Generalized microscopic theory of ion selectivity in voltage-gated ion channels

TL;DR

This paper develops a comprehensive microscopic theory explaining how ion channels achieve high selectivity and conductance, integrating physical and biochemical mechanisms for specific ions in various channels.

Contribution

It introduces a generalized microscopic framework that clarifies the physico-biochemical mechanisms behind ion selectivity and high conductance in voltage-gated ion channels.

Findings

Identifies five key conditions for ion selectivity and conductance.

Explains the role of dehydration energy and pore size in selectivity.

Provides a unified theory applicable to multiple ion channel types.

Abstract

Ion channels are specific proteins present in the membranes of living cells. They control the flow of specific ions through a cell, initiated by an ion channel's electrochemical gradient. In doing so, they control important physiological processes such as muscle contraction and neuronal connectivity, which cannot be properly activated if these channels go haywire, leading to life-threatening diseases and psychological disorders. Here, we will develop a generalized microscopic theory of ion selectivity applicable to KcsA, Na$_{\rm v}$Rh and Ca$_{\rm v}$ (L-type) ion channels. We unambiguously expose why and how a given ion-channel can be highly selective, and yet has a conductance of the order of one million ions per second, or higher. We will identify and prove the correct physico-biochemical mechanisms that are responsible for the high selectivity of a particular ion in a given ion channel. The above mechanisms consist of five conditions, which can be directly associated to these parameters - (i) dehydration energy, (ii) concentration of the "correct" ions (iii) Coulomb-van-der-Waals attraction, (iv) pore and ionic sizes, and indirectly to (v) the thermodynamic stability and (vi) the "knock-on" assisted permeation.