Voltage mapping in subcellular nanodomains using electro-diffusion modeling

TL;DR

This study uses electro-diffusion modeling to explore how voltage varies in tiny cellular compartments, revealing the influence of membrane shape, channel arrangement, and narrow passages on local voltage regulation.

Contribution

It introduces a Poisson-Nernst-Planck based computational model to analyze subcellular voltage distribution, highlighting factors affecting voltage regulation at nanoscales.

Findings

Voltage distribution follows a logarithmic I-V relationship influenced by membrane curvature.

Local channel organization can cause voltage perturbations over nanometer scales.

Neck resistance in dendritic spines can be bypassed by boundary transporters.

Abstract

Voltage distribution in sub-cellular micro-domains such as neuronal synapses, small protrusions or dendritic spines regulates the opening and closing of ionic channels, energy production and thus cellular homeostasis and excitability. Yet how voltage changes at such a small scale in vivo remains challenging due to the experimental diffraction limit, large signal fluctuations and the still limited resolution of fast voltage indicators. Here, we study the voltage distribution in nano-compartments using a computational approach based on the Poisson-Nernst-Planck equations for the electro-diffusion motion of ions, where inward and outward fluxes are generated between channels. We report a current-voltage (I-V) logarithmic relationship generalizing Nernst law that reveals how the local membrane curvature modulates the voltage. We further find that an influx current penetrating a cellular electrolyte can lead to perturbations from tens to hundreds of nanometers deep depending on the local channels organization. Finally, we show that the neck resistance of dendritic spines can be completely shunted by the transporters located on the head boundary, facilitating ionic flow. To conclude, we propose that voltage is regulated at a subcellular level by channels organization, membrane curvature and narrow passages.