Voltage-induced closure of β-barrel channels as electrochemical gating

Most β-barrel channels exhibit voltage gating, transitioning from high- to low-conducting states under high transmembrane potentials. Unlike flexible alpha-helical channels in which a physical occlusion appears, these rigid structures lack a clear gating mechanism. Using the bacterial porin OmpF from E. coli as a model system, we reveal a non-linear dependence of gating kinetics on electrolyte concentration, explained by a model based on Debye screening with high-concentration adjustments. Also, we demonstrate a large variability in low-conducting state conductances and a striking inversion in ion selectivity, switching from cationic in the high-conducting states to anionic in the low-conducting ones. Based on this and previous data, like the lack of a defined closed-state structure with major structural changes or narrowing of the pore, we hypothesize that OmpF channel closure could be understood as an electrochemical gating process. We suggest a non-steric mechanism in which low-conducting states arise from the disruption of the electrochemical gradient occurring when the external voltage causes subtle, collective reorganizations of channel residues, leading to surface dewetting at diverse locations of the channel. This model brings ideas from solid state nanopores were gating occurs without structural movements, offering a fresh perspective on β-barrel channel closure.