Cardiac action potential generation mechanisms via an intramembrane photoswitch. A simulation study

Area of Science:

• Biophysics
• Cardiology
• Computational Biology

Background:

• Optical stimulation offers precise control over biological processes.
• Ziapin2, a novel light-sensitive compound, modulates cardiac cell excitability and contractility.
• The precise mechanism of light-driven action potential generation involving stretch-activated channels (SACs) remains unclear.

Purpose of the Study:

• To elucidate the role of SACs in Ziapin2-mediated photostimulation.
• To clarify the mechanism of light-driven action potential generation in cardiomyocytes.
• To develop a computational model for predicting cell behavior under optical stimulation.

Main Methods:

• Developed a computational model of murine action potential incorporating Ziapin2 photoisomerization effects.
• Included light-induced changes in membrane capacitance and SAC activation due to Ziapin2.
• Validated the model against experimental data from adult mouse ventricular myocytes (AMVMs).

Main Results:

• The computational model accurately reproduced Ziapin2-induced alterations in cell capacitance and membrane potential.
• The model highlighted the critical role of calcium (Ca2+)-selective SACs in action potential generation.
• The study elucidated the mechanism of photostimulation in cardiac cells.

Conclusions:

• Ziapin2-mediated optical stimulation precisely regulates cardiac excitation-contraction coupling.
• Calcium-selective SACs are pivotal in light-induced action potential generation.
• The developed computational model is a valuable tool for future optical stimulation experiments.