Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca²⁺ Channel Activation in Guinea Pig...

This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (I_Ca,L) in Guinea pig ventricular cardiomyocytes.

Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated I_Ca,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes.

Light pulses activated I_Ca,L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca²⁺ channel blocker, nifedipine. Light-triggered I_Ca,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation.

OEPC-mediated activation of I_Ca,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of I_Ca,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices.

Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.