Intercalated disc abnormalities, reduced Na+ current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes

Cardiovascular Research

Volumn 95, Issue 4, 2012, Pages 409-418

  Rizzo, Stefania ^a   Lodder, Elisabeth M ^b   Verkerk, Arie O ^b   Wolswinkel, Rianne ^b   Beekman, Leander ^b   Pilichou, Kalliopi ^a   Basso, Cristina ^a   Remme, Carol Ann ^b   Thiene, Gaetano ^a   Bezzina, Connie R ^b  

^a UNIVERSITY OF PADOVA   (Italy)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

Arrhythmias; ARVC; Desmoglein 2; Electrophysiology; Sudden cardiac death

Indexed keywords

DESMOGLEIN 2; MUTANT PROTEIN; SODIUM CHANNEL NAV1.5;

ACTION POTENTIAL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARDIOMYOPATHY; CELL DEATH; CONTROLLED STUDY; DESMOSOME; ELECTRON MICROSCOPY; ELECTROPHYSIOLOGY; FIBROSIS; HEART ARRHYTHMIA; IMMUNOPRECIPITATION; IN VIVO STUDY; ISOLATED HEART; MOUSE; MUTATION; NECROSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SODIUM CURRENT; TRANSGENIC MOUSE; VELOCITY; WILD TYPE;

ACTION POTENTIALS; ADHERENS JUNCTIONS; ANIMALS; ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA; CARDIAC PACING, ARTIFICIAL; CELL DEATH; DESMOGLEIN 2; DESMOSOMES; DISEASE MODELS, ANIMAL; ELECTROCARDIOGRAPHY; FIBROSIS; GENETIC PREDISPOSITION TO DISEASE; HEART CONDUCTION SYSTEM; IMMUNOPRECIPITATION; MICE; MICE, TRANSGENIC; MICROSCOPY, ELECTRON, TRANSMISSION; MUTATION; MYOCYTES, CARDIAC; NAV1.5 VOLTAGE-GATED SODIUM CHANNEL; PERFUSION; PHENOTYPE; SODIUM; TACHYCARDIA, VENTRICULAR; TIME FACTORS;

EID: 84865214658     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvs219     Document Type: Article

References (32)

1. Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. Lancet 2009;373:1289-1300.
2. McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A et al. Identification of a deletion in plakoglobin in arrhythmogenic right ventricular car-diomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 2000;355:2119-2124.
3. Rampazzo A, Nava A, Malacrida S, Beffagna G, Bauce B, Rossi V et al. Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy. Am J Hum Genet 2002;71: 1200-1206.
4. Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA et al. Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 2004;36:1162-1164.
5. Pilichou K, Nava A, Basso C, Beffagna G, Bauce B, Lorenzon A et al. Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyop-athy. Circulation 2006;113:1171-1179.
6. Syrris P, Ward D, Evans A, Asimaki A, Gandjbakhch E, Sen-Chowdhry S et al. Arrhyth-mogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2. Am J Hum Genet 2006;79:978-984.
7. Pilichou K, Remme CA, Basso C, Campian ME, Rizzo S, Barnett P et al. Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmo-genic right ventricular cardiomyopathy. J Exp Med 2009;206:1787-1802.
8. Delmar M, McKenna WJ. The cardiac desmosome and arrhythmogenic cardiomyopathies: from gene to disease. Circ Res 2010;107:700-714.
9. Bauce B, Basso C, Rampazzo A, Beffagna G, Daliento L, Frigo G et al. Clinical profile of four families with arrhythmogenic right ventricular cardiomyopathy caused by dominant desmoplakin mutations. Eur Heart J 2005;26:1666-1675.
10. Kaplan SR, Gard JJ, Protonotarios N, Tsatsopoulou A, Spiliopoulou C, Anastasakis A et al. Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardio-myopathy due to a deletion in plakoglobin (Naxos disease). Heart Rhythm 2004;1: 3-11.
11. Franke WW, Borrmann CM, Grund C, Pieperhoff S. The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol 2006;85:69-82.
12. Sato PY, Coombs W, Lin X, Nekrasova O, Green KJ, Isom LL et al. Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res 2011;109:193-201.
13. Saffitz JE. Dependence of electrical coupling on mechanical coupling in cardiac myo-cytes: insights gained from cardiomyopathies caused by defects in cell-cell connections. Ann N Y Acad Sci 2005;1047:336-344.
14. Delmar M. The intercalated disk as a single functional unit. Heart Rhythm 2004;1: 12-13.
15. Meadows LS, Isom LL. Sodium channels as macromolecular complexes: implications for inherited arrhythmia syndromes. Cardiovasc Res 2005;67:448-458.
16. Asimaki A, Tandri H, Huang H, Halushka MK, Gautam S, Basso C et al. A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy. N Engl J Med 2009; 360:1075; author reply 2785-1084.
17. Li J, Radice GL. A new perspective on intercalated disc organization: implications for heart disease. Dermatol Res Pract 2010;2010:207835.
18. https://grenada.lumc.nl/LOVD2/ARVC/.
19. Basso C, Czarnowska E, Della Barbera M, Bauce B, Beffagna G, Wlodarska EK et al. Ultrastructural evidence of intercalated disc remodelling in arrhythmogenic right ventricular cardiomyopathy: an electron microscopy investigation on endomyocardial biopsies. Eur Heart J 2006;27:1847-1854.
20. Fawcett DW, McNutt NS. The ultrastructure of the cat myocardium. I. Ventricular papillary muscle. J Cell Biol 1969;42:1-45.
21. + current in cardiac myocytes at physiological conditions. PLoS ONE 2010;5:e15772.
22. Marquez-Rosado L, Solan JL, Dunn CA, Norris RP, Lampe PD. Connexin43 phos-phorylation in brain, cardiac, endothelial and epithelial tissues. Biochim Biophys Acta 2011;818:1985-1992.
23. Sato PY, Musa H, Coombs W, Guerrero-Serna G, Patino GA, Taffet SM et al. Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res 2009;105:523-526.
24. Delmar M, Liang FX. Connexin43, and the regulation of intercalated disc function. Heart Rhythm 2012;9:835-838.
25. Jansen JA, Noorman M, Musa H, Stein M, de Jong S, van der Nagel R et al. Reduced heterogeneous expression of Cx43 results in decreased Nav1.5 expression and reduced sodium current which accounts for arrhythmia vulnerability in conditional Cx43 knockout mice. Heart Rhythm 2012;9:600-607.
26. Stein M, van Veen TA, Hauer RN, de Bakker JM, van Rijen HV. A 50% reduction of excitability but not of intercellular coupling affects conduction velocity restitution and activation delay in the mouse heart. PLoS ONE 2011;6:e20310.
27. Nagar B, Overduin M, Ikura M, Rini JM. Structural basis of calcium-induced E-cadherin rigidification and dimerization. Nature 1996;380:360-364.
28. Kant S, Krull P, Eisner S, Leube RE, Krusche CA. Histological and ultrastructural abnormalities in murine desmoglein 2-mutant hearts. Cell Tissue Res 2012;348:249-259.
29. Sen-Chowdhry S, Syrris P, Prasad SK, Hughes SE, Merrifield R, Ward D et al. Left-dominant arrhythmogenic cardiomyopathy: an under-recognized clinical entity. J Am Coll Cardiol 2008;52:2175-2187.
30. Sen-Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E, McKenna WJ. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation 2007;115:1710-1720.
31. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J 2010;31:806-814.
32. Pilichou K, Bezzina CR, Thiene G, Basso C. Arrhythmogenic cardiomyopathy: trans-genic animal models provide novel insights into disease pathobiology. Circ Cardiovasc Genet 2011;4:318-326.