The Experts below are selected from a list of 10272 Experts worldwide ranked by ideXlab platform
Richard Kempter - One of the best experts on this subject based on the ideXlab platform.
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contribution of action Potentials to the Extracellular Field Potential in the nucleus laminaris of barn owl
Journal of Neurophysiology, 2018Co-Authors: Paula T Kuokkanen, Go Ashida, Anna Kraemer, Thomas Mccolgan, Kazuo Funabiki, Hermann Wagner, Christine Koppl, Catherine E Carr, Richard KempterAbstract:Extracellular Field Potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl’s n...
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on the origin of the Extracellular Field Potential in the nucleus laminaris of the barn owl tyto alba
Journal of Neurophysiology, 2010Co-Authors: Paula T Kuokkanen, Go Ashida, Hermann Wagner, Catherine E Carr, Richard KempterAbstract:The neurophonic is a sound-evoked, frequency-following Potential that can be recorded Extracellularly in nucleus laminaris of the barn owl. The origin of the neurophonic, and thus the mechanisms th...
Michael George - One of the best experts on this subject based on the ideXlab platform.
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impedance and combined Extracellular Field Potential recordings of cipa reference compounds on ips cardiomyocytes
Biophysical Journal, 2016Co-Authors: Corina Bot, Sonja Stoelzlefeix, Nadine Becker, Krisztina Juhasz, Ulrich Thomas, Leo Doerr, Rodolfo J Haedo, Matthias Beckler, Joerg Oestreich, Michael GeorgeAbstract:Drug induced arrhythmia is one of the most common causes of drug development failure. Human induced pluripotent stem cell-derived cardiomyocytes (iPSCMs) show great promise for cardiovascular research and predictive in-vitro cardiac safety screening.We present data recorded on the CardioExcyte 96, a hybrid screening instrument that combines impedance (cell contractility) with MEA-like Extracellular Field Potential (EFP) recordings. A case study showing impaired excitation-contraction coupling will be presented. This indicates the importance of testing compounds in assays complementary to patch clamp electrophysiology to provide a more complete safety profile. Furthermore, in accordance with the Comprehensive In Vitro Proarrhythmia Assay (CiPA) guidelines, standard reference compounds were tested on iPS-derived cardiomyocytes. Changes in the impedance signal indicate effects on cell contractility and shape whereas the Field Potential parameters provide information about the electrophysiological activity of the beating network of cells. Pharmacological effects of a number of reference compounds including those designated high risk (e.g. Dofetilide), intermediate risk (e.g. Cisapride) or low risk (e.g. Verapamil) were evaluated and summarized in this study.The CardioExcyte 96 system provides a non-invasive, label-free, high temporal resolution approach for safety screening. It can be either used in an incubator or, by utilizing the dedicated incubation system, directly on a lab bench. Furthermore, the system is capable of electrically pacing the cells, which allows for screening of cells which beat with individual frequencies and, in addition, investigations of frequency dependent compound inhibition.
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label free high throughput cardiotoxicity assays using combined impedance and Extracellular Field Potential measurements
Biophysical Journal, 2015Co-Authors: Corina Bot, Sonja Stoelzlefeix, Ulrich Thomas, Leo Doerr, Rodolfo J Haedo, Matthias Beckler, Joerg Oestreich, David Guinot, George Okeyo, Michael GeorgeAbstract:A new trend in the industry utilizes induced pluripotent stem cells (iPSCs) for functional assays to identify cardiac pathologies and their genetic underpinnings (such as Long QT Syndrome (LQTS)), in addition to cardiotoxicity profiling of pharmaceutical compounds.The here utilized CardioExcyte® 96 system is a hybrid instrument that combines impedance readout (a correlate of cell contractility) with electric Field Potential recordings of the compound signal that is generated by cellular action Potentials. These electrophysiological measurements are label-free and allow investigations in High Throughput format. In addition, the instrument is capable of electrical stimulation of the cellular monolayer, while the rapid acquisition rate of 1ms allows a more accurate description of signal features and nuances stemming from pharmacological effects. A dedicated software package for rapid data handling and real-time analysis is based on novel algorithms that allow a comprehensive investigation of the cellular beat signal.A broad range of cell lines was successfully validated, such as stem cell-derived cardiomyocytes from Axiogenesis (human: Cor4U®, murine: CorAt®), GE Healthcare (Cytiva), Cellectis (human, 3D-clusters: hES-CMC™) and CDI (iCell®). Furthermore, the pharmacological effects of a number of reference compounds on these cell types were evaluated and their phenotype correctly identified. For example, the effects of compounds like Blebbistatin, which blocks contraction without disrupting the electric Field Potential can be easily identified since it is an inhibitor of the myosin II which is mainly responsible for the contraction of cardiomyocytes, while it has no effect to the ion channels. Other compound classes like hERG inhibitors were validated as well and example data will be shown. They induce typical arrhythmia since hERG ion channels are affected.
Hermann Wagner - One of the best experts on this subject based on the ideXlab platform.
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contribution of action Potentials to the Extracellular Field Potential in the nucleus laminaris of barn owl
Journal of Neurophysiology, 2018Co-Authors: Paula T Kuokkanen, Go Ashida, Anna Kraemer, Thomas Mccolgan, Kazuo Funabiki, Hermann Wagner, Christine Koppl, Catherine E Carr, Richard KempterAbstract:Extracellular Field Potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl’s n...
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on the origin of the Extracellular Field Potential in the nucleus laminaris of the barn owl tyto alba
Journal of Neurophysiology, 2010Co-Authors: Paula T Kuokkanen, Go Ashida, Hermann Wagner, Catherine E Carr, Richard KempterAbstract:The neurophonic is a sound-evoked, frequency-following Potential that can be recorded Extracellularly in nucleus laminaris of the barn owl. The origin of the neurophonic, and thus the mechanisms th...
Paula T Kuokkanen - One of the best experts on this subject based on the ideXlab platform.
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contribution of action Potentials to the Extracellular Field Potential in the nucleus laminaris of barn owl
Journal of Neurophysiology, 2018Co-Authors: Paula T Kuokkanen, Go Ashida, Anna Kraemer, Thomas Mccolgan, Kazuo Funabiki, Hermann Wagner, Christine Koppl, Catherine E Carr, Richard KempterAbstract:Extracellular Field Potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl’s n...
-
on the origin of the Extracellular Field Potential in the nucleus laminaris of the barn owl tyto alba
Journal of Neurophysiology, 2010Co-Authors: Paula T Kuokkanen, Go Ashida, Hermann Wagner, Catherine E Carr, Richard KempterAbstract:The neurophonic is a sound-evoked, frequency-following Potential that can be recorded Extracellularly in nucleus laminaris of the barn owl. The origin of the neurophonic, and thus the mechanisms th...
Chris Pollard - One of the best experts on this subject based on the ideXlab platform.
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assessment of Extracellular Field Potential and ca2 transient signals for early qt pro arrhythmia detection using human induced pluripotent stem cell derived cardiomyocytes
Journal of Pharmacological and Toxicological Methods, 2017Co-Authors: Najah Abigerges, Amy Pointon, Karen Oldman, Martin R Brown, Mark Pilling, Clare E Sefton, Helen Garside, Chris PollardAbstract:Abstract Cardiovascular toxicity is a prominent reason for failures in drug development, resulting in the demand for assays that can predict this liability in early drug discovery. We investigated whether iCell® cardiomyocytes have utility as an early QT/TdP screen. Thirty clinical drugs with known QT/TdP outcomes were evaluated blind using label-free microelectrode array (parameters measured were beating period (BP), Field Potential duration (FPD), fast Na + amplitude and slope) and live cell, fast kinetic fluorescent Ca 2 + transient FLIPR® Tetra (parameters measured were peak count, width, amplitude) systems. Many FPD-altering drugs also altered BP. Correction for BP, using a Log-Log (LL) model, was required to appropriately interpret direct drug effects on FPD. In comparison with human QT effects and when drug activity was to be predicted at top test concentration (TTC), LL-corrected FPD and peak count had poor assay sensitivity and specificity values: 13%/64% and 65%/11%, respectively. If effective free therapeutic plasma concentration (EFTPC) was used instead of TTC, the values were 0%/100% and 6%/100%, respectively. When compared to LL-corrected FPD and peak count, predictive values of uncorrected FPD, BP, width and amplitude were not much different. If pro-arrhythmic risk was to be predicted using Ca 2 + transient data, the values were 67%/100% and 78%/53% at EFTPC and TTC, respectively. Thus, iCell® cardiomyocytes have limited value as an integrated QT/TdP assay, highlighting the urgent need for improved experimental alternatives that may offer an accurate integrated cardiomyocyte safety model for supporting the development of new drugs without QT/TdP effects.
