twelve patients (seven with coronary artery disease and five with aortic valvular disease) had sinus rhythm, and five patients (all with mitral valvular disease) had chronic, permanent AF. A piece of right atrial appendage tissue (0.5 g) was obtained during surgery. RT-PCR was used to evaluate the expression of L-type $Ca^{2+}$ channels, ryanodine receptor (RyR2), sarcoplasmic reticular $Ca^{2+}$-ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier $I_{kr}$ (HERG), gene encoding calcium-independent transient outward current $I_{to1}$ (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier $I_{ku}$ (Kv1.5), $K^+$ channel-interacting protein 2 (KChIP2), hyperpolarization-activated cation channel 2 associated with the pacemaker current $I_f$ (HCN2), and gene encoding $Na^+$ channel (SCN5A). Results: Reduced L-type $Ca^{2+}$ channel, RyR2, SERCA2, Kv1.5, and KChIP2 expression and borderline increased HCN2 expression were observed in the patients with AF and mitral valvular heart disease. Left atrial diameter was negatively correlated with RyR2 and KChIP2 expression. Fractional area shortening of the left atrium was positively correlated with RyR2 and KChIP2 expression. Conclusions: Alterations in ion channel expression and the anatomical substrate may favor the initiation and maintenance of AF in patients with mitral valvular heart disease.

Keywords

References

  1. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 1995;92:1954-1968. https://doi.org/10.1161/01.CIR.92.7.1954
  2. Sun H, Chartier D, Leblanc N, Nattel S. Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes. Cardiovasc Res 2001;49:751-761. https://doi.org/10.1016/S0008-6363(00)00294-7
  3. Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415:219-226. https://doi.org/10.1038/415219a
  4. Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, Nerbonne JM. Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res 1997;80:772-81. https://doi.org/10.1161/01.RES.80.6.772
  5. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kuhlkamp V. Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 1999;44:121-131. https://doi.org/10.1016/S0008-6363(99)00178-9
  6. Van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM, Nerbonne JM. Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res 1999;85:428-436. https://doi.org/10.1161/01.RES.85.5.428
  7. Allessie MA, Boyden PA, Camm AJ, et al. Pathophysiology and prevention of atrial fibrillation. Circulation 2001;103:769-777. https://doi.org/10.1161/01.CIR.103.5.769
  8. Van Wagoner DR, Nerbonne JM. Molecular basis of electrical remodeling in atrial fibrillation. J Mol Cell Cardiol 2000;32:1101-1117. https://doi.org/10.1006/jmcc.2000.1147
  9. Lai LP, Su MJ, Lin JL, et al. Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca (2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling. J Am Coll Cardiol 1999;33:1231-1237. https://doi.org/10.1016/S0735-1097(99)00008-X
  10. Lai LP, Su MJ, Lin JL, et al. Measurement of funny current (I(f)) channel mRNA in human atrial tissue: correlation with left atrial filling pressure and atrial fibrillation. J Cardiovasc Electrophysiol 1999;10:947-953. https://doi.org/10.1111/j.1540-8167.1999.tb01265.x
  11. Nabauer M, Beuckelmann DJ, Erdmann E. Characteristics of transient outward current in human ventricular myocytes from patients with terminal heart failure. Circ Res 1993;73:386-394. https://doi.org/10.1161/01.RES.73.2.386
  12. Jeck C, Pinto J, Boyden P. Transient outward currents in subendocardial Purkinje myocytes surviving in the infarcted heart. Circulation 1995;92:465-473. https://doi.org/10.1161/01.CIR.92.3.465
  13. Greenstein JL, Wu R, Po S, Tomaselli GF, Winslow RL. Role of the calcium-independent transient outward current I(to1) in shaping action potential morphology and duration. Circ Res 2000;87:1026-1033. https://doi.org/10.1161/01.RES.87.11.1026
  14. An WF, Bowlby MR, Betty M, et al. Modulation of A-type potassium channels by a family of calcium sensors. Nature 2000;403:553-556. https://doi.org/10.1038/35000592
  15. Decher N, Uyguner O, Scherer CR, et al. $hKChIP_2$ is a functional modifier of hKv4.3 potassium channels: cloning and expression of a short $hKChIP_2$ splice variant. Cardiovasc Res 2001;52:255-264. https://doi.org/10.1016/S0008-6363(01)00374-1
  16. Brundel BJ, Van Gelder IC, Henning RH, et al. Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. Circulation 2001;103:684-690. https://doi.org/10.1161/01.CIR.103.5.684
  17. Ohya S, Morohashi Y, Muraki K, et al. Molecular cloning and expression of the novel splice variants of K(+) channelinteracting protein 2. Biochem Biophys Res Commun 2001;282:96-102. https://doi.org/10.1006/bbrc.2001.4558
  18. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M. Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J 1999;18:2323-2329. https://doi.org/10.1093/emboj/18.9.2323
  19. Ohkusa T, Ueyama T, Yamada J, et al. Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation. J Am Coll Cardiol 1999;34:255-263. https://doi.org/10.1016/S0735-1097(99)00169-2
  20. Grammer JB, Zeng X, Bosch RF, Kuhlkamp V. Atrial L-type Ca2+-channel, beta-adrenorecptor, and 5-hydroxytryptamine type 4 receptor mRNAs in human atrial fibrillation. Basic Res Cardiol 2001;96:82-90. https://doi.org/10.1007/s003950170081
  21. van der Velden HMW, van der Zee L, Wijffels MC, et al. Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization. J Cardiovasc Electrophysiol 2000;11:1262-1269. https://doi.org/10.1046/j.1540-8167.2000.01262.x
  22. Grammer JB, Bosch RF, Kuhlkamp V, Seipel L. Molecular and electrophysiological evidence for "remodeling" of the L-type Ca2+ channel in persistent atrial fibrillation in humans. Z Kardiol 2000;89 Suppl 4:IV23-IV29. https://doi.org/10.1007/PL00022882
  23. Grammer JB, Bosch RF, Kuhlkamp V, Seipel L. Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation. J Cardiovasc Electrophysiol 2000;11:626-633. https://doi.org/10.1111/j.1540-8167.2000.tb00024.x
  24. Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000;101:2612-2617. https://doi.org/10.1161/01.CIR.101.22.2612
  25. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 2002;106:331-336. https://doi.org/10.1161/01.CIR.0000022665.18619.83

Cited by

  1. TLR2 was overexpressed independent of IL-6 in patients with valvular atrial fibrillation vol.25, pp.3, 2010, https://doi.org/10.1016/s1674-8301(11)60023-7
  2. Atrial Fibrillation and Early Clinical Outcomes After Mitral Valve Surgery in Patients with Rheumatic vs. Non-Rheumatic Mitral Stenosis vol.13, pp.4, 2010, https://doi.org/10.4103/1995-705x.105730
  3. Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria vol.591, pp.17, 2010, https://doi.org/10.1113/jphysiol.2013.254987
  4. Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges vol.9, pp.None, 2018, https://doi.org/10.3389/fphys.2018.01221
  5. Patient-Specific and Gene-Corrected Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Short QT Syndrome vol.124, pp.1, 2010, https://doi.org/10.1161/circresaha.118.313518
  6. Artificial light at night suppresses the expression of sarco/endoplasmic reticulum Ca 2+ ‐ATPase in the left ventricle of the heart in normotensive and hypertensive rats vol.106, pp.8, 2010, https://doi.org/10.1113/ep089594