Abstract
The heart is a complex multicellular organ comprising both cardiomyocytes (CM), which make up the majority of the cardiac volume, and non-myocytes (NM), which represent the majority of cardiac cells. CM drive the pumping action of the heart, triggered via rhythmic electrical activity. NM, on the other hand, have many essential functions including generating extracellular matrix, regulating CM activity, and aiding in repair following injury. NM include neurons and interstitial, immune, and endothelial cells. Understanding the role of specific cell types and their interactions with one another may be key to developing new therapies with minimal side effects to treat cardiac disease. However, assessing cell-type-specific behavior in situ using standard techniques is challenging. Optogenetics enables population-specific observation and control, facilitating studies into the role of specific cell types and subtypes. Optogenetic models targeting the most important cardiac cell types have been generated and used to investigate non-canonical roles of those cell populations, e.g., to better understand how cardiac pacing occurs and to assess potential translational possibilities of optogenetics. So far, cardiac optogenetic studies have primarily focused on validating models and tools in the healthy heart. The field is now in a position where animal models and tools should be utilized to improve our understanding of the complex heterocellular nature of the heart, how this changes in disease, and from there to enable the development of cell-specific therapies and improved treatments.
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Abbreviations
- AAV:
-
Adeno-associated viral [particles]
- ACR:
-
Anion channelrhodopsins
- AV:
-
Atrioventricular
- ChR2:
-
Chlamyodomonas reinhardtii channelrhodopsin-2
- CM:
-
Cardiomyocytes
- ECG:
-
Electrocardiogram
- ICNS:
-
Intrinsic cardiac nervous system
- NM:
-
Non-myocytes
- NpHR:
-
Natromonas pharaonis halorhodopsin
- PN:
-
Parasympathetic neurons
- RA:
-
Right atrial
- SN:
-
Sympathetic neurons
- VSFP:
-
Voltage-sensitive fluorescent protein
References
All AH, Zeng X, Teh DBL et al (2019) Expanding the toolbox of upconversion nanoparticles for in vivo optogenetics and neuromodulation. Adv Mater 31:1–15. https://doi.org/10.1002/adma.201803474
Arrenberg AB, Stainier DYR, Baier H, Huisken J (2010) Optogenetic control of cardiac function. Science 330:971–974. https://doi.org/10.1126/science.1195929
Baxter WT, Mironov SF, Zaitsev AV et al (2001) Visualizing excitation waves inside cardiac muscle using transillumination. Biophys J 80:516–530. https://doi.org/10.1016/S0006-3495(01)76034-1
Bernal Sierra YA, Rost BR, Pofahl M et al (2018) Potassium channel-based optogenetic silencing. Nat Commun 9:4611. https://doi.org/10.1038/s41467-018-07038-8
Bish LT, Morine K, Sleeper MM et al (2008) Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat. Hum Gene Ther 19:1359–1368. https://doi.org/10.1089/hum.2008.123
Boyden ES, Zhang F, Bamberg E et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268. https://doi.org/10.1038/nn1525
Bruegmann T, Malan D, Hesse M et al (2010) Optogenetic control of heart muscle in vitro and in vivo. Nat Methods 7:897–900. https://doi.org/10.1038/nmeth.1512
Bruegmann T, Boyle PM, Vogt CC et al (2016) Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations. J Clin Invest 126:3894–3904. https://doi.org/10.1172/JCI88950
Bruegmann T, Beiert T, Vogt CC et al (2018) Optogenetic termination of atrial fibrillation in mice. Cardiovasc Res 114:713–723. https://doi.org/10.1093/cvr/cvx250
Chi NC, Shaw RM, Jungblut B et al (2008) Genetic and physiologic dissection of the vertebrate cardiac conduction system. PLoS Biol 6:1006–1019. https://doi.org/10.1371/journal.pbio.0060109
Chi NC, Bussen M, Brand-Arzamendi K et al (2010) Cardiac conduction is required to preserve cardiac chamber morphology. Proc Natl Acad Sci U S A 107:14662–14667. https://doi.org/10.1073/pnas.0909432107
Crocini C, Ferrantini C, Coppini R et al (2016) Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation. Sci Rep 6:1–7. https://doi.org/10.1038/srep35628
Despa S, Shui B, Bossuyt J et al (2014) Junctional cleft [Ca2+]i measurements using novel cleft-targeted Ca2+ sensors. Circ Res 115:339–347. https://doi.org/10.1161/CIRCRESAHA.115.303582
Funken M, Malan D, Sasse P, Bruegmann T (2019) Optogenetic hyperpolarization of cardiomyocytes terminates ventricular arrhythmia. Front Physiol 10:1–7. https://doi.org/10.3389/fphys.2019.00498
Goshima K, Tonomura Y (1969) Synchronized beating of embryonic mouse myocardial cells mediated by FL cells in monolayer culture. Exp Cell Res 56:387–392. https://doi.org/10.1016/0014-4827(69)90029-9
Gourdie RG, Dimmeler S, Kohl P (2016) Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease. Nat Rev Drug Discov 15(9):620–638. https://www.nature.com/articles/nrd.2016.89. Accessed 10 Jan 2020
Govorunova EG, Cunha SR, Sineshchekov OA, Spudich JL (2016) Anion channelrhodopsins for inhibitory cardiac optogenetics. Sci Rep 6:33530. https://doi.org/10.1038/srep33530
He B, Lu Z, He W et al (2013) The effects of atrial ganglionated plexi stimulation on ventricular electrophysiology in a normal canine heart. J Interv Card Electrophysiol 37:1–8. https://doi.org/10.1007/s10840-012-9774-2
Hou JH, Kralj JM, Douglass AD et al (2014) Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents. Front Physiol 5:344. https://doi.org/10.3389/fphys.2014.00344
Hulsmans M, Sam F, Nahrendorf M (2016) Monocyte and macrophage contributions to cardiac remodeling. J Mol Cell Cardiol 93:149–155. https://doi.org/10.1016/j.yjmcc.2015.11.015
Hulsmans M, Clauss S, Xiao L et al (2017) Macrophages facilitate electrical conduction in the heart. Cell 169:510–522.e20. https://doi.org/10.1016/j.cell.2017.03.050
Ishizuka T, Kakuda M, Araki R, Yawo H (2006) Kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels. Neurosci Res 54:85–94. https://doi.org/10.1016/j.neures.2005.10.009
Kapuria S, Yoshida T, Lien C-L (2018) Coronary Vasculature in Cardiac Development and Regeneration. J Cardiovasc Dev Dis 5:59. https://doi.org/10.3390/jcdd5040059
Kim S, Kyung T, Chung J et al (2020) Non-invasive optical control of endogenous Ca2+ channels in awake mice. Nat Commun 11:210. https://doi.org/10.1038/s41467-019-14005-4
Kopton RA, Baillie JS, Rafferty SA et al (2018) Cardiac electrophysiological effects of light-activated chloride channels. Front Physiol 9:1806. https://doi.org/10.3389/FPHYS.2018.01806
Li X, Gutierrez DV, Hanson MG et al (2005) Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proc Natl Acad Sci 102:17816–17821. https://doi.org/10.1073/pnas.0509030102
Liao MLC, De Boer TP, Mutoh H et al (2015) Sensing cardiac electrical activity with a cardiac myocyte-targeted optogenetic voltage indicator. Circ Res 117:401–412. https://doi.org/10.1161/CIRCRESAHA.117.306143
Ljubojevic S, Radulovic S, Leitinger G et al (2014) Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure. Circulation 130:244–255. https://doi.org/10.1161/CIRCULATIONAHA.114.008927
Lu Z, Scherlag BJ, Lin J et al (2009) Autonomic mechanism for initiation of rapid firing from atria and pulmonary veins: evidence by ablation of ganglionated plexi. Cardiovasc Res 84:245–252. https://doi.org/10.1093/cvr/cvp194
Lu X, Ginsburg KS, Kettlewell S et al (2013) Measuring local gradients of intramitochondrial [Ca2+] in cardiac myocytes during sarcoplasmic reticulum Ca2+ release. Circ Res 112:424–431. https://doi.org/10.1161/CIRCRESAHA.111.300501
Marina N, Tang F, Figueiredo M et al (2013) Purinergic signalling in the rostral ventro-lateral medulla controls sympathetic drive and contributes to the progression of heart failure following myocardial infarction in rats. Basic Res Cardiol 108:1–10. https://doi.org/10.1007/s00395-012-0317-x
Mastitskaya S, Marina N, Gourine A et al (2012) Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones. Cardiovasc Res 95:487–494. https://doi.org/10.1093/cvr/cvs212
Miesenböck G (2009) The optogenetic catechism. Science 326:395–399
Monakhov M, Matlashov M, Colavita M, et al (2019) Bright near-infrared genetically encoded voltage indicator for all-optical electrophysiology. bioRxiv 536359. https://doi.org/10.1101/536359
Moreno A, Endicott K, Skancke M et al (2019) Sudden heart rate reduction upon optogenetic release of acetylcholine from cardiac parasympathetic neurons in perfused hearts. Front Physiol 10:16. https://doi.org/10.3389/fphys.2019.00016
Nagel G, Ollig D, Fuhrmann M et al (2002) Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:2395–2398. https://doi.org/10.1126/science.1072068
Nagel G, Szellas T, Huhn W et al (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100:13940–13945. https://doi.org/10.1073/pnas.1936192100
Nagel G, Brauner M, Liewald JF et al (2005) Light activation of Channelrhodopsin-2 in excitable cells of caenorhabditis elegans triggers rapid behavioral responses. Curr Biol 15:2279–2284. https://doi.org/10.1016/j.cub.2005.11.032
Nussinovitch U, Gepstein L (2015) Optogenetics for in vivo cardiac pacing and resynchronization therapies. Nat Biotechnol 33:750–754. https://doi.org/10.1038/nbt.3268
Nyns ECA, Kip A, Bart CI et al (2017) Optogenetic termination of ventricular arrhythmias in the whole heart: towards biological cardiac rhythm management. Eur Heart J 38:2132–2136. https://doi.org/10.1093/eurheartj/ehw574
Nyns ECA, Poelma RH, Volkers L et al (2019) An automated hybrid bioelectronic system for autogenous restoration of sinus rhythm in atrial fibrillation. Sci Transl Med 11:1–12. https://doi.org/10.1126/scitranslmed.aau6447
Oda K, Vierock J, Oishi S et al (2018) Crystal structure of the red light-activated channelrhodopsin Chrimson. Nat Commun 9:1–11. https://doi.org/10.1038/s41467-018-06421-9
Pacak CA, Mah CS, Thattaliyath BD et al (2006) Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res 99:e3–e9. https://doi.org/10.1161/01.RES.0000237661.18885.f6
Prando V, Da Broi F, Franzoso M et al (2018) Dynamics of neuroeffector coupling at cardiac sympathetic synapses. J Physiol 596:2055–2075. https://doi.org/10.1113/JP275693
Prasad K-MR, Xu Y, Yang Z et al (2011) Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution. Gene Ther 18:43–52. https://doi.org/10.1038/gt.2010.105
Prigge M, Schneider F, Tsunoda SP et al (2012) Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem 287:31804–31812. https://doi.org/10.1074/jbc.M112.391185
Quinn TA, Camelliti P, Rog-Zielinska EA et al (2016) Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics. Proc Natl Acad Sci 113:14852–14857. https://doi.org/10.1073/pnas.1611184114
Rajendran PS, Challis RC, Fowlkes CC et al (2019) Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies. Nat Commun 10:1–13. https://doi.org/10.1038/s41467-019-09770-1
Rost BR, Schneider-Warme F, Schmitz D, Hegemann P (2017) Optogenetic tools for subcellular applications in neuroscience. Neuron 96:572–603. https://doi.org/10.1016/j.neuron.2017.09.047
Rubart M, Tao W, Lu X-L et al (2017) Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart. Cardiovasc Res 107:1011–1020. https://doi.org/10.1093/cvr/cvx163
Scardigli M, Müllenbroich C, Margoni E et al (2018) Real-time optical manipulation of cardiac conduction in intact hearts. J Physiol 596:3841–3858. https://doi.org/10.1113/JP276283
Scherlag BJ, Po S (2006) The intrinsic cardiac nervous system and atrial fibrillation. Curr Opin Cardiol 21:51–54. https://doi.org/10.1097/01.hco.0000198980.40390.e4
Schneider F, Grimm C, Hegemann P (2015) Biophysics of channelrhodopsin. Annu Rev Biophys 44:167–186. https://doi.org/10.1146/annurev-biophys-060414-034014
Shang W, Lu F, Sun T et al (2014) Imaging Ca2+ nanosparks in heart with a new targeted biosensor. Circ Res 114:412–420. https://doi.org/10.1161/CIRCRESAHA.114.302938
Sineshchekov OA, Jung K-H, Spudich JL (2002) Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii. Proc Natl Acad Sci U S A 99:8689–8694. https://doi.org/10.1073/pnas.122243399
Stoyek MR, Quinn TA (2018) One fish, two fish, red fish, blue fish*: zebrafish as a model for cardiac research. Prog Biophys Mol Biol 138:1–2. https://doi.org/10.1016/j.pbiomolbio.2018.11.003
Suzuki T, Yamasaki K, Fujita S et al (2003) Archaeal-type rhodopsins in chlamydomonas: model structure and intracellular localization. Biochem Biophys Res Commun 301:711–717. https://doi.org/10.1016/S0006-291X(02)03079-6
Tallini YN, Ohkura M, Choi B-R et al (2006) Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca2+ indicator GCaMP2. Proc Natl Acad Sci U S A 103:4753–4758. https://doi.org/10.1073/pnas.0509378103
Tallini YN, Brekke JF, Shui B et al (2007) Propagated endothelial Ca2+ waves and arteriolar dilation in vivo: measurements in Cx40BAC-GCaMP2 transgenic mice. Circ Res 101:1300–1309. https://doi.org/10.1161/CIRCRESAHA.107.149484
Vogt CC, Bruegmann T, Malan D et al (2015) Systemic gene transfer enables optogenetic pacing of mouse hearts. Cardiovasc Res 106:338–343. https://doi.org/10.1093/cvr/cvv004
Wake E, Brack K (2016) Characterization of the intrinsic cardiac nervous system. Auton Neurosci Basic Clin 199:3–16. https://doi.org/10.1016/j.autneu.2016.08.006
Wang Y, Lin WK, Crawford W et al (2017) Optogenetic control of heart rhythm by selective stimulation of cardiomyocytes derived from pnmt + cells in murine heart. Sci Rep 7:40687. https://doi.org/10.1038/srep40687
Weber M, Scherf N, Meyer AM et al (2017) Cell-accurate optical mapping across the entire developing heart. elife 6:1–23. https://doi.org/10.7554/eLife.28307
Wengrowski AM, Wang X, Tapa S et al (2015) Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function. Cardiovasc Res 105:143–150. https://doi.org/10.1093/cvr/cvu258
Winslow RL, Varghese A, Noble D et al (1993) Generation and propagation of ectopic beats induced by spatially localized Na-K pump inhibition in atrial network models. Proc R Soc B Biol Sci 253:55–61. https://doi.org/10.1098/rspb.1993.0126
Wu Y, Li SS, Jin X et al (2015) Optogenetic approach for functional assays of the cardiovascular system by light activation of the vascular smooth muscle. Vasc Pharmacol 71:192–200. https://doi.org/10.1016/j.vph.2015.03.006
Wu X, Zhu X, Chong P et al (2019) Sono-optogenetics facilitated by a circulation delivered rechargeable light source for minimally invasive optogenetics. Proc Natl Acad Sci U S A 116:26332–26342. https://doi.org/10.1073/pnas.1914387116
Yu L, Zhou L, Cao G et al (2017) Optogenetic modulation of cardiac sympathetic nerve activity to prevent ventricular arrhythmias. J Am Coll Cardiol 70:2778–2790. https://doi.org/10.1016/j.jacc.2017.09.1107
Zaglia T, Pianca N, Borile G et al (2015) Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of Channel Rhodopsin-2. Proc Natl Acad Sci 112:E4495–E4504. https://doi.org/10.1073/pnas.1509380112
Zgierski-Johnston CM, Ayub S, Fernández MC et al (2019) Cardiac pacing using transmural multi-LED probes in channelrhodopsin-expressing mouse hearts. Prog Biophys Mol Biol 154:51–61. https://doi.org/10.1016/j.pbiomolbio.2019.11.004
Zhang S, Cui N, Wu Y et al (2015) Optogenetic intervention to the vascular endothelium. Vasc Pharmacol 74:122–129. https://doi.org/10.1016/j.vph.2015.05.009
Acknowledgments
We thank all members of the Institute of Experimental Cardiovascular Medicine for critical discussion of the manuscript. This research was funded by the German Research Foundation DFG (SPP1926: FS1486/1-2, ZG58/1-1, and an Emmy-Noether-Fellowship: FS1486/2-1). Both authors are members of the DFG-funded Collaborative Research Centre 1425.
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Zgierski-Johnston, C.M., Schneider-Warme, F. (2021). Observing and Manipulating Cell-Specific Cardiac Function with Light. In: Yawo, H., Kandori, H., Koizumi, A., Kageyama, R. (eds) Optogenetics. Advances in Experimental Medicine and Biology, vol 1293. Springer, Singapore. https://doi.org/10.1007/978-981-15-8763-4_24
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