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

L.G.J. Tertoolen (Corresponding Author), S. R. Braam, B.J. van Meer, R. Passier, C. L. Mummery

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Abstract

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.

Original languageEnglish
Pages (from-to)1135-1141
Number of pages7
JournalBiochemical and biophysical research communications
Volume497
Issue number4
DOIs
Publication statusPublished - 18 Mar 2018

Fingerprint

Pluripotent Stem Cells
Stem cells
Cardiac Myocytes
Toxicity
Screening
Electrodes
Pharmacology
Action Potentials
Clamping devices
Throughput
Pharmaceutical Preparations
Induced Pluripotent Stem Cells
Preclinical Drug Evaluations
Clinical Pharmacology
Sudden Cardiac Death
Drug-Related Side Effects and Adverse Reactions
Assays
Theoretical Models
Safety

Keywords

  • Action potential
  • Cardiomyocytes
  • Cardiotoxicity
  • Computational simulation
  • Field potential
  • Multi electrode array

Cite this

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abstract = "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.",
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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. (Corresponding Author); Braam, S. R.; van Meer, B.J.; Passier, R.; Mummery, C. L.

In: Biochemical and biophysical research communications, Vol. 497, No. 4, 18.03.2018, p. 1135-1141.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Passier, R.

AU - Mummery, C. L.

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