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Mathematically Modelling the Functional Consequences of the SQT2 Mutation

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Modelling the Short QT Syndrome Gene Mutations

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Abstract

Variant 2 of the SQTS (SQT2) is associated with gain-of-function mutations to the KCNQ1 protein [1, 2], which when co-expressed with KCNE1 (mink; β-subunit) recapitulates the IKs channel [3, 4] that is partly responsible for repolarization of the action potential

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References

  1. Bellocq C, van Ginneken ACG, Bezzina CR, Alders M, Escande D, Mannens MMAM et al (2004) Mutation in the KCNQ1 gene leading to the short QT-interval syndrome. Circulation 109(20):2394–2397

    Article  Google Scholar 

  2. Hong K, Piper DR, Diaz-Valdecantos A, Brugada J, Oliva A, Burashnikov E et al (2005) De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc Res 68(3):433–440

    Article  Google Scholar 

  3. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (1996) K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384(6604):78–80

    Article  ADS  Google Scholar 

  4. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL et al (1996) Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature 384(6604):80–83

    Article  ADS  Google Scholar 

  5. Courtemanche M, Ramirez RJ, Nattel S (1998) Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. Am J Physiol 275(1 Pt 2):H301–H321

    Google Scholar 

  6. ten Tusscher KHWJ, Noble D, Noble PJ, Panfilov AV (2004) A model for human ventricular tissue. Am J Physiol Heart Circ Physiol 286(4):H1573–H1589

    Article  Google Scholar 

  7. Zhang H, Kharche S, Holden AV, Hancox JC (2008) Repolarization and vulnerability to re-entry in the human heart with short QT syndrome arising from KCNQ1 mutation–a simulation study. Prog Biophys Mol Biol 96(1–3):112–131

    Article  Google Scholar 

  8. El Harchi A, McPate MJ, Zhang YH, Zhang H, Hancox JC (2010) Action potential clamp and mefloquine sensitivity of recombinant IKS channels incorporating the V307L KCNQ1 mutation. J Physiol Pharmacol 61(2):123–131

    Google Scholar 

  9. ten Tusscher KHWJ, Panfilov AV (2006) Alternans and spiral breakup in a human ventricular tissue model. Am J Physiol Heart Circ Physiol 291(3):H1088–H1100

    Article  Google Scholar 

  10. Priebe L, Beuckelmann DJ (1998) Simulation study of cellular electric properties in heart failure. Circ Res 82(11):1206–1223

    Article  Google Scholar 

  11. Silva J, Rudy Y (2005) Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation 112(10):1384–1391

    Article  Google Scholar 

  12. Rudy Y, Silva JR (2006) Computational biology in the study of cardiac ion channels and cell electrophysiology. Q Rev Biophys 39(1):57–116

    Article  Google Scholar 

  13. Osteen JD, Sampson KJ, Kass RS (2010) The cardiac IKs channel, complex indeed. Proc Natl Acad Sci USA 107(44):18751–18752

    Article  ADS  Google Scholar 

  14. Jespersen T, Grunnet M, Olesen S-P (2005) The KCNQ1 potassium channel: from gene to physiological function. Physiology (Bethesda) 20:408–416

    Article  Google Scholar 

  15. Cross B, Homoud M, Link M, Foote C, Garlitski A, Weinstock J et al (2011) The short QT syndrome. J Intervent Card Electrophysiol 31(1):25–31

    Article  Google Scholar 

  16. Gussak I, Brugada P, Brugada J, Wright RS, Kopecky SL, Chaitman BR et al (2000) Idiopathic short QT interval: a new clinical syndrome? Cardiology 94(2):99–102

    Article  Google Scholar 

  17. Couderc J-P, Lopes CM (2010) Short and long QT syndromes: does QT length really matter? J Electrocardiol 43(5):396–399

    Google Scholar 

  18. Patel U, Pavri BB (2009) Short QT syndrome: a review. Cardiol Rev 17(6):300–303

    Article  Google Scholar 

  19. Giustetto C, Di Monte F, Wolpert C, Borggrefe M, Schimpf R, Sbragia P et al (2006) Short QT syndrome: clinical findings and diagnostic-therapeutic implications. Eur Heart J 27(20):2440–2447

    Article  Google Scholar 

  20. Brugada R, Hong K, Cordeiro JM, Dumaine R (2005) Short QT syndrome. CMAJ 173(11):1349–1354

    Article  Google Scholar 

  21. Gima K, Rudy Y (2002) Ionic current basis of electrocardiographic waveforms: a model study. Circ Res 90(8):889–896

    Article  Google Scholar 

  22. Adeniran I, McPate MJW, Witchel HJ, Hancox JC, Zhang H (2011) Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 Short QT Syndrome. Plos Comput Biol 7(12):e1002313

    Google Scholar 

  23. Adeniran I, El Harchi A, Hancox JC, Zhang H (2012) Proarrhythmia in KCNJ2-linked short QT syndrome—insights from modelling. Cardiovasc Res 94(1):66–76

    Google Scholar 

  24. Yan GX, Shimizu W, Antzelevitch C (1998) Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations. Circulation 98(18):1921–1927

    Article  Google Scholar 

  25. Drouin E, Charpentier F, Gauthier C, Laurent K, Le Marec H (1995) Electrophysiologic characteristics of cells spanning the left ventricular wall of human heart: evidence for presence of M cells. J Am Coll Cardiol 26(1):185–192

    Article  Google Scholar 

  26. Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A et al (2005) A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 96(7):800–807

    Article  Google Scholar 

  27. Schimpf R, Wolpert C, Gaita F, Giustetto C, Borggrefe M (2005) Short QT syndrome. Cardiovasc Res 67(3):357–366

    Article  Google Scholar 

  28. Maury P, Extramiana F, Sbragia P, Giustetto C, Schimpf R, Duparc A et al (2008) Short QT syndrome, update on a recent entity. Arch Cardiovasc Dis 101(11–12):779–786

    Article  Google Scholar 

  29. Schimpf R, Borggrefe M, Wolpert C (2008) Clinical and molecular genetics of the short QT syndrome. Curr Opin Cardiol 23(3):192–198

    Article  Google Scholar 

  30. Watanabe H, Makiyama T, Koyama T, Kannankeril PJ, Seto S, Okamura K et al (2010) High prevalence of early repolarization in short QT syndrome. Heart Rhythm 7(5):647–652

    Article  Google Scholar 

  31. Hancox JC, McPate MJ, Harchi A, Duncan RS, Dempsey CE, Witchel HJ et al (2011) The Short QT syndrome. In: Tripathi ON, Ravens U, Sanguinetti MC (eds) Heart rate and rhythm (Internet). Springer, Heidelberg, pp 4–49 Available via DIALOG. http://www.springerlink.com/content/m8l86l8n3h81w43m/. Accessed 10 Jul 2011

  32. Schimpf R, Wolpert C, Bianchi F, Giustetto C, Gaita F, Bauersfeld U et al (2003) Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery. J Cardiovasc Electrophysiol 14(12):1273–1277

    Article  Google Scholar 

  33. Schimpf R, Bauersfeld U, Gaita F, Wolpert C (2005) Short QT syndrome: successful prevention of sudden cardiac death in an adolescent by implantable cardioverter-defibrillator treatment for primary prophylaxis. Heart Rhythm 2(4):416–417

    Article  Google Scholar 

  34. Anttonen O, Junttila J, Giustetto C, Gaita F, Linna E, Karsikas M et al (2009) T-Wave morphology in short QT syndrome. Ann Noninvasive Electrocardiol 14(3):262–267

    Article  Google Scholar 

  35. Bjerregaard P, Jahangir A, Gussak I (2006) Targeted therapy for short QT syndrome. Expert Opin Ther Targets 10(3):393–400

    Article  Google Scholar 

  36. Duncan RS, McPate MJ, Ridley JM, Gao Z, James AF, Leishman DJ et al (2007) Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin. Biochem Pharmacol 74(3):425–437

    Article  Google Scholar 

  37. Lerche C, Bruhova I, Lerche H, Steinmeyer K, Wei AD, Strutz-Seebohm N et al (2007) Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter. Mol Pharmacol 71(6):1503–1511

    Article  Google Scholar 

  38. Billman GE (2010) Novel therapeutic targets for antiarrhythmic drugs, 1st edn. Wiley, New York

    Google Scholar 

  39. Towart R, Linders JTM, Hermans AN, Rohrbacher J, van der Linde HJ, Ercken M et al (2009) Blockade of the I(Ks) potassium channel: an overlooked cardiovascular liability in drug safety screening? J Pharmacol Toxicol Methods 60(1):1–10

    Article  Google Scholar 

  40. Curtis MJ (2004) Is cardiac IKs a relevant drug target? Cardiovasc Res 61(4):651–652

    Article  Google Scholar 

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Authors and Affiliations

  1. Biological Physics Group School of Physics and Astronomy, University of Manchester, Manchester, UK

    Ismail Adeniran

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  1. Ismail Adeniran
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Correspondence to Ismail Adeniran .

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Adeniran, I. (2014). Mathematically Modelling the Functional Consequences of the SQT2 Mutation. In: Modelling the Short QT Syndrome Gene Mutations. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-319-07200-5_7

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