Journal of Molecular and Cellular Cardiology
Volume 47, Issue 2 , Pages 203-209 , August 2009

Cardiac ankyrins in health and disease

  • Seyed M. Hashemi

      Affiliations

    • Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
    • ,
  • Thomas J. Hund

      Affiliations

    • Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
    • ,
  • Peter J. Mohler

      Affiliations

    • Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
    • Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
    • Corresponding Author InformationCorresponding author. 285 Newton Road, CBRB 2283, Iowa City, IA 52242, USA. Fax: +1 319 353 5552.

Received 3 March 2009 ,Revised 10 April 2009 ,Accepted 17 April 2009.

References 

  1. Ayalon G, Davis JQ, Scotland PB, Bennett V. An ankyrin-based mechanism for functional organization of dystrophin and dystroglycan. Cell. 2008;135(7):1189–1200
  2. Kizhatil K, Baker SA, Arshavsky VY, Bennett V. Ankyrin-G promotes cyclic nucleotide-gated channel transport to rod photoreceptor sensory cilia. Science. 2009;323(5921):1614–1617
  3. Kizhatil K, Sandhu NK, Peachey NS, Bennett V. Ankyrin-B is required for coordinated expression of beta-2-spectrin, the Na/K-ATPase and the Na/Ca exchanger in the inner segment of rod photoreceptors. Exp. Eye Res. 2009;88(1):57–64
  4. Bennett V, Baines AJ. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol. Rev. 2001;81(3):1353–1392
  5. Bennett V. Purification of an active proteolytic fragment of the membrane attachment site for human erythrocyte spectrin. J. Biol. Chem. 1978;253(7):2292–2299
  6. Eber SW, Gonzalez JM, Lux ML, Scarpa AL, Tse WT, Dornwell M, et al. Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. Nat. Genet. 1996;13(2):214–218
  7. Li ZP, Burke EP, Frank JS, Bennett V, Philipson KD. The cardiac Na+–Ca2+ exchanger binds to the cytoskeletal protein ankyrin. J. Biol. Chem. 1993;268(16):11489–11491
  8. Mohler PJ, Gramolini AO, Bennett V. The ankyrin-B C-terminal domain determines activity of ankyrin-B/G chimeras in rescue of abnormal inositol 1,4,5-trisphosphate and ryanodine receptor distribution in ankyrin-B (−/−) neonatal cardiomyocytes. J. Biol. Chem. 2002;277(12):10599–10607
  9. Bourguignon LY, Jin H. Identification of the ankyrin-binding domain of the mouse T-lymphoma cell inositol 1,4,5-trisphosphate (IP3) receptor and its role in the regulation of IP3-mediated internal Ca2+ release. J. Biol. Chem. 1995;270(13):7257–7260
  10. Mohler PJ, Schott JJ, Gramolini AO, Dilly KW, Guatimosim S, duBell WH, et al. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature. 2003;421(6923):634–639
  11. Mohler PJ, Davis JQ, Davis LH, Hoffman JA, Michaely P, Bennett V. Inositol 1,4,5-trisphosphate receptor localization and stability in neonatal cardiomyocytes requires interaction with ankyrin-B. J. Biol. Chem. 2004;279(13):12980–12987
  12. Mohler PJ, Rivolta I, Napolitano C, Lemaillet G, Lambert S, Priori SG, et al. Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc. Natl. Acad. Sci. U. S. A. 2004;101(50):17533–17538
  13. Mohler PJ, Davis JQ, Bennett V. Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP(3) receptor in a cardiac T-tubule/SR microdomain. PLoS Biol. 2005;3(12):e423
  14. Bhasin N, Cunha SR, Mudannayake M, Gigena MS, Rogers TB, Mohler PJ. Molecular basis for PP2A regulatory subunit B56{alpha} targeting in cardiomyocytes. Am. J. Physiol., Heart Circ. Physiol. 2007;293(1):H109–H119
  15. Cunha SR, Bhasin N, Mohler PJ. Targeting and stability of Na/Ca exchanger 1 in cardiomyocytes requires direct interaction with the membrane adaptor ankyrin-B. J. Biol. Chem. 2007;282(7):4875–4883
  16. Lowe JS, Palygin O, Bhasin N, Hund TJ, Boyden PA, Shibata E, et al. Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. J. Cell Biol. 2008;180(1):173–186
  17. Le Scouarnec S, Bhasin N, Vieyres C, Hund TJ, Cunha SR, Koval O, et al. Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc. Natl. Acad. Sci. U. S. A. 2008;105(40):15617–15622
  18. Cunha SR, Mohler PJ. Cardiac ankyrins: essential components for development and maintenance of excitable membrane domains in heart. Cardiovasc. Res. 2006;71(1):22–29
  19. Cunha SR, Le Scouarnec S, Schott JJ, Mohler PJ. Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease. J. Mol. Cell. Cardiol. 2008;45(6):724–734
  20. Kunimoto M. A neuron-specific isoform of brain ankyrin, 440-kD ankyrinB, is targeted to the axons of rat cerebellar neurons. J. Cell Biol. 1995;131(6 Pt 2):1821–1829
  21. Kontrogianni-Konstantopoulos A, Jones EM, Van Rossum DB, Bloch RJ. Obscurin is a ligand for small ankyrin 1 in skeletal muscle. Mol. Biol. Cell. 2003;14(3):1138–1148
  22. Kontrogianni-Konstantopoulos A, Bloch RJ. The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin. J. Biol. Chem. 2003;278(6):3985–3991
  23. Bagnato P, Barone V, Giacomello E, Rossi D, Sorrentino V. Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles. J. Cell Biol. 2003;160(2):245–253
  24. Zhou D, Birkenmeier CS, Williams MW, Sharp JJ, Barker JE, Bloch RJ. Small, membrane-bound, alternatively spliced forms of ankyrin 1 associated with the sarcoplasmic reticulum of mammalian skeletal muscle. J. Cell Biol. 1997;136(3):621–631
  25. Birkenmeier CS, Sharp JJ, Gifford EJ, Deveau SA, Barker JE. An alternative first exon in the distal end of the erythroid ankyrin gene leads to production of a small isoform containing an NH2-terminal membrane anchor. Genomics. 1998;50(1):79–88
  26. Gallagher PG, Forget BG. An alternate promoter directs expression of a truncated, muscle-specific isoform of the human ankyrin 1 gene. J. Biol. Chem. 1998;273(3):1339–1348
  27. Cunha SR, Mohler PJ. Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line. J. Biol. Chem. 2008;283(46):31968–31980
  28. Mohler PJ, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K, et al. A cardiac arrhythmia syndrome caused by loss of ankyrin-B function. Proc. Natl. Acad. Sci. U. S. A. 2004;101(24):9137–9142
  29. Mohler PJ, Gramolini AO, Bennett V. Ankyrins. J. Cell. Sci. 2002;115(Pt 8):1565–1566
  30. Nelson WJ, Veshnock PJ. Ankyrin binding to (Na++K+) ATPase and implications for the organization of membrane domains in polarized cells. Nature. 1987;328(6130):533–536
  31. Koob R, Zimmermann M, Schoner W, Drenckhahn D. Colocalization and coprecipitation of ankyrin and Na+,K+-ATPase in kidney epithelial cells. Eur. J. Cell Biol. 1988;45(2):230–237
  32. Morrow JS, Cianci CD, Ardito T, Mann AS, Kashgarian M. Ankyrin links fodrin to the alpha subunit of Na,K-ATPase in Madin–Darby canine kidney cells and in intact renal tubule cells. J. Cell Biol. 1989;108(2):455–465
  33. Devaux J, Alcaraz G, Grinspan J, Bennett V, Joho R, Crest M, et al. Kv3.1b is a novel component of CNS nodes. J. Neurosci. 2003;23(11):4509–4518
  34. Lopez C, Metral S, Eladari D, Drevensek S, Gane P, Chambrey R, et al. The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells. J. Biol. Chem. 2005;280(9):8221–8228
  35. Michaely P, Bennett V. Mechanism for binding site diversity on ankyrin. Comparison of binding sites on ankyrin for neurofascin and the Cl−/HCO3− anion exchanger. J. Biol. Chem. 1995;270(52):31298–31302
  36. Michaely P, Bennett V. The ANK repeats of erythrocyte ankyrin form two distinct but cooperative binding sites for the erythrocyte anion exchanger. J. Biol. Chem. 1995;270(37):22050–22057
  37. Bennett V, Stenbuck PJ. Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin. J. Biol. Chem. 1979;254(7):2533–2541
  38. Bodine DMt, Birkenmeier CS, Barker JE. Spectrin deficient inherited hemolytic anemias in the mouse: characterization by spectrin synthesis and mRNA activity in reticulocytes. Cell. 1984;37(3):721–729
  39. Liu SC, Derick LH, Agre P, Palek J. Alteration of the erythrocyte membrane skeletal ultrastructure in hereditary spherocytosis, hereditary elliptocytosis, and pyropoikilocytosis. Blood. 1990;76(1):198–205
  40. Hanspal M, Yoon SH, Yu H, Hanspal JS, Lambert S, Palek J, et al. Molecular basis of spectrin and ankyrin deficiencies in severe hereditary spherocytosis: evidence implicating a primary defect of ankyrin. Blood. 1991;77(1):165–173
  41. Jenkins SM, Bennett V. Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments. J. Cell Biol. 2001;155(5):739–746
  42. Kizhatil K, Bennett V. Lateral membrane biogenesis in human bronchial epithelial cells requires 190-kDa ankyrin-G. J. Biol. Chem. 2004;279(16):16706–16714
  43. Yang Y, Ogawa Y, Hedstrom KL, Rasband MN. betaIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG. J. Cell Biol. 2007;176(4):509–519
  44. Yang Y, Lacas-Gervais S, Morest DK, Solimena M, Rasband MN. BetaIV spectrins are essential for membrane stability and the molecular organization of nodes of Ranvier. J. Neurosci. 2004;24(33):7230–7240
  45. Davis LH, Davis JQ, Bennett V. Ankyrin regulation: an alternatively spliced segment of the regulatory domain functions as an intramolecular modulator. J. Biol. Chem. 1992;267(26):18966–18972
  46. Hall TG, Bennett V. Regulatory domains of erythrocyte ankyrin. J. Biol. Chem. 1987;262(22):10537–10545
  47. Mohler PJ, Hoffman JA, Davis JQ, Abdi KM, Kim CR, Jones SK, et al. Isoform specificity among ankyrins: an amphipathic alpha-helix in the divergent regulatory domain of ankyrin-B interacts with the molecular co-chaperone Hdj1/Hsp40. J. Biol. Chem. 2004;279(24):25798–25804
  48. Abdi KM, Mohler PJ, Davis JQ, Bennett V. Isoform specificity of ankyrin-B: a site in the divergent c-terminal domain is required for intramolecular association. J. Biol. Chem. 2006;281(9):5741–5749
  49. Mohler PJ, Le Scouarnec S, Denjoy I, Lowe JS, Guicheney P, Caron L, et al. Defining the cellular phenotype of “ankyrin-B syndrome” variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation. 2007;115(4):432–441
  50. Borzok MA, Catino DH, Nicholson JD, Kontrogianni-Konstantopoulos A, Bloch RJ. Mapping the binding site on small ankyrin 1 for obscurin. J. Biol. Chem. 2007;282(44):32384–32396
  51. Del Rio M, Imam A, DeLeon M, Gomez G, Mishra J, Ma Q, et al. The death domain of kidney ankyrin interacts with Fas and promotes Fas-mediated cell death in renal epithelia. J. Am. Soc. Nephrol. 2004;15(1):41–51
  52. Kizhatil K, Davis JQ, Davis L, Hoffman J, Hogan BL, Bennett V. Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. J Biol Chem. 2007;282(36):26552–26561
  53. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000;102(10):1178–1185
  54. Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu F, Towbin JA, et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy. Circulation. 1995;92(12):3381–3386
  55. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995;80(5):795–803
  56. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat. Genet. 1996;12(1):17–23
  57. Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, et al. Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum. Mol. Genet. 1995;4(9):1603–1607
  58. Schott JJ, Charpentier F, Peltier S, Foley P, Drouin E, Bouhour JB, et al. Mapping of a gene for long QT syndrome to chromosome 4q25–27. Am. J. Hum. Genet. 1995;57(5):1114–1122
  59. Berlin JR, Cannell MB, Lederer WJ. Cellular origins of the transient inward current in cardiac myocytes. Role of fluctuations and waves of elevated intracellular calcium. Circ. Res. 1989;65(1):115–126
  60. Schlotthauer K, Bers DM. Sarcoplasmic reticulum Ca(2+) release causes myocyte depolarization. Underlying mechanism and threshold for triggered action potentials. Circ. Res. 2000;87(9):774–780
  61. Egdell RM, De Souza AI, Macleod KT. Relative importance of SR load and cytoplasmic calcium concentration in the genesis of aftercontractions in cardiac myocytes. Cardiovasc. Res. 2000;47(4):769–777
  62. Mank-Seymour AR, Richmond JL, Wood LS, Reynolds JM, Fan YT, Warnes GR, et al. Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes. Am. Heart J. 2006;152(6):1116–1122
  63. Sherman J, Tester DJ, Ackerman MJ. Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects. Heart Rhythm. 2005;2(11):1218–1223
  64. Mangrum JM, DiMarco JP. The evaluation and management of bradycardia. N. Engl. J. Med. 2000;342(10):703–709
  65. Lev M. Aging changes in the human sinoatrial node. J. Gerontol. 1954;9(1):1–9
  66. Bernstein AD, Parsonnet V. Survey of cardiac pacing in the United States in 1989. Am. J. Cardiol. 1992;69(4):331–338
  67. Demoulin JC, Kulbertus HE. Histopathological correlates of sinoatrial disease. Br. Heart J. 1978;40(12):1384–1389
  68. Benson DW, Wang DW, Dyment M, Knilans TK, Fish FA, Strieper MJ, et al. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J. Clin. Invest. 2003;112(7):1019–1028
  69. Smits JP, Koopmann TT, Wilders R, Veldkamp MW, Opthof T, Bhuiyan ZA, et al. A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J. Mol. Cell. Cardiol. 2005;38(6):969–981
  70. Ueda K, Nakamura K, Hayashi T, Inagaki N, Takahashi M, Arimura T, et al. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J. Biol. Chem. 2004;279(26):27194–27198
  71. Klein G, Schroder F, Vogler D, Schaefer A, Haverich A, Schieffer B, et al. Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. role of phosphatase 2A. Cardiovasc. Res. 2003;59(1):37–45
  72. De Arcangelis V, Soto D, Xiang Y. Phosphodiesterase 4 and phosphatase 2A differentially regulate cAMP/protein kinase a signaling for cardiac myocyte contraction under stimulation of beta1 adrenergic receptor. Mol. Pharmacol. 2008;74(5):1453–1462
  73. Davare MA, Avdonin V, Hall DD, Peden EM, Burette A, Weinberg RJ, et al. A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2. Science. 2001;293(5527):98–101
  74. Davare MA, Horne MC, Hell JW. Protein phosphatase 2A is associated with class C L-type calcium channels (Cav1.2) and antagonizes channel phosphorylation by cAMP-dependent protein kinase. J. Biol. Chem. 2000;275(50):39710–39717
  75. Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000;101(4):365–376
  76. DeSouza N, Reiken S, Ondrias K, Yang YM, Matkovich S, Marks AR. Protein kinase A and two phosphatases are components of the inositol 1,4,5-trisphosphate receptor macromolecular signaling complex. J. Biol. Chem. 2002;277(42):39397–39400
  77. Lecuona E, Dada LA, Sun H, Butti ML, Zhou G, Chew TL, et al. Na,K-ATPase alpha1-subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane. FASEB J. 2006;20(14):2618–2620
  78. Borisov AB, Raeker MO, Kontrogianni-Konstantopoulos A, Yang K, Kurnit DM, Bloch RJ, et al. Rapid response of cardiac obscurin gene cluster to aortic stenosis: differential activation of Rho-GEF and MLCK and involvement in hypertrophic growth. Biochem. Biophys. Res. Commun. 2003;310(3):910–918
  79. Borisov AB, Sutter SB, Kontrogianni-Konstantopoulos A, Bloch RJ, Westfall MV, Russell MW. Essential role of obscurin in cardiac myofibrillogenesis and hypertrophic response: evidence from small interfering RNA-mediated gene silencing. Histochem. Cell Biol. 2006;125(3):227–238
  80. Terentyev D, Belevych AE, Terentyeva R, Martin MM, Malana GE, Kuhn DE, et al. miR-1 overexpression enhances Ca2+ release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56{alpha} and causing CaMKII-dependent hyperphosphorylation of RyR2. Circ. Res. 2009;104:514–521
  81. Hund TJ, Wright PJ, Dun W, Snyder JS, Boyden PA, Mohler PJ. Regulation of the ankyrin-B-based targeting pathway following myocardial infarction. Cardiovasc. Res. 2009;81(4):742–749
  82. Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol. Rev. 1989;69(4):1049–1169
  83. Pinto JM, Boyden PA. Electrical remodeling in ischemia and infarction. Cardiovasc. Res. 1999;42(2):284–297
  84. Baba S, Dun W, Cabo C, Boyden PA. Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. Circulation. 2005;112(16):2386–2396
  85. Pu J, Boyden PA. Alterations of Na+ currents in myocytes from epicardial border zone of the infarcted heart. A possible ionic mechanism for reduced excitability and postrepolarization refractoriness. Circ. Res. 1997;81(1):110–119
  86. Priori SG, Bloise R, Crotti L. The long QT syndrome. Europace. 2001;3(1):16–27
  87. Priori SG, Napolitano C, Schwartz PJ. Electrophysiologic mechanisms involved in the development of torsades de pointes. Cardiovasc. Drugs Ther./sponsored by the Int. Soc. Cardiovasc. Pharmacother. 1991;5(1):203–212
  88. Gaita F, Giustetto C, Bianchi F, Wolpert C, Schimpf R, Riccardi R, et al. Short QT syndrome: a familial cause of sudden death. Circulation. 2003;108(8):965–970
  89. Keating MT, Sanguinetti MC. Molecular and cellular mechanisms of cardiac arrhythmias. Cell. 2001;104(4):569–580
  90. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995;80(5):805–811
  91. Pfeufer A, Jalilzadeh S, Perz S, Mueller JC, Hinterseer M, Illig T, et al. Common variants in myocardial ion channel genes modify the QT interval in the general population: results from the KORA study. Circ. Res. 2005;96(6):693–701
  92. Sedlacek K, Stark K, Cunha SR, Pfeufer A, Weber S, Berger I, et al. Common genetic variants in ANK2 modulate QT interval: results from the KORA study. Circulation: Cardiovasc. Genet. 2008;1(2):93–99
  93. Akyol M, Jalilzadeh S, Sinner MF, Perz S, Beckmann BM, Gieger C, et al. The common non-synonymous variant G38S of the KCNE1-(minK)-gene is not associated to QT interval in Central European Caucasians: results from the KORA study. Eur. Heart J. 2007;28(3):305–309
  94. Arking DE, Pfeufer A, Post W, Kao WH, Newton-Cheh C, Ikeda M, et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat. Genet. 2006;38(6):644–651
  95. Bennett PB, Yazawa K, Makita N, George AL. Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995;376(6542):683–685
  96. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998;392(6673):293–296
  97. Schott JJ, Alshinawi C, Kyndt F, Probst V, Hoorntje TM, Hulsbeek M, et al. Cardiac conduction defects associate with mutations in SCN5A. Nat. Genet. 1999;23(1):20–21
  98. Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J. Cell Biol. 1998;143(5):1295–1304
  99. Jenkins SM, Bennett V. Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. Proc. Natl. Acad. Sci. U. S. A. 2002;99(4):2303–2308
  100. Flucher BE, Daniels MP. Distribution of Na+ channels and ankyrin in neuromuscular junctions is complementary to that of acetylcholine receptors and the 43 kD protein. Neuron. 1989;3(2):163–175
  101. Kordeli E, Ludosky MA, Deprette C, Frappier T, Cartaud J. AnkyrinG is associated with the postsynaptic membrane and the sarcoplasmic reticulum in the skeletal muscle fiber. J. Cell. Sci. 1998;111(Pt 15):2197–2207
  102. Wood SJ, Slater CR. beta-Spectrin is colocalized with both voltage-gated sodium channels and ankyrinG at the adult rat neuromuscular junction. J. Cell Biol. 1998;140(3):675–684
  103. Kordeli E, Lambert S, Bennett V. AnkyrinG. A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J. Biol. Chem. 1995;270(5):2352–2359
  104. Davis JQ, Lambert S, Bennett V. Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain−) and NrCAM at nodal axon segments. J. Cell Biol. 1996;135(5):1355–1367
  105. Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, et al. A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J. Neurosci. 2006;26(10):2599–2613
  106. Hill AS, Nishino A, Nakajo K, Zhang G, Fineman JR, Selzer ME, et al. Ion channel clustering at the axon initial segment and node of Ranvier evolved sequentially in early chordates. PLoS Genet. 2008;4(12):e1000317
  107. Garrido JJ, Giraud P, Carlier E, Fernandes F, Moussif A, Fache MP, et al. A targeting motif involved in sodium channel clustering at the axonal initial segment. Science. 2003;300(5628):2091–2094
  108. Lemaillet G, Walker B, Lambert S. Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits. J. Biol. Chem. 2003;278(30):27333–27339
  109. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, et al. Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2005;2(4):429–440
  110. Priori SG. Inherited arrhythmogenic diseases: the complexity beyond monogenic disorders. Circ. Res. 2004;94(2):140–145
  111. Priori SG, Napolitano C. Genetics of cardiac arrhythmias and sudden cardiac death. Ann. N.Y. Acad. Sci. 2004;1015:96–110
  112. Smits JP, Eckardt L, Probst V, Bezzina CR, Schott JJ, Remme CA, et al. Genotype–phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. J. Am. Coll. Cardiol. 2002;40(2):350–356
  113. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002;105(11):1342–1347

PII: S0022-2828(09)00181-3

doi: 10.1016/j.yjmcc.2009.04.010

Journal of Molecular and Cellular Cardiology
Volume 47, Issue 2 , Pages 203-209 , August 2009

Article Tools

* Image Usage & Resolution