ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Distinct subunits in heteromeric kainate receptors mediate ionotropic and metabotropic function at hippocampal mossy fiber synapses.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 148 citations in OpenAlex.
- Loss of presenilin 2 function age-dependently increases susceptibility to kainate-induced acute seizures and blunts hippocampal kainate-type glutamate receptor expression.Experimental neurology · 2026Article
- Activation of kainate receptor GluK2-Neto2 complex.Nature structural & molecular biology · 2025Article
- Loss of presenilin 2 function age-dependently increases susceptibility to kainate-induced acute seizures and blunts hippocampal kainate-type glutamate receptor expression.bioRxiv : the preprint server for biology · 2025Article
- GluK1 kainate receptors are necessary for functional maturation of parvalbumin interneurons regulating amygdala circuit function.Molecular psychiatry · 2024Article
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
- Behavioral analysis of kainate receptor KO mice and the role of GluK3 subunit in anxiety.Scientific reports · 2024Article
- The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2.Experimental physiology · 2024Review
- GluK2 Q/R editing regulates kainate receptor signaling and long-term potentiation of AMPA receptors.iScience · 2023Article
- Activation of Extrasynaptic Kainate Receptors Drives Hilar Mossy Cell Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Olfactory rule learning-induced enhancement in intrinsic neuronal excitability is maintained by shutdown of the cholinergic M-current.Frontiers in cellular neuroscience · 2022Article
- Pathological Human Tau Induces Alterations in the Brain Insulin Signaling Cascade.Frontiers in neuroscience · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- The Role of Glutamate in Language and Language Disorders - Evidence from ERP and Pharmacologic Studies.Neuroscience and biobehavioral reviews · 2020Review
- Kainate receptors regulate development of glutamatergic synaptic circuitry in the rodent amygdala.eLife · 2020Article
- The glutamate receptor GluK2 contributes to the regulation of glucose homeostasis and its deterioration during aging.Molecular metabolism · 2019Article
- Stereotypical patterns of epileptiform calcium signal in hippocampal CA1, CA3, dentate gyrus and entorhinal cortex in freely moving mice.Scientific reports · 2019Article
- Ionotropic and metabotropic kainate receptor signalling regulates ClThe Journal of physiology · 2019Article
- Ca2+ Signals in Astrocytes Facilitate Spread of Epileptiform Activity.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- The Role of Kainate Receptors in the Pathophysiology of Hypoxia-Induced Seizures in the Neonatal Mouse.Scientific reports · 2018Article
- Kainate Receptors Inhibit Glutamate Release Via Mobilization of Endocannabinoids in Striatal Direct Pathway Spiny Projection Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
3 more citing papers are in PubMed but not listed here.
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5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heteromeric kainate receptors (KARs) containing both glutamate receptor 6 (GluR6) and KA2 subunits are involved in KAR-mediated EPSCs at mossy fiber synapses in CA3 pyramidal cells. We report that endogenous glutamate, by activating KARs, reversibly inhibits the slow Ca2+-activated K+ current I(sAHP) and increases neuronal excitability through a G-protein-coupled mechanism. Using KAR knockout mice, we show that KA2 is essential for the inhibition of I(sAHP) in CA3 pyramidal cells by low nanomolar concentrations of kainate, in addition to GluR6. In GluR6(-/-) mice, both ionotropic synaptic transmission and inhibition of I(sAHP) by endogenous glutamate released from mossy fibers was lost. In contrast, inhibition of I(sAHP) was absent in KA2(-/-) mice despite the preservation of KAR-mediated EPSCs. These data indicate that the metabotropic action of KARs did not rely on the activation of a KAR-mediated inward current. Biochemical analysis of knock-out mice revealed that KA2 was required for the interaction of KARs with Galpha(q/11)-proteins known to be involved in I(sAHP) modulation. Finally, the ionotropic and metabotropic actions of KARs at mossy fiber synapses were differentially sensitive to the competitive glutamate receptor ligands kainate (5 nM) and kynurenate (1 mM). We propose a model in which KARs could operate in two modes at mossy fiber synapses: through a direct ionotropic action of GluR6, and through an indirect G-protein-coupled mechanism requiring the binding of glutamate to KA2.
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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.