ArticleThe Journal of biological chemistry2009
Isolation and characterization of a high affinity peptide inhibitor of ClC-2 chloride channels.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Properties and Pharmacology of Scorpion Toxins and Their Biotechnological Potential in Agriculture and Medicine.Toxins · 2025Review
- Biophysical and Pharmacological Insights to CLC Chloride Channels.Handbook of experimental pharmacology · 2024Article
- Diagnostic and Therapeutic Approaches for Glioblastoma and Neuroblastoma Cancers Using Chlorotoxin Nanoparticles.Cancers · 2023Review
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- Peptides with Diverse Functions from Scorpion Venom: A Great Opportunity for the Treatment of a Wide Variety of Diseases.Iranian biomedical journal · 2023Article
- Pharmacological modulation of chloride channels as a therapeutic strategy for neurological disorders.Frontiers in physiology · 2023Review
- ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease.Journal of molecular neuroscience : MN · 2021Article
- Development and validation of a potent and specific inhibitor for the CLC-2 chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Evasion of a Human Cytomegalovirus Entry Inhibitor with Potent Cysteine Reactivity Is Concomitant with the Utilization of a Heparan Sulfate Proteoglycan-Independent Route of Entry.Journal of virology · 2020Article
- A Novel Loss-of-Function Variant in the Chloride Ion Channel Gene Clcn2 Associates with Atrial Fibrillation.Scientific reports · 2020Article
- Venoms of Iranian Scorpions (Arachnida, Scorpiones) and Their Potential for Drug Discovery.Molecules (Basel, Switzerland) · 2019Review
- A selective class of inhibitors for the CLC-Ka chloride ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Venom-based peptide therapy: insights into anti-cancer mechanism.Oncotarget · 2017Review
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Chloride channel ClC- 2 enhances intestinal epithelial tight junction barrier function via regulation of caveolin-1 and caveolar trafficking of occludin.Experimental cell research · 2017Article
- Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion.Toxins · 2015Review
- Chloride channelopathies of ClC-2.International journal of molecular sciences · 2013Review
- The Concise Guide to PHARMACOLOGY 2013/14: ion channels.British journal of pharmacology · 2013Article
- Regulation of ClC-2 gating by intracellular ATP.Pflugers Archiv : European journal of physiology · 2013Article
- Novel diuretic targets.American journal of physiology. Renal physiology · 2013Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The ClC protein family includes voltage-gated chloride channels and chloride/proton exchangers. In eukaryotes, ClC proteins regulate membrane potential of excitable cells, contribute to epithelial transport, and aid in lysosomal acidification. Although structure/function studies of ClC proteins have been aided greatly by the available crystal structures of a bacterial ClC chloride/proton exchanger, the availability of useful pharmacological tools, such as peptide toxin inhibitors, has lagged far behind that of their cation channel counterparts. Here we report the isolation, from Leiurus quinquestriatus hebraeus venom, of a peptide toxin inhibitor of the ClC-2 chloride channel. This toxin, GaTx2, inhibits ClC-2 channels with a voltage-dependent apparent K(D) of approximately 20 pm, making it the highest affinity inhibitor of any chloride channel. GaTx2 slows ClC-2 activation by increasing the latency to first opening by nearly 8-fold but is unable to inhibit open channels, suggesting that this toxin inhibits channel activation gating. Finally, GaTx2 specifically inhibits ClC-2 channels, showing no inhibitory effect on a battery of other major classes of chloride channels and voltage-gated potassium channels. GaTx2 is the first peptide toxin inhibitor of any ClC protein. The high affinity and specificity displayed by this toxin will make it a very powerful pharmacological tool to probe ClC-2 structure/function.
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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.