Effects of electrical polarization on the opening rate constant of a voltage-gated ion channel

Ion channel gating kinetics can be described using Kramers' diffusion theory of reaction rates between several closed and open states, where transition rates between states depend exponentially on the membrane potential V. It has been suggested that transition rates have a more complex dependence on V at voltage extremes, but this has never been quantified. We measured the rate constant of the last closed to open transition in a voltage-gated ion channel and show that it does not depend exponentially on membrane potential at values of V greater than approximate to 150 mV. To explain this behavior, we estimate the effects of electrical polarization of the water contained in crevices within the channel protein, using an electrostatic model of the approximate three-dimensional geometry and the nonlinear effects of charges on the polarization of water.