Nernst equilibrium, rectification, and saturation: Insights into ion channel behavior

The dissipation of electrochemical gradients through ion channels plays a central role in biology. Herein we use voltage-responsive kinetic models of ion channels to explore how electrical and chemical potentials differentially influence ion transport properties. These models demonstrate how electrically driven flux is greater than the Nernstian equivalent chemically driven flux yet still perfectly cancels when the two gradients oppose each other. We find that the location and relative stability of ion-binding sites dictates rectification properties by shifting the location of the most voltage-sensitive transitions. However, these rectification properties invert when bulk concentrations increase relative to the binding-site stabilities, moving the rate-limiting steps from uptake into a relatively empty channel to release from an ion-blocked full channel. Additionally, the origin of channel saturation is shown to depend on the free energy of uptake relative to bulk concentrations. Collectively these insights provide a framework for interpreting and predicting how channel properties manifest in electrochemical transport behavior.