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Model Development

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Modelling the Short QT Syndrome Gene Mutations

Part of the book series: Springer Theses ((Springer Theses))

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Abstract

In the absence of phenotypically accurate experimental models of K+ channel mutation linked SQTS variants (SQT1–SQT3), in silico models offer the best complementary method to in vivo and in vitro electrophysiology for investigating the functional consequences of these and other gene mutations.

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References

  1. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (Lond) 117(4):500–544

    Google Scholar 

  2. Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer Associates, Sunderland

    Google Scholar 

  3. Armstrong CM, Hille B (1998) Voltage-gated ion channels and electrical excitability. Neuron 20(3):371–380

    Article  Google Scholar 

  4. Sakmann B, Neher E (2009) Single-channel recording, 2nd edn, 1995 2nd printing. Springer, New York

    Google Scholar 

  5. Cannon RC, D’Alessandro G (2006) The ion channel inverse problem: neuroinformatics meets biophysics. PLoS Comput Biol 2(8):e91

    Article  ADS  Google Scholar 

  6. Armstrong CM, Bezanilla F (1977) Inactivation of the sodium channel. II. Gating current experiments. J Gen Physiol 70(5):567–590

    Article  Google Scholar 

  7. Bezanilla F, Armstrong CM (1977) Inactivation of the sodium channel. I. Sodium current experiments. J Gen Physiol 70(5):549–566

    Article  Google Scholar 

  8. Aldrich RW (1981) Inactivation of voltage-gated delayed potassium current in molluscan neurons. A kinetic model. Biophys J 36(3):519–532

    Article  Google Scholar 

  9. 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 

  10. Fitzhugh R (1965) A kinetic model of the conductance changes in nerve membrane. J Cell Compar Physiol 66(S2):111–117

    Article  Google Scholar 

  11. Colquhoun D, Hawkes AG (1981) On the stochastic properties of single ion channels. Proc R Soc Lond B Biol Sci 211(1183):205–235

    Article  ADS  Google Scholar 

  12. Stevens CF (1978) Interactions between intrinsic membrane protein and electric field. An approach to studying nerve excitability. Biophys J 22(2):295–306

    Article  Google Scholar 

  13. Stewart WJ (1994) Introduction to the numerical solution of Markov chains, 1st edn. Princeton University Press, Princeton

    Google Scholar 

  14. Meyn S, Tweedie RL (2009) Markov chains and stochastic stability, 2nd edn. Cambridge University Press, Cambridge

    Google Scholar 

  15. Kemeny JG, Snell JL (1960) Finite Markov chains. D. Van Nostrand, Princeton

    Google Scholar 

  16. Johnson FH, Eyring HJ, Stover BJ (1974) Theory of rate processes in biology and medicine. Wiley, New York

    Google Scholar 

  17. Eyring HJ, Lin SH, Lin SM (1980) Basic chemical kinetics. Wiley, New York

    Google Scholar 

  18. Destexhe A, Huguenard JR (2000) Nonlinear thermodynamic models of voltage-dependent currents. J Comput Neurosci 9(3):259–270

    Article  Google Scholar 

  19. Tsien RW, Noble D (1969) A transition state theory approach to the kinetics of conductance changes in excitable membranes. J Membr Biol 1:248–273

    Article  Google Scholar 

  20. Hill TL, Chen Y-D (1972) On the theory of ion transport across the nerve membrane. Biophys J 12(8):948–959

    Article  Google Scholar 

  21. Andersen OS, Koeppe RE 2nd (1992) Molecular determinants of channel function. Physiol Rev 72(4 Suppl):S89–S158

    Google Scholar 

  22. Kiehn J, Lacerda AE, Brown AM (1999) Pathways of HERG inactivation. Am J Physiol 277(1 Pt 2):H199–H210

    Google Scholar 

  23. Clancy CE, Rudy Y (2001) Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death. Cardiovasc Res 50(2):301–313

    Article  Google Scholar 

  24. Lu Y, Mahaut-Smith MP, Varghese A, Huang CL, Kemp PR, Vandenberg JI (2001) Effects of premature stimulation on HERG K(+) channels. J Physiol (Lond) 537(Pt 3):843–851

    Article  Google Scholar 

  25. Wang S, Liu S, Morales MJ, Strauss HC, Rasmusson RL (1997) A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes. J Physiol (Lond) 502(Pt 1):45–60

    Article  Google Scholar 

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

    Article  Google Scholar 

  27. McPate MJ, Duncan RS, Milnes JT, Witchel HJ, Hancox JC (2005) The N588K-HERG K + channel mutation in the “short QT syndrome”: mechanism of gain-in-function determined at 37 °C. Biochem Biophys Res Commun 334(2):441–449

    Article  Google Scholar 

  28. Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M et al (2004) Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 109(1):30–35

    Article  Google Scholar 

  29. McPate MJ, Duncan RS, Hancox JC, Witchel HJ (2008) Pharmacology of the short QT syndrome N588K-hERG K + channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol 155(6):957–966

    Article  Google Scholar 

  30. McPate MJ, Zhang H, Adeniran I, Cordeiro JM, Witchel HJ, Hancox JC (2009) Comparative effects of the short QT N588K mutation at 37 °C on hERG K + channel current during ventricular, Purkinje fibre and atrial action potentials: an action potential clamp study. J Physiol Pharmacol 60(1):23–41

    Google Scholar 

  31. Broyden CG (1970) The convergence of a class of double-rank minimization algorithms 1. General considerations. IMA J Appl Math 6(1):76–90

    Article  MATH  MathSciNet  Google Scholar 

  32. Press WH, Teukolsky SA, Vetterling WT, Flannery BP (2007) Numerical recipes, 3rd edn. The art of scientific computing, 3rd edn. Cambridge University Press, Cambridge

    Google Scholar 

  33. Adeniran I, Hancox J, Zhang H (2010) Development of a biophysically detailed model of the rapid-delayed rectifier potassium channel. Comput Cardiol 37:637–640

    Google Scholar 

  34. Koren G, Liman ER, Logothetis DE, Nadal-Ginard B, Hess P (1990) Gating mechanism of a cloned potassium channel expressed in frog oocytes and mammalian cells. Neuron 4(1):39–51

    Article  Google Scholar 

  35. Zagotta WN, Hoshi T, Aldrich RW (1994) Shaker potassium channel gating. III: evaluation of kinetic models for activation. J Gen Physiol 103(2):321–362

    Article  Google Scholar 

  36. Kupershmidt S, Yang IC-H, Sutherland M, Wells KS, Yang T, Yang P et al (2002) Cardiac-enriched LIM domain protein fhl2 is required to generate I(Ks) in a heterologous system. Cardiovasc Res 56(1):93–103

    Article  Google Scholar 

  37. Virág L, Iost N, Opincariu M, Szolnoky J, Szécsi J, Bogáts G et al (2001) The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes. Cardiovasc Res 49(4):790–797

    Article  Google Scholar 

  38. Zagotta WN, Hoshi T, Dittman J, Aldrich RW (1994) Shaker potassium channel gating. II: transitions in the activation pathway. J Gen Physiol 103(2):279–319

    Article  Google Scholar 

  39. Silverman WR, Roux B, Papazian DM (2003) Structural basis of two-stage voltage-dependent activation in K + channels. Proc Natl Acad Sci USA 100(5):2935–2940

    Article  ADS  Google Scholar 

  40. Lu Z, Kamiya K, Opthof T, Yasui K, Kodama I (2001) Density and kinetics of I(Kr) and I(Ks) in guinea pig and rabbit ventricular myocytes explain different efficacy of I(Ks) blockade at high heart rate in guinea pig and rabbit: implications for arrhythmogenesis in humans. Circulation 104(8):951–956

    Article  Google Scholar 

  41. Loussouarn G, Park K-H, Bellocq C, Baró I, Charpentier F, Escande D (2003) Phosphatidylinositol-4, 5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K + channels. EMBO J 22(20):5412–5421

    Article  Google Scholar 

  42. Pusch M, Bertorello L, Conti F (2000) Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels. Biophys J 78(1):211–226

    Article  Google Scholar 

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

    Google Scholar 

  44. Nelder JA, Mead R (1965) A simplex method for function minimization. Comput J 7(4):308–313

    Article  MATH  Google Scholar 

  45. 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 

  46. 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 

  47. ten Tusscher KHWJ, Panfilov AV (2006) Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions. Phys Med Biol 51(23):6141–6156

    Article  Google Scholar 

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

    Article  Google Scholar 

  49. Sakmann B, Trube G (1984) Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol (Lond) 347:659–683

    Google Scholar 

  50. Bailly P, Mouchonière M, Bénitah JP, Camilleri L, Vassort G, Lorente P (1998) Extracellular K + dependence of inward rectification kinetics in human left ventricular cardiomyocytes. Circulation 98(24):2753–2759

    Article  Google Scholar 

  51. Yan D-H, Ishihara K (2005) Two Kir2.1 channel populations with different sensitivities to Mg(2 +) and polyamine block: a model for the cardiac strong inward rectifier K(+) channel. J Physiol (Lond) 563(Pt 3):725–744

    Google Scholar 

  52. 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 

  53. El Harchi A, McPate MJ, Hong ZY, Zhang H, Hancox JC (2009) Action potential clamp and chloroquine sensitivity of mutant Kir2.1 channels responsible for variant 3 short QT syndrome. J Mol Cell Cardiol 47(5):743–747

    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). Model Development. In: Modelling the Short QT Syndrome Gene Mutations. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-319-07200-5_4

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