ArticleThe Journal of physiology2001
Blocking swelling-activated chloride current inhibits mouse liver cell proliferation.
Article in The Journal of physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 129 citations in OpenAlex.
- 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
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC).Channels (Austin, Tex.) · 2022Review
- How Dysregulated Ion Channels and Transporters Take a Hand in Esophageal, Liver, and Colorectal Cancer.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Review
- NPPB prevents postoperative peritoneal adhesion formation by blocking volume-activated ClNaunyn-Schmiedeberg's archives of pharmacology · 2020Article
- The Volume-Regulated Anion Channel LRRC8/VRAC Is Dispensable for Cell Proliferation and Migration.International journal of molecular sciences · 2019Article
- A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel.The Journal of general physiology · 2019Review
- ClC5 Decreases the Sensitivity of Multiple Myeloma Cells to Bortezomib via Promoting Prosurvival Autophagy.Oncology research · 2018Article
- Downregulation of Leucine-Rich Repeat-Containing 8A Limits Proliferation and Increases Sensitivity of Glioblastoma to Temozolomide and Carmustine.Frontiers in oncology · 2018Article
- Study on the role of transient receptor potential C6 channels in esophageal squamous cell carcinoma radiosensitivity.Journal of thoracic disease · 2017Article
- Ion channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration.Mechanisms of development · 2017Article
- LRRC8A channels support TNFα-induced superoxide production by Nox1 which is required for receptor endocytosis.Free radical biology & medicine · 2016Article
- Bioelectrical regulation of cell cycle and the planarian model system.Biochimica et biophysica acta · 2015Review
- Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance.Channels (Austin, Tex.) · 2015Review
- Low-voltage-activated T-type Ca2+ channel inhibitors as new tools in the treatment of glioblastoma: the role of endostatin.Pflugers Archiv : European journal of physiology · 2014Review
- Expression patterns of As-ClC gene of Artemia sinica in early development and under salinity stress.Molecular biology reports · 2013Article
- Cell volume regulation in epithelial physiology and cancer.Frontiers in physiology · 2013Review
- DCPIB, a specific inhibitor of volume-regulated anion channels (VRACs), inhibits astrocyte proliferation and cell cycle progression via G1/S arrest.Journal of molecular neuroscience : MN · 2012Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A non-transformed mouse liver cell line (AML12) was used to show that blocking swelling-activated membrane Cl- current inhibits hepatocyte proliferation. Two morphologically distinguishable cell populations exhibited distinctly different responses to hypotonic stress. Hypotonic stress (from 280 to 221 mosmol kg(-1)) to rounded, dividing cells activated an ATP-dependent, outwardly rectifying, whole-cell Cl- current, which took 10 min to reach maximum conductance. A similar anionic current was present spontaneously in 20 % of the dividing cells. Hypotonic stress to flattened, non-dividing cells activated no additional current. The Eisenman halide permeability sequence of swelling-activated anionic current in the dividing cells was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate. Addition of either 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), tamoxifen or mibefradil inhibited swelling-activated anionic current. Hyperosmolarity by added sucrose inhibited the spontaneous anionic current in dividing cells. Added Cl- channel blockers NPPB (IC50 = 40 microM), DIDS (IC50 = 31 microM), tamoxifen (IC50 = 1.3 microM) and mibefradil (IC50 = 7 microM) inhibited proliferative growth of AML12 as determined by cell counts over 4 days or by protein accumulation over 2 days. Only the inhibitory effects of NPPB and mibefradil reversed with the drug washout. Hyperosmolarity by added sucrose (50 and 100 mM) also inhibited cell proliferation. Of the hydrophobic inhibitors neither NPPB at 40 microM nor tamoxifen at 1.3 microM, added for 48 h, reduced cellular ATP; however, DIDS at 31 microM significantly reduced cellular ATP with an equivalent increase in cellular ADP. We conclude that those membrane Cl- currents that can be activated by hypotonic stress are involved in mechanisms controlling liver cell growth, and that NPPB, tamoxifen and mibefradil at their IC50 for growth do not suppress the metabolism of mouse hepatocytes.
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