Display options
Cite
Gauthier LD, Greenstein JL, Winslow RL. Toward an integrative computational model of the Guinea pig cardiac myocyte. Front Physiol. 2012;3:244doi: 10.3389/fphys.2012.00244.
Gauthier, L. D., Greenstein, J. L., & Winslow, R. L. (2012). Toward an integrative computational model of the Guinea pig cardiac myocyte. Frontiers in physiology, 3244. https://doi.org/10.3389/fphys.2012.00244
Gauthier, Laura Doyle, et al. "Toward an integrative computational model of the Guinea pig cardiac myocyte." Frontiers in physiology vol. 3 (2012): 244. doi: https://doi.org/10.3389/fphys.2012.00244
Gauthier LD, Greenstein JL, Winslow RL. Toward an integrative computational model of the Guinea pig cardiac myocyte. Front Physiol. 2012 Jul 05;3:244. doi: 10.3389/fphys.2012.00244. eCollection 2012. PMID: 22783206; PMCID: PMC3389778.
Copy Download .nbib Format: NLM
Share it on

Front Physiol. 2012 Jul 05;3:244. doi: 10.3389/fphys.2012.00244. eCollection 2012.

Toward an integrative computational model of the Guinea pig cardiac myocyte.

Frontiers in physiology

Laura Doyle Gauthier, Joseph L Greenstein, Raimond L Winslow

Affiliations

  1. Department of Biomedical Engineering, Institute for Computational Medicine, The Johns Hopkins University School of Medicine and Whiting School of Engineering Baltimore, MD, USA.

PMID: 22783206 PMCID: PMC3389778 DOI: 10.3389/fphys.2012.00244

Abstract

The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca(2+)) release occurs at the nanodomain level, where openings of single L-type Ca(2+) channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca(2+) transient is a smooth continuous function of influx of Ca(2+) through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca(2+) release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca(2+) and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca(2+) transients, thus influencing tissue level electromechanical function.

Keywords: calcium cycling; calcium-induced calcium-release; cardiac myocyte; computational model; excitation-contraction coupling; mitochondrial energetics

References

  1. Biophys J. 2007 Mar 1;92(5):1522-43 - PubMed
  2. Biophys J. 2000 May;78(5):2392-404 - PubMed
  3. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6061-6 - PubMed
  4. Am J Physiol Heart Circ Physiol. 2003 Feb;284(2):H598-604 - PubMed
  5. J Gen Physiol. 1999 Feb;113(2):177-86 - PubMed
  6. J Physiol. 2009 Nov 1;587(Pt 21):5197-209 - PubMed
  7. Biophys J. 2011 Jun 22;100(12):2894-903 - PubMed
  8. J Gen Physiol. 1985 Feb;85(2):247-89 - PubMed
  9. Prog Biophys Mol Biol. 2004 Jun-Jul;85(2-3):279-99 - PubMed
  10. Biophys J. 2000 Jan;78(1):334-43 - PubMed
  11. J Comp Physiol B. 1996;166(2):150-5 - PubMed
  12. Am J Physiol Cell Physiol. 2004 Nov;287(5):C1396-403 - PubMed
  13. J Physiol. 1992 Feb;447:649-73 - PubMed
  14. Biophys J. 1999 Oct;77(4):1871-84 - PubMed
  15. J Physiol. 1987 Aug;389:205-22 - PubMed
  16. Biophys J. 2002 Dec;83(6):2918-45 - PubMed
  17. Biophys J. 2003 Apr;84(4):2734-55 - PubMed
  18. Acta Physiol Scand. 2001 Jan;171(1):17-28 - PubMed
  19. Biophys J. 2011 Jun 22;100(12):2904-12 - PubMed
  20. Biophys J. 2004 Nov;87(5):3351-71 - PubMed
  21. J Physiol. 1994 Nov 1;480 ( Pt 3):411-21 - PubMed
  22. Circulation. 1996 Jan 1;93(1):168-77 - PubMed
  23. Pflugers Arch. 2006 Feb;451(5):625-30 - PubMed
  24. Neuron. 1999 Mar;22(3):549-58 - PubMed
  25. Biophys J. 2006 Jan 1;90(1):77-91 - PubMed
  26. Biophys J. 1992 Aug;63(2):497-517 - PubMed
  27. Circulation. 2005 Sep 6;112(10):1384-91 - PubMed
  28. Circ Res. 1995 Mar;76(3):351-65 - PubMed
  29. J Gen Physiol. 2001 Feb;117(2):119-31 - PubMed
  30. Circ Res. 2003 May 16;92(9):950-2 - PubMed
  31. J Physiol. 2005 Jun 1;565(Pt 2):441-7 - PubMed
  32. J Cardiovasc Electrophysiol. 1996 Apr;7(4):307-21 - PubMed
  33. Biophys J. 1998 Mar;74(3):1149-68 - PubMed
  34. Mol Cell Proteomics. 2011 Jul;10(7):M111.008037 - PubMed
  35. Am J Physiol. 1999 Jan;276(1):H9-H18 - PubMed
  36. Biophys J. 2006 Aug 15;91(4):1564-89 - PubMed
  37. Circ Res. 1995 Aug;77(2):354-60 - PubMed
  38. Biophys J. 1999 Sep;77(3):1666-82 - PubMed
  39. Biophys J. 2004 Dec;87(6):3723-36 - PubMed
  40. J Physiol. 1998 Dec 1;513 ( Pt 2):425-42 - PubMed
  41. Cardiovasc Res. 1993 Jun;27(6):946-50 - PubMed
  42. Am J Physiol. 1995 May;268(5 Pt 1):C1313-9 - PubMed
  43. Heart Rhythm. 2006 Feb;3(2):179-86 - PubMed
  44. J Pharmacol Exp Ther. 2005 Apr;313(1):207-15 - PubMed
  45. J Mol Cell Cardiol. 2010 Oct;49(4):617-24 - PubMed
  46. Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1573-89 - PubMed
  47. J Gen Physiol. 1991 Aug;98(2):265-85 - PubMed
  48. Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H913-31 - PubMed
  49. Circ Res. 1995 Jan;76(1):102-9 - PubMed
  50. Circ Res. 2008 Oct 10;103(8):e105-15 - PubMed
  51. J Physiol. 2003 Jan 1;546(Pt 1):5-18 - PubMed
  52. Biophys J. 2008 Mar 1;94(5):1867-79 - PubMed
  53. Pflugers Arch. 1987 Dec;410(6):596-603 - PubMed
  54. Physiol Rev. 2005 Oct;85(4):1205-53 - PubMed
  55. Am J Physiol. 1997 Sep;273(3 Pt 2):H1246-54 - PubMed
  56. Am J Physiol. 1999 Jan;276(1):H269-83 - PubMed
  57. Circ Res. 1996 Aug;79(2):194-200 - PubMed
  58. J Physiol. 1992 Oct;456:267-84 - PubMed
  59. J Cell Sci. 2009 Apr 1;122(Pt 7):1005-13 - PubMed
  60. Biophys J. 1999 Dec;77(6):2930-41 - PubMed
  61. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15096-101 - PubMed
  62. Biophys J. 2008 Jan 15;94(2):392-410 - PubMed
  63. Circ Res. 2001 Apr 27;88(8):794-801 - PubMed
  64. Circ Res. 2002 Sep 6;91(5):414-20 - PubMed
  65. Circ Res. 1982 May;50(5):651-62 - PubMed
  66. J Cardiovasc Electrophysiol. 1996 Jun;7(6):503-11 - PubMed
  67. Nature. 1960 Nov 5;188:495-7 - PubMed
  68. Biophys Chem. 1998 May 5;72(1-2):87-100 - PubMed
  69. PLoS One. 2009 Sep 21;4(9):e7069 - PubMed
  70. Biophys J. 2000 Apr;78(4):1906-20 - PubMed
  71. Circ Res. 2002 Feb 8;90(2):182-9 - PubMed
  72. Circ Res. 1993 Mar;72(3):671-87 - PubMed
  73. Am J Physiol. 1988 Dec;255(6 Pt 1):C798-807 - PubMed
  74. Am J Physiol Heart Circ Physiol. 2000 Jan;278(1):H249-55 - PubMed
  75. J Physiol. 1986 Jul;376:507-30 - PubMed
  76. Circ Res. 1999 Sep 17;85(6):e7-e16 - PubMed
  77. J Physiol. 1994 Nov 1;480 ( Pt 3):423-38 - PubMed
  78. Am J Physiol. 1993 Jun;264(6 Pt 1):C1587-93 - PubMed
  79. J Physiol. 1990 Apr;423:91-110 - PubMed
  80. Circ Res. 1995 Jul;77(1):140-52 - PubMed
  81. Pflugers Arch. 1988 Dec;413(2):127-33 - PubMed
  82. Circulation. 1999 May 11;99(18):2466-74 - PubMed
  83. Circ Res. 1993 Aug;73(2):379-85 - PubMed
  84. Circ Res. 2005 Jan 7;96(1):91-9 - PubMed
  85. Circ Res. 1996 Aug;79(2):208-21 - PubMed
  86. Prog Biophys Mol Biol. 2011 Oct;107(1):147-55 - PubMed
  87. J Physiol. 2009 Oct 15;587(Pt 20):4863-72 - PubMed
  88. Crit Care Med. 2000 Jun;28(6):1713-20 - PubMed
  89. Am J Physiol Heart Circ Physiol. 2010 Jul;299(1):H134-43 - PubMed
  90. J Physiol. 1991 Apr;435:605-30 - PubMed
  91. Circ Res. 1996 Jan;78(1):166-71 - PubMed
  92. Circ Res. 2010 Jan 8;106(1):185-92 - PubMed
  93. J Physiol. 1991 Oct;442:191-209 - PubMed
  94. J Physiol. 1952 Aug;117(4):500-44 - PubMed
  95. Pflugers Arch. 1985 Oct;405(3):294-6 - PubMed
  96. J Physiol. 1995 Nov 15;489 ( Pt 1):1-17 - PubMed
  97. J Am Coll Cardiol. 1998 Oct;32(4):1063-7 - PubMed
  98. J Physiol. 1994 Feb 1;474(3):463-71 - PubMed
  99. Biophys J. 2011 Dec 7;101(11):2601-10 - PubMed
  100. Am J Physiol. 1991 Aug;261(2 Pt 1):C393-7 - PubMed
  101. Circ Res. 2006 Jul 21;99(2):172-82 - PubMed
  102. J Mol Histol. 2004 Sep;35(7):679-86 - PubMed
  103. Am J Physiol. 1998 Apr;274(4):C1158-73 - PubMed
  104. Circ Res. 2003 Apr 4;92(6):651-8 - PubMed

Publication Types

Grant support