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

Abstract

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.