ArticlePloS one2014
Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Individuals with reported and novel KDM5C variants present with seizures, a feature recapitulated in a Drosophila model.Human molecular genetics · 2026Article
- Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate KFEBS open bio · 2025Article
- Unanticipated domain requirements for Drosophila Wnk kinase in vivo.PLoS genetics · 2023Article
- SIK3 and Wnk converge on Fray to regulate glial K+ buffering and seizure susceptibility.PLoS genetics · 2023Article
- Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.Nutrients · 2022Review
- Chloride oscillation in pacemaker neurons regulates circadian rhythms through a chloride-sensing WNK kinase signaling cascade.Current biology : CB · 2022Article
- Bidirectional regulation of glial potassium buffering - glioprotection versus neuroprotection.eLife · 2021Article
- Investigating rare and ultrarare epilepsy syndromes withFaculty reviews · 2021Review
- AeLife · 2020Article
- Wrapping glia regulates neuronal signaling speed and precision in the peripheral nervous system of Drosophila.Nature communications · 2020Article
- Investigating Developmental and Epileptic Encephalopathy UsingInternational journal of molecular sciences · 2020Review
- SIK3 suppresses neuronal hyperexcitability by regulating the glial capacity to buffer KThe Journal of cell biology · 2019Article
- The Drosophila ERG channel seizure plays a role in the neuronal homeostatic stress response.PLoS genetics · 2019Article
- The glial sodium-potassium-2-chloride cotransporter is required for synaptic transmission in the Drosophila visual system.Scientific reports · 2019Article
- Investigation of Seizure-Susceptibility in aGenetics · 2017Article
- TRAP-seq Profiling and RNAi-Based Genetic Screens Identify Conserved Glial Genes Required for Adult Drosophila Behavior.Frontiers in molecular neuroscience · 2016Article
- Drosophila sodium channel mutations: Contributions to seizure-susceptibility.Experimental neurology · 2015Review
- Disruption of Endocytosis with the Dynamin Mutant shibirets1 Suppresses Seizures in Drosophila.Genetics · 2015Article
- K-Cl cotransporters, cell volume homeostasis, and neurological disease.Trends in molecular medicine · 2015Review
- Glial cell regulation of rhythmic behavior.Methods in enzymology · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.
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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.