Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca<SUP>2+</SUP> Channel Activation in Guinea Pig Cardiomyocytes Using Organic Photovoltaic Devices

Abstract

Objective: 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,I-L) in Guinea pig ventricular cardiomyocytes. Methods: Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated I-Ca,I-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. Results: Light pulses activated I-Ca,I-L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered I-Ca,I-L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. Conclusion: OEPC-mediated activation of I-Ca,I-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,I-L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices. Significance: 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.Objective: 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,I-L) in Guinea pig ventricular cardiomyocytes. Methods: Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated I-Ca,I-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. Results: Light pulses activated I-Ca,I-L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered I-Ca,I-L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. Conclusion: OEPC-mediated activation of I-Ca,I-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,I-L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices. Significance: 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.