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

• Published in: IEEE transactions on biomedical engineering 2024-06, Vol.71 (6), p.1980-1992
• Main Authors: Rienmuller, Theresa, Shrestha, Niroj, Polz, Mathias, Stoppacher, Sara, Ziesel, Daniel, Migliaccio, Ludovico, Pelzmann, Brigitte, Lang, Petra, Zorn-Pauly, Klaus, Langthaler, Sonja, Opancar, Aleksandar, Baumgartner, Christian, Ucal, Muammer, Schindl, Rainer, Derek, Vedran, Scheruebel, Susanne
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Action Potentials - radiation effects; Animals; Calcium Channels, L-Type - metabolism; Computer Simulation; Guinea Pigs; Light; Models, Cardiovascular; Myocytes, Cardiac - physiology; Patch-Clamp Techniques
• ISSN: 0018-9294; 1558-2531
• DOI: 10.1109/TBME.2024.3358240

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 ) in Guinea pig ventricular cardiomyocytes. Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated I 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 , with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca channel blocker, nifedipine. Light-triggered I inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. OEPC-mediated activation of I 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 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.