Quantized Dehydration and the Determinants of Selectivity in the NaChBac Bacterial Sodium Channel

Abstract

A discrete electrostatic/diffusion model has been developed to describe the selective permeation of ion channels, based on ionic Coulomb blockade (ICB) and quantised dehydration (QD). It has been applied to describe selectivity phenomena measured in the bacterial NaChBac sodium channel and some of its mutants. Site-directed mutagenesis and the whole-cell patch-clamp technique were used to investigate how the value Q f of the fixed charge at the selectivity filter (SF) affected both valence and alike-charge selectivity. The new ICB/QD model predicts that increasing Q f should lead to a shift of selectivity sequences towards larger ion sizes and charges, a result that agrees with the present experiments and with earlier work. Comparison of the model with experimental data provides evidence for an effective charge Q * f at the SF that is smaller in magnitude than the nominal Q f corresponding to the charge on the isolated protein residues. Furthermore, Q * f was different for aspartate and glutamate charged rings and also depended on their position within the SF. It is suggested that protonation of the residues within the restricted space is an important factor in significantly reducing the effective charge of the EEEE ring. Values of Q * f derived from experiments on the anomalous mole fraction effect (AMFE) agree well with expectations based on the ICB/QD model and have led to the first clear demonstration of the expected ICB oscillations in Ca 2+ conduction as a function of the fixed charge. Pilot studies of the dependence of Ca 2+ conduction on pH are consistent with the predictions of the model.

Optimal transport and colossal ionic mechano-conductance in graphene crown ethers

“…While the transport mechanism is different for unstrained pores, the colossal mechano-conductance change is present at low voltage, regardless of the partial charge. In both partial charge scenarios, the free-energy profile becomes smoother with increasing strain, tending toward "barrierless transport" (19,21): Pulling charged oxygens away from the pore center reduces their coupling to translocating ions. The colossal change in conductance indicates that there are optimal structural positions for the oxygens: Picometer changes in their position do not change the dehydration contribution to the central barrier (see the Supplementary Materials), but it vastly changes the transport rate, maintaining exclusion of other ions but enhancing transport rates by several fold.…”