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Updated: May 26, 2026
Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: December 22, 2020
Measurement of action potential generation in isolated canine left ventricular midmyocardial myocytes
Daniel M Johnson1, Leyla Hussein, Roel L H M G Spätjens
1Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
Abstract:
Proarrhythmic side effects are a major limitation during the drug development process for cardiac and non-cardiac compounds. Because changes in cardiac action potential (AP) are undesirable, the evaluation of the effects of test compounds on the AP is essential before advancing new compounds to clinical testing. However, an increase in repolarization duration alone is not always proarrhythmic, and newer surrogate markers have been suggested to better predict the occurrence of arrhythmia. Described in this unit is a protocol for assessing changes in AP duration in canine ventricular myocytes utilizing optical imaging techniques. This protocol can be used at an early stage of drug discovery due to its relatively fast throughput. Additionally, a protocol is presented for assessing the occurrence of after-depolarizations, as well as a novel parameter for proarrhythmic risk, beat-to-beat variability of repolarization. This protocol can be used at a later stage of the drug discovery process to assess proarrhythmic potential.
Insights
New methods assess drug-induced arrhythmia risk early in development. Optical imaging of action potential duration and novel proarrhythmic risk parameters improve safety evaluations for cardiac and non-cardiac compounds.
Area of Science:
- Cardiovascular Pharmacology
- Drug Discovery
- Electrophysiology
Background:
- Proarrhythmic side effects are a significant hurdle in drug development.
- Assessing drug effects on cardiac action potential (AP) is crucial.
- Traditional markers like repolarization duration may not fully predict arrhythmia risk.
Purpose of the Study:
- To present protocols for evaluating proarrhythmic potential of compounds.
- To enable early-stage drug safety assessment.
- To introduce novel parameters for predicting arrhythmia.
Main Methods:
- Optical imaging techniques to assess AP duration in canine ventricular myocytes.
- Protocol for evaluating after-depolarizations.
- Measurement of beat-to-beat variability of repolarization as a novel proarrhythmic risk parameter.
Main Results:
- A fast-throughput protocol for early-stage AP duration assessment.
- A protocol for later-stage evaluation of after-depolarizations and repolarization variability.
- Identification of novel parameters for enhanced proarrhythmic risk assessment.
Conclusions:
- The presented protocols facilitate early and later-stage drug safety evaluations.
- Optical imaging and novel parameters offer improved prediction of proarrhythmic potential.
- These methods aid in mitigating drug development risks associated with cardiac side effects.
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