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Anomalous mole fraction effect, electrostatics, and binding in ionic channels

W Nonner1, D P Chen, B Eisenberg

  • 1Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101-4819, USA.

Biophysical Journal
|May 20, 1998
PubMed
Summary

The anomalous mole fraction effect (AMFE) in ion channels is explained by localized ion binding, not single-file ion movement. This electrostatic effect, predicted by Poisson-Nernst-Planck theory, redefines understanding of ion channel permeation.

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Area of Science:

  • Biophysics
  • Physical Chemistry
  • Computational Biology

Background:

  • The anomalous mole fraction effect (AMFE) is observed when ion channels conduct less current in mixed electrolyte solutions compared to pure solutions.
  • Historically, AMFE has been attributed to single-file pores with multiple ions occupying the channel simultaneously.

Purpose of the Study:

  • To demonstrate that AMFE arises from localized ion-specific binding and electrostatic interactions, as described by Poisson-Nernst-Planck (PNP) theory.
  • To challenge the long-held view that AMFE necessitates single-file permeation and multiple ion occupancy.

Main Methods:

  • Utilized Poisson-Nernst-Planck (PNP) theory to model ion flux and electric fields within ion channels.
  • Analyzed ion-ion interactions mediated by the mean field, without enforcing single-file constraints.

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Main Results:

  • PNP theory predicts AMFE due to localized ion-specific binding, even with less than one ion on average in the pore.
  • AMFE arises from a depletion layer created by ion-specific binding sites, which repels nearby ions of like charge.
  • The conductance is limited by a series resistance model, including binding, depletion, and unbinding regions.

Conclusions:

  • AMFE is an electrostatic phenomenon driven by localized binding and depletion layers, not solely by single-file permeation.
  • The presence of AMFE does not imply multiple ion occupancy or single-file passage through ion channels.
  • Revises the fundamental understanding of ion permeation mechanisms in biological and synthetic channels.