ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 172 citations in OpenAlex.
- A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.The Journal of biological chemistry · 2012Trial
- Acid-sensing ion channels in ischemic stroke: amplifying and constraining neuronal injury in a phase-specific framework.Pflugers Archiv : European journal of physiology · 2026Review
- ASIC currents in cultured primate retinal rod and cone cells.Pflugers Archiv : European journal of physiology · 2026Article
- Acid-sensing ion channels as sensors of brain metabolic state.Pflugers Archiv : European journal of physiology · 2026Review
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- Acid-sensing ion channels and their role in controlling pain in the post-operative stage.International journal of physiology, pathophysiology and pharmacology · 2026Review
- ASIC currents in cultured primate retinal amacrine/ganglion cells.Physiological reports · 2025Article
- Article
- Article
- Functional characterization of acid-sensing ion channels in the cerebellum-originating medulloblastoma cell line DAOY and in cerebellar granule neurons.Pflugers Archiv : European journal of physiology · 2023Article
- Zinc activation of OTOP proton channels identifies structural elements of the gating apparatus.eLife · 2023Article
- Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial.ERJ open research · 2023Article
- The Role of Zinc in Modulating Acid-Sensing Ion Channel Function.Biomolecules · 2023Review
- Investigating role of ASIC2 in synaptic and behavioral responses to drugs of abuse.Frontiers in molecular biosciences · 2023Article
- Derivatives of 2-aminobenzimidazole potentiate ASIC open state with slow kinetics of activation and desensitization.Frontiers in physiology · 2023Article
- 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
- Acid-Sensing Ion Channel 2: Function and Modulation.Membranes · 2022Review
- Large Acid-Evoked Currents, Mediated by ASIC1a, Accompany Differentiation in Human Dopaminergic Neurons.Frontiers in cellular neuroscience · 2021Article
- Changes in HFrontiers in cellular neuroscience · 2021Article
- Histidine Residues Are Responsible for Bidirectional Effects of Zinc on Acid-Sensing Ion Channel 1a/3 Heteromeric Channels.Biomolecules · 2020Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Acid-sensing ion channels (ASICs), a novel class of ligand-gated cation channels activated by protons, are highly expressed in peripheral sensory and central neurons. Activation of ASICs may play an important role in physiological processes such as nociception, mechanosensation, and learning-memory, and in the pathology of neurological conditions such as brain ischemia. Modulation of the activities of ASICs is expected to have a significant influence on the roles that these channels can play in both physiological and/or pathological processes. Here we show that the divalent cation Zn2+, an endogenous trace element, dose-dependently inhibits ASIC currents in cultured mouse cortical neurons at nanomolar concentrations. With ASICs expressed in Chinese hamster ovary cells, Zn2+ inhibits currents mediated by homomeric ASIC1a and heteromeric ASIC1a-ASIC2a channels, without affecting currents mediated by homomeric ASIC1beta, ASIC2a, or ASIC3. Consistent with ASIC1a-specific modulation, high-affinity Zn2+ inhibition is absent in neurons from ASIC1a knock-out mice. Current-clamp recordings and Ca2+-imaging experiments demonstrated that Zn2+ inhibits acid-induced membrane depolarization and the increase of intracellular Ca2+. Mutation of lysine-133 in the extracellular domain of the ASIC1a subunit abolishes the high-affinity Zn2+ inhibition. Our studies suggest that Zn2+ may play an important role in a negative feedback system for preventing overexcitation of neurons during normal synaptic transmission and ASIC1a-mediated excitotoxicity in pathological conditions.
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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.