ArticleThe Journal of physiology2004
Cooperative effect of S4-S5 loops in domains D3 and D4 on fast inactivation of the Na+ channel.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 34 citations in OpenAlex.
- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
- New phenotype of severe neonatal episodic laryngospasm due to a missense mutation in SCN4A: A case report and literature review.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Review
- The clinical and genetic heterogeneity analysis of five families with primary periodic paralysis.Channels (Austin, Tex.) · 2021Article
- Up-regulation of voltage-gated sodium channels by peptides mimicking S4-S5 linkers reveals a variation of the ligand-receptor mechanism.Scientific reports · 2020Article
- Up-regulation of voltage-gated sodium channels by peptides mimicking S4-S5 linkers reveals a variation of the ligand-receptor mechanism.Scientific reports · 2020Article
- Detection of NaBiophysical journal · 2019Article
- Novel Mutations in SCN4A Gene Cause Myotonia Congenita with Scoliosis.Chinese medical journal · 2018Article
- Distinct modulation of inactivation by a residue in the pore domain of voltage-gated NaScientific reports · 2018Article
- Mechanisms and models of cardiac sodium channel inactivation.Channels (Austin, Tex.) · 2017Review
- Sodium channelopathies of skeletal muscle result from gain or loss of function.Pflugers Archiv : European journal of physiology · 2010Review
- Mutations at opposite ends of the DIII/S4-S5 linker of sodium channel Na V 1.7 produce distinct pain disorders.Molecular pain · 2010Article
- The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na(+) channel.The Journal of general physiology · 2009Article
- Paroxysmal extreme pain disorder mutations within the D3/S4-S5 linker of Nav1.7 cause moderate destabilization of fast inactivation.The Journal of physiology · 2008Article
- Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel.Circulation research · 2008Article
- Charge immobilization of skeletal muscle Na+ channels: role of residues in the inactivation linker.Biophysical journal · 2007Article
- NA+- and K+-channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres.British journal of pharmacology · 2007Article
- Central charged residues in DIIIS4 regulate deactivation gating in skeletal muscle sodium channels.Cellular and molecular neurobiology · 2007Article
- Modeling of single noninactivating Na+ channels: evidence for two open and several fast inactivated states.Biophysical journal · 2006Article
- Cu2+ (1,10 phenanthroline)3 is an open-channel blocker of the human skeletal muscle sodium channel.British journal of pharmacology · 2006Article
- Sodium channel genes and the evolution of diversity in communication signals of electric fishes: convergent molecular evolution.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytoplasmic S4-S5 loops have been shown to be involved in fast inactivation of voltage-gated ion channels. We studied mutations in these loops and their potential cooperative effects in domains D3 (N1151C, A1152C, I1160C/A) and D4 (F1473C, L1482C/A) of the human skeletal muscle Na(+) channel alpha-subunit (hNa(v)1.4) using expression in tsA201 cells and the whole cell patch-clamp technique. All cysteine mutations were accessible to intracellularly applied sulfhydryl reagents which considerably destabilized fast inactivation. For different combinations of corresponding D3/D4 double mutations, fast inactivation could be almost completely removed. Thermodynamic cycle analysis indicated an additive effect for N1151C/F1473C and a significant cooperative effect for I1160/L1482 double mutations. Application of oxidizing reagents such as Cu-phenanthroline to link two cysteines via a disulfide bridge did not reveal evidence for a direct physical interaction of cysteines in D3 and D4. In addition to the pronounced alterations of fast inactivation, mutations of I1160 shifted steady-state activation in the hyperpolarizing direction and slowed the kinetics of both activation and deactivation. Sulfhydryl reagents had charge-dependent effects on I1160C suggesting interaction with negative charges in another protein region. We conclude that fast inactivation of the Na(+) channel involves both S4-S5 loops in D3 and D4 in a cooperative manner. D3/S4-S5 also plays an important role in activation and deactivation.
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.