Numerical Modeling of PEF Effect on the Action Potential produced by Nanoscale Protein Channels in the Plasma Membrane of Excitable Spherical Cells during Electropermeabilization

Pulsed electric fields (PEF) affect the plasma membrane and voltage-gated ion channels of excitable cells at a nanoscale molecular level, altering the action potential generated. However, there have been only a few studies conducted on these effects. We propose a model that combines a continuous, three-dimensional mesoscopic representation of a spherical cell with equivalent circuits to simulate and analyze the increase in membrane permeability resulting from nanopore formation, alterations in ion channels, and action potentials during electropermeabilization. The model integrates McIntyre’s action potential framework with Krassowska’s electroporation equations and is numerically solved in spherical coordinates using the finite difference method. A monophasic electric field of 40 kV/m (100–200 µs) was applied, and transmembrane potentials were evaluated at different angular positions on the spherical cell. The simulations indicate that when the induced transmembrane potential exceeds 200 mV, nanopores predominantly form at membrane regions perpendicular to the applied field, resulting in a transient increase in conductance and pore radius. These effects cause spatial variations in the action potential across the cell, which normalize within milliseconds after the pulse. The model enhances our understanding of pore formation and the modulation of membrane protein function during electroporation, which is crucial for cell biology and medical applications.