ArticleThe Journal of physiology2017
Subunit-dependent oxidative stress sensitivity of LRRC8 volume-regulated anion channels.
Article in The Journal of physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 62 citations in OpenAlex.
- Sphingosine-1-phosphate activates IJournal of molecular and cellular cardiology · 2026Article
- LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Excitotoxic neuronal death requires superoxide entry into neurons through volume-regulated anion channels.Science advances · 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
- In silico pan-cancer analysis of VRAC subunits and their prognostic roles in human cancers.Scientific reports · 2025Article
- 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
- Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- LRRC8A promotesVirulence · 2023Article
- Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022.Frontiers in pharmacology · 2023Article
- A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC).Channels (Austin, Tex.) · 2022Review
- Lysosomal solute and water transport.The Journal of cell biology · 2022Review
- Molecular determinants underlying volume-regulated anion channel subunit-dependent oxidation sensitivity.The Journal of physiology · 2022Article
- Structure-function relationships of the LRRC8 subunits and subdomains of the volume-regulated anion channel (VRAC).Frontiers in cellular neuroscience · 2022Review
- Genome-wide analysis reveals associations between climate and regional patterns of adaptive divergence and dispersal in American pikas.Heredity · 2021Article
- On the molecular nature of large-pore channels.Journal of molecular biology · 2021Review
- TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase.International journal of molecular sciences · 2021Article
- Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1.The Journal of physiology · 2021Article
- Zinc pyrithione activates the volume-regulated anion channel through an antioxidant-sensitive mechanism.American journal of physiology. Cell physiology · 2021Article
- LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.American journal of physiology. Cell physiology · 2021Article
Corrections and comments
- Commented on by
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
key pointsSwelling-activated anion currents are modulated by oxidative conditions, but it is unknown if oxidation acts directly on the LRRC8 channel-forming proteins or on regulatory factors. We found that LRRC8A-LRRC8E heteromeric channels are dramatically activated by oxidation of intracellular cysteines, whereas LRRC8A-LRRC8C and LRRC8A-LRRC8D heteromers are inhibited by oxidation. Volume-regulated anion currents in Jurkat T lymphocytes were inhibited by oxidation, in agreement with a low expression of the LRRC8E subunit in these cells. Our results show that LRRC8 channel proteins are directly modulated by oxidation in a subunit-specific manner. ABSTRACT: The volume-regulated anion channel (VRAC) is formed by heteromers of LRRC8 proteins containing the essential LRRC8A subunit and at least one among the LRRC8B-E subunits. Reactive oxygen species (ROS) play physiological and pathophysiological roles and VRAC channels are highly ROS sensitive. However, it is unclear if ROS act directly on the channels or on molecules involved in the activation pathway. We used fluorescently tagged LRRC8 proteins that yield large constitutive currents to test direct effects of oxidation. We found that 8A/8E heteromers are dramatically potentiated (more than 10-fold) by oxidation of intracellular cysteine residues by chloramine-T or tert-butyl hydroperoxide. Oxidation was, however, not necessary for hypotonicity-induced activation. In contrast, 8A/8C and 8A/8D heteromers were strongly inhibited by oxidation. Endogenous VRAC currents in Jurkat T lymphocytes were similarly inhibited by oxidation, in agreement with the finding that LRRC8C and LRRC8D subunits were more abundantly expressed than LRRC8E in Jurkat cells. Our results show that LRRC8 channels are directly modulated by oxidation in a subunit-dependent manner.
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.