Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca2+ 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: Amplifiers; Biomedical measurement; Biomedical modeling and simulation; Calcium; Calcium channels (L-type); Calcium channels (voltage-gated); Calcium ions; cardiac physiology; Cardiomyocytes; Channel gating; Deactivation; Electrodes; Electronic equipment; electrophysiology; Equivalent circuits; Europe; Guinea pigs; Heart; Inactivation; Indium tin oxide; Intracellular; Light modulation; Modeling; Nifedipine; Optoelectronic devices; patch-clamp; Photovoltaic cells; Photovoltaics; Physiology; Quality of life; Stimulation; Voltage control; voltage-gated ion channels; Wireless sensor networks
• ISSN: 0018-9294; 1558-2531; 1558-2531
• DOI: 10.1109/TBME.2024.3358240

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,L ) in Guinea pig ventricular cardiomyocytes. Methods: 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. Results: Light pulses activated I Ca,L , with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca 2+ channel blocker, nifedipine. Light-triggered I Ca,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. Conclusion: 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. 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.