ArticleCell2016
LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength.
Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers, 1 of them a synthesis that pooled it.
What it found
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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
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Who cites it
176 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.
- Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression.International journal of molecular sciences · 2023Pooled it
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.Nature communications · 2026Article
- 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
- Piezo1-mediated mechanohydraulic control of cell volume drives cardiac morphogenesis.Science advances · 2026Article
- Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators.Science (New York, N.Y.) · 2026Article
- Endothelial LRRC8C Associates With LRRC8A and LRRC8B to Regulate Vascular Reactivity and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Subunit-specific roles of LRRC8 proteins in determining glutamate permeability of astrocytic volume-regulated anion channels.American journal of physiology. Cell physiology · 2026Article
- LRRC8A: A multifaceted regulator in cancer, neurological disorders, metabolic diseases and immune modulation.Genes & diseases · 2026Review
- Review
- Mechanism of action of two potent LRRC8/VRAC channel inhibitors.Research square · 2026Article
- Article
- CD109 Drives Stemness and Chemoresistance in Colorectal Cancer via LRRC8A/AKAP12/PKCα-Mediated STAT3 Activation and WNT Signaling.International journal of biological sciences · 2026Article
- Exploring the selective inhibitory effects of Flavoxate and its analogues on two chloride channels and neuronal action potentials.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- Assembly and lipid-gating of LRRC8A:D volume-regulated anion channels.Nature communications · 2025Article
- Structural basis of PANX1 permeation and positive modulation by mefloquine.Nature communications · 2025Article
- LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LRRC8A constitutively inhibits pain hypersensitivity in rodent models by restraining NMDA receptor activity at spinal cord synapses.Science translational medicine · 2025Article
- A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.Communications biology · 2025Article
116 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The volume-regulated anion channel (VRAC) is activated when a cell swells, and it plays a central role in maintaining cell volume in response to osmotic challenges. SWELL1 (LRRC8A) was recently identified as an essential component of VRAC. However, the identity of the pore-forming subunits of VRAC and how the channel is gated by cell swelling are unknown. Here, we show that SWELL1 and up to four other LRRC8 subunits assemble into heterogeneous complexes of ∼800 kDa. When reconstituted into bilayers, LRRC8 complexes are sufficient to form anion channels activated by osmolality gradients. In bilayers, as well as in cells, the single-channel conductance of the complexes depends on the LRRC8 composition. Finally, low ionic strength (Γ) in the absence of an osmotic gradient activates the complexes in bilayers. These data demonstrate that LRRC8 proteins together constitute the VRAC pore and that hypotonic stress can activate VRAC through a decrease in cytoplasmic Γ.
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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.