Permeation Energetics in a Model Potassium Channel

Summary

Known structures of selective ion channels share a common property: a narrow constriction, presumably crucial for ionic discrimination. This region can be fairly long, imposing single file motion on waters and ion(s). We apply the semi-microscopic Monte Carlo approach to study permeation in the KcsA channel, decomposing energetics into a three-step process: cation dehydration; ion transfer into a uniform low ε dielectric; and transfer from the uniform dielectric into the channel. The influence of individual channel structural features is separately assessed. The aqueous cavity has only a modest stabilizing effect on nearby ions in the filter. Ionic solvation in the filter reflects the combined influence of the single file waters, the binding pockets' carbonyls, the α helices directed at the cavity and the negative residues near the extracellular surface of the channel; no one feature dominates. At all sites along the permeation pathway there is substantial discrimination favouring K⁺ over Na⁺; conversely, there is little discrimination among the larger alkali cations. Selectivity for K⁺ over Na⁺; appears due to the inability of the filter's carbonyl oxygens to ideally coordinate Na⁺.