Effect of local binding on stochastic transport in ion channels

Abstract

Abstract-Ionic Coulomb blockade is an electrostatic phenomenon recently discovered in low-capacitance ion channels/nanopores. Depending on the fixed charge that is present, Coulomb blockade strongly and selectively influences the ease with which a given type of ion can permeate the pore. The phenomenon arises from the discreteness of the charge-carriers and it manifests itself strongly for divalent ions (e.g. Ca 2+ ). Ionic Coulomb blockade is closely analogous to electronic Coulomb blockade in quantum dots. In addition to the non-local 1D Coulomb interaction considered in the standard Coulomb blockade approach, we now propose a correction to take account of the singular part of the attraction to the binding site (i.e. local site binding). We show that this correction leads to a geometrydependent shift of the single-ion barrierless resonant conduction points M0. We also show that local ion-ion repulsion accounts for a splitting of Ca 2+ profiles observed earlier in Brownian dynamics simulations.

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

“…ICB is closely similar to its electronic counterpart in quantum dots [19,20] and nanostructures [21,22]. The basic ICB model for the permeation and selectivity of ion channels [18] has recently been enhanced [23,24] by the introduction of shift/corrections to allow for the singular part of the ionic attraction to the binding site (i.e. local site-binding), as well as for arbitrary additional ion excess chemical potential ∆µ ex .…”

“…This excess chemical potential ∆µ ex arises from different sources [35][36][37]. Inclusion of the ICB barrier-less condition ∆µ ex = 0 leads to a "shift equation" [23,24,33]…”

“…In order to go further, we now combine the ideas of the QD models [8,13] with the Eisenman-inspired model of barrier-less selectivity [2,5,7] and, in particular, with the enhanced ICB model [17,23,24]. In the picture proposed, the difference in ∆U DH is not enough per se to determine which species will be selected over the other as this choice could be changed or even inverted by the value of Q f needed to provide barrier-less conduction, i.e.…”

“…local site-binding), as well as for arbitrary additional ion excess chemical potential ∆µ ex . The geometry-dependent shift of the ICB calcium resonant point, following from this correction, leads to a change in the divalent (calcium) blockade threshold IC 50 [23].…”

A review of Handbook of Ion Channels, by Jie Zheng and Matthew C. Trudeau

“…The result is resonant barrier-less conduction for the favoured ionic species, very much in accord with what is seen experimentally. Generally, the ICB model predicts/explains well the phenomena of valence selectivity, including the famous divalent blockade of monovalent currents [15,21] in Ca 2+ channels, which has also been observed and investigated in the NaChBac channel and its mutants [22,23]. The ICB model was recently extended on the firm basis of very general statistical principles [24].…”