scholarly journals Structural model of the open–closed–inactivated cycle of prokaryotic voltage-gated sodium channels

2014 ◽  
Vol 145 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Claire Bagnéris ◽  
Claire E. Naylor ◽  
Emily C. McCusker ◽  
B.A. Wallace
Keyword(s):  
Sodium Channels ◽  
Conformational Changes ◽  
Structural Model ◽  
Transmembrane Helix ◽  
Activation Mechanism ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Recovery Processes ◽  
Voltage Gated Sodium Channels ◽  
Activation Gate

In excitable cells, the initiation of the action potential results from the opening of voltage-gated sodium channels. These channels undergo a series of conformational changes between open, closed, and inactivated states. Many models have been proposed for the structural transitions that result in these different functional states. Here, we compare the crystal structures of prokaryotic sodium channels captured in the different conformational forms and use them as the basis for examining molecular models for the activation, slow inactivation, and recovery processes. We compare structural similarities and differences in the pore domains, specifically in the transmembrane helices, the constrictions within the pore cavity, the activation gate at the cytoplasmic end of the last transmembrane helix, the C-terminal domain, and the selectivity filter. We discuss the observed differences in the context of previous models for opening, closing, and inactivation, and present a new structure-based model for the functional transitions. Our proposed prokaryotic channel activation mechanism is then compared with the activation transition in eukaryotic sodium channels.

scholarly journals RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels

2015 ◽  
Vol 112 (9) ◽  
pp. 2859-2864 ◽  
Author(s):  
Kazutoyo Ogino ◽  
Sean E. Low ◽  
Kenta Yamada ◽  
Louis Saint-Amant ◽  
Weibin Zhou ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Ring Finger ◽  
Membrane Localization ◽  
Ring Finger Protein ◽  
Excitable Cells ◽  
Gene Encoding ◽  
Voltage Gated ◽  
Finger Protein ◽  
Voltage Gated Sodium Channels ◽  
New Gene

Following their synthesis in the endoplasmic reticulum (ER), voltage-gated sodium channels (NaV) are transported to the membranes of excitable cells, where they often cluster, such as at the axon initial segment of neurons. Although the mechanisms by which NaV channels form and maintain clusters have been extensively examined, the processes that govern their transport and degradation have received less attention. Our entry into the study of these processes began with the isolation of a new allele of the zebrafish mutant alligator, which we found to be caused by mutations in the gene encoding really interesting new gene (RING) finger protein 121 (RNF121), an E3-ubiquitin ligase present in the ER and cis-Golgi compartments. Here we demonstrate that RNF121 facilitates two opposing fates of NaV channels: (i) ubiquitin-mediated proteasome degradation and (ii) membrane localization when coexpressed with auxiliary NaVβ subunits. Collectively, these results indicate that RNF121 participates in the quality control of NaV channels during their synthesis and subsequent transport to the membrane.

scholarly journals Mapping of voltage sensor positions in resting and inactivated mammalian sodium channels by LRET

2017 ◽  
Vol 114 (10) ◽  
pp. E1857-E1865 ◽  
Author(s):  
Tomoya Kubota ◽  
Thomas Durek ◽  
Bobo Dang ◽  
Rocio K. Finol-Urdaneta ◽  
David J. Craik ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Structural Changes ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Voltage Sensor ◽  
Structural Basis ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Voltage Dependent

Voltage-gated sodium channels (Navs) play crucial roles in excitable cells. Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. We have assessed the structural changes of the Nav voltage sensor domain using lanthanide-based resonance energy transfer (LRET) between the rat skeletal muscle voltage-gated sodium channel (Nav1.4) and fluorescently labeled Nav1.4-targeting toxins. We generated donor constructs with genetically encoded lanthanide-binding tags (LBTs) inserted at the extracellular end of the S4 segment of each domain (with a single LBT per construct). Three different Bodipy-labeled, Nav1.4-targeting toxins were synthesized as acceptors: β-scorpion toxin (Ts1)-Bodipy, KIIIA-Bodipy, and GIIIA-Bodipy analogs. Functional Nav-LBT channels expressed inXenopusoocytes were voltage-clamped, and distinct LRET signals were obtained in the resting and slow inactivated states. Intramolecular distances computed from the LRET signals define a geometrical map of Nav1.4 with the bound toxins, and reveal voltage-dependent structural changes related to channel gating.

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

Sign in / Sign up

Export Citation Format

Share Document