TY - JOUR
T1 - Shedding Light on Cardiac Excitation
T2 - In Vitro and In Silico Analysis of Native Ca2+ Channel Activation in Guinea Pig Cardiomyocytes using Organic Photovoltaic Devices
AU - Rienmüller, Theresa Margarethe
AU - Shrestha, Niroj
AU - Polz, Mathias
AU - Stoppacher, Sara
AU - Ziesel, Daniel
AU - Migliaccio, Ludovico
AU - Pelzmann, Brigitte
AU - Lang, Petra
AU - Langthaler, Sonja
AU - Opančar, Aleksandar
AU - Baumgartner, Christian
AU - Ücal, Muammer
AU - Schindl, Rainer
AU - Derek, Vedran
AU - Scheruebel, Susanne
PY - 2024
Y1 - 2024
N2 - 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 (Ca,L) in Guinea pig ventricular
cardiomyocytes. Whole-cell patch-clamp recordings were employed to
examine light-triggered OEPC mediated 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 Ca,L, with amplitudes similar
to voltage-clamp activation and high sensitivity to the L-type Ca2+
channel blocker, nifedipine. Light-triggered Ca,L inactivation
exhibited kinetic parameters comparable to voltage-induced inactivation.
OEPC-mediated activation of 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
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.
AB - 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 (Ca,L) in Guinea pig ventricular
cardiomyocytes. Whole-cell patch-clamp recordings were employed to
examine light-triggered OEPC mediated 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 Ca,L, with amplitudes similar
to voltage-clamp activation and high sensitivity to the L-type Ca2+
channel blocker, nifedipine. Light-triggered Ca,L inactivation
exhibited kinetic parameters comparable to voltage-induced inactivation.
OEPC-mediated activation of 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
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.
KW - calcium
KW - Calcium
KW - Indium tin oxide
KW - Europe
KW - patch-clamp
KW - Ions
KW - Optoelectronic devices
KW - cardiac physiology
KW - Electrodes
KW - Wireless sensor networks
KW - electrophysiology
KW - biomedical modeling and simulation
KW - Recording
KW - voltage-gated ion channels
UR - http://www.scopus.com/inward/record.url?scp=85188420084&partnerID=8YFLogxK
U2 - 10.1109/TBME.2024.3358240
DO - 10.1109/TBME.2024.3358240
M3 - Article
SN - 0018-9294
VL - 2024
SP - 1
EP - 12
JO - IEEE Transactions on Biomedical Engineering
JF - IEEE Transactions on Biomedical Engineering
ER -