An effect of large permanent charge: Decreasing flux to zero with increasing transmembrane potential to infinity

TL;DR

This study uses a Poisson-Nernst-Planck model to reveal how large permanent charges in ion channels can cause ionic fluxes to decrease to zero as transmembrane potential increases, highlighting complex charge effects.

Contribution

It demonstrates that large permanent charges can lead to flux suppression of both cations and anions, with distinct mechanisms explaining these phenomena, which was previously unclear.

Findings

Large positive permanent charges inhibit cation flux.

Anion flux decreases with increasing transmembrane potential under certain conditions.

Different mechanisms explain flux reduction in different ionic regions.

Abstract

In this work, we examine effects of large permanent charges on ionic flow through ion channels based on a quasi-one dimensional Poisson-Nernst-Planck model. It turns out large positive permanent charges inhibit the flux of cation as expected, but strikingly, as the transmembrane electrochemical potential for anion increases in a particular way, the flux of anion decreases. The latter phenomenon was observed experimentally but the cause seemed to be unclear. The mechanisms for these phenomena are examined with the help of the profiles of the ionic concentrations, electric fields and electrochemical potentials. The underlying reasons for the near zero flux of cation and for the decreasing flux of anion are shown to be different over different regions of the permanent charge. Our model is oversimplified. More structural detail and more correlations between ions can and should be included. But the basic finding seems striking and important and deserving of further investigation.