ArticleBiophysical journal2003
Tryptophan scanning of D1S6 and D4S6 C-termini in voltage-gated sodium channels.
Article in Biophysical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- Structural and functional mechanisms underlying activation gate dynamics and IFM motif accessibility in human NaNature communications · 2026Article
- A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaScience advances · 2025Article
- A sodium channel mutant removes fast inactivation with the inactivation particle bound.The Journal of general physiology · 2025Article
- Article
- A mechanistic reinterpretation of fast inactivation in voltage-gated NaNature communications · 2023Article
- A Mechanistic Reinterpretation of Fast Inactivation in Voltage-Gated Na+ Channels.Research square · 2023Article
- A Mechanistic Reinterpretation of Fast Inactivation in Voltage-Gated NabioRxiv : the preprint server for biology · 2023Article
- Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current.Nature cardiovascular research · 2022Article
- Differential effects of modified batrachotoxins on voltage-gated sodium channel fast and slow inactivation.Cell chemical biology · 2022Article
- Extended-ensemble docking to probe dynamic variation of ligand binding sites during large-scale structural changes of proteins.Chemical science · 2022Article
- Effects of FGF14 and NaThe Journal of general physiology · 2019Article
- Distinct modulation of inactivation by a residue in the pore domain of voltage-gated NaScientific reports · 2018Article
- Article
- Mechanisms and models of cardiac sodium channel inactivation.Channels (Austin, Tex.) · 2017Review
- Single rat muscle NaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Pharmacology of the NaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Small molecule modulation of voltage gated sodium channels.Current opinion in structural biology · 2017Review
- Regulation of NaThe Journal of general physiology · 2017Article
- Congruent pattern of accessibility identifies minimal pore gate in a non-symmetric voltage-gated sodium channel.Nature communications · 2016Article
- The hitchhiker's guide to the voltage-gated sodium channel galaxy.The Journal of general physiology · 2016Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Recent reports suggest that four S6 C-termini may jointly close the voltage-gated cation channel at the cytoplasmic side, probably as an inverted teepee structure. In this study we substituted individually a total of 18 residues at D1S6 and D4S6 C-terminal ends of the rNav1.4 Na(+) channel alpha-subunit with tryptophan (W) and examined their corresponding gating properties when expressed in Hek293t cells along with beta1 subunit. Several W-mutants displayed significant changes in activation, fast inactivation, and/or slow inactivation gating. In particular, five S6 W-mutants showed incomplete fast inactivation with noninactivating maintained currents present. Cysteine (C) substitutions of these five residues resulted in two mutants with slightly more maintained currents. Multiple substitutions at these five positions yielded two mutants (L437C/A438W, L435W/L437C/A438W) that exhibited phenotypes with minimal fast inactivation. Unexpectedly, such inactivation-deficient mutants expressed Na(+) currents as well as did the wild-type. Furthermore, all mutants with impaired fast inactivation exhibited an enhanced slow inactivation phenotype. Implications of these results will be discussed in terms of indirect allosteric modulations via amino acid substitutions and/or a direct involvement of S6 C-termini in Na(+) channel gating.
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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.