Internal motions in proteins and gating kinetics of ionic channels

Abstract

Single-channel current recordings have revealed a complex kinetic behavior of ionic channels. Many channels exhibit closed-time distributions in which long waiting times occur with a much higher frequency than predicted by a simple exponential decay function. In this paper a model for opening-closing transitions that accounts for internal motions in the protein matrix is discussed. The model is based on the notion that the transition between a conductive and a nonconductive state of the channel represents a local process in the protein, such as the movement of a small segment of a peptide chain or the rotation of a single amino-acid residue. When the blocking group moves into the ion pathway, a structural defect is created consisting in a region of loose packing and/or poor hydrogen bonding. By rearrangements of neighboring groups, the defect may migrate within the protein matrix, carrying out a kind of random walk. Once the defect has moved away from the site where it was formed, a transition back to the open state of the channel is possible only when the defect has returned by chance to the original position. The kinetic properties of this model are analyzed by stochastic simulation of defect diffusion in a small domain of the protein. With a suitable choice of domain size and diffusion rate, the model is found to predict closed-time distributions that agree with experimental observations.