ArticleThe Journal of physiology2014
LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 129 citations in OpenAlex.
- Large-Pore Channels at the Maternal-Fetal Interface: Progress and Open Research Avenues.Biology · 2026Review
- Binding to Albumin and Off-Target Toxicity Confound the Use of LRRC8/VRAC Channel Blockers in Cell Physiology Assays.bioRxiv : the preprint server for biology · 2026Article
- LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism.The Journal of physiology · 2026Article
- LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy.International journal of molecular sciences · 2026Article
- LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.Stroke and vascular neurology · 2025Article
- Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.The Journal of physiology · 2025Article
- Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.The Journal of physiology · 2025Review
- Molecular permeation through large pore channels: computational approaches and insights.The Journal of physiology · 2025Review
- Mechanistic insight into the initiation of spreading depolarizations: Is it really all about potassium?The Journal of physiology · 2025Article
- In silico pan-cancer analysis of VRAC subunits and their prognostic roles in human cancers.Scientific reports · 2025Article
- Disruption of Swell1/VRAC function impairs initial hemodynamics and activates compensatory leukotriene signaling in zebrafish circulation development.Frontiers in cell and developmental biology · 2025Article
- Separate mechanisms regulating accumbal taurine levels during baseline conditions and following ethanol exposure in the rat.Scientific reports · 2024Article
- Activation of osmo-sensitive LRRC8 anion channels in macrophages is important for micro-crystallin joint inflammation.Nature communications · 2024Article
- Spatiotemporally selective astrocytic ATP dynamics encode injury information sensed by microglia following brain injury in mice.Nature neuroscience · 2024Article
- Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.Aging and disease · 2024Review
- Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release.The journal of physiological sciences : JPS · 2024Review
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- Article
- Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels.Nature structural & molecular biology · 2023Article
- Conditional deletion of LRRC8A in the brain reduces stroke damage independently of swelling-activated glutamate release.iScience · 2023Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In mammals, cellular swelling activates release of small organic osmolytes, including the excitatory amino acids (EAA) glutamate and aspartate, via a ubiquitously expressed volume-regulated chloride/anion channel (VRAC). Pharmacological evidence suggests that VRAC plays plural physiological and pathological roles, including excitotoxic release of glutamate in stroke. However, the molecular identity of this pathway was unknown. Two recent studies discovered that LRRC8 gene family members encode heteromeric VRAC composed of LRRC8A plus LRRC8B-E, which mediate swelling-activated Cl(-) currents and taurine release in human non-neural cells (Z. Qiu et al. Cell 157: 447, 2014; F.K. Voss et al. Science 344: 634, 2014). Here, we tested the contribution of LRRC8A to the EAA release in brain glia. We detected and quantified expression levels of LRRC8A-E in primary rat astrocytes with quantitative RT-PCR and then downregulated LRRC8A with gene-specific siRNAs. In astrocytes exposed to hypo-osmotic media, LRRC8A knockdown dramatically reduced swelling-activated release of the EAA tracer D-[(3)H]aspartate. In parallel HPLC assays, LRRC8A siRNA prevented hypo-osmotic media-induced loss of the endogenous intracellular L-glutamate and taurine. Furthermore, downregulation of LRRC8A completely ablated the ATP-stimulated release of D-[(3)H]aspartate and [(14)C]taurine from non-swollen astrocytes. Overall, these data indicate that LRRC8A is an indispensable component of a permeability pathway that mediates both swelling-activated and agonist-induced amino acid release in brain glial cells.
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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.