Effect of Charge Fluctuations on Conduction in Biological Ion Channels

Abstract

How open ion channels are able to conduct ions with a throughput comparable to free diffusion, and yet remain highly selective, is an unresolved scientific conundrum of long standing. To shed new light on this problem, the effect of charge fluctuations on the conduction of open ion channels is investigated theoretically. The model considered is a cylindrical channel across the membrane bathed by two solutions of different concentration. The charge fluctuations at the channel mouth are analyzed using Brownian Dynamics simulations and shown to have the form of trichotomous noise on the timescale of nanoseconds. The channel potential with a local minimum at the selectivity site due to the fixed wall charge is calculated by solution of the 3D Poisson equation for two configurations, with one ion moving along the channel axis in the presence or absence of the fluctuating charge at the channel mouth. It is shown that narrow channels act as electrostatic amplifiers of the modulation of the potential barriers at the selectivity site, due to charge fluctuations at the channel mouths. This modulation at the selectivity site was largely neglected in earlier research. It results in a leading order contribution to the transition rates of open ion channels. The proposed model of ion permeation takes into account the dynamical effect of the charge fluctuations through the resultant shot noise, which flips the electrostatic potential at the selectivity site, causing it to fluctuate between three values at a rate corresponding to the random arrivals of ions at the channel mouth. The model is applied to calculation of the current-voltage characteristics of Gramicidin A channel for different concentrations and is shown to be in good agreement with experimental results, including the effect of current saturation at high concentrations.