title: Alterations in T-tubule and dyad structure in heart disease: challenges and opportunities for computational analyses.
abstract: Compelling recent experimental results make clear that sub-cellular structures are altered in ventricular myocytes during the development of heart failure, in both human samples and diverse experimental models. These alterations can include, but are not limited to, changes in the clusters of sarcoplasmic reticulum (SR) Ca(2+)-release channels, ryanodine receptors, and changes in the average distance between the cell membrane and ryanodine receptor clusters. In this review, we discuss the potential consequences of these structural alterations on the triggering of SR Ca(2+) release during excitation-contraction coupling. In particular, we describe how mathematical models of local SR Ca(2+) release can be used to predict functional changes resulting from diverse modifications that occur in disease states. We review recent studies that have used simulations to understand the consequences of sub-cellular structural changes, and we discuss modifications that will allow for future modelling studies to address unresolved questions. We conclude with a discussion of improvements in both experimental and mathematical modelling techniques that will be required to provide a stronger quantitative understanding of the functional consequences of changes in sub-cellular structure in heart disease.
authors: Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave Levy Place, Box 1215, New York, NY 10029, USA.
authors: Eva
authors: E
authors: Poláková
authors: Eric A
authors: EA
authors: Sobie
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D006331:Heart Diseases / Q000473:pathology*; D006801:Humans; D008962:Models, Theoretical; D032383:Myocytes, Cardiac / Q000473:pathology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
references: Prog Biophys Mol Biol. 2011 Jan;104(1-3):2-21
references: 20303361
references: Circ Res. 2000 Nov 24;87(11):1040-7
references: 11090550
references: Prog Biophys Mol Biol. 2008 Jan-Apr;96(1-3):377-98
references: 17959231
references: Biophys J. 2009 Mar 18;96(6):2466-78
references: 19289071
references: Exp Physiol. 2009 May;94(5):509-19
references: 19297389
references: J Physiol. 2010 Nov 1;588(Pt 21):4249-60
references: 20837647
references: Biophys J. 2011 Sep 21;101(6):1287-96
references: 21943409
references: Biophys J. 1994 Nov;67(5):1942-56
references: 7858131
references: Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4305-10
references: 16537526
references: Wiley Interdiscip Rev Syst Biol Med. 2011 Jul-Aug;3(4):392-413
references: 20865780
references: Circ Res. 2011 Apr 1;108(7):847-56
references: 21311044
references: Cardiovasc Res. 2003 Mar 15;57(4):986-95
references: 12650876
references: Biophys J. 2009 Nov 18;97(10):2664-73
references: 19917219
references: Circ Res. 2008 Feb 15;102(3):338-46
references: 18079411
references: Biophys J. 2011 Jun 22;100(12):2904-12
references: 21689523
references: J Mol Cell Cardiol. 2013 Jan;54:98-100
references: 23123322
references: J Clin Invest. 2006 Sep;116(9):2510-20
references: 16932808
references: Circ Res. 2004 Oct 15;95(8):807-13
references: 15388639
references: Biophys J. 2006 Aug 1;91(3):779-92
references: 16679359
references: Science. 1997 May 2;276(5313):800-6
references: 9115206
references: PLoS Biol. 2007 Feb;5(2):e21
references: 17214508
references: J Mol Cell Cardiol. 2013 May;58:32-40
references: 23159441
references: Biophys J. 1992 Aug;63(2):497-517
references: 1330031
references: J Mol Cell Cardiol. 2012 Feb;52(2):304-11
references: 21767546
references: PLoS One. 2011;6(10):e25100
references: 22022376
references: Circulation. 2002 May 28;105(21):2543-8
references: 12034663
references: Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6854-9
references: 19342485
references: J Physiol. 2003 Nov 15;553(Pt 1):229-42
references: 12949221
references: J Physiol. 2005 Jun 1;565(Pt 2):441-7
references: 15817631
references: Science. 1993 Oct 29;262(5134):740-4
references: 8235594
references: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22275-80
references: 20018773
references: J Physiol. 2006 Jul 15;574(Pt 2):519-33
references: 16709642
references: Cardiovasc Res. 2003 Jul 1;59(1):67-77
references: 12829177
references: PLoS One. 2011;6(9):e24404
references: 21912691
references: J Mol Cell Cardiol. 2013 May;58:92-9
references: 23026728
references: J Gen Physiol. 1999 Mar;113(3):469-89
references: 10051521
references: FASEB J. 2010 Sep;24(9):3321-9
references: 20430793
references: Biophys J. 2008 Apr 1;94(7):L54-6
references: 18223001
references: Biophys J. 2011 Nov 16;101(10):2370-9
references: 22098735
references: J Biomech. 2012 Mar 15;45(5):815-23
references: 22226404
references: J Muscle Res Cell Motil. 2006;27(5-7):297-306
references: 16897575
references: J Physiol. 2012 Jun 1;590(11):2555-67
references: 22495591
references: Biophys J. 2009 Feb 18;96(4):1264-74
references: 19217846
references: Circ Res. 2008 Oct 10;103(8):e105-15
references: 18787194
references: Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3997-4001
references: 22355118
references: J Physiol. 2003 Jan 1;546(Pt 1):5-18
references: 12509475
references: Biophys J. 2012 Apr 18;102(8):L31-3
references: 22768959
references: Circ Res. 2012 Sep 14;111(7):837-41
references: 22891046
references: Biophys J. 2010 Jun 2;98(11):2515-23
references: 20513395
references: Expert Opin Biol Ther. 2010 Jan;10(1):29-41
references: 20078230
references: J Physiol. 2012 Sep 15;590(18):4403-22
references: 22495592
references: Biophys J. 2002 Jul;83(1):59-78
references: 12080100
references: PLoS One. 2011 Mar 09;6(3):e17901
references: 21408028
references: Cardiovasc Res. 2011 Sep 1;91(4):598-605
references: 21613275
references: Biophys J. 2000 Nov;79(5):2682-91
references: 11053140
references: Circ Res. 2012 Feb 17;110(4):588-97
references: 22253411
references: Circ Res. 2012 Jun 22;111(1):28-36
references: 22628577
references: Circ Res. 2002 Sep 6;91(5):414-20
references: 12215490
references: Cardiovasc Res. 2012 Sep 1;95(4):430-8
references: 22707157
references: Circ Res. 2010 Aug 20;107(4):520-31
references: 20576937
references: Cardiovasc Res. 2008 Jan 15;77(2):315-24
references: 18006436
references: Circulation. 2001 Aug 7;104(6):688-93
references: 11489776
references: J Biomed Biotechnol. 2010;2010:503906
references: 20396394
references: PLoS Comput Biol. 2010 Oct 28;6(10):e1000972
references: 21060856
references: Biophys J. 2009 Jun 17;96(12):4826-33
references: 19527642
references: Biophys J. 2010 Sep 8;99(5):1377-86
references: 20816049
references: Circ Res. 2012 Aug 3;111(4):402-14
references: 22723297
references: Circulation. 2011 Mar 8;123(9):979-88
references: 21339484
references: J Theor Biol. 2007 May 21;246(2):332-54
references: 17286986
references: Biophys J. 2008 Aug;95(3):1412-27
references: 18390622
references: Front Physiol. 2012 Sep 10;3:351
references: 23060801
references: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11759-64
references: 13130076
references: J Cell Physiol. 2011 Sep;226(9):2235-43
references: 21660947
references: Cardiovasc Res. 2001 Feb 1;49(2):298-307
references: 11164840
references: Am J Physiol Heart Circ Physiol. 2012 Mar 15;302(6):H1250-60
references: 22198169
references: Am J Physiol Heart Circ Physiol. 2009 Apr;296(4):H1069-79
references: 19201998
references: J Physiol. 1994 Feb 1;474(3):463-71
references: 8014907