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A Cardiac Microphysiological System for Studying Ca2+ Propagation via Non-genetic Optical Stimulation
Published on: March 21, 2025
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Modulating cardiac physiology in engineered heart tissue with the bidirectional optogenetic tool BiPOLES
Barbora Schwarzová1, Tim Stüdemann1,2, Muhammed Sönmez1,2
1Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Pflugers Archiv : European Journal of Physiology
|October 20, 2023
Summary
Bidirectional Pair of Opsins for Light-induced Excitation and Silencing (BiPOLES) can control cardiomyocyte activity. Short light pulses activate cardiac cells, while continuous light silences contractility, offering new optogenetic control methods.
Area of Science:
- Optogenetics
- Cardiology
- Stem Cell Biology
Background:
- Optogenetic actuators control excitable cells like neurons and cardiomyocytes.
- Channelrhodopsins enable neuronal excitation (cation) or inhibition (anion).
- Bidirectional optogenetic tools combine opsins with low spectral overlap for simultaneous control.
Purpose of the Study:
- To investigate the effects of BiPOLES activation in cardiomyocytes.
- To assess the potential of BiPOLES for controlling cardiac cell physiology.
Main Methods:
- Knocked in BiPOLES into the AAVS1 locus of human-induced pluripotent stem cells (hiPSC).
- Differentiated hiPSCs into cardiomyocytes and generated engineered heart tissue (EHT).
- Physiologically characterized EHTs expressing BiPOLES under different light stimulation conditions.
Main Results:
- Continuous light activation of GtACR2 (blue) or Chrimson (red) caused cardiomyocyte depolarization, halting EHT contractility.
- Short light pulses (blue or red) triggered action potentials (APs) in cardiomyocytes, reaching rates up to 240 bpm.
- Demonstrated that both cation and anion channelrhodopsins can activate cardiomyocytes with pulsed light and silence them with prolonged light.
Conclusions:
- BiPOLES can be used to both activate and silence stem cell-derived cardiomyocytes.
- Pulsed photostimulation with BiPOLES enables activation of cardiac cells.
- Prolonged photostimulation with BiPOLES effectively silences cardiac contractility.
