Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
| Autor: | Leon G.J. Tertoolen, B.J. van Meer, Christine L. Mummery, Robert Passier, Stefan R. Braam |
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| Přispěvatelé: | Applied Stem Cell Technologies |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Drug-Related Side Effects and Adverse Reactions Induced Pluripotent Stem Cells Drug Evaluation Preclinical Biophysics Action Potentials 030204 cardiovascular system & hematology Pharmacology Biochemistry Article Mice 03 medical and health sciences 0302 clinical medicine Electrode array Animals Humans Computer Simulation Myocytes Cardiac Patch clamp Induced pluripotent stem cell Molecular Biology Cardiomyocytes Chemistry Safety pharmacology food and beverages Cardiac action potential Action potential Cell Biology Multi electrode array Models Theoretical Embryonic stem cell Cardiotoxicity Electrophysiology 030104 developmental biology Toxicity Computational simulation Microelectrodes Neuroscience Field potential |
| Zdroj: | Biochemical and biophysical research communications, 497(4), 1135-1141. Academic Press Biochemical and Biophysical Research Communications |
| ISSN: | 0006-291X |
| Popis: | Multi electrode arrays (MEAs) are increasingly used to detect external field potentials in electrically active cells. Recently, in combination with cardiomyocytes derived from human (induced) pluripotent stem cells they have started to become a preferred tool to examine newly developed drugs for potential cardiac toxicity in pre-clinical safety pharmacology. The most important risk parameter is proarrhythmic activity in cardiomyocytes which can cause sudden cardiac death. Whilst MEAs can provide medium- to high- throughput noninvasive assay platform, the translation of a field potential to cardiac action potential (normally measured by low-throughput patch clamp) is complex so that accurate assessment of drug risk to the heart is in practice still challenging. To address this, we used computational simulation to study the theoretical relationship between aspects of the field potential and the underlying cardiac action potential. We then validated the model in both primary mouse- and human pluripotent (embryonic) stem cell-derived cardiomyocytes showing that field potentials measured in MEAs could be converted to action potentials that were essentially identical to those determined directly by electrophysiological patch clamp. The method significantly increased the amount of information that could be extracted from MEA measurements and thus combined the advantages of medium/high throughput with more informative readouts. We believe that this will benefit the analysis of drug toxicity screening of cardiomyocytes using in time and accuracy. Highlights • Computational model for the translation of field potential to action potential. • Validation of the model using patch clamp and multi electrode array. • Quantification of INA modulation, prolongation and triangulation from MEA data. • Validation of the correlations by measurements with known cardioactive drugs. |
| Databáze: | OpenAIRE |
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