Calcium versus potassium selectivity in a nanopore: The effect of charge inversion at localized pore charges

The Anomalous Mole Fraction Effect (AMFE) in negatively charged pores has been considered as a signature of Ca2+ vs. monovalent ion (K+, in this study) selectivity. Increasing the mole fraction of CaCl2 in the KCl/CaCl2 mixture, the total conductance first declines as Ca2+ ions replace K+ ions inside the pore, then it increases as Ca2+ becomes the main charge carrier. While the AMFE was first pointed out in calcium selective ion channels, in a previous study (Gillespie et al., Biophys. J. 95 (2008) 609-619.) we showed that it is also present in synthetic nanopores. Here we use the Local Equilibrium Monte Carlo method coupled to the Nernst-Planck transport equation to study a simple model of a finite nanopore in a membrane with ions being explicitly modeled as charged hard spheres and water as an implicit continuum. The novel component of the model is the treatment of the pore charges that are present in localized COO groups on the wall of the nanopore. Therefore, we study the effect of localizing the pore charges instead of smearing them as a continuous surface charge. Localized charges profoundly influence Ca2+ vs. K+ selectivity because they enhance charge inversion at the pore wall. Ca2+ ions overcharge the pore wall at which the K+ ions have a disadvantage in the K+ vs. Ca2+ competition because the overcharged pore wall does not attract them so strongly. (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).