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Review Article

Cell Junctions in the Specialized Conduction System of the Heart

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Pages 149-159 | Received 03 Mar 2014, Accepted 16 Mar 2014, Published online: 16 Apr 2014

REFERENCES

  • Anderson RH, Yanni J, Boyett MR, Chandler NJ, Dobrzynski H (2009). The anatomy of the cardiac conduction system. Clin Anat. 22: 99–113.
  • Atkinson A, Inada S, Li J, Tellez JO, Yanni J, Sleiman R, Allah EA, Anderson RH, Zhang H, Boyett MR, Dobrzynski H (2011). Anatomical and molecular mapping of the left and right ventricular His-Purkinje conduction networks. J Mol Cell Cardiol. 51: 689–701.
  • Bae MH, Kim JH, Jang SY, Park SH, Lee JH, Yang DH, Park HS, Cho Y, Chae SC (2013). Changes in follow-up ECG and signal-averaged ECG in patients with arrhythmogenic right ventricular cardiomyopathy. Pacing Clin Electrophysiol. 37: 430–438.
  • Bagwe S, Berenfeld O, Vaidya D, Morley GE, Jalife J (2005). Altered right atrial excitation and propagation in connexin40 knockout mice. Circulation. 112: 2245–2253.
  • Balderramo DC, Caeiro AA (2004). [Arrhythmogenic right ventricular dysplasia and sick sinus syndrome]. Medicina (B Aires). 64: 439–441.
  • Bao J, Wang J, Yao Y, Wang Y, Fan X, Sun K, He DS, Marcus FI, Zhang S, Hui R, Song L (2013). Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy. Circ Cardiovasc Genet. 6: 552–556.
  • Bevilacqua LM, Simon AM, Maguire CT, Gehrmann J, Wakimoto H, Paul DL, Berul CI (2000). A targeted disruption in connexin40 leads to distinct atrioventricular conduction defects. J Interv Card Electrophysiol. 4: 459–467.
  • Boyett MR (2009). ‘And the beat goes on.’ The cardiac conduction system: the wiring system of the heart. Exp Physiol. 94: 1035–1049.
  • Cerrone M, Lin X, Zhang M, Agullo-Pascual E, Pfenniger A, Chkourko-Gusky H, Novelli V, Kim C, Tirasawadichai T, Judge DP, Rothenberg E, Chen HS, Napolitano C, Priori S, Delmar M (2013).Missense mutations in plakophilin-2 cause sodium current deficit and associate with a brugada syndrome phenotype. Circulation.
  • Cerrone M, Noorman M, Lin X, Chkourko H, Liang FX, van der Nagel R, Hund T, Birchmeier W, Mohler P, van Veen TA, van Rijen HV, Delmar M (2012). Sodium current deficit and arrhythmogenesis in a murine model of plakophilin-2 haploinsufficiency. Cardiovasc Res. 95: 460–468.
  • Chandler N, Aslanidi O, Buckley D, Inada S, Birchall S, Atkinson A, Kirk D, Monfredi O, Molenaar P, Anderson R, Sharma V, Sigg D, Zhang H, Boyett M, Dobrzynski H (2011). Computer three-dimensional anatomical reconstruction of the human sinus node and a novel paranodal area. Anat Rec (Hoboken). 294: 970–979.
  • Coppen SR, Kaba RA, Halliday D, Dupont E, Skepper JN, Elneil S, Severs NJ (2003). Comparison of connexin expression patterns in the developing mouse heart and human foetal heart. Mol Cell Biochem. 242: 121–127.
  • Coppen SR, Kodama I, Boyett MR, Dobrzynski H, Takagishi Y, Honjo H, Yeh HI, Severs NJ (1999a). Connexin45, a major connexin of the rabbit sinoatrial node, is co-expressed with connexin43 in a restricted zone at the nodal-crista terminalis border. J Histochem Cytochem. 47: 907–918.
  • Coppen SR, Severs NJ, Gourdie RG (1999b). Connexin45 (alpha 6) expression delineates an extended conduction system in the embryonic and mature rodent heart. Dev Genet. 24: 82–90.
  • Cox MG, van der Zwaag PA, van der Werf C, van der Smagt JJ, Noorman M, Bhuiyan ZA, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, Dooijes D, van den Wijngaard A, Houweling AC, Jongbloed JD, Jordaens L, Cramer MJ, Doevendans PA, de Bakker JM, Wilde AA, van Tintelen JP, Hauer RN (2011). Arrhythmogenic right ventricular dysplasia/cardiomyopathy: pathogenic desmosome mutations in index-patients predict outcome of family screening: dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study. Circulation. 123: 2690–2700.
  • Danik SB, Liu F, Zhang J, Suk HJ, Morley GE, Fishman GI, Gutstein DE (2004). Modulation of cardiac gap junction expression and arrhythmic susceptibility. Circ Res. 95: 1035–1041.
  • Delva E, Tucker DK, Kowalczyk AP (2009). The desmosome. Cold Spring Harb Perspect Biol. 1: a002543.
  • Dobrzynski H, Anderson RH, Atkinson A, Borbas Z, D’Souza A, Fraser JF, Inada S, Logantha SJ, Monfredi O, Morris GM, Moorman AF, Nikolaidou T, Schneider H, Szuts V, Temple IP, Yanni J, Boyett MR (2013). Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues. Pharmacol Ther. 139: 260–288.
  • Dobrzynski H, Rothery SM, Marples DDR, Coppen SR, Takagishi Y, Honjo H, Tamkun MM, Henderson Z, Kodama I, Severs NJ, Boyett MR (2000). Presence of the Kv1.5 K+ Channel in the Sinoatrial Node. J Histochem Cytochem. 48: 769–780.
  • Fedorov VV, Glukhov AV, Chang R (2012). Conduction barriers and pathways of the sinoatrial pacemaker complex: their role in normal rhythm and atrial arrhythmias. Am J Physiol Heart Circ Physiol. 302: H1773–H1783.
  • Frank M, Wirth A, Andrié RP, Kreuzberg MM, Dobrowolski R, Seifert G, Offermanns S, Nickenig G, Willecke K, Schrickel JW (2012). Connexin45 provides optimal atrioventricular nodal conduction in the adult mouse heart. Circ Res. 111: 1528–1538.
  • Garcia-Gras E, Lombardi R, Giocondo MJ, Willerson JT, Schneider MD, Khoury DS, Marian AJ (2006). Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest. 116: 2012–2021.
  • Gros D, Théveniau-Ruissy M, Bernard M, Calmels T, Kober F, Söhl G, Willecke K, Nargeot J, Jongsma HJ, Mangoni ME (2010). Connexin 30 is expressed in the mouse sino- atrial node and modulates heart rate. Cardiovasc Res. 85: 45–55.
  • Gustafson-Wagner EA, Sinn HW, Chen YL, Wang DZ, Reiter RS, Lin JL, Yang B, Williamson RA, Chen J, Lin CI, Lin JJ (2007). Loss of mXinalpha, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects. Am J. Physiol Heart Circ Physiol. 293: H2680–H2692.
  • Gutstein DE, Morley GE, Tamaddon H, Vaidya D, Schneider MD, Chen J, Chien KR, Stuhlmann H, Fishman GI (2001a). Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Circ Res. 88: 333–339.
  • Gutstein DE, Morley GE, Vaidya D, Liu F, Chen FL, Stuhlmann H, Fishman GI (2001b). Heterogeneous expression of gap junction channels in the heart leads to conduction defects and ventricular dysfunction. Circulation. 104: 1194–1199.
  • Hagendorff A, Schumacher B, Kirchhoff S, Lüderitz B, Willecke K (1999). Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. Circulation. 99: 1508–1515.
  • Hatzfeld M, Wolf A, Keil R (2014). Plakophilins in desmosomal adhesion and signaling. Cell Commun Adhes. 21: 25–42.
  • Holle AW, Tang X, Vijayraghavan D, Vincent LG, Fuhrmann A, Choi YS, del Álamo JC, Engler AJ (2013). In situ mechanotransduction via vinculin regulates stem cell differentiation. Stem Cells. 31: 2467–2477.
  • Kanter HL, Beyer EC, Saffitz JE (1995). Structural and molecular determinants of intercellular coupling in cardiac myocytes. Microsc Res Tech. 31: 357–363.
  • Kass S, MacRae C, Graber HL, Sparks EA, McNamara D, Boudoulas H, Basson CT, Baker PB 3rd, Cody RJ, Fishman MC, Cox N, Kong A, Wooley CF, Seidman JG, Seidman CE (1994). A gene defect that causes conduction system disease and dilated cardiomyopathy maps to chromosome 1p1–1q1. Nat Genet. 7: 546–551.
  • Kirchhof P, Fabritz L, Zwiener M, Witt H, Schafers M, Zellerhoff S, Paul M, Athai T, Hiller KH, Baba HA, Breithardt G, Ruiz P, Wichter T, Levkau B (2006). Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation. 114: 1799–1806.
  • Kirchhoff S, Nelles E, Hagendorff A, Krüger O, Traub O, Willecke K (1998). Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice. Curr Biol. 8: 299–302.
  • Koetsier JL, Amargo EV, Todorović V, Green KJ, Godsel LM (2014). Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and integrin protein expression. J Invest Dermatol. 134: 112–122.
  • Kostetskii I, Li J, Xiong Y, Zhou R, Ferrari VA, Patel VV, Molkentin JD, Radice GL (2005). Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res. 96: 346–354.
  • Kreuzberg MM, Schrickel JW, Ghanem A, Kim JS, Degen J, Janssen-Bienhold U, Lewalter T, Tiemann K, Willecke K (2006). Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node. Proc Natl Acad Sci U S A. 103: 5959–5964.
  • Kreuzberg MM, Söhl G, Kim JS, Verselis VK, Willecke K, Bukauskas FF (2005). Functional properties of mouse connexin30.2 expressed in the conduction system of the heart. Circ Res. 96: 1169–1177.
  • Leaf DE, Feig JE, Vasquez C, Riva PL, Yu C, Lader JM, Kontogeorgis A, Baron EL, Peters NS, Fisher EA, Gutstein DE, Morley GE (2008). Connexin40 imparts conduction heterogeneity to atrial tissue. Circ Res. 103: 1001–1008.
  • Li D, Liu Y, Maruyama M, Zhu W, Chen H, Zhang W, Reuter S, Lin SF, Haneline LS, Field LJ, Chen PS, Shou W (2011). Restrictive loss of plakoglobin in cardiomyocytes leads to arrhythmogenic cardiomyopathy. Hum Mol Genet. 20: 4582–4596.
  • Li J, Levin MD, Xiong Y, Petrenko N, Patel VV, Radice GL (2008). N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility. J Mol Cell Cardiol. 44: 597–606.
  • Li J, Patel VV, Kostetskii I, Xiong Y, Chu AF, Jacobson JT, Yu C, Morley GE, Molkentin JD, Radice GL (2005). Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis. Circ Res. 97: 474–481.
  • Lim B-K, Xiong D, Dorner A, Youn T-J, Yung A, Liu TI, Gu Y, Dalton ND, Wright AT, Evans SM, Chen J, Peterson KL, McCulloch AD, Yajima T, Knowlton KU (2008). Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart. J Clin Invest. 118: 2758–2770.
  • Lisewski U, Shi Y, Wrackmeyer U, Fischer R, Chen C, Schirdewan A, Juttner R, Rathjen F, Poller W, Radke MH, Gotthardt M (2008). The tight junction protein CAR regulates cardiac conduction, cell-cell communication. J Exp Med. 205: 2369–2379.
  • Lübkemeier I, Requardt RP, Lin X, Sasse P, Andrié R, Schrickel JW, Chkourko H, Bukauskas FF, Kim JS, Frank M, Malan D, Zhang J, Wirth A, Dobrowolski R, Mohler PJ, Offermanns S, Fleischmann BK, Delmar M, Willecke K (2013). Deletion of the last five C-terminal amino acid residues of connexin43 leads to lethal ventricular arrhythmias in mice without affecting coupling via gap junction channels. Basic Res Cardiol. 108: 348.
  • Lyon RC, Mezzano V, Wright A, Pfeiffer E, Chuang J, Banares K, Castaneda A, Ouyang K, Cui L, Gu Y, Evans S, Omens J, Peterson KL, McCulloch A, Sheikh F (2014). Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model. Hum Mol Genet, 23: 1134–1150.
  • Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W, Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M, Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M (2012). A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. Circ Arrhythm Electrophysiol. 5: 163–172.
  • Mangoni ME, Nargeot J (2008). Genesis and regulation of the heart automaticity. Physiol Rev. 88: 919–982.
  • Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MG, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DM, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W (2010). Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 121: 1533–1541.
  • Miquerol L, Beyer S, Kelly RG (2011). Establishment of the mouse ventricular conduction system. Cardiovasc Res. 91: 232–242.
  • Miquerol L, Meysen S, Mangoni M, Bois P, van Rijen HV, Abran P, Jongsma H, Nargeot J, Gros D (2004). Architectural and functional asymmetry of the His-Purkinje system of the murine heart. Cardiovasc Res. 63: 77–86.
  • Morady F, Shen EN, Scheinman MM (1984). Unusual features of arrhythmogenic right ventricular dysplasia. Am J Cardiol. 53: 639–640.
  • Nikolaidou T, Aslanidi OV, Zhang H, Efimov IR (2012). Structure-function relationship in the sinus and atrioventricular nodes. Pediatr Cardiol. 33: 890–899.
  • Nogami A, Adachi S, Nitta J, Taniguchi K, Marumo F, Aonuma K, Iesaka Y, Hiroe M (1990). Arrhythmogenic right ventricular dysplasia with sick sinus syndrome and atrioventricular conduction disturbance. Jpn Heart J. 31: 417–423.
  • Pallante BA, Giovannone S, Fang-Yu L, Zhang J, Liu N, Kang G, Dun W, Boyden PA, Fishman GI (2010). Contactin-2 expression in the cardiac Purkinje fiber network. Circ Arrhythm Electrophysiol. 3: 186–194.
  • Pieperhoff S, Borrmann C, Grund C, Barth M, Rizzo S, Franke WW (2010). The area composita of adhering junctions connecting heart muscle cells of vertebrates. VII. The different types of lateral junctions between the special cardiomyocytes of the conduction system of ovine and bovine hearts. Eur J Cell Biol. 89: 365–378.
  • Pilichou K, Remme CA, Basso C, Campian ME, Rizzo S, Barnett P, Scicluna BP, Bauce B, van den Hoff MJ, de Bakker JM, Tan HL, Valente M, Nava A, Wilde AA, Moorman AF, Thiene G, Bezzina CR (2009). Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy. J Exp Med. 206: 1787–1802.
  • Quarta G, Muir A, Pantazis A, Syrris P, Gehmlich K, Garcia-Pavia P, Ward D, Sen-Chowdhry S, Elliott PM, McKenna WJ (2011). Familial evaluation in arrhythmogenic right ventricular cardiomyopathy: impact of genetics and revised task force criteria. Circulation. 123: 2701–2709.
  • Rentschler S, Vaidya DM, Tamaddon H, Degenhardt K, Sassoon D, Morley GE, Jalife J, Fishman GI (2001). Visualization and functional characterization of the developing murine cardiac conduction system. Development. 128: 1785–1792.
  • Rizzo S, Lodder EM, Verkerk AO, Wolswinkel R, Beekman L, Pilichou K, Basso C, Remme CA, Thiene G, Bezzina CR (2012). Intercalated disc abnormalities, reduced Na(+) current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes. Cardiovasc Res. 95: 409–418.
  • Rubenstein JJ, Schulman CL, Yurchak PM, DeSanctis RW (1972). Clinical spectrum of the sick sinus syndrome. Circulation. 46: 5–13.
  • Saffitz JE, Green KG, Schuessler RB (1997). Structural determinants of slow conduction in the canine sinus node. J Cardiovasc Electrophysiol. 8: 738–744.
  • Severs NJ, Bruce AF, Dupont E, Rothery S (2008). Remodelling of gap junctions and connexin expression in diseased myocardium. Cardiovasc Res. 80: 9–19.
  • Sheikh F, Ross RS, Chen J (2009). Cell-cell connection to cardiac disease. Trends Cardiovasc Med. 19: 182–90.
  • Shimada T, Kawazato H, Yasuda A, Ono N, Sueda K (2004). Cytoarchitecture and intercalated disks of the working myocardium and the conduction system in the mammalian heart. Anat Rec A Discov Mol Cell Evol Biol. 280: 940–951.
  • Simon AM, Goodenough DA, Paul DL (1998). Mice lacking connexin40 have cardiac conduction abnormalities characteristic of atrioventricular block and bundle branch block. Curr Biol. 8: 295–298.
  • Stiles MK, Brooks AG, Roberts-Thomson KC, Kuklik P, John B, Young GD, Kalman JM, Sanders P (2010). High-density mapping of the sinus node in humans: role of preferential pathways and the effect of remodeling. J Cardiovasc Electrophysiol. 21: 532–539.
  • Swope D, Cheng L, Gao E, Li J, Radice GL (2012). Loss of cadherin-binding proteins beta- catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis. Mol Cell Biol. 32: 1056–1067.
  • Takemura N, Kono K, Tadokoro K, Shinbo G, Ito I, Abe C, Matsuhashi N, Iemura T, Nishikimi T, Horinaka S, Matsuoka H (2008). Right atrial abnormalities in a patient with arrhythmogenic right ventricular cardiomyopathy without ventricular tachycardia. J Cardiol. 51: 205–209.
  • Tamaddon HS, Vaidya D, Simon AM, Paul DL, Jalife J, Morley GE (2000). High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system. Circ Res. 87: 929–936.
  • Tuomi JM, Tyml K, Jones DL (2011). Atrial tachycardia/fibrillation in the connexin 43 G60S mutant (Oculodentodigital dysplasia) mouse. Am J Physiol Heart Circ Physiol. 300: H1402–H1411.
  • van Rijen HV, Eckardt D, Degen J, Theis M, Ott T, Willecke K, Jongsma HJ, Opthof T, de Bakker JM (2004). Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation. 109: 1048–1055.
  • van Rijen HV, van Veen TA, van Kempen MJ, Wilms-Schopman FJ, Potse M, Krueger O, Willecke K, Opthof T, Jongsma HJ, de Bakker JM (2001). Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40. Circulation. 103: 1591–1598.
  • VanderBrink BA, Sellitto C, Saba S, Link MS, Zhu W, Homoud MK, Estes NA III, Paul DL, Wang PJ (2000). Connexin40-deficient mice exhibit atrioventricular nodal and infra- Hisian conduction abnormalities. J Cardiovasc Electrophysiol. 11: 1270–1276.
  • Vassall-Adams PR (1983). Ultrastructure of the human atrioventricular conduction tissues. Eur Heart J. 4: 449–460.
  • Verheule S, van Batenburg CA, Coenjaerts FE, Kirchhoff S, Willecke K, Jongsma HJ (1999). Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40. J Cardiovasc Electrophysiol. 10: 1380–1389.
  • Xu J, Lim SB, Ng MY, Ali SM, Kausalya JP, Limviphuvadh V, Maurer-Stroh S, Hunziker W (2012). ZO-1 regulates Erk, Smad1/5/8, Smad2, and RhoA activities to modulate self- renewal and differentiation of mouse embryonic stem cells. Stem Cells. 30: 1885–1900.
  • Yanni J, Boyett MR, Anderson RH, Dobrzynski H (2009). The extent of the specialized atrioventricular ring tissues. Heart Rhythm. 6: 672–680.
  • Zemljic-Harpf AE, Miller JC, Henderson SA, Wright AT, Manso AM, Elsherif L, Dalton ND, Thor AK, Perkins GA, McCulloch AD, Ross RS (2007). Cardiac-myocyte-specific excision of the vinculin gene disrupts cellular junctions, causing sudden death or dilated cardiomyopathy. Mol Cell Biol. 27: 7522–7537.
  • Zemljic-Harpf AE, Ponrartana S, Avalos RT, Jordan MC, Roos KP, Dalton ND, Phan VQ, Adamson ED, Ross RS (2004). Heterozygous inactivation of the vinculin gene predisposes to stress-induced cardiomyopathy. Am J Pathol. 165: 1033–1044.
  • Zhu W, Saba S, Link MS, Bak E, Homoud MK, Estes NA 3rd, Paul DL, Wang PJ (2005). Atrioventricular nodal reverse facilitation in connexin40-deficient mice. Heart Rhythm. 2: 1231–1237.
  • Zusterzeel R, Ter Bekke RM, Volders PG, Leijten FM, van den Wijngaard A, Serroyen J, Gorgels AP (2013).Right-ventricular enlargement in arrhythmogenic right-ventricular cardiomyopathy is associated with decreased QRS amplitudes and T-wave negativity. Ann Noninvasive Electrocardiol. 18: 555–563.

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