ArticleNeurobiology of disease2015
Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 84 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- Enhanced expression of spinal PTP1B contributes to peripheral inflammation- induced glycinergic disinhibition and mechanical pain.Communications biology · 2026Article
- Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.Psychopharmacology · 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
- Article
- 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
- Animal Models of Hypertension (ISIAH Rats), Catatonia (GC Rats), and Audiogenic Epilepsy (PM Rats) Developed by Breeding.Biomedicines · 2023Review
- Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39.CNS neuroscience & therapeutics · 2023Review
- The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission.Pharmacological reports : PR · 2023Article
- 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
- Article
- Neuronal signalling of zinc: from detection and modulation to function.Open biology · 2022Review
- Article
- Control of coronary vascular resistance by eicosanoids via a novel GPCR.American journal of physiology. Cell physiology · 2022Article
- 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
- Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons CulturedFrontiers in aging neuroscience · 2022Article
- Activation of GPR39 with TC-G 1008 attenuates neuroinflammation via SIRT1/PGC-1α/Nrf2 pathway post-neonatal hypoxic-ischemic injury in rats.Journal of neuroinflammation · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor mZnR/GPR39 in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of mZnR/GPR39 enhances inhibitory drive in the hippocampus by upregulating neuronal K(+)/Cl(-) co-transporter 2 (KCC2) activity. Here, we first show that mZnR/GPR39 knockout (KO) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type (WT) littermates. Kainate also substantially enhances seizure-associated gamma oscillatory activity in juvenile mZnR/GPR39 KO hippocampal slices, a phenomenon that can be reproduced in WT tissue by extracellular Zn(2+) chelation. Importantly, kainate-induced synaptic Zn(2+) release enhances surface expression and transport activity of KCC2 in WT, but not mZnR/GPR39 KO hippocampal neurons. Kainate-dependent upregulation of KCC2 requires mZnR/GPR39 activation of the Gαq/phospholipase C/extracellular regulated kinase (ERK1/2) signaling cascade. We suggest that mZnR/GPR39-dependent upregulation of KCC2 activity provides homeostatic adaptation to an excitotoxic stimulus by increasing inhibition. As such, mZnR/GPR39 may provide a novel pharmacological target for dampening epileptic seizure activity.
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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.