Role of Gap Junction in Atrial Fibrillation Pathophysiology
Abstract
Initiation of atrial fibrillation (AF) occurred when there is a combination of triggering factors (mainly originated from thoracic veins) and arrhytmogenic substrate, such as : reduction of effective refractory period (ERP), increase in refractory spatial dispersion, or abnormal atrial impulse conduction.Atrial fibrillation has an ability to maintain its own progression, so called ‘AF begets AF’. Prologed AF episodes will lead to structural and electrical remodeling, making the patient prone to the recurrent and sustained AF. Structural remodeling, detected in the late phase, involve changes in mitochodrial size, disorder of sarcoplasmic reticulum in subcellular level, and myocardial cell hypertrophy, fiber disarray and elevated collagen deposition in the tissue level. Meanwhile, electrical remodeling of AF will cause delayed effective refractory period, promoting reentry mechanisms. Changes in gap junction regulation and distribution has been noted as part of this remodeling process. Mutation of connexin40 gene, a component protein of gap junction, also has a role in some cases of lone AF.
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References
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Van Veen TAB, Van Rijen HVM, Opthof T. Cardiac gap junction channels:Modulation of expression and channel properties. Cardiovasc Res 2001;51:217-29.
Saffitz JE, Lerner DL, Yamada KA. Gap junction distribution and regulation in the heart. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cells to Bedside. Fourth ed. Philadelphia: WB Saunders; 2004:181-91.
Francis D, Siergiopoulos K, Ek Vitorin JF, Cao FL, Taffet SM, Delmar M. Connexin diversity and gap junction regulation by pH. Dev Genet 1999;24:123-36.
Van Kempen MJA, Wessels A, Oosthoek PW, Gros D, Jongsma HJ. Differential connexin distribution accomodates cardiac function in different species. Microsc Res Tech 1995;31:420-36.
Vozzi C, Dupont E, Coppen SR, Yeh HI, Severs NJ. Chamber related differences in connexin expression in the human heart. J Mol Cell Cardiol 1999;31:991-1003.
Chaldoupi SM, Loh P, Hauer RN, de Bakker JMT, van Rijen HVM. The role of connexin40 in atrial fibrillation. Cardiovasc Res 2009;84:15-23.
Jansen JA, Van Veen TAB, de Bakker JMT, Van Rijen HVM. Cardiac connexins and impulse propagation. In: J Mol Cell Cardiol; 2009.
Eckardt D, Theis M, Degen J, Ott T, Van Rijen HVM, Kirschoff S. Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion. J Mol Cell Cardiol 2004;36:101-10.
Kanagaratnam P, Rothery S, Patel P, Severs NJ, Peters NS. Relative expression of immunolocalized connexins 40 and 43 corellates with human atrial conduction properties. J Am Coll Cardiol 2002;39:116-23.
Beauchamp P, Yamada KA, Baertschi AJ, et al. Relative contributions of connexin 40 and 43 to atrial impulse prapagation in synthetic strands of neonatal and fetal murine cardiomyocytes. Circ Res 2006;99:1216-24.
Severs NJ, Bruce AF, Dupont E, Rothery S. Remodeling of gap junction and connexin expression in diseased myocardium. Cardiovasc Res 2008;80:9-19.
Gollob MH. Begetting atrial fibrillation : connexin and arrhythmogenesis. Heart Rhythm 2008;5:888-91.
Van der Velden, Ausma J, Rook MB, Hellemons AJ, van Veen TA, Allessie MA et al. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 2000;46:476–486.
Ausma J, van der Velden HMW, Lenders MH, van Ankeren EP, Jongsma HJ, Ramaekers FC et al. Reverse structural and gap junctional remodeling after prolonged atrial fibrillation in the goat. Circulation2003;107:2051–2058.
Thijssen VL, van der Velden HMW, van Ankeren EP, Ausma J, Allessie MA,Borgers M et al. Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovasc Res 2002;54:427–437.
Dupont E, Ko Y, Rothery S, Coppen SR, Baghai M, Haw M et al. The gap junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation. Circulation 2001;103:842–849.
Nao T, Ohkusa T, Hisamatsu Y, Inoue N, Matsumoto T, Yamada J et al. Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm.Am J Cardiol2003;91:678–683.
Saito T, Waki K, Becker AE. Left atrial myocardial extension onto pulmonary veins in humans: anatomic observations relevant for atrial arrhythmias. J Cardiovasc Electrophysiol 2000;11:888–894.
Arora R, Verheule S, Scott L, Navarrete A, Katari V, Wilson E et al. Arrhythmogenic substrate of the pulmonary veins assessed by high resolution optical mapping. Circulation2003;107:1816–1821.
Verheule S, Wilson EE, Arora R, Engle SK, Scott LR, Olgin JE. Tissue structure and connexin expression of canine pulmonary veins. Cardiovasc Res2002;55:727–738.
Chen YJ, Chen YC, Yeh HI, Lin CI, Chen SA. Electrophysiology and arrhythmogenic activity of single cardiomyocytes from canine superior vena cava. Circulation2002;105:2679–2685.
Firouzi M, Ramanna H, Kok B, Jongsma HJ, Koeleman BP, Doevendans PA et al. Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation. Circ Res2004;95:e29–e33.
Juang JM, Chern YR, Tsai CT, Chiang FT, Lin JL, Hwang JJ et al. The association of human connexin 40 genetic polymorphisms with atrial fibrillation. Int J Cardiol2007;116:107–112.
Wit AL, Duffy HS. Drug development for treatment of cardiac arrhythmias:targeting the gap junctions. Am J Physiol Heart Circ Physiol 2008;294:H16-H18.
Van Veen TAB, Van Rijen HVM, Opthof T. Cardiac gap junction channels:Modulation of expression and channel properties. Cardiovasc Res 2001;51:217-29.
Saffitz JE, Lerner DL, Yamada KA. Gap junction distribution and regulation in the heart. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cells to Bedside. Fourth ed. Philadelphia: WB Saunders; 2004:181-91.
Francis D, Siergiopoulos K, Ek Vitorin JF, Cao FL, Taffet SM, Delmar M. Connexin diversity and gap junction regulation by pH. Dev Genet 1999;24:123-36.
Van Kempen MJA, Wessels A, Oosthoek PW, Gros D, Jongsma HJ. Differential connexin distribution accomodates cardiac function in different species. Microsc Res Tech 1995;31:420-36.
Vozzi C, Dupont E, Coppen SR, Yeh HI, Severs NJ. Chamber related differences in connexin expression in the human heart. J Mol Cell Cardiol 1999;31:991-1003.
Chaldoupi SM, Loh P, Hauer RN, de Bakker JMT, van Rijen HVM. The role of connexin40 in atrial fibrillation. Cardiovasc Res 2009;84:15-23.
Jansen JA, Van Veen TAB, de Bakker JMT, Van Rijen HVM. Cardiac connexins and impulse propagation. In: J Mol Cell Cardiol; 2009.
Eckardt D, Theis M, Degen J, Ott T, Van Rijen HVM, Kirschoff S. Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion. J Mol Cell Cardiol 2004;36:101-10.
Kanagaratnam P, Rothery S, Patel P, Severs NJ, Peters NS. Relative expression of immunolocalized connexins 40 and 43 corellates with human atrial conduction properties. J Am Coll Cardiol 2002;39:116-23.
Beauchamp P, Yamada KA, Baertschi AJ, et al. Relative contributions of connexin 40 and 43 to atrial impulse prapagation in synthetic strands of neonatal and fetal murine cardiomyocytes. Circ Res 2006;99:1216-24.
Severs NJ, Bruce AF, Dupont E, Rothery S. Remodeling of gap junction and connexin expression in diseased myocardium. Cardiovasc Res 2008;80:9-19.
Gollob MH. Begetting atrial fibrillation : connexin and arrhythmogenesis. Heart Rhythm 2008;5:888-91.
Van der Velden, Ausma J, Rook MB, Hellemons AJ, van Veen TA, Allessie MA et al. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 2000;46:476–486.
Ausma J, van der Velden HMW, Lenders MH, van Ankeren EP, Jongsma HJ, Ramaekers FC et al. Reverse structural and gap junctional remodeling after prolonged atrial fibrillation in the goat. Circulation2003;107:2051–2058.
Thijssen VL, van der Velden HMW, van Ankeren EP, Ausma J, Allessie MA,Borgers M et al. Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovasc Res 2002;54:427–437.
Dupont E, Ko Y, Rothery S, Coppen SR, Baghai M, Haw M et al. The gap junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation. Circulation 2001;103:842–849.
Nao T, Ohkusa T, Hisamatsu Y, Inoue N, Matsumoto T, Yamada J et al. Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm.Am J Cardiol2003;91:678–683.
Saito T, Waki K, Becker AE. Left atrial myocardial extension onto pulmonary veins in humans: anatomic observations relevant for atrial arrhythmias. J Cardiovasc Electrophysiol 2000;11:888–894.
Arora R, Verheule S, Scott L, Navarrete A, Katari V, Wilson E et al. Arrhythmogenic substrate of the pulmonary veins assessed by high resolution optical mapping. Circulation2003;107:1816–1821.
Verheule S, Wilson EE, Arora R, Engle SK, Scott LR, Olgin JE. Tissue structure and connexin expression of canine pulmonary veins. Cardiovasc Res2002;55:727–738.
Chen YJ, Chen YC, Yeh HI, Lin CI, Chen SA. Electrophysiology and arrhythmogenic activity of single cardiomyocytes from canine superior vena cava. Circulation2002;105:2679–2685.
Firouzi M, Ramanna H, Kok B, Jongsma HJ, Koeleman BP, Doevendans PA et al. Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation. Circ Res2004;95:e29–e33.
Juang JM, Chern YR, Tsai CT, Chiang FT, Lin JL, Hwang JJ et al. The association of human connexin 40 genetic polymorphisms with atrial fibrillation. Int J Cardiol2007;116:107–112.
Wit AL, Duffy HS. Drug development for treatment of cardiac arrhythmias:targeting the gap junctions. Am J Physiol Heart Circ Physiol 2008;294:H16-H18.
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How to Cite
Tondas, A., & Yuniadi, Y. (1). Role of Gap Junction in Atrial Fibrillation Pathophysiology. Indonesian Journal of Cardiology, 31(1), 48-57. https://doi.org/10.30701/ijc.v31i1.158
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