Energetics of ion competition in the DEKA selectivity filter of neuronal sodium channels

TL;DR

This study models the energetics of ion selectivity in neuronal sodium channels' DEKA filter, revealing how K+ ions are excluded by entropy and Ca2+ by energetic penalties, independent of protein dielectric properties.

Contribution

It introduces a simple model and Monte Carlo simulations to analyze ion competition and selectivity mechanisms in the DEKA filter of sodium channels.

Findings

K+ ions are excluded by entropic hard sphere effects.

Ca2+ ions are energetically penalized and excluded.

Protein dielectric constant does not influence selectivity.

Abstract

The energetics of ionic selectivity in the neuronal sodium channels is studied. A simple model constructed for the selectivity filter of the channel is used. The selectivity filter of this channel type contains aspartate (D), glutamate (E), lysine (K), and alanine (A) residues (the DEKA locus). We use Grand Canonical Monte Carlo simulations to compute equilibrium binding selectivity in the selectivity filter and to obtain various terms of the excess chemical potential from a particle insertion procedure based on Widom's method. We show that K$^{+}$ ions in competition with Na$^{+}$ are efficiently excluded from the selectivity filter due to entropic hard sphere exclusion. The dielectric constant of protein has no effect on this selectivity. Ca$^{2+}$ ions, on the other hand, are excluded from the filter due to a free energetic penalty which is enhanced by the low dielectric constant of protein.