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Title: Bases of Bacterial Sodium Channel Selectivity Among Organic Cations

Abstract

Hille’s (1971) seminal study of organic cation selectivity of eukaryotic voltage-gated sodium channels showed a sharp size cut-off for ion permeation, such that no ion possessing a methyl group was permeant. Using the prokaryotic channel, NaChBac, we found some similarity and two peculiar differences in the selectivity profiles for small polyatomic cations. First, we identified a diverse group of minimally permeant cations for wildtype NaChBac, ranging in sizes from ammonium to guanidinium and tetramethylammonium; and second, for both ammonium and hydrazinium, the charge-conserving selectivity filter mutation (E191D) yielded substantial increases in relative permeability (P X/P Na). The relative permeabilities varied inversely with relative Kd calculated from 1D Potential of Mean Force profiles (PMFs) for the single cations traversing the channel. Several of the cations bound more strongly than Na +, and hence appear to act as blockers, as well as charge carriers. Consistent with experimental observations, the E191D mutation had little impact on Na+ binding to the selectivity filter, but disrupted the binding of ammonium and hydrazinium, consequently facilitating ion permeation across the NaChBac-like filter. We concluded that for prokaryotic sodium channels, a fine balance among filter size, binding affinity, occupancy, and flexibility seems to contribute to observed functional differences.

Authors:
 [1]; ORCiD logo [2];  [3]; ORCiD logo [4]; ORCiD logo [4]
+ Show Author Affiliations
  1. Chinese Academy of Sciences (CAS), Changchun (China); Univ. of Calgary, AB (Canada)
  2. Univ. of Calgary, AB (Canada); Univ. of Wollongong, NSW (Australia)
  3. Univ. of Calgary, AB (Canada); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. Univ. of Calgary, AB (Canada)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1574758
Report Number(s):
LA-UR-19-29893
Journal ID: ISSN 2045-2322
Grant/Contract Number:  
89233218CNA000001
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Sodium Ion Channels

Citation Formats

Wang, Yibo, Finol-Urdaneta, Rocio K., Ngo, Van Anh, French, Robert J., and Noskov, Sergei Yu. Bases of Bacterial Sodium Channel Selectivity Among Organic Cations. United States: N. p., 2019. Web. doi:10.1038/s41598-019-51605-y.
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Wang, Yibo, Finol-Urdaneta, Rocio K., Ngo, Van Anh, French, Robert J., & Noskov, Sergei Yu. Bases of Bacterial Sodium Channel Selectivity Among Organic Cations. United States. doi:10.1038/s41598-019-51605-y.
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Wang, Yibo, Finol-Urdaneta, Rocio K., Ngo, Van Anh, French, Robert J., and Noskov, Sergei Yu. Thu . "Bases of Bacterial Sodium Channel Selectivity Among Organic Cations". United States. doi:10.1038/s41598-019-51605-y. https://www.osti.gov/servlets/purl/1574758.
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@article{osti_1574758,
title = {Bases of Bacterial Sodium Channel Selectivity Among Organic Cations},
author = {Wang, Yibo and Finol-Urdaneta, Rocio K. and Ngo, Van Anh and French, Robert J. and Noskov, Sergei Yu.},
abstractNote = {Hille’s (1971) seminal study of organic cation selectivity of eukaryotic voltage-gated sodium channels showed a sharp size cut-off for ion permeation, such that no ion possessing a methyl group was permeant. Using the prokaryotic channel, NaChBac, we found some similarity and two peculiar differences in the selectivity profiles for small polyatomic cations. First, we identified a diverse group of minimally permeant cations for wildtype NaChBac, ranging in sizes from ammonium to guanidinium and tetramethylammonium; and second, for both ammonium and hydrazinium, the charge-conserving selectivity filter mutation (E191D) yielded substantial increases in relative permeability (PX/PNa). The relative permeabilities varied inversely with relative Kd calculated from 1D Potential of Mean Force profiles (PMFs) for the single cations traversing the channel. Several of the cations bound more strongly than Na+, and hence appear to act as blockers, as well as charge carriers. Consistent with experimental observations, the E191D mutation had little impact on Na+ binding to the selectivity filter, but disrupted the binding of ammonium and hydrazinium, consequently facilitating ion permeation across the NaChBac-like filter. We concluded that for prokaryotic sodium channels, a fine balance among filter size, binding affinity, occupancy, and flexibility seems to contribute to observed functional differences.},
doi = {10.1038/s41598-019-51605-y},
journal = {Scientific Reports},
number = 1,
volume = 9,
place = {United States},
year = {2019},
month = {10}
}
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DOI:  10.1038/s41598-019-51605-y
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