Ionic Coulomb blockade and anomalous mole fraction effect in NaChBac bacterial ion channels

TL;DR

This study investigates how fixed charge and ionic concentrations influence bacterial ion channel conduction, demonstrating that the ionic Coulomb blockade model explains key experimental phenomena like anomalous mole fraction effects and divalent blockade.

Contribution

It provides experimental validation of the ionic Coulomb blockade model in bacterial ion channels, linking fixed charge modifications to conduction and selectivity behaviors.

Findings

The Coulomb blockade model accurately predicts divalent blockade effects.

Mutations altering fixed charge affect ion conduction consistent with model predictions.

Concentration-dependent shifts in conduction patterns were observed.

Abstract

We report an experimental study of the influences of the fixed charge and bulk ionic concentrations on the conduction of biological ion channels, and we consider the results within the framework of the ionic Coulomb blockade model of permeation and selectivity. Voltage clamp recordings were used to investigate the Na$^+$/Ca$^{2+}$ anomalous mole fraction effect (AMFE) exhibited by the bacterial sodium channel NaChBac and its mutants. Site-directed mutagenesis was used to study the effect of either increasing or decreasing the fixed charge in their selectivity filters for comparison with the predictions of the Coulomb blockade model. The model was found to describe well some aspects of the experimental (divalent blockade and AMFE) and simulated (discrete multi-ion conduction and occupancy band) phenomena, including a concentration-dependent shift of the Coulomb staircase. These results substantially extend the understanding of ion channel selectivity and may also be applicable to biomimetic nanopores with charged walls.