Selective optogenetic stimulation of fibroblasts enables quantification of hetero-cellular coupling to cardiomyocytes in a three-dimensional model of heart tissue

Funken, Maximilian; Bruegmann, Tobias; Sasse, Philipp

doi:10.1093/europace/euaa128

Cited by 10 publications

(4 citation statements)

References 21 publications

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“…The differential regulation of Cx43 expression in cardiac fibroblasts and cardiomyocytes was proposed to be mediated via the activation of β‐adrenergic receptors upon cardiac injury, which results in reduced Cx43 expression in cardiomyocytes, but increased expression in fibroblasts [96]. Such interaction can be studied in heterocellular cardiac tissue models allowing to quantify electric interactions between fibroblasts and cardiomyocytes in vitro by cell type‐specific optogenetic manipulation of membrane potential [97]. Funken et al .…”

Section: Communication Between Fibroblasts and Cardiomyocytesmentioning

confidence: 99%

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

et al. 2021

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Cardiac fibroblasts constitute a major cell population in the heart. They secrete extracellular matrix components and various other factors shaping the microenvironment of the heart. In silico analysis of intercellular communication based on single‐cell RNA sequencing revealed that fibroblasts are the source of the majority of outgoing signals to other cell types. This observation suggests that fibroblasts play key roles in orchestrating cellular interactions that maintain organ homeostasis but that can also contribute to disease states. Here, we will review the current knowledge of fibroblast interactions in the healthy, diseased, and aging heart. We focus on the interactions that fibroblasts establish with other cells of the heart, specifically cardiomyocytes, endothelial cells and immune cells, and particularly those relying on paracrine, electrical, and exosomal communication modes.

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Section: Communication Between Fibroblasts and Cardiomyocytesmentioning

confidence: 99%

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

et al. 2021

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“…For instance, optogenetics has been used to modulate conduction in the distal AV node by ChR2-based depolarization of electrotonically coupled macrophages [ 133 ]. In cell culture systems, ChR2-expressing fibroblasts were used to pace cardiomyocytes at different frequencies following illumination [ 127 , 130 , 132 ], as recently also proposed for whole-hearts post-myocardial infarction [ 131 ]. Making use of cell-specific targeting of VSFP2.3, electrical coupling between non-myocytes and cardiomyocytes was demonstrated in the border zone of cryoablation scars [ 128 ].…”

Section: Optogeneticsmentioning

confidence: 99%

Cardiac optogenetics: shining light on signaling pathways

Leemann,

Schneider-Warme,

Kleinlogel

2023

Pflugers Arch - Eur J Physiol

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In the early 2000s, the field of neuroscience experienced a groundbreaking transformation with the advent of optogenetics. This innovative technique harnesses the properties of naturally occurring and genetically engineered rhodopsins to confer light sensitivity upon target cells. The remarkable spatiotemporal precision offered by optogenetics has provided researchers with unprecedented opportunities to dissect cellular physiology, leading to an entirely new level of investigation. Initially revolutionizing neuroscience, optogenetics quickly piqued the interest of the wider scientific community, and optogenetic applications were expanded to cardiovascular research. Over the past decade, researchers have employed various optical tools to observe, regulate, and steer the membrane potential of excitable cells in the heart. Despite these advancements, achieving control over specific signaling pathways within the heart has remained an elusive goal. Here, we review the optogenetic tools suitable to control cardiac signaling pathways with a focus on GPCR signaling, and delineate potential applications for studying these pathways, both in healthy and diseased hearts. By shedding light on these exciting developments, we hope to contribute to the ongoing progress in basic cardiac research to facilitate the discovery of novel therapeutic possibilities for treating cardiovascular pathologies.

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“…This hypothesis was eventually confirmed in native tissue, using optogenetic expression of GEVI in cardiac non-myocytes (Quinn et al, 2016 ). Furthermore, expression of Channelrhodpsin-2 (ChR2) or Archaerhodopsin (ArchT) was achieved in primary cardiac fibroblasts, and heterocellular coupling with CM was further investigated (Yu and Entcheva, 2016 ; Funken et al, 2020 ; Simone et al, 2020 ; Boyle et al, 2021 ; Kostecki et al, 2021 ). ChR2 expression in smooth muscle cells of the coronary vessels has shown to be a potent tool to control vascular tone, demonstrating local and rapidly induced light-activated vasospasm (Wu et al, 2015 ).…”

Section: The Use Of Light To Manipulate and Measure Cardiac Electrophysiologymentioning

confidence: 99%

Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review

et al. 2021

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Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities for regional and tissue-level electrophysiological control and hold promise for future novel clinical applications. This article, which emerged from the international NOTICE workshop in 20181, reviews the state-of-the-art optical techniques used for cardiac electrophysiological research and the underlying biophysics. The design and performance of optical reporters and optogenetic actuators are reviewed along with limitations of current probes. The physics of light interaction with cardiac tissue is detailed and associated challenges with the use of optical sensors and actuators are presented. Case studies include the use of fluorescence recovery after photobleaching and super-resolution microscopy to explore the micro-structure of cardiac cells and a review of two photon and light sheet technologies applied to cardiac tissue. The emergence of cardiac optogenetics is reviewed and the current work exploring the potential clinical use of optogenetics is also described. Approaches which combine optogenetic manipulation and optical voltage measurement are discussed, in terms of platforms that allow real-time manipulation of whole heart electrophysiology in open and closed-loop systems to study optimal ways to terminate spiral arrhythmias. The design and operation of optics-based approaches that allow high-throughput cardiac electrophysiological assays is presented. Finally, emerging techniques of photo-acoustic imaging and stress sensors are described along with strategies for future development and establishment of these techniques in mainstream electrophysiological research.

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Selective optogenetic stimulation of fibroblasts enables quantification of hetero-cellular coupling to cardiomyocytes in a three-dimensional model of heart tissue

Cited by 10 publications

References 21 publications

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

Cardiac optogenetics: shining light on signaling pathways

Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review

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