ArticleBiochemical pharmacology2016
Copper and protons directly activate the zinc-activated channel.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Structural basis of human zinc-activated channel (ZAC) signaling and modulation.Cell discovery · 2026Article
- ZACN Associated with Poor Prognosis Promotes Proliferation of Kidney Renal Clear Cell Carcinoma Cells by Inhibiting JTC801-Induced Alkaliptosis.Applied biochemistry and biotechnology · 2025Article
- Structural insights into the activation mechanism of the human zinc-activated channel.Nature communications · 2025Article
- VHH Nanobody Versatility against Pentameric Ligand-Gated Ion Channels.Journal of medicinal chemistry · 2024Review
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.British journal of pharmacology · 2023Article
- Zinc activation of OTOP proton channels identifies structural elements of the gating apparatus.eLife · 2023Article
- Evolutionary conservation of Zinc-Activated Channel (ZAC) functionality in mammals: a range of mammalian ZACs assemble into cell surface-expressed functional receptors.Frontiers in molecular biosciences · 2023Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Molecular Mingling: Multimodal Predictions of Ligand Promiscuity in Pentameric Ligand-Gated Ion Channels.Frontiers in molecular biosciences · 2022Article
- Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC).Biochemical pharmacology · 2021Article
- Discovery and functional characterization of N-(thiazol-2-yl)-benzamide analogs as the first class of selective antagonists of the Zinc-Activated Channel (ZAC).Biochemical pharmacology · 2021Article
- Delineation of the functional properties exhibited by the Zinc-Activated Channel (ZAC) and its high-frequency ThrPharmacological research · 2021Article
- Fluorescence-detection size-exclusion chromatography utilizing nanobody technology for expression screening of membrane proteins.Communications biology · 2021Article
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The zinc-activated channel (ZAC) is a cationic ion channel belonging to the superfamily of Cys-loop receptors, which consists of pentameric ligand-gated ion channels. ZAC is the least understood member of this family so in the present study we sought to characterize the properties of this channel further. We demonstrate that not only zinc (Zn(2+)) but also copper (Cu(2+)) and protons (H(+)) are agonists of ZAC, displaying potencies and efficacies in the rank orders of H(+)>Cu(2+)>Zn(2+) and H(+)>Zn(2+)>Cu(2+), respectively. The responses elicited by Zn(2+), Cu(2+) and H(+) through ZAC are all characterized by low degrees of desensitization. In contrast, currents evoked by high concentrations of the three agonists comprise distinctly different activation and decay components, with transitions to and from an open state being significantly faster for H(+) than for the two metal ions. The permeabilities of ZAC for Na(+) and K(+) relative to Cs(+) are indistinguishable, whereas replacing all of extracellular Na(+) and K(+) with the divalent cations Ca(2+) or Mg(2+) results in complete elimination of Zn(2+)-activated currents at both negative and positive holding potentials. This indicates that ZAC is non-selectively permeable to monovalent cations, whereas Ca(2+) and Mg(2+) inhibit the channel. In conclusion, this is the first report of a Cys-loop receptor being gated by Zn(2+), Cu(2+) and H(+). ZAC could be an important mediator of some of the wide range of physiological functions regulated by or involving Zn(2+), Cu(2+) and H(+).
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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.