Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart

In 1791 Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakt...

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Main Authors: Bub, G, Daniels, M
Format: Journal article
Language:English
Published: Bentham Science Publishers 2019
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author Bub, G
Daniels, M
author_facet Bub, G
Daniels, M
author_sort Bub, G
collection OXFORD
description In 1791 Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental material, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.
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spelling oxford-uuid:10851bc2-b2e6-4b97-b6e8-22ee8eedf79e2022-03-26T09:56:53ZFeasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heartJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:10851bc2-b2e6-4b97-b6e8-22ee8eedf79eEnglishSymplectic Elements at OxfordBentham Science Publishers2019Bub, GDaniels, MIn 1791 Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental material, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.
spellingShingle Bub, G
Daniels, M
Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart
title Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart
title_full Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart
title_fullStr Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart
title_full_unstemmed Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart
title_short Feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping – from the single cell to the whole heart
title_sort feasibility of using adjunctive optogenetic technologies in cardiomyocyte phenotyping from the single cell to the whole heart
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AT danielsm feasibilityofusingadjunctiveoptogenetictechnologiesincardiomyocytephenotypingfromthesinglecelltothewholeheart