10 research outputs found
Introducing simulated IK1 into human iPSC-cardiomyocytes using dynamic clamp on an automated patch clamp system
A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of Ik1 Ion Channels in Real-Time
An important aspect of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) proposal is the use of human stem cell-derived cardiomyocytes and the confirmation of their predictive power in drug safety assays. The benefits of this cell source are clear; drugs can be tested in vitro on human cardiomyocytes, with patient-specific genotypes if needed, and differentiation efficiencies are generally excellent, resulting in a virtually limitless supply of cardiomyocytes. There are, however, several challenges that will have to be surmounted before successful establishment of hSC-CMs as an all-round predictive model for drug safety assays. An important factor is the relative electrophysiological immaturity of hSC-CMs, which limits arrhythmic responses to unsafe drugs that are pro-arrhythmic in humans. Potentially, immaturity may be improved functionally by creation of hybrid models, in which the dynamic clamp technique joins simulations of lacking cardiac ion channels (e.g., IK1) with hSC-CMs in real-time during patch clamp experiments. This approach has been used successfully in manual patch clamp experiments, but throughput is low. In this study, we combined dynamic clamp with automated patch clamp of iPSC-CMs in current clamp mode, and demonstrate that IK1 conductance can be added to iPSC-CMs on an automated patch clamp platform, resulting in an improved electrophysiological maturity
A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform : Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of IIon Channels in Real-Time
An important aspect of the ComprehensiveIn VitroProarrhythmia Assay (CiPA) proposal is the use of human stem cell-derived cardiomyocytes and the confirmation of their predictive power in drug safety assays. The benefits of this cell source are clear; drugs can be testedin vitroon human cardiomyocytes, with patient-specific genotypes if needed, and differentiation efficiencies are generally excellent, resulting in a virtually limitless supply of cardiomyocytes. There are, however, several challenges that will have to be surmounted before successful establishment of hSC-CMs as an all-round predictive model for drug safety assays. An important factor is the relative electrophysiological immaturity of hSC-CMs, which limits arrhythmic responses to unsafe drugs that are pro-arrhythmic in humans. Potentially, immaturity may be improved functionally by creation of hybrid models, in which the dynamic clamp technique joins simulations of lacking cardiac ion channels (e.g., IK1) with hSC-CMs in real-time during patch clamp experiments. This approach has been used successfully in manual patch clamp experiments, but throughput is low. In this study, we combined dynamic clamp with automated patch clamp of iPSC-CMs in current clamp mode, and demonstrate that IK1conductance can be added to iPSC-CMs on an automated patch clamp platform, resulting in an improved electrophysiological maturity
Electrophysiology-Based Assays to Detect Subtype-Selective Modulation of Human Nicotinic Acetylcholine Receptors
An update on the advancing high-throughput screening techniques for patch clamp-based ion channel screens: implications for drug discovery
An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes
Novel method for action potential measurements from intact cardiac monolayers with multiwell microelectrode array technology
Quantitative Model for Ion Transport and Cytoplasm Conductivity of Chinese Hamster Ovary Cells
Potentiation effect of the AMPK activator A-769662 on cardiac myocytes metabolism and survival
Abstract 286 van Poster session 2 Frontiers in CardioVascular Biology, London 30th March – 1st April 2012 Second Congress of the ESC Council on Basic Cardiovascular Science