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