Abstract
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 Q(f) at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Q(f)=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 Q(f) for the sodium-calcium channels family. An increase of Q(f) 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 Q(f)(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 Ca(2+)/Na(+) valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.
Highlights
At the molecular level, an understanding of living systems requires the application of physics and this is true in the case of biological ion channels
An increase of Qf leads to an increase of calcium selectivity: L0 → M0 → L1 → M1
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, sodiumselective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table
Summary
An understanding of living systems requires the application of physics and this is true in the case of biological ion channels. We have recently used parametric Brownian dynamics (BD) simulations of ionic currents for different Qf in a generic model of calcium channels to show that the Ca2+ conduction and Ca2+/Na+ valence selectivity form a regular pattern of narrow conduction and selectivity bands as a function of Qf , separated by regions of nonconduction. These discrete bands relate to saturated, self-sustained Ca2+ conductivity with different numbers of ions involved in the conduction; they correspond to the phase transitions obtained analytically in Ref.
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