Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family

Kaufman, Igor and Luchinsky, Dmitrii G. and Tindjong, Rodrigue and McClintock, Peter V. E. and Eisenberg, Robert S. (2013) Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family. Physical Review E, 88 (5): 052712. ISSN 1539-3755

[thumbnail of PRE2013EnergeticsOfDiscreteSelectivityBands]
PDF (PRE2013EnergeticsOfDiscreteSelectivityBands)
PRE2013EnergeticsOfDiscreteSelectivityBands.pdf - Published Version

Download (2MB)


We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Qf at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Qf = 1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Qf for the sodium-calcium channels family. An increase of Qf leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Qf (z,i) = ze(1/2 + i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca2+/Na+ valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

Item Type:
Journal Article
Journal or Publication Title:
Physical Review E
Additional Information:
Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.
Uncontrolled Keywords:
?? statistical and nonlinear physicsstatistics and probabilitycondensed matter physics ??
ID Code:
Deposited By:
Deposited On:
25 Nov 2013 11:45
Last Modified:
13 May 2024 00:13