Position-dependent stochastic diffusion model of ion channel gating

Abstract: A position-dependent stochastic diffusion model of gating in ion channels is developed by considering the spatial variation of the diffusion coefficient between the closed and open states. It is assumed that a sensor which regulates the opening of the ion channel experiences Brownian motion in a closed region $R_{c}$ and a transition region $R_{m}$, where the dynamics is described by probability densities $p_{c}(x,t)$ and $p_{m}(x,t)$ which satisfy interacting Fokker-Planck equations with diffusion coefficient $D_{c}(x)=D_{c}\exp(\gamma_{c}x)$ and $D_{m}(x)=D_{m} \exp(-\gamma_{m}x)$. The analytical solution of the coupled equations may be approximated by the lowest frequency relaxation, a short time after the application of a depolarizing voltage clamp, when $D_{m} \ll D_{c}$ or the diffusion parameter $\gamma_{m}$ is sufficiently large. Thus, an empirical rate equation that describes gating transitions may be derived from a stochastic diffusion model if there is a large diffusion (or potential) barrier between open and closed states.