Cargando…

Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes

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 pot...

Descripción completa

Detalles Bibliográficos
Autores principales: Tertoolen, L.G.J., Braam, S.R., van Meer, B.J., Passier, R., Mummery, C.L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854265/
https://www.ncbi.nlm.nih.gov/pubmed/28153730
http://dx.doi.org/10.1016/j.bbrc.2017.01.151
_version_ 1783306879864143872
author Tertoolen, L.G.J.
Braam, S.R.
van Meer, B.J.
Passier, R.
Mummery, C.L.
author_facet Tertoolen, L.G.J.
Braam, S.R.
van Meer, B.J.
Passier, R.
Mummery, C.L.
author_sort Tertoolen, L.G.J.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5854265
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-58542652018-03-18 Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes Tertoolen, L.G.J. Braam, S.R. van Meer, B.J. Passier, R. Mummery, C.L. Biochem Biophys Res Commun Article 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. Elsevier 2018-03-18 /pmc/articles/PMC5854265/ /pubmed/28153730 http://dx.doi.org/10.1016/j.bbrc.2017.01.151 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tertoolen, L.G.J.
Braam, S.R.
van Meer, B.J.
Passier, R.
Mummery, C.L.
Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
title Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
title_full Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
title_fullStr Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
title_full_unstemmed Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
title_short Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
title_sort interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854265/
https://www.ncbi.nlm.nih.gov/pubmed/28153730
http://dx.doi.org/10.1016/j.bbrc.2017.01.151
work_keys_str_mv AT tertoolenlgj interpretationoffieldpotentialsmeasuredonamultielectrodearrayinpharmacologicaltoxicityscreeningonprimaryandhumanpluripotentstemcellderivedcardiomyocytes
AT braamsr interpretationoffieldpotentialsmeasuredonamultielectrodearrayinpharmacologicaltoxicityscreeningonprimaryandhumanpluripotentstemcellderivedcardiomyocytes
AT vanmeerbj interpretationoffieldpotentialsmeasuredonamultielectrodearrayinpharmacologicaltoxicityscreeningonprimaryandhumanpluripotentstemcellderivedcardiomyocytes
AT passierr interpretationoffieldpotentialsmeasuredonamultielectrodearrayinpharmacologicaltoxicityscreeningonprimaryandhumanpluripotentstemcellderivedcardiomyocytes
AT mummerycl interpretationoffieldpotentialsmeasuredonamultielectrodearrayinpharmacologicaltoxicityscreeningonprimaryandhumanpluripotentstemcellderivedcardiomyocytes