Do Bistable Steric Poisson-Nernst-Planck Models Describe Single-Channel Gating?

Experiments measuring currents through single protein channels show unstable currents, a phenomena called the gating of a single channel. Channels switch between an "open" state with a well-defined single amplitude of current and "closed" states with nearly zero current. The existing mean-field theory of ion channels focuses almost solely on the open state. The physical modeling of the dynamical features of ion channels is still in its infancy and does not describe the transitions between open and closed states nor the distribution of the duration times of open states. One hypothesis is that gating corresponds to noise-induced fast transitions between multiple steady (equilibrium) states of the underlying system. In this work, we aim to test this hypothesis. Particularly, our study focuses on the (high-order) steric Poisson-Nernst-Planck (PNP)-Cahn-Hilliard model since it has been successful in predicting permeability and selectivity of ionic channels in their open state and since it gives rise to multiple steady states. We show that this system gives rise to a gatinglike behavior, but that important features of this switching behavior are different from the defining features of gating in biological systems. Furthermore, we show that noise prohibits switching in the system of study. The above phenomena are expected to occur in other PNP-type models, strongly suggesting that one has to go beyond overdamped (gradient flow) Nernst-Planck type dynamics to explain the spontaneous gating of single channels.