Optogenetic Termination of Cardiac Arrhythmia: Mechanistic Enlightenment and Therapeutic Application?

Sasse, Philipp; Funken, Maximilian; Beiert, Thomas; Bruegmann, Tobias

doi:10.3389/fphys.2019.00675

Cited by 36 publications

(26 citation statements)

References 90 publications

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“…Compared with conventional electrical methods, cardiac optogenetics presents many remarkable advantages in optical manipulation, including precision and flexibility as well as being contactless and painless. These advantages highlight its potential in various translational applications in clinical devices for managing heart rhythm and function [14,26,27]. In most experiments, ChR2 and its mutant (ChR2-H134R) have been widely used as optogenetic actuators with a corresponding action spectrum at ∼470 nm but displayed poor tissue penetration.…”

Section: Discussionmentioning

confidence: 99%

Near-infrared light driven tissue-penetrating cardiac optogenetics via upconversion nanoparticles in vivo

Rao

Wang

Cheng

et al. 2020

Biomed. Opt. Express

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This study determines whether near-infrared (NIR) light can drive tissue-penetrating cardiac optical control with upconversion luminescent materials. Adeno-associated virus (AAV) encoding channelrhodopsin-2 (ChR2) was injected intravenously to rats to achieve ChR2 expression in the heart. The upconversion nanoparticles (UCNP) NaYF4:Yb/Tm or upconversion microparticles (UCMP) NaYF4 to upconvert blue light were selected to fabricate freestanding polydimethylsiloxane films. These were attached on the ventricle and covered with muscle tissue. Additionally, a 980-nm NIR laser was programmed and illuminated on the film or the tissue. The NIR laser successfully captured ectopic paced rhythm in the heart, which displays similar manipulation characteristics to those triggered by blue light. Our results highlight the feasibility of tissue-penetration cardiac optogenetics by NIR and demonstrate the potential to use external optical manipulation for non-invasive or weakly invasive applications in cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Near-infrared light driven tissue-penetrating cardiac optogenetics via upconversion nanoparticles in vivo

Rao

Wang

Cheng

et al. 2020

Biomed. Opt. Express

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“…With optical actuation, light modulates cellular behaviour using techniques such as optogenetics and optically caged compounds [30,31,84,[90][91][92][93][94]. Bruegmann et al [93,94] have illustrated optogenetic actuation of in vitro and in vivo mouse cardiac tissues including defibrillation of ventricular tachycardia.…”

Section: Optical Techniques In Tissue Culturementioning

confidence: 99%

“…With optical actuation, light modulates cellular behaviour using techniques such as optogenetics and optically caged compounds [ 30 , 31 , 84 , 90 – 94 ]. Bruegmann et al .…”

Section: In Vitro Approaches To Examine Neuro-cardiac Interamentioning

confidence: 99%

Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis

et al. 2020

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Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and in silico models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.

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“…Functionally, ChRs are divided into cation and anion channelrhodopsins (CCRs and ACRs, respectively) (8). Both ChR classes serve for photocontrol of excitable cells, such as neurons and cardiomyocytes, via a biotechnique known as optogenetics (9, 10). However, structural determinants for cation and anion selectivity in ChRs remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Cation and anion channelrhodopsins: Sequence motifs and taxonomic distribution

Govorunova

Sineshchekov

et al. 2021

Preprint

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Cation and anion channelrhodopsins (CCRs and ACRs, respectively) primarily from two algal species, Chlamydomonas reinhardtii and Guillardia theta, have become widely used as optogenetic tools to control cell membrane potential with light. We mined algal and other protist polynucleotide sequencing projects and metagenomic samples to identify 75 channelrhodopsin homologs from three channelrhodopsin families, including one revealed in dinoflagellates in this study. We carried out electrophysiological analysis of 33 natural channelrhodopsin variants from different phylogenetic lineages and 10 metagenomic homologs in search of sequence determinants of ion selectivity, photocurrent desensitization, and spectral tuning in channelrhodopsins. Our results show that association of a reduced number of glutamates near the conductance path with anion selectivity depends on a wider protein context, because prasinophyte homologs with the identical glutamate pattern as in cryptophyte ACRs are cation-selective. Desensitization is also broadly context-dependent, as in one branch of stramenopile ACRs and their metagenomic homologs its extent roughly correlates with phylogenetic relationship of their sequences. Regarding spectral tuning, two prasinophyte CCRs exhibit red-shifted spectra to 585 nm, although their retinal-binding pockets do not match those of previously known similarly red-shifted channelrhodopsins. In cryptophyte ACRs we identified three specific residue positions in the retinal-binding pocket that define the wavelength of their spectral maxima. Lastly, we found that dinoflagellate rhodopsins with a TCP motif in the third transmembrane helix and a metagenomic homolog exhibit channel activity.IMPORTANCEChannelrhodopsins are widely used in neuroscience and cardiology as research tools and are considered as prospective therapeutics, but their natural diversity and mechanisms remain poorly characterized. Genomic and metagenomic sequencing projects are producing an ever-increasing wealth of data, whereas biophysical characterization of the encoded proteins lags behind. In this study we used manual and automated patch clamp recording of representative members of four channelrhodopsin families including a family that we report in this study in dinoflagellates. Our results contribute to a better understanding of molecular determinants of ionic selectivity, photocurrent desensitization, and spectral tuning in channelrhodopsins.

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Optogenetic Termination of Cardiac Arrhythmia: Mechanistic Enlightenment and Therapeutic Application?

Cited by 36 publications

References 90 publications

Near-infrared light driven tissue-penetrating cardiac optogenetics via upconversion nanoparticles in vivo

Near-infrared light driven tissue-penetrating cardiac optogenetics via upconversion nanoparticles in vivo

Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis

Cation and anion channelrhodopsins: Sequence motifs and taxonomic distribution

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