ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Upregulation of KCC2 activity by zinc-mediated neurotransmission via the mZnR/GPR39 receptor.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 146 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- ZIP-ZnT1 complexes mediate a local ZnCellular and molecular life sciences : CMLS · 2026Article
- Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.Psychopharmacology · 2025Article
- The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The zinc receptor, ZnR/GPR39, modulates taste sensitivity by regulating ion secretion in mouse salivary gland.iScience · 2025Article
- Loss of the zinc receptor ZnR/GPR39 in mice enhances anxiety-related behavior and motor deficits, and modulates KCC2 expression in the amygdala.Behavioral and brain functions : BBF · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- The role of zinc in the premature brain: functions, outcomes and future research perspectives.Frontiers in pediatrics · 2024Review
- The role ofJournal of pharmaceutical analysis · 2023Review
- What Are the Functions of Zinc in the Nervous System?Neurology · 2023Article
- GPR39 Knockout Worsens Microcirculatory Response to Experimental Stroke in a Sex-Dependent Manner.Translational stroke research · 2023Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission.Pharmacological reports : PR · 2023Article
- Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39.CNS neuroscience & therapeutics · 2023Review
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.Cellular and molecular life sciences : CMLS · 2023Article
- Neuronal signalling of zinc: from detection and modulation to function.Open biology · 2022Review
- The ZIP3 Zinc Transporter Is Localized to Mossy Fiber Terminals and Is Required for Kainate-Induced Degeneration of CA3 Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- SNAP23 regulates KCC2 membrane insertion and activity following mZnR/GPR39 activation in hippocampalneurons.iScience · 2022Article
- Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential.Translational neurodegeneration · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Vesicular Zn(2+) regulates postsynaptic neuronal excitability upon its corelease with glutamate. We previously demonstrated that synaptic Zn(2+) acts via a distinct metabotropic zinc-sensing receptor (mZnR) in neurons to trigger Ca(2+) responses in the hippocampus. Here, we show that physiological activation of mZnR signaling induces enhanced K(+)/Cl(-) cotransporter 2 (KCC2) activity and surface expression. As KCC2 is the major Cl(-) outward transporter in neurons, Zn(2+) also triggers a pronounced hyperpolarizing shift in the GABA(A) reversal potential. Mossy fiber stimulation-dependent upregulation of KCC2 activity is eliminated in slices from Zn(2+) transporter 3-deficient animals, which lack synaptic Zn(2+). Importantly, activity-dependent ZnR signaling and subsequent enhancement of KCC2 activity are also absent in slices from mice lacking the G-protein-coupled receptor GPR39, identifying this protein as the functional neuronal mZnR. Our work elucidates a fundamentally important role for synaptically released Zn(2+) acting as a neurotransmitter signal via activation of a mZnR to increase Cl(-) transport, thereby enhancing inhibitory tone in postsynaptic cells.
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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.