Flux ratios and channel structures

TL;DR

This paper analyzes ionic flux ratios in membrane channels using Poisson-Nernst-Planck models, revealing conditions under which flux ratios are universal or specific to channel structure, and proposing improved experimental designs.

Contribution

It provides a detailed analysis of flux ratios in ion channels, identifying when they depend on channel structure and suggesting better experimental methods for estimating channel properties.

Findings

Universal flux ratios depend only on bulk conditions.

Most flux ratio estimation methods depend on permanent charge distribution.

Proposed experimental design yields universal flux ratios for main ion flux.

Abstract

We investigate Ussing's unidirectional fluxes and flux ratios of charged tracers motivated particularly by the insightful proposal of Hodgkin and Keynes on a relation between flux ratios and channel structure. Our study is based on analysis of quasi-one-dimensional Poisson-Nernst-Planck type models for ionic flows through membrane channels. This class of models includes the Poisson equation that determines the electrical potential from the charges present and is in that sense consistent. Ussing's flux ratios generally depend on all physical parameters involved in ionic flows, particularly, on bulk conditions and channel structures. Certain setups of ion channel experiments result in flux ratios that are universal in the sense that their values depend on bulk conditions but not on channel structures; other setups lead to flux ratios that are specific in the sense that their values depend on channel structures too. Universal flux ratios could serve some purposes better than specific flux ratios in some circumstances and worse in other circumstances. We focus on two treatments of tracer flux measurements that serve as estimators of important properties of ion channels. The first estimator determines the flux of the main ion species from measurements of the flux of its tracer. Our analysis suggests a better experimental design so that the flux ratio of the tracer flux and the main ion flux is universal. The second treatment of tracer fluxes concerns ratios of fluxes and experimental setups that try to determine some properties of channel structure. We analyze the two widely used experimental designs of estimating flux ratios and show that the most widely used method depends on the spatial distribution of permanent charge so this flux ratio is specific and thus allows estimation of (some of) the properties of that permanent charge, even with ideal ionic solutions. ...