Capacitance-Driven Modulation of Cardiac Impulse Conduction by an Intramembrane Molecular Photoswitch

Membrane-targeted photoswitches are emerging as innovative tools to modulate cardiac excitability with high spatiotemporal precision. Ziapin2, a membrane-integrating azobenzene derivative, undergoes light-driven trans-cis isomerization that alters membrane capacitance (Cm). In its trans configuration, Ziapin2 increases Cm, while illumination relaxes the membrane and restores Cm toward baseline. Here, we investigated whether Ziapin2 can modulate conduction velocity (CV) in strands of neonatal or fetal murine cardiomyocytes cultured on microelectrode arrays. In the dark, trans-Ziapin2 significantly reduced CV, consistent with increased capacitive load slowing action potential propagation. Unexpectedly, photostimulation further decreased CV, likely reflecting the documented transient, capacitive-driven perturbations of the membrane potential, occurring without alterations in cellular conductances. These findings suggest that non-genetic light modulation of membrane capacitance can influence cardiac conduction and establish Ziapin2 as a novel optical tool to modulate cardiac impulse propagation.