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Updated: Feb 17, 2026
Advanced Cardiac Rhythm Management by Applying Optogenetic Multi-Site Photostimulation in Murine Hearts
Published on: August 26, 2021
Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic Stimulation
Susanne Rehnelt1, Daniela Malan2, Krisztina Juhasz3,4
1Institute of Physiology I, Medical Faculty, University of Bonn, 53127 Bonn, Germany. s4surehn@uni-bonn.de.
Abstract:
Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of drugs on Na⁺, Ca2+ and K⁺ channel function indicated by FP prolongation, FP shortening and the slowing of the FP downstroke component, as well as generation of afterdepolarisations. Taken together, we present a scalable approach for preclinical frequency-dependent screening of drug effects on cardiac electrophysiology. Importantly, we show that the recording and analysis can be fully automated and the technology is readily available using commercial products.
Insights
A new optogenetic system automates cardiac ion channel screening in human cardiomyocytes. This allows for faster, frequency-dependent analysis of drug cardiotoxicity, reducing risks associated with drug development.
Area of Science:
- Biomedical Engineering
- Cardiovascular Pharmacology
- Optogenetics
Background:
- Drug-induced cardiac ion channel dysfunction can cause lethal arrhythmias, leading to market withdrawals.
- Current field potential (FP) recording methods for cardiotoxicity assessment are limited by spontaneous beating and manual analysis.
Purpose of the Study:
- To develop a novel optogenetic system for automated, parallel, frequency-dependent analysis of drug effects on cardiomyocyte electrophysiology.
- To enable high-throughput preclinical screening of drug candidates for cardiotoxicity.
Main Methods:
- Optimized viral transduction and mRNA transfection for Channelrhodopsin-2 expression in human-induced pluripotent stem cell-derived cardiomyocytes.
- Utilized a novel LED lid for optical stimulation in a 96-well FP recording system.
- Implemented automated recording and analysis of field potentials.
Main Results:
- Successfully achieved reliable pacing at physiological heart rates and robust FP recording.
- Detected rate-dependent drug effects on Na+, Ca2+, and K+ channel function via FP prolongation, shortening, and downstroke changes.
- Observed drug-induced afterdepolarizations, indicating potential arrhythmogenic effects.
Conclusions:
- The presented optogenetic system offers a scalable and automated approach for preclinical cardiotoxicity screening.
- This technology facilitates frequency-dependent analysis of cardiac electrophysiology, improving drug safety assessment.
- The system is readily available using commercial components, promoting widespread adoption.
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