title: A comprehensive multiscale framework for simulating optogenetics in the heart.
abstract: Optogenetics has emerged as an alternative method for electrical control of the heart, where illumination is used to elicit a bioelectric response in tissue modified to express photosensitive proteins (opsins). This technology promises to enable evocation of spatiotemporally precise responses in targeted cells or tissues, thus creating new possibilities for safe and effective therapeutic approaches to ameliorate cardiac function. Here we present a comprehensive framework for multiscale modelling of cardiac optogenetics, allowing both mechanistic examination of optical control and exploration of potential therapeutic applications. The framework incorporates accurate representations of opsin channel kinetics and delivery modes, spatial distribution of photosensitive cells, and tissue illumination constraints, making possible the prediction of emergent behaviour resulting from interactions at sub-organ scales. We apply this framework to explore how optogenetic delivery characteristics determine energy requirements for optical stimulation and to identify cardiac structures that are potential pacemaking targets with low optical excitation thresholds.
authors: Institute for Computational Medicine, Johns Hopkins University, 3400 N Charles St, 316 Hackerman Hall, Baltimore, Maryland 21218, USA.
authors: Patrick M
authors: PM
authors: Boyle
authors: John C
authors: JC
authors: Williams
authors: Christina M
authors: CM
authors: Ambrosi
authors: Emilia
authors: E
authors: Entcheva
authors: Natalia A
authors: NA
authors: Trayanova
mesh_terms: D054849:Cardiac Electrophysiology / Q000379:methods*; D002460:Cell Line; D000075402:Channelrhodopsins; D004558:Electric Stimulation / Q000379:methods; D006321:Heart / Q000502:physiology; D006801:Humans; D008027:Light; D009206:Myocardium / Q000378:metabolism*; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation / Q000379:methods
chemical_list: D000075402:Channelrhodopsins
references: Circ Res. 2011 Jan 7;108(1):113-28
references: 21212393
references: Biophys J. 2010 Jun 16;98(12):L57-9
references: 20550885
references: Biophys J. 2005 Dec;89(6):3911-8
references: 16169986
references: Heart. 2004 Dec;90(12):1443-6
references: 15547025
references: Cell. 2010 Apr 2;141(1):154-165
references: 20303157
references: Sci Transl Med. 2011 Aug 31;3(98):98ra83
references: 21885405
references: Heart Rhythm. 2011 May;8(5):752-9
references: 21185403
references: Circ Res. 2007 Jun 22;100(12):e87-101
references: 17540975
references: Am J Physiol Heart Circ Physiol. 2013 May;304(9):H1179-91
references: 23457014
references: Biophys J. 2010 Jun 2;98(11):2420-31
references: 20513385
references: J Neurosci Methods. 2005 Feb 15;141(2):171-98
references: 15661300
references: Am J Physiol Heart Circ Physiol. 2010 Feb;298(2):H699-718
references: 19933417
references: Nat Methods. 2010 Nov;7(11):897-900
references: 20881965
references: Pacing Clin Electrophysiol. 2011 Mar;34(3):348-53
references: 21077915
references: Biochem Biophys Res Commun. 2006 Sep 22;348(2):673-81
references: 16890205
references: Circulation. 1986 Jan;73(1):73-81
references: 3940671
references: J Electrocardiol. 2003;36 Suppl:69-74
references: 14716595
references: Circ Arrhythm Electrophysiol. 2011 Oct;4(5):753-60
references: 21828312
references: PLoS One. 2011;6(8):e22400
references: 21850224
references: Biophys J. 2011 Sep 21;101(6):1326-34
references: 21943413
references: Heart Rhythm. 2013 Mar;10(3):444-51
references: 23207137
references: Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):3015-21
references: 22923228
references: J Gene Med. 2011 Jun;13(6):333-41
references: 21674736
references: Nat Methods. 2011 Jan;8(1):26-9
references: 21191368
references: Circulation. 2004 Dec 14;110(24):3661-6
references: 15569843
references: Circ Res. 2010 Mar 19;106(5):981-91
references: 20093630
references: J Comput Neurosci. 2011 Aug;31(1):87-103
references: 21174227
references: Nat Rev Genet. 2007 Aug;8(8):573-87
references: 17607305
references: Circ Res. 2000 Oct 27;87(9):797-804
references: 11055984
references: Lancet. 1997 Oct 25;350(9086):1210-6
references: 9652562
references: Pacing Clin Electrophysiol. 2012 Feb;35(2):204-14
references: 22040178
references: Heart Rhythm. 2011 Dec;8(12):1881-6
references: 21816127
references: Pacing Clin Electrophysiol. 2000 Nov;23(11 Pt 1):1632-7
references: 11138300
references: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:4669-72
references: 22255379
references: IEEE Trans Biomed Eng. 2002 Nov;49(11):1260-9
references: 12450356
references: Biophys J. 2006 Apr 15;90(8):2938-45
references: 16443665
references: IEEE Trans Biomed Eng. 2007 Mar;54(3):389-99
references: 17355050
references: Biophys J. 2008 Jan 15;94(2):392-410
references: 18160660
references: Circulation. 1997 Sep 16;96(6):2038-47
references: 9323097
references: N Engl J Med. 2002 Mar 21;346(12):877-83
references: 11907286
references: JAMA. 2006 Apr 26;295(16):1929-34
references: 16639052
references: J Interv Card Electrophysiol. 2007 Sep;19(3):213-6
references: 17846876
references: IEEE Trans Biomed Eng. 2011 Jun;58(6):1742-51
references: 21324771
references: Ann Biomed Eng. 2010 Feb;38(2):456-68
references: 19876737
references: Cardiol J. 2012;19(4):412-7
references: 22825904
references: Europace. 2013 Jan;15(1):83-8
references: 22933662
references: Indian Pacing Electrophysiol J. 2012 May;12(3):102-13
references: 22665959
references: Front Physiol. 2012 Jul 03;3:235
references: 22783201
references: Photochem Photobiol. 2009 Jan-Feb;85(1):400-11
references: 19161406
references: Circ Res. 1994 Apr;74(4):604-19
references: 8137497
references: Biophys J. 2010 Sep 8;99(5):1408-15
references: 20816052
references: Philos Trans A Math Phys Eng Sci. 2009 Jun 13;367(1896):2225-55
references: 19414454
references: Science. 2010 Nov 12;330(6006):971-4
references: 21071670
references: Stem Cells. 2007 Aug;25(8):2128-38
references: 17495112
references: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):15025-30
references: 19706471
references: Nat Med. 2003 Jan;9(1):123-8
references: 12514725
references: Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1088-100
references: 16565318
references: Biomech Model Mechanobiol. 2011 Jun;10(3):295-306
references: 20589408
references: Prog Biophys Mol Biol. 2008 Jan-Apr;96(1-3):3-18
references: 17900668