Characterization of hERG Channel Modulators in Optically Paced Human iPSC-Derived Cardiomyocytes Using Ultra-widefield Optopatch

Hecht, Vivian; Ferrante, John; Atwater, Nicholas; Werley, Kit; McManus, Owen B.; Urbán, László; Dempsey, Graham T.

doi:10.1016/j.vascn.2017.09.229

Cited by 1 publication

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“…This is inefficient, and therefore impossible to apply in a screening pipeline as the arrhythmia would not be present when observed, and even if it were observed it would not be standardised either for a particular arrhythmia size, shape, or speed. Since optogenetic control comes from light, although typically stimulation required for a toxicology assay is little more complex than "point and shoot", adopting shape based light stimulations to print stereotyped patterns onto 2D [18], or 3D shapes [23] repeatedly is possible. Since re-entrant arrhythmia (AF, VT) is a scourge of modern medicine, one argument for the current lack of effective therapies is the absence of appropriate models for drug development and testing; the optogenetic strategy appears to offer a solution to this problem.…”

Section: Resultsmentioning

confidence: 99%

Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart

Bub

Daniels

2020

CPB

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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 materials, 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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Section: Resultsmentioning

confidence: 99%