Kinetic modeling for the channel gating process from single channel patch clamp data

Abstract

Allosteric interactions play a crucial role in the regulation of protein-ligand binding. The single-channel recordings of Na+ channels revealed deviations from the Hodgkin-Huxley mechanism, that may be explained in the context of protein co-operativity. In this paper, we present a Na+ channel gating model based on the allosteric nature of the channel proteins. The model contains a co-operative parameter c and a subunit interaction parameter s, in addition to four Hodgkin-Huxley kinetic parameters. Thus, in our model a deviation from the Hodgkin-Huxley mechanism is measured by these two parameters (i.e., whether they are different from unity). We then discuss how to estimate the kinetic parameters in the model from the single channel recordings. Our method of estimating the parameters is tested with Monte Carlo runs with very good results.