The Connexin40A96S mutation from a patient with atrial fibrillation causes decreased atrial conduction velocities and sustained episodes of induced atrial fibrillation in mice

Journal of Molecular and Cellular Cardiology

Volumn 65, Issue , 2013, Pages 19-32

  Lübkemeier, Indra ^a   Andrié, René ^a   Lickfett, Lars ^a   Bosen, Felicitas ^a   Stöckigt, Florian ^a   Dobrowolski, Radoslaw ^b   Draffehn, Astrid M ^a   Fregeac, Julien ^c   Schultze, Joachim L ^a   Bukauskas, Feliksas F ^c   Schrickel, Jan Wilko ^a   Willecke, Klaus ^a  

^a UNIVERSITY OF BONN   (Germany)

^b RUTGERS UNIVERSITY   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Atrial fibrillation; Connexin40; Gap junctions

Indexed keywords

CONNEXIN 40;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHANNEL GATING; CONTROLLED STUDY; ELECTROPHYSIOLOGY; GAP JUNCTION; HEART ATRIUM CONDUCTION; HEART ATRIUM FIBRILLATION; HELA CELL; HETEROZYGOSITY; HUMAN; HUMAN CELL; IMMUNOCHEMISTRY; ION CONDUCTANCE; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSGENIC MOUSE;

MAMMALIA; MUS;

AF; ARP; ATRIAL FIBRILLATION; ATRIAL REFRACTORY PERIOD; AV-NODAL REFRACTORY PERIOD; AVNRP; CONDUCTION VELOCITY; CONNEXIN; CONNEXIN40; CV; CX; CX40A96S; EAM; ECG; ED; ELECTROCARDIOGRAM; ELECTROPHYSIOLOGICAL INVESTIGATION; EMBRYONIC DAY; EPI; EPICARDIAL ACTIVATION MAPPING; G(J); GAP JUNCTION; GAP JUNCTIONS; GJ; JUNCTIONAL CONDUCTANCE; MUTATION IN THE CONNEXIN40 SEQUENCE THAT LEADS TO THE EXCHANGE OF AMINO ACID RESIDUE ALANINE WITH SERINE AT POSITION 96 OF THE CX40 PEPTIDE SEQUENCE; PD; POSTNATAL DAY; SAECG; STANDARD AVERAGE ECG RECORDING; VENTRICULAR REFRACTORY PERIOD; VRP; WBP; WENCKEBACH PERIODICITY;

ANIMALS; ATRIAL FIBRILLATION; CONNEXIN 43; CONNEXINS; ELECTROCARDIOGRAPHY; ENDOMYOCARDIAL FIBROSIS; EPICARDIAL MAPPING; GAP JUNCTIONS; HEART ATRIA; HEART CONDUCTION SYSTEM; HELA CELLS; HUMANS; ION CHANNEL GATING; MICE; MICE, TRANSGENIC; MUTATION; PROTEIN TRANSPORT; TIME FACTORS; TRANSFECTION;

EID: 84885537887     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2013.09.008     Document Type: Article

References (63)

1. Wolf P.A., Abbott R.D., Kannel W.B. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991, 22:983-988.
2. Neijssen J., Herberts C., Drijfhout J.W., Reits E., Janssen L., Neefjes J. Cross-presentation by intercellular peptide transfer through gap junctions. Nature 2005, 434:83-88.
3. Söhl G., Willecke K. An update on connexin genes and their nomenclature in mouse and man. Cell Commun Adhes 2003, 10:173-180.
4. Gros D.B., Jongsma H.J. Connexins in mammalian heart function. Bioessays 1996, 18:719-730.
5. Kirchhoff S., Nelles E., Hagendorff A., Krüger O., Traub O., Willecke K. Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice. Curr Biol 1998, 8:299-302.
6. Verheule S., Van Batenburg C.A., Coenjaerts F.E., Kirchhoff S., Willecke K., Jongsma H.J. Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40. J Cardiovasc Electrophysiol 1999, 10:1380-1389.
7. Hagendorff A., Schumacher B., Kirchhoff S., Lüderitz B., Willecke K. Conduction disturbances and increased atrial vulnerability in connexin40-deficient mice analyzed by transesophageal stimulation. Circulation 1999, 99:1508-1515.
8. Gollob M.H., Jones D.L., Krahn A.D., Danis L., Gong X.-Q., Shao Q., et al. Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med 2006, 354:2677-2688.
9. Yang Y.-Q., Zhang X.-L., Wang X.-H., Tan H.-W., Shi H.-F., Jiang W.-F., et al. Connexin40 nonsense mutation in familial atrial fibrillation. Int J Mol Med 2010, 26:605-610.
10. Yang Y.-Q., Liu X., Zhang X.-L., Wang X.-H., Tan H.-W., Shi H.-F., et al. Novel connexin40 missense mutations in patients with familial atrial fibrillation. Europace 2010, 12:1421-1427.
11. Christophersen I.E., Holmegard H.N., Jabbari J., Haunsø S., Tveit A., Svendsen J.H., et al. Rare variants in GJA5 are associated with early-onset lone atrial fibrillation. Can J Cardiol 2012, 29:111-116.
12. Shi H.-F., Yang J.-F., Wang Q., Li R.-G., Xu Y.-J., Qu X.-K., et al. Prevalence and spectrum of GJA5 mutations associated with lone atrial fibrillation. Mol Med Rep 2013, 7:767-774.
13. Sun Y., Yang Y.-Q., Gong X.-Q., Wang X.-H., Li R.-G., Tan H.-W., et al. Novel germline GJA5/Connexin40 mutations associated with lone atrial fibrillation impair gap junctional intercellular communication. Hum Mutat 2013, 34:603-609.
14. Thibodeau I.L., Xu J., Li Q., Liu G., Lam K., Veinot J.P., et al. Paradigm of genetic mosaicism and lone atrial fibrillation: physiological characterization of a connexin 43-deletion mutant identified from atrial tissue. Circulation 2010, 122:236-244.
15. Lübkemeier I., Machura K., Kurtz L., Neubauer B., Dobrowolski R., Schweda F., et al. The connexin 40 A96S mutation causes renin-dependent hypertension. J Am Soc Nephrol 2011, 22:1031-1040.
16. Chen Y.-H., Xu S.-J., Bendahhou S., Wang X.-L., Wang Y., Xu W.-Y., et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003, 299:251-254.
17. Juang J.-M., Chern Y.-R., Tsai C.-T., Chiang F.-T., Lin J.-L., Hwang J.-J., et al. The association of human connexin 40 genetic polymorphisms with atrial fibrillation. Int J Cardiol 2007, 116:107-112.
18. Firouzi M., Kok B., Spiering W., Busjahn A., Bezzina C.R., Ruijter J.M., et al. Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men. J Hypertens 2006, 24:325-330.
19. Wirka R.C., Gore S., Van Wagoner D.R., Arking D.E., Lubitz S.A., Lunetta K.L., et al. A common connexin-40 gene promoter variant affects connexin-40 expression in human atria and is associated with atrial fibrillation. Circ Arrhythm Electrophysiol 2011, 4:87-93.
20. Kreuzberg M.M., Schrickel J.W., Ghanem A., Kim J.-S., Degen J., Janssen-Bienhold U., et al. Connexin30.2 containing gap junction channels decelerate impulse propagation through the atrioventricular node. Proc Natl Acad Sci U S A 2006, 103:5959-5964.
21. Schrickel J.W., Bielik H., Yang A., Schimpf R., Shlevkov N., Burkhardt D., et al. Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing. Basic Res Cardiol 2002, 97:452-460.
22. Schrickel J.W., Brixius K., Herr C., Clemen C.S., Sasse P., Reetz K., et al. Enhanced heterogeneity of myocardial conduction and severe cardiac electrical instability in annexin A7-deficient mice. Cardiovasc Res 2007, 76:257-268.
23. Schrickel J.W., Lickfett L., Lewalter T., Tiemann K., Nickenig G., Baba H., et al. Cardiomyocyte-specific deletion of survivin causes global cardiac conduction defects. Basic Res Cardiol 2012, 107:299-302.
24. Coronel R., Wilms-Schopman F.J., De Groot J.R., Janse M.J., Van Capelle F.J., De Bakker J.M. Laplacian electrograms and the interpretation of complex ventricular activation patterns during ventricular fibrillation. J Cardiovasc Electrophysiol 2000, 11:1119-1128.
25. Rackauskas M., Kreuzberg M.M., Pranevicius M., Willecke K., Verselis V.K., Bukauskas F.F. Gating properties of heterotypic gap junction channels formed of connexins 40, 43, and 45. Biophys J 2007, 92:1952-1965.
26. Paulauskas N., Pranevicius M., Pranevicius H., Bukauskas F.F. A stochastic four-state model of contingent gating of gap junction channels containing two "fast" gates sensitive to transjunctional voltage. Biophys J 2009, 96:3936-3948.
27. Paulauskas N., Pranevicius H., Mockus J., Bukauskas F.F. Stochastic 16-state model of voltage gating of gap-junction channels enclosing fast and slow gates. Biophys J 2012, 102:2471-2480.
28. Nakajima H., Nakajima H.O., Dembowsky K., Pasumarthi K.B.S., Field L.J. Cardiomyocyte cell cycle activation ameliorates fibrosis in the atrium. Circ Res 2006, 98:141-148.
29. Wilgenbus K.K., Kirkpatrick C.J., Knuechel R., Willecke K., Traub O. Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. Int J Cancer 1992, 51:522-529.
30. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970, 227:680-685.
31. Hennemann H., Schwarz H.J., Willecke K. Characterization of gap junction genes expressed in F9 embryonic carcinoma cells: molecular cloning of mouse connexin31 and -45 cDNAs. Eur J Cell Biol 1992, 57:51-58.
32. Wilders R., Jongsma H.J. Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels. Biophys J 1992, 63:942-953.
33. Bukauskas F.F., Elfgang C., Willecke K., Weingart R. Biophysical properties of gap junction channels formed by mouse connexin40 in induced pairs of transfected human HeLa cells. Biophys J 1995, 68:2289-2298.
34. Beblo D.A., Wang H.Z., Beyer E.C., Westphale E.M., Veenstra R.D. Unique conductance, gating, and selective permeability properties of gap junction channels formed by connexin40. Circ Res 1995, 77:813-822.
35. Bruzzone R., Haefliger J.A., Gimlich R.L., Paul D.L. Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell 1993, 4:7-20.
36. Hennemann H., Suchyna T., Lichtenberg-Fraté H., Jungbluth S., Dahl E., Schwarz J., et al. Molecular cloning and functional expression of mouse connexin40, a second gap junction gene preferentially expressed in lung. J Cell Biol 1992, 117:1299-1310.
37. Traub O., Eckert R., Lichtenberg-Fraté H., Elfgang C., Bastide B., Scheidtmann K.H., et al. Immunochemical and electrophysiological characterization of murine connexin40 and -43 in mouse tissues and transfected human cells. Eur J Cell Biol 1994, 64:101-112.
38. Gollob M.H. Begetting atrial fibrillation: connexins and arrhythmogenesis. Heart Rhythm 2008, 5:888-891.
39. Van Veen T. Cardiac gap junction channels: modulation of expression and channel properties. Cardiovasc Res 2001, 51:217-229.
40. Rackauskas M., Verselis V.K., Bukauskas F.F. Permeability of homotypic and heterotypic gap junction channels formed of cardiac connexins mCx30.2, Cx40, Cx43, and Cx45. Am J Physiol Heart Circ Physiol 2007, 293:H1729-H1736.
41. Haubrich S., Schwarz H.J., Bukauskas F., Lichtenberg-Fraté H., Traub O., Weingart R., et al. Incompatibility of connexin 40 and 43 Hemichannels in gap junctions between mammalian cells is determined by intracellular domains. Mol Biol Cell 1996, 7:1995-2006.
42. White T.W., Paul D.L., Goodenough D.A., Bruzzone R. Functional analysis of selective interactions among rodent connexins. Mol Biol Cell 1995, 6:459-470.
43. Becker A.E. How structurally normal are human atria in patients with atrial fibrillation?. Heart Rhythm 2004, 1:627-631.
44. Dilaveris P.E., Gialafos E.J., Sideris S.K., Theopistou A.M., Andrikopoulos G.K., Kyriakidis M., et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 1998, 135:733-738.
45. Psaty B.M., Manolio T.A., Kuller L.H., Kronmal R.A., Cushman M., Fried L.P., et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation 1997, 96:2455-2461.
46. Ge J., Sun A., Paajanen V., Wang S., Su C., Yang Z., et al. Molecular and clinical characterization of a novel SCN5A mutation associated with atrioventricular block and dilated cardiomyopathy. Circ Arrhythm Electrophysiol 2008, 1:83-92.
47. Beck J.A., Lloyd S., Hafezparast M., Lennon-Pierce M., Eppig J.T., Festing M.F., et al. Genealogies of mouse inbred strains. Nat Genet 2000, 24:23-25.
48. Chaldoupi S.-M., Loh P., Hauer R.N.W., De Bakker J.M.T., Van Rijen H.V.M. The role of connexin40 in atrial fibrillation. Cardiovasc Res 2009, 84:15-23.
49. Jobs A., Schmidt K., Schmidt V.J., Lübkemeier I., Van Veen T.A.B.., Kurtz A., et al. Defective cx40 maintains cx37 expression but intact cx40 is crucial for conducted dilations irrespective of hypertension. Hypertension 2012, 60:1422-1429.
50. Duffy H.S. The ever-shrinking world of cardiac ion channel remodeling: the role of microRNAs in heart disease. Heart Rhythm 2009, 6:1810-1811.
51. Callis T.E., Pandya K., Seok H.Y., Tang R.-H., Tatsuguchi M., Huang Z.-P., et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 2009, 119:2772-2786.
52. Xiao J., Liang D., Zhang Y., Liu Y., Zhang H., Liu Y., et al. MicroRNA expression signature in atrial fibrillation with mitral stenosis. Physiol Genomics 2011, 43:655-664.
53. Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I., Liebhaber S.A., et al. MicroRNA silencing through RISC recruitment of eIF6. Nature 2007, 447:823-828.
54. Humphreys D.T., Westman B.J., Martin D.I.K., Preiss T. MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 2005, 102:16961-16966.
55. Petersen C.P., Bordeleau M.-E., Pelletier J., Sharp P.A. Short RNAs repress translation after initiation in mammalian cells. Mol Cell 2006, 21:533-542.
56. Guo H., Ingolia N.T., Weissman J.S., Bartel D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010, 466:835-840.
57. Gomes A.V., Young G.W., Wang Y., Zong C., Eghbali M., Drews O., et al. Contrasting proteome biology and functional heterogeneity of the 20S proteasome complexes in mammalian tissues. Mol Cell Proteomics 2009, 8:302-315.
58. Drews O., Wildgruber R., Zong C., Sukop U., Nissum M., Weber G., et al. Mammalian proteasome subpopulations with distinct molecular compositions and proteolytic activities. Mol Cell Proteomics 2007, 6:2021-2031.
59. Wang X., Su H., Ranek M.J. Protein quality control and degradation in cardiomyocytes. J Mol Cell Cardiol 2008, 45:11-27.
60. Kurtz L., Janssen-Bienhold U., Kurtz A., Wagner C. Connexin expression in renin-producing cells. J Am Soc Nephrol 2009, 20:506-512.
61. Hervé J.-C., Bourmeyster N., Sarrouilhe D., Duffy H.S. Gap junctional complexes: from partners to functions. Prog Biophys Mol Biol 2007, 94:29-65.
62. Kannel W.B., Wolf P.A., Benjamin E.J., Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998, 82:2N-9N.
63. Sinner M.F., Ellinor P.T., Meitinger T., Benjamin E.J., Kääb S. Genome-wide association studies of atrial fibrillation: past, present, and future. Cardiovasc Res 2011, 89:701-709.