ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 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
83 citing papers in PubMed, 161 citations in OpenAlex.
- Unveiling β Subunit-Dependent Gating Defects in CaNeuroscience bulletin · 2026Article
- Biallelic Truncating Variants in SCN3B Encoding Nav Channel Subunit β3 Lead to Neurodevelopmental Phenotype with and without Epilepsy and Ataxia.Annals of neurology · 2025Article
- NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.Journal of cell science · 2024Article
- Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion.Communications biology · 2023Article
- Dysfunctional sodium channel kinetics as a novel epilepsy mechanism in chromosome 15q11-q13 duplication syndrome.Epilepsia · 2023Article
- Concise Review: Stem Cell Models ofCells · 2022Review
- Neddylation stabilizes Nav1.1 to maintain interneuron excitability and prevent seizures in murine epilepsy models.The Journal of clinical investigation · 2021Article
- The L1624Q Variant inFrontiers in pharmacology · 2021Article
- Dravet VariantFrontiers in cellular neuroscience · 2021Article
- Nucleic Acid Aptamers for Molecular Therapy of Epilepsy and Blood-Brain Barrier Damages.Molecular therapy. Nucleic acids · 2020Review
- Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Article
- Supramolecular clustering of the cardiac sodium channel Nav1.5 in HEK293F cells, with and without the auxiliary β3-subunit.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Sexually Divergent Mortality and Partial Phenotypic Rescue After Gene Therapy in a Mouse Model of Dravet Syndrome.Human gene therapy · 2020Article
- SCN9A Epileptic Encephalopathy Mutations Display a Gain-of-function Phenotype and Distinct Sensitivity to Oxcarbazepine.Neuroscience bulletin · 2020Article
- AnFrontiers in cell and developmental biology · 2020Article
- Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review.Frontiers in pharmacology · 2020Review
- Voltage-gated sodium channel β subunits: The power outside the pore in brain development and disease.Neuropharmacology · 2018Review
- Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.Pharmacological reviews · 2018Review
- Voltage-Gated Sodium Channel β Subunits and Their Related Diseases.Handbook of experimental pharmacology · 2018Review
- Mechanisms of noncovalent β subunit regulation of NaThe Journal of general physiology · 2017Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel alpha subunit. The mutation decreased modulation of the alpha subunit by beta1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of beta1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type alpha subunit with the beta1 or beta3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for beta subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the alpha and beta1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility.
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.