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Related Experiment Video

Updated: Jul 12, 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
PubMed
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.

Keywords:
Cardiac physiologyOptogeneticStem cellsTissue engineering

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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.