Jump to main content
Jump to site search

Issue 44, 2017
Previous Article Next Article

On the selectivity of the NaChBac channel: an integrated computational and experimental analysis of sodium and calcium permeation

Author affiliations

Abstract

Ion channel selectivity is essential for their function, yet the molecular basis of a channel's ability to select between ions is still rather controversial. In this work, using a combination of molecular dynamics simulations and electrophysiological current measurements we analyze the ability of the NaChBac channel to discriminate between calcium and sodium. Our simulations show that a single calcium ion can access the Selectivity Filter (SF) interacting so strongly with the glutamate ring so as to remain blocked inside. This is consistent with the tiny calcium currents recorded in our patch-clamp experiments. Two reasons explain this scenario. The first is the higher free energy of ion/SF binding of Ca2+ with respect to Na+. The second is the strong electrostatic repulsion exerted by the resident ion that turns back a second potentially incoming Ca2+, preventing the knock-on permeation mechanism. Finally, we analyzed the possibility of the Anomalous Mole Fraction Effect (AMFE), i.e. the ability of micromolar Ca2+ concentrations to block Na+ currents. Current measurements in Na+/Ca2+ mixed solutions excluded the AMFE, in agreement with metadynamics simulations showing the ability of a sodium ion to by-pass and partially displace the resident calcium. Our work supports a new scenario for Na+/Ca2+ selectivity in the bacterial sodium channel, challenging the traditional notion of an exclusion mechanism strictly confining Ca2+ ions outside the channel.

Graphical abstract: On the selectivity of the NaChBac channel: an integrated computational and experimental analysis of sodium and calcium permeation

Back to tab navigation

Supplementary files

Publication details

The article was received on 30 Aug 2017, accepted on 09 Oct 2017 and first published on 01 Nov 2017


Article type: Paper
DOI: 10.1039/C7CP05928K
Citation: Phys. Chem. Chem. Phys., 2017,19, 29840-29854
  • Open access: Creative Commons BY license
  •   Request permissions

    On the selectivity of the NaChBac channel: an integrated computational and experimental analysis of sodium and calcium permeation

    C. Guardiani, O. A. Fedorenko, S. K. Roberts and I. A. Khovanov, Phys. Chem. Chem. Phys., 2017, 19, 29840
    DOI: 10.1039/C7CP05928K

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements