Selectivity Filter Residues Contribute Unequally to Pore Stabilization in Voltage-Gated Sodium Channels†

Biochemistry ◽  
2005 ◽  
Vol 44 (42) ◽  
pp. 13874-13882 ◽  
Author(s):  
Karlheinz Hilber ◽  
Walter Sandtner ◽  
Touran Zarrabi ◽  
Eva Zebedin ◽  
Oliver Kudlacek ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Selectivity Filter ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Changes in Ion Selectivity Following the Asymmetrical Addition of Charge to the Selectivity Filter of Bacterial Sodium Channels

Entropy ◽  
2020 ◽  
Vol 22 (12) ◽  
pp. 1390
Author(s):  
Olena A. Fedorenko ◽  
Igor A. Khovanov ◽  
Stephen K. Roberts ◽  
Carlo Guardiani
Keyword(s):  
Molecular Dynamics ◽  
Sodium Channels ◽  
Ion Selectivity ◽  
Selectivity Filter ◽  
Na Channels ◽  
Site Specific ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Gating Charge ◽  
Dynamics Simulations

Voltage-gated sodium channels (NaVs) play fundamental roles in eukaryotes, but their exceptional size hinders their structural resolution. Bacterial NaVs are simplified homologues of their eukaryotic counterparts, but their use as models of eukaryotic Na+ channels is limited by their homotetrameric structure at odds with the asymmetric Selectivity Filter (SF) of eukaryotic NaVs. This work aims at mimicking the SF of eukaryotic NaVs by engineering radial asymmetry into the SF of bacterial channels. This goal was pursued with two approaches: the co-expression of different monomers of the NaChBac bacterial channel to induce the random assembly of heterotetramers, and the concatenation of four bacterial monomers to form a concatemer that can be targeted by site-specific mutagenesis. Patch-clamp measurements and Molecular Dynamics simulations showed that an additional gating charge in the SF leads to a significant increase in Na+ and a modest increase in the Ca2+ conductance in the NavMs concatemer in agreement with the behavior of the population of random heterotetramers with the highest proportion of channels with charge −5e. We thus showed that charge, despite being important, is not the only determinant of conduction and selectivity, and we created new tools extending the use of bacterial channels as models of eukaryotic counterparts.

Protonation state of the selectivity filter of bacterial voltage‐gated sodium channels is modulated by ions

2019 ◽  
Vol 88 (3) ◽  
pp. 527-539 ◽  
Author(s):  
Ana Damjanovic ◽  
Ada Y. Chen ◽  
Robert L. Rosenberg ◽  
Daniel R. Roe ◽  
Xiongwu Wu ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Selectivity Filter ◽  
Protonation State ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Erratum to: Voltage-gated Sodium Channels and Blockers: An Overview and Where Will They Go?

2020 ◽  
Author(s):  
Zhi-mei Li ◽  
Li-xia Chen ◽  
Hua Li
Keyword(s):  
Open Access ◽  
Sodium Channels ◽  
Voltage Gated ◽  
Internet Portal ◽  
Creative Commons ◽  
Link Type ◽  
Voltage Gated Sodium Channels

The article “Voltage-gated Sodium Channels and Blockers: An Overview and Where Will They Go?”, written by Zhi-mei LI, Li-xia CHEN, Hua LI, was originally published electronically on the publisher’s internet portal on December 2019 without open access. With the author(s)’ decision to opt for Open Choice, the copyright of the article is changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The original article has been corrected.Corresponding authors: Li-xia CHEN, Hua LI

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