ArticleNeuron2019
Glutamate-Releasing SWELL1 Channel in Astrocytes Modulates Synaptic Transmission and Promotes Brain Damage in Stroke.
Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 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
142 citing papers in PubMed, 249 citations in OpenAlex.
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 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
- Targeting the posterior thalamic hub: hemispheric-specific encoding of pain-depression comorbidity after hemorrhagic stroke.BMC medicine · 2026Article
- Microglial SWELL1 deficiency drives male-specific seizure vulnerability but paradoxical neuroprotection through impaired phagocytosis.JCI insight · 2026Article
- Ratiometric iGluSnFr imaging to assess tonic glutamate in the cerebral cortex.bioRxiv : the preprint server for biology · 2026Article
- Subunit-specific roles of LRRC8 proteins in determining glutamate permeability of astrocytic volume-regulated anion channels.American journal of physiology. Cell physiology · 2026Article
- Water channel changes in astrocytes associated with buprenorphine administration in a rat model of diffuse traumatic brain injury.Research square · 2026Article
- LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism.The Journal of physiology · 2026Article
- LRRC8A: A multifaceted regulator in cancer, neurological disorders, metabolic diseases and immune modulation.Genes & diseases · 2026Review
- Serum Amino Acid and Fatty Acid Metabolites as Predictors of Sleep Disorders in Children: A Risk Prediction Model.Biomedicines · 2026Article
- VRAC coordinates the trade-off between nutrient absorption and antimicrobial defense in enterocytes against inflammation.Nature communications · 2026Article
- LRRC8-Mediated Glutamate Release from Astrocytes Is Not Increased During the Initiation of Experimental Temporal Lobe Epilepsy.International journal of molecular sciences · 2026Article
- From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis.Frontiers in neuroscience · 2026Review
- Temporal Variability Analysis of Cortical Blood Flow in Rats with Hyperacute Cerebral Ischemia.Neuroscience bulletin · 2026Article
- Brain-gut communication and potential applications of microecological treatments in stroke.Frontiers in neuroscience · 2026Review
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- Photoactivated adenylyl cyclase in cortical astrocytes promotes synaptic potentiation and reveals alterations in Huntington's disease.iScience · 2025Article
- LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.Stroke and vascular neurology · 2025Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
By releasing glutamate, astrocytes actively regulate synaptic transmission and contribute to excitotoxicity in neurological diseases. However, the mechanisms of astrocytic glutamate release have been debated. Here, we report non-vesicular release of glutamate through the glutamate-permeable volume-regulated anion channel (VRAC). Both cell swelling and receptor stimulation activated astrocytic VRAC, which requires its only obligatory subunit, Swell1. Astrocyte-specific Swell1 knockout mice exhibited impaired glutamatergic transmission due to the decreases in presynaptic release probability and ambient glutamate level. Consistently, the mutant mice displayed hippocampal-dependent learning and memory deficits. During pathological cell swelling, deletion of astrocytic Swell1 attenuated glutamate-dependent neuronal excitability and protected mice from brain damage after ischemic stroke. Our identification of a new molecular mechanism for channel-mediated glutamate release establishes a role for astrocyte-neuron interactions in both synaptic transmission and brain ischemia. It provides a rationale for targeting VRAC for the treatment of stroke and other neurological diseases associated with excitotoxicity.
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.