Permeation models and structure-function relationships in ion channels

Abstract. Recent determination of the molecular structures of potassium and mechanosensitive channels from x-ray crystallography has led to a renewed interest in ion channels. The challenge for permeation models is to understand the functional properties of channels from the available structural information. Here we give a critical review of the three main contenders, namely, continuum theories, Brownian dynamics and molecular dynamics. Continuum theories are shown to be invalid in a narrow channel environment because they ignore the self-energy of ions arising from the induced charges on the dielectric boundary. Brownian and molecular dynamics are thus the only physically valid methods for studying the structure-function relations in ion channels. Applications of these methods to potassium and calcium channels are presented, which illustrate the multi-ion nature of the permeation mechanism in selective biological channels