Multiple action potentials and complex calcium dynamics following electroporation of S-HEK cells depend on gap junction coupling
- 1Faculty of Electrical Engineering, University of Ljubljana, Tržaška Cesta 25, 1000 Ljubljana, Slovenia
Abstract
In recent years, irreversible electroporation has been increasingly used to treat cardiac arrhythmias, an approach termed pulsed field ablation. The mechanisms of how electroporation affects the generation and propagation of action potentials (AP) in the myocardium (and other excitable tissues) remain to be elucidated. In our previous in vitro studies using genetically engineered S-HEK cells as a simple model of excitable cells we identified two unexpected phenomena that remain unexplained: (1) multiple APs triggered by a single electric pulse, and (2) a pulse-induced complex (bi- or multiphasic) calcium response not observed in their non-excitable counterparts NS-HEK cells. In this study, we employed fluorescence microscopy for optical monitoring of APs and intracellular calcium, pharmacological interventions targeting specific ion channels, and molecular biology techniques to characterize the expression of selected ion channels in S-HEK and NS-HEK cells. Our findings show that (1) multiple APs result primarily from sustained AP propagation along the cell monolayer through gap junctions, and (2) the complex calcium response in S-HEK cells reflects synchronized calcium influx during these propagating APs, with extracellular calcium being primary source rather than internal store release.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-63712-8.
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BibTeX
@article{napotnik2026multiple,
title = {{Multiple action potentials and complex calcium dynamics following electroporation of S-HEK cells depend on gap junction coupling}},
author = {Tina Batista Napotnik and Anja Blažič and Vid Jan and Klara Bulc Rozman and Rok Šmerc and Lea Rems},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-63712-8},
url = {https://doi.org/10.1038/s41598-026-63712-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multiple action potentials and complex calcium dynamics following electroporation of S-HEK cells depend on gap junction coupling
AU - Tina Batista Napotnik
AU - Anja Blažič
AU - Vid Jan
AU - Klara Bulc Rozman
AU - Rok Šmerc
AU - Lea Rems
PY - 2026
DA - 2026/07/28
JO - Scientific Reports
DO - 10.1038/s41598-026-63712-8
UR - https://doi.org/10.1038/s41598-026-63712-8
AB - In recent years, irreversible electroporation has been increasingly used to treat cardiac arrhythmias, an approach termed pulsed field ablation. The mechanisms of how electroporation affects the generation and propagation of action potentials (AP) in the myocardium (and other excitable tissues) remain to be elucidated. In our previous in vitro studies using genetically engineered S-HEK cells as a simple model of excitable cells we identified two unexpected phenomena that remain unexplained: (1) multiple APs triggered by a single electric pulse, and (2) a pulse-induced complex (bi- or multiphasic) calcium response not observed in their non-excitable counterparts NS-HEK cells. In this study, we employed fluorescence microscopy for optical monitoring of APs and intracellular calcium, pharmacological interventions targeting specific ion channels, and molecular biology techniques to characterize the expression of selected ion channels in S-HEK and NS-HEK cells. Our findings show that (1) multiple APs result primarily from sustained AP propagation along the cell monolayer through gap junctions, and (2) the complex calcium response in S-HEK cells reflects synchronized calcium influx during these propagating APs, with extracellular calcium being primary source rather than internal store release. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-63712-8.
SN - 2045-2322
ER -