ArticleJournal of neurophysiology2014
Knock-in model of Dravet syndrome reveals a constitutive and conditional reduction in sodium current.
Article in Journal of neurophysiology, 2014. 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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47 citing papers in PubMed, 63 citations in OpenAlex.
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- In vitro human ion channel assays predictive of drug-induced seizure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Replication of seizure-suppressing effects of alpha-linolenic acid on themicroPublication biology · 2025Article
- Commensal bacteria exacerbate seizure-like phenotypes in Drosophila voltage-gated sodium channel mutants.Genes, brain, and behavior · 2024Article
- Enhancing the action of serotonin by three different mechanisms prevents spontaneous seizure-induced mortality in Dravet mice.Epilepsia · 2024Article
- The fruit flyFrontiers in pharmacology · 2024Article
- Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.Physiological reviews · 2023Review
- Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in theFrontiers in molecular neuroscience · 2023Article
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- Serotonin receptors in epilepsy: Novel treatment targets?Epilepsia open · 2022Review
- Generation and Characterization of theLife (Basel, Switzerland) · 2021Article
- Fly seizure EEG: field potential activity in theJournal of neurogenetics · 2021Article
- Channelopathy of Dravet Syndrome and Potential Neuroprotective Effects of Cannabidiol.Journal of central nervous system disease · 2021Review
- Persistent sodium currents inBrain communications · 2021Article
- Investigating Developmental and Epileptic Encephalopathy UsingInternational journal of molecular sciences · 2020Review
- Reduced Function of the Glutathione S-Transferase S1 Suppresses Behavioral Hyperexcitability inG3 (Bethesda, Md.) · 2020Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
Hundreds of mutations in the SCN1A sodium channel gene confer a wide spectrum of epileptic disorders, requiring efficient model systems to study cellular mechanisms and identify potential therapeutic targets. We recently demonstrated that Drosophila knock-in flies carrying the K1270T SCN1A mutation known to cause a form of genetic epilepsy with febrile seizures plus (GEFS+) exhibit a heat-induced increase in sodium current activity and seizure phenotype. To determine whether different SCN1A mutations cause distinct phenotypes in Drosophila as they do in humans, this study focuses on a knock-in line carrying a mutation that causes a more severe seizure disorder termed Dravet syndrome (DS). Introduction of the DS SCN1A mutation (S1231R) into the Drosophila sodium channel gene para results in flies that exhibit spontaneous and heat-induced seizures with distinct characteristics and lower onset temperature than the GEFS+ flies. Electrophysiological studies of GABAergic interneurons in the brains of adult DS flies reveal, for the first time in an in vivo model system, that a missense DS mutation causes a constitutive and conditional reduction in sodium current activity and repetitive firing. In addition, feeding with the serotonin precursor 5-HTP suppresses heat-induced seizures in DS but not GEFS+ flies. The distinct alterations of sodium currents in DS and GEFS+ GABAergic interneurons demonstrate that both loss- and gain-of-function alterations in sodium currents are capable of causing reduced repetitive firing and seizure phenotypes. The mutation-specific effects of 5-HTP on heat-induced seizures suggest the serotonin pathway as a potential therapeutic target for DS.
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