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 (C_m). In its trans configuration, Ziapin2 increases C_m, while illumination relaxes the membrane and restores C_m 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.