ABSTRACT
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 framework for interpreting and predicting how channel properties manifest in electrochemical transport behavior.
SIGNIFICANCE Understanding how electrochemical potentials, such as the proton motive force, drive ion transport is a complex challenge due to the intricate coupling between electrical and chemical gradients, which can have seemingly equivalent effects. This study investigates how channel properties are differentially influenced by these driving forces to enhance or decrease directional flux. Using model systems, we demonstrate how voltage induces greater flux than the Nernstian equivalent chemical gradient yet is still perfectly balanced when the two forces oppose each other. Our findings reveal how binding site locations dictate rectification properties that flip under low and high bulk concentrations. These insights enhance our understanding of channels and transporters, providing foundational relationships between protein properties and electrochemical outcomes.
Competing Interest Statement
The authors have declared no competing interest.
