Computer Simulation of Altered Sodium Channel Gating in Rabbit and HumanVentricular Myocytes

  • Eleonora Grandi
  • Jose L. Puglisi
  • Stefano Severi
  • Donald M. Bers
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4466)


Mathematical models were used to explore sodium (Na) current alterations. Markovian representations were chosen to describe the Na current behavior under pathological conditions, such as genetic defects (Long QT and Brugada syndromes) or acquired diseases (heart failure). These Na current formulations were subsequently introduced in an integrated model of the ventricular myocyte to investigate their effects on the ventricular action potential. This “in silico” approach is a powerful tool, providing new insights into arrhythmia susceptibility due to inherited and/or acquired Na channelopathies.


Na channelopathies action potential arrhythmias 


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  1. 1.
    Tan, HL.: Sodium channel variants in heart disease: expanding horizons. J. Cardiovasc Electrophysiol 17(1), S151–S157 Review (2006)CrossRefGoogle Scholar
  2. 2.
    Rivolta, I., Abriel, H., Tateyama, M., Liu, H., Memmi, M., Vardas, P., Napolitano, C., Priori, S.G., Kass, R.S.: Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J. Biol. Chem. 17;276(33), 30623–30630 (2001)CrossRefGoogle Scholar
  3. 3.
    Veldkamp, M.W., Viswanathan, P.C., Bezzina, C., Baartscheer, A., Wilde, A.A.M., Balser, J.R.: Two distinct congenital arrhythmias evoked by a multidysfunctional Na+ channel. Circ. Res. 86, E91–E97 (2000)Google Scholar
  4. 4.
    Clancy, C.E., Rudy, Y.: Na+ Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes. Circulation 105, 1208–1213 (2002)CrossRefGoogle Scholar
  5. 5.
    Maier, L.S., Bers, D.M.: Role of Ca(2+)/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart. Cardiovasc Res. (November 10, 2006)Google Scholar
  6. 6.
    Wagner, S., Dybkova, N., Rasenack, E.C., Jacobshagen, C., Fabritz, L., Kirchhof, P., Maier, S.K., Zhang, T., Hasenfuss, G., Brown, J.H., Bers, D.M., Maier, L.S.: Ca/calmodulin-dependent protein kinase II regulates cardiac Na channels. J. Clin Invest. 116(12), 3127–3138 (2006)CrossRefGoogle Scholar
  7. 7.
    Vecchietti, S., Grandi, E., Severi, S., Rivolta, I., Napolitano, C., Priori, S.G., Cavalcanti, S.: In silico assessment of Y1795C and Y1795H SCN5A mutations. Implication for inherited arrhythmogenic syndromes. Am. J. Physiol Heart Circ Physiol 292, H56–H65 (2007)CrossRefGoogle Scholar
  8. 8.
    ten Tusscher, K.H., Noble, D., Noble, P.J., Panfilov, A.V.: A model for human ventricular tissue. Am. J. Physiol Heart Circ Physiol. 286(4), H1573–1589 (2004)CrossRefGoogle Scholar
  9. 9.
    Puglisi, J.L., Bers, D.M.: LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport. Am. J. Physiol Cell Physiol. 281(6), C2049–C2060 (2001)Google Scholar
  10. 10.
    Maltsev, V.A., Undrovinas, A.I.: A multi-modal composition of the late Na+ current in human ventricular cardiomyocytes. Cardiovasc Res. 69(1), 116–127 (2006)CrossRefGoogle Scholar

Copyright information

© Springer Berlin Heidelberg 2007

Authors and Affiliations

  • Eleonora Grandi
    • 1
  • Jose L. Puglisi
    • 2
  • Stefano Severi
    • 1
  • Donald M. Bers
    • 2
  1. 1.Department of Electronics Computer Science and Systems, University of Bologna, Viale Risorgimento 2, 40136 BolognaItaly
  2. 2.Department of Physiology, Loyola University Chicago, 2160 South First Ave, 60153 Maywood, ILUSA

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