ArticleNeuron2010
A nonproton ligand sensor in the acid-sensing ion channel.
Article in Neuron, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed.
- A Blood-Brain Barrier-Permeable Guanylhydrazone Analogue of the ASIC3 Activator GMQ Inhibits Human Glioblastoma Stem Cell Growth In Vitro.ChemMedChem · 2026Article
- Cannabinoid CB1 Receptor in Nociceptors Mediates Postoperative Analgesia via ASIC3 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Acid-sensing ion channels in the vasculature: emerging roles in systemic and pulmonary circulations.Pflugers Archiv : European journal of physiology · 2026Review
- Acid-sensing ion channels and their role in controlling pain in the post-operative stage.International journal of physiology, pathophysiology and pharmacology · 2026Review
- Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche.The Journal of clinical investigation · 2025Article
- Mechanism of capsaicin entry into buried vanilloid sites in TRPV1.Nature chemical biology · 2025Article
- Modulating ion channels with nanobodies.Synthetic and systems biotechnology · 2025Review
- Neuroimmunology of psoriasis: Possible roles for calcitonin gene-related peptide in its pathogenesis.Brain, behavior, & immunity - health · 2025Review
- Review
- Acid-sensing ion channel 3 is a new potential therapeutic target for the control of glioblastoma cancer stem cells growth.Scientific reports · 2024Article
- Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.Nature communications · 2024Article
- Opioid Analgesic as a Positive Allosteric Modulator of Acid-Sensing Ion Channels.International journal of molecular sciences · 2024Article
- Acid-Sensing Ion Channels' Immunoreactivity in Nerve Profiles and Glomus Cells of the Human Carotid Body.International journal of molecular sciences · 2023Article
- Structure and mechanism of a neuropeptide-activated channel in the ENaC/DEG superfamily.Nature chemical biology · 2023Article
- Cancer-nerve interplay in cancer progression and cancer-induced bone pain.Journal of bone and mineral metabolism · 2023Review
- Acid-sensing ion channel blocker diminazene facilitates proton-induced excitation of afferent nerves in a similar manner that NaFrontiers in cellular neuroscience · 2023Article
- Acid-sensing ion channel 3 is required for agmatine-induced histamine-independent itch in mice.Frontiers in molecular neuroscience · 2023Article
- Calcium regulates acid-sensing ion channel 3 activation by competing with protons in the channel pore and at an allosteric binding site.Open biology · 2022Article
- pH and proton-sensitive receptors in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Structural determinants of acid-sensing ion channel potentiation by single chain lipids.The Journal of general physiology · 2022Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid-sensing ion channels (ASICs) have long been considered as extracellular proton (H(+))-gated cation channels, and peripheral ASIC3 channels seem to be a natural sensor of acidic pain. Here, we report the identification of a nonproton sensor on ASIC3. We show first that 2-guanidine-4-methylquinazoline (GMQ) causes persistent ASIC3 channel activation at the normal pH. Using GMQ as a probe and combining mutagenesis and covalent modification analysis, we then uncovered a ligand sensor lined by residues around E423 and E79 of the extracellular "palm" domain of the ASIC3 channel that is crucial for activation by nonproton activators. Furthermore, we show that GMQ activates sensory neurons and causes pain-related behaviors in an ASIC3-dependent manner, indicating the functional significance of ASIC activation by nonproton ligands. Thus, natural ligands beyond protons may activate ASICs under physiological and pathological conditions through the nonproton ligand sensor, serving for channel activation independent of abrupt and marked acidosis.
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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.