ArticleProceedings of the National Academy of Sciences of the United States of America2015
Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
- Optoelectronic Biohybrid Platform Enables Light-Controlled Cardiac Structural and Functional Feedback.Cell biomaterials · 2026Article
- A wearable non-invasive sonogenetic pacemaker.Nature biomedical engineering · 2026Article
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Review
- Modulating cardiac physiology in engineered heart tissue with the bidirectional optogenetic tool BiPOLES.Pflugers Archiv : European journal of physiology · 2023Article
- DbhNature communications · 2023Article
- Recent advances and current limitations of available technology to optically manipulate and observe cardiac electrophysiology.Pflugers Archiv : European journal of physiology · 2023Review
- Article
- Cardiogenic control of affective behavioural state.Nature · 2023Article
- The physiological response during optogenetic-based cardiac pacing in awake freely moving mice.Frontiers in physiology · 2023Article
- Optogenetic manipulation of cardiac repolarization gradients using sub-threshold illumination.Frontiers in physiology · 2023Article
- Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals.American journal of physiology. Heart and circulatory physiology · 2022Review
- Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons.International journal of molecular sciences · 2022Article
- Review
- Optogenetic manipulation of cardiac electrical dynamics using sub-threshold illumination: dissecting the role of cardiac alternans in terminating rapid rhythms.Basic research in cardiology · 2022Article
- Optogenetics for light control of biological systems.Nature reviews. Methods primers · 2022Article
- Editorial: Cardiac optogenetics: Using light to observe and excite the heart.Frontiers in physiology · 2022Article
- Optogenetic Control of Heart Rhythm: Lightly Guiding the Cardiac Pace.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Multiphoton Imaging of CaJournal of clinical medicine · 2021Article
- Cardiac optogenetics: a decade of enlightenment.Nature reviews. Cardiology · 2021Review
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Extrasystoles lead to several consequences, ranging from uneventful palpitations to lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role of working versus conducting cardiomyocytes, as well as the tissue requirements (minimal cell number) for the generation of extrasystoles, and the properties leading ectopies to become arrhythmia triggers (topology), in the normal and diseased heart, have not been determined directly in vivo. Here, we used optogenetics in transgenic mice expressing ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system to achieve cell type-specific, noninvasive control of heart activity with high spatial and temporal resolution. By combining measurement of optogenetic tissue activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts, we demonstrated that focal ectopies require, in the normal mouse heart, the simultaneous depolarization of at least 1,300-1,800 working cardiomyocytes or 90-160 Purkinje fibers. The optogenetic assay identified specific areas in the heart that were highly susceptible to forming extrasystolic foci, and such properties were correlated to the local organization of the Purkinje fiber network, which was imaged in three dimensions using optical projection tomography. Interestingly, during the acute phase of myocardial ischemia, focal ectopies arising from this location, and including both Purkinje fibers and the surrounding working cardiomyocytes, have the highest propensity to trigger sustained arrhythmias. In conclusion, we used cell-specific optogenetics to determine with high spatial resolution and cell type specificity the requirements for the generation of extrasystoles and the factors causing ectopies to be arrhythmia triggers during myocardial ischemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.