An ab initio Molecular Orbital Study on Effect of Electric Field Strength on Ionic Selectivity of the Sodium Channel

Abstract

The effect of electric field strength of the selectivity filter on ionic selectivity of the sodium channel has been studied by ab initio molecular orbital calculations. On the basis of the previous method, two kinds of model systems, the FCO2M system and the FCO2M-H2O system, were studied. In this study, a FCO-2 molecule, which is substituted for a HCO-2 molecule, was used as a model for the selectivity filter. This substitution corresponds to weakening the electric field strength of the selectivity filter. For this system, geometries of ground and transition states were optimized with MINI-3 basis sets. The FCO2-H2O system, for which we evaluated thermochemical parameters and cross-sections, is a good model for ionic permeation of the sodium channel. When the results of the FCO2M-H2O system were compared with those of the HCO2M-H2O system, we concluded that permeabilities of Li+ and Na+ are smaller and that of K+ is larger as the field strength of the selectivity filter is weakened. Namely, the permeation of K+ is relatively favorable when the field strength of the selectivity filter is weakened. This conclusion is in accordance with the prediction of Eisenman's theory.