ArticleProceedings of the National Academy of Sciences of the United States of America2012
Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 17 citations in OpenAlex.
- Barium senses subtle pore changes in a voltage-gated KScience advances · 2026Article
- Molecular genetics of skeletal muscle channelopathies.Journal of human genetics · 2025Review
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Static Magnetic Field Stimulation Enhances Shunting Inhibition via a SLC26 Family ClThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Anionic omega currents from single countercharge mutants in the voltage-sensing domain of Ci-VSP.The Journal of general physiology · 2024Article
- Optical measurement of gating pore currents in hypokalemic periodic paralysis model cells.Disease models & mechanisms · 2023Article
- Historical Perspective of the Characterization of Conotoxins Targeting Voltage-Gated Sodium Channels.Marine drugs · 2023Review
- In Silico Analysis of Tetrodotoxin Binding in Voltage-Gated Sodium Ion Channels from Toxin-Resistant Animal Lineages.Marine drugs · 2022Article
- Naview: A d3.js Based JavaScript Library for Drawing and Annotating Voltage-Gated Sodium Channels Membrane Diagrams.Frontiers in bioinformatics · 2022Article
- Druggability of Voltage-Gated Sodium Channels-Exploring Old and New Drug Receptor Sites.Frontiers in pharmacology · 2022Review
- Lidocaine Binding Enhances Inhibition of Nav1.7 Channels by the Sulfonamide PF-05089771.Molecular pharmacology · 2020Article
- Article
- The voltage-gated sodium channel pore exhibits conformational flexibility during slow inactivation.The Journal of general physiology · 2018Article
- Improving the characterization of calcium channel gating pore currents with Stac3.The Journal of general physiology · 2018Article
- Pharmacology of the NaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mapping of voltage sensor positions in resting and inactivated mammalian sodium channels by LRET.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.Neurology · 2016Article
- Understanding Sodium Channel Function and Modulation Using Atomistic Simulations of Bacterial Channel Structures.Current topics in membranes · 2016Article
- The hitchhiker's guide to the voltage-gated sodium channel galaxy.The Journal of general physiology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 7 institutions in 3 countries.
Funding
Abstract
Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.