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A Cardiac Microphysiological System for Studying Ca2+ Propagation via Non-genetic Optical Stimulation
Published on: March 21, 2025
Capacitance-Driven Modulation of Cardiac Impulse Conduction by an Intramembrane Molecular Photoswitch.
Chiara Florindi1,2, Alessio Ostini3,4, Chiara Bertarelli2,5
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
This study shows that Ziapin2, a photoswitch, alters cardiac membrane capacitance. Light-activated Ziapin2 unexpectedly slowed cardiac conduction velocity, suggesting a new optical method for modulating heart electrical activity.
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Area of Science:
- Cardiovascular Physiology
- Biophotonics
- Molecular Cardiology
Background:
- Membrane-targeted photoswitches offer precise control over cellular functions.
- Ziapin2, an azobenzene derivative, modifies membrane capacitance (Cm) via light-induced isomerization.
- Understanding photoswitch effects on cardiac electrophysiology is crucial for therapeutic development.
Purpose of the Study:
- To investigate the impact of Ziapin2 on cardiac conduction velocity (CV) in cardiomyocytes.
- To determine if light modulation of membrane capacitance affects action potential propagation.
- To establish Ziapin2 as a tool for optical control of cardiac impulse propagation.
Main Methods:
- Primary cardiomyocyte cultures from neonatal/fetal murine hearts.
- Culturing cells on microelectrode arrays for electrophysiological recordings.
- Utilizing Ziapin2 and controlled light stimulation to assess changes in Cm and CV.
Main Results:
- Trans-Ziapin2 significantly reduced CV in cardiomyocyte strands, consistent with increased capacitive load.
- Photostimulation of Ziapin2 unexpectedly further decreased CV.
- Observed CV changes occurred without alterations in cellular conductances, indicating capacitive effects.
Conclusions:
- Non-genetic light modulation of membrane capacitance influences cardiac conduction.
- Ziapin2 serves as a novel optical tool for modulating cardiac impulse propagation.
- These findings open new avenues for optogenetic-like control in cardiac electrophysiology.

