ArticleThe Journal of biological chemistry2011
Alternative splicing modulates inactivation of type 1 voltage-gated sodium channels by toggling an amino acid in the first S3-S4 linker.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Case-control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B and epilepsy.Human genetics · 2014Pooled it
- Alternative splicing in voltage-gated sodium channels: mechanisms, regulatory networks and therapeutic implications.Annals of medicine · 2026Review
- Voltage-Gated Sodium Channel Dysfunction in Epilepsy: Zebrafish Models for Therapeutics.Biomedicines · 2025Review
- Imperatives and co-benefits of research into climate change and neurological disease.Nature reviews. Neurology · 2025Review
- The Influence of Climatic Factors on the Provocation of Epileptic Seizures.Journal of clinical medicine · 2024Article
- Development of automated patch clamp assays to overcome the burden of variants of uncertain significance in inheritable arrhythmia syndromes.Frontiers in physiology · 2023Review
- Spliced isoforms of the cardiac Nav1.5 channel modify channel activation by distinct structural mechanisms.The Journal of general physiology · 2022Article
- Climate change and epilepsy: Insights from clinical and basic science studies.Epilepsy & behavior : E&B · 2021Review
- Transcriptome Analysis Reveals Higher Levels of Mobile Element-Associated Abnormal Gene Transcripts in Temporal Lobe Epilepsy Patients.Frontiers in genetics · 2021Article
- Transcranial magnetic stimulation as a tool to understand genetic conditions associated with epilepsy.Epilepsia · 2020Review
- SCN1A and SCN2A polymorphisms are associated with response to valproic acid in Chinese epilepsy patients.European journal of clinical pharmacology · 2019Article
- Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.Lancet (London, England) · 2018Article
- Distribution and function of voltage-gated sodium channels in the nervous system.Channels (Austin, Tex.) · 2017Review
- Conservation of alternative splicing in sodium channels reveals evolutionary focus on release from inactivation and structural insights into gating.The Journal of physiology · 2017Article
- De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis.Epilepsy research · 2017Article
- Alternatively Spliced Isoforms of KV10.1 Potassium Channels Modulate Channel Properties and Can Activate Cyclin-dependent Kinase in Xenopus Oocytes.The Journal of biological chemistry · 2015Article
- Seizure suppression through manipulating splicing of a voltage-gated sodium channel.Brain : a journal of neurology · 2015Article
- Regulation of membrane excitability: a convergence on voltage-gated sodium conductance.Molecular neurobiology · 2015Review
- Article
- Cortical inhibition, pH and cell excitability in epilepsy: what are optimal targets for antiepileptic interventions?The Journal of physiology · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Voltage-gated sodium channels underlie the upstroke of action potentials and are fundamental to neuronal excitability. Small changes in the behavior of these channels are sufficient to change neuronal firing and trigger seizures. These channels are subject to highly conserved alternative splicing, affecting the short linker between the third transmembrane segment (S3) and the voltage sensor (S4) in their first domain. The biophysical consequences of this alternative splicing are incompletely understood. Here we focus on type 1 sodium channels (Nav1.1) that are implicated in human epilepsy. We show that the functional consequences of alternative splicing are highly sensitive to recording conditions, including the identity of the major intracellular anion and the recording temperature. In particular, the inactivation kinetics of channels containing the alternate exon 5N are more sensitive to intracellular fluoride ions and to changing temperature than channels containing exon 5A. Moreover, Nav1.1 channels containing exon 5N recover from inactivation more rapidly at physiological temperatures. Three amino acids differ between exons 5A and 5N. However, the changes in sensitivity and stability of inactivation were reproduced by a single conserved change from aspartate to asparagine in channels containing exon 5A, which was sufficient to make them behave like channels containing the complete exon 5N sequence. These data suggest that splicing at this site can modify the inactivation of sodium channels and reveal a possible interaction between splicing and anti-epileptic drugs that stabilize sodium channel inactivation.
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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.