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. 2001 Dec;81(6):3324–3331. doi: 10.1016/S0006-3495(01)75965-6

Ionic charge conservation and long-term steady state in the Luo-Rudy dynamic cell model.

T J Hund 1, J P Kucera 1, N F Otani 1, Y Rudy 1
PMCID: PMC1301789  PMID: 11720995

Abstract

It has been postulated that cardiac cell models accounting for changes in intracellular ion concentrations violate a conservation principle, and, as a result, computed parameters (e.g., ion concentrations and transmembrane potential, V(m)) drift in time, never attaining steady state. To address this issue, models have been proposed that invoke the charge conservation principle to calculate V(m) from ion concentrations ("algebraic" method), rather than from transmembrane current ("differential" method). The aims of this study are to compare model behavior during prolonged periods of pacing using the algebraic and differential methods, and to address the issue of model drift. We pace the Luo-Rudy dynamic model of a cardiac ventricular cell and compare the time-dependent behavior of computed parameters using the algebraic and differential methods. When ions carried by the stimulus current are taken into account, the algebraic and differential methods yield identical results and neither shows drift in computed parameters. The present study establishes the proper pacing protocol for simulation studies of cellular behavior during long periods of rapid pacing. Such studies are essential for mechanistic understanding of arrhythmogenesis, since cells are subjected to rapid periodic stimulation during many arrhythmias.

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Selected References

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  1. Beeler G. W., Reuter H. Reconstruction of the action potential of ventricular myocardial fibres. J Physiol. 1977 Jun;268(1):177–210. doi: 10.1113/jphysiol.1977.sp011853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DiFrancesco D., Noble D. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc Lond B Biol Sci. 1985 Jan 10;307(1133):353–398. doi: 10.1098/rstb.1985.0001. [DOI] [PubMed] [Google Scholar]
  3. Endresen L. P., Hall K., Høye J. S., Myrheim J. A theory for the membrane potential of living cells. Eur Biophys J. 2000;29(2):90–103. doi: 10.1007/s002490050254. [DOI] [PubMed] [Google Scholar]
  4. Faber G. M., Rudy Y. Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study. Biophys J. 2000 May;78(5):2392–2404. doi: 10.1016/S0006-3495(00)76783-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Guan S., Lu Q., Huang K. A discussion about the DiFrancesco-Noble model. J Theor Biol. 1997 Nov 7;189(1):27–32. doi: 10.1006/jtbi.1997.0486. [DOI] [PubMed] [Google Scholar]
  6. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Luo C. H., Rudy Y. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ Res. 1994 Jun;74(6):1071–1096. doi: 10.1161/01.res.74.6.1071. [DOI] [PubMed] [Google Scholar]
  8. Luo C. H., Rudy Y. A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. Circ Res. 1991 Jun;68(6):1501–1526. doi: 10.1161/01.res.68.6.1501. [DOI] [PubMed] [Google Scholar]
  9. McAllister R. E., Noble D., Tsien R. W. Reconstruction of the electrical activity of cardiac Purkinje fibres. J Physiol. 1975 Sep;251(1):1–59. doi: 10.1113/jphysiol.1975.sp011080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Michailova A., McCulloch A. Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte. Biophys J. 2001 Aug;81(2):614–629. doi: 10.1016/S0006-3495(01)75727-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. NOBLE D. A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials. J Physiol. 1962 Feb;160:317–352. doi: 10.1113/jphysiol.1962.sp006849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rappel Wouter-Jan. Filament instability and rotational tissue anisotropy: A numerical study using detailed cardiac models. Chaos. 2001 Mar;11(1):71–80. doi: 10.1063/1.1338128. [DOI] [PubMed] [Google Scholar]
  13. Varghese A., Sell G. R. A conservation principle and its effect on the formulation of Na-Ca exchanger current in cardiac cells. J Theor Biol. 1997 Nov 7;189(1):33–40. doi: 10.1006/jtbi.1997.0487. [DOI] [PubMed] [Google Scholar]
  14. Winslow R. L., Rice J., Jafri S., Marbán E., O'Rourke B. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, II: model studies. Circ Res. 1999 Mar 19;84(5):571–586. doi: 10.1161/01.res.84.5.571. [DOI] [PubMed] [Google Scholar]
  15. Yehia Ali R., Jeandupeux Dominique, Alonso Francisco, Guevara Michael R. Hysteresis and bistability in the direct transition from 1:1 to 2:1 rhythm in periodically driven single ventricular cells. Chaos. 1999 Dec;9(4):916–931. doi: 10.1063/1.166465. [DOI] [PubMed] [Google Scholar]
  16. Zeng J., Rudy Y. Early afterdepolarizations in cardiac myocytes: mechanism and rate dependence. Biophys J. 1995 Mar;68(3):949–964. doi: 10.1016/S0006-3495(95)80271-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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