Affinage

GRIK1

Glutamate receptor ionotropic, kainate 1 · UniProt P39086

Length
918 aa
Mass
104.0 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIK1 (GluK1/GluR5) encodes a kainate-type ionotropic glutamate receptor subunit that assembles as homomers or heteromers with GluK2, GluK3, and KA2 to form ligand-gated cation channels with distinct gating and desensitization properties, and additionally signals metabotropically through direct interaction with Goα proteins via its C-terminal domain (PMID:1977421, PMID:10493729, PMID:25834043). Channel function is shaped by RNA editing at the Q/R site—which requires an intronic complementary sequence and reduces current density approximately sixfold—by alternative C-terminal splicing that controls ER retention through an Arg-896-dependent signal modulated by phosphorylation, and by auxiliary subunits NETO1 and NETO2 that oppositely tune desensitization kinetics and drive GluK1 selectively to silent synapses (PMID:8700852, PMID:10516295, PMID:14527949, PMID:26720915). Across brain regions including hippocampus, amygdala, anterior cingulate cortex, and spinal cord, GluK1-containing receptors on interneurons and presynaptic terminals modulate both excitatory and inhibitory transmission—most prominently by depolarizing GABAergic interneurons to increase tonic inhibitory tone onto principal neurons—and contribute to nociceptive processing, gamma oscillation regulation, and neuroprotection against ischemia (PMID:9335499, PMID:10196544, PMID:15509753, PMID:15673679, PMID:18678878). Structural studies reveal a ligand-binding cavity 40% larger than AMPA receptors, with Ser741 forming a critical interdomain bridge that confers selectivity for bulky kainate-selective agonists such as ATPA, and antagonists inducing a novel hyperextended conformation distinct from other glutamate receptors (PMID:15721240, PMID:15710405, PMID:12488532, PMID:16540562).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 High

    Cloning of GluR5 established that GRIK1 encodes a glutamate receptor subunit capable of forming functional homomeric ion channels, placing it in a distinct kainate receptor subfamily separate from AMPA receptors.

    Evidence cDNA cloning and electrophysiology in Xenopus oocytes

    PMID:1977421

    Open questions at the time
    • Homomeric channels responded weakly to glutamate, leaving native subunit composition unknown
    • No information on in vivo expression pattern or synaptic function
  2. 1996 High

    Identification of the intronic editing site complementary sequence required for Q/R site RNA editing revealed how a post-transcriptional modification alters GluK1 channel properties, resolving how editing specificity is achieved.

    Evidence Minigene transfection in PC-12 and HEK293 cells with transcript analysis

    PMID:8700852

    Open questions at the time
    • The enzyme responsible (ADAR) was coexpressed but isoform specificity not resolved
    • Functional consequences of editing on native neuronal channels not yet measured
  3. 1997 High

    Heteromeric assembly of GluK1 with KA-2 was demonstrated in trigeminal ganglion neurons, and structure-function mutagenesis identified specific residues (N721, A689) controlling agonist sensitivity and desensitization, establishing that native kainate receptors are heteromers with distinct gating determinants.

    Evidence Chimeric/point-mutant electrophysiology in oocytes/HEK cells; RT-PCR and patch-clamp in trigeminal ganglion neurons

    PMID:9254673 PMID:9354337

    Open questions at the time
    • Heteromeric stoichiometry not determined
    • Whether these residues control gating in intact tetrameric receptors remained unclear
  4. 1997 High

    Pharmacological isolation of GluK1-mediated modulation of GABAergic transmission in hippocampal CA1 first demonstrated a circuit-level function: GluK1 activation on interneurons regulates inhibitory tone and may underlie kainate's epileptogenic effects.

    Evidence Hippocampal slice electrophysiology with selective GluK1 agonist ATPA and antagonist LY294486

    PMID:9335499

    Open questions at the time
    • Whether GluK1 acted pre- or postsynaptically on interneurons was not resolved
    • Contribution relative to GluK2-containing receptors remained unclear
  5. 1998 High

    The cellular mechanism for GluK1's circuit role was resolved: GluK1 activation directly depolarizes CA1 interneurons causing repetitive firing and massive tonic GABAergic inhibition of pyramidal neurons, while presynaptic GluK1 also depresses excitatory transmission in hippocampus and mediates postsynaptic currents in the basolateral amygdala.

    Evidence Whole-cell patch-clamp in hippocampal and BLA slices with selective pharmacology; paired-pulse analysis

    PMID:10196544 PMID:9849664 PMID:9849665

    Open questions at the time
    • Whether amygdala and hippocampal GluK1 receptors have identical subunit compositions was unknown
    • Metabotropic signaling component not yet suspected
  6. 1999 High

    GluK1 was shown to promiscuously coassemble with GluK2 and GluK3, producing heteromers with altered desensitization; separately, Q/R site editing was shown to reduce native DRG kainate current density sixfold in knock-in mice, quantifying editing's physiological impact.

    Evidence Coexpression in Xenopus oocytes with rectification analysis; GluR5(R) knock-in mice with DRG patch-clamp

    PMID:10493729 PMID:10516295

    Open questions at the time
    • Behavioral consequences of reduced DRG current were minimal, leaving the in vivo purpose of editing uncertain
    • Native heteromer combinations in specific brain regions not mapped
  7. 2003 High

    Multiple trafficking and selectivity mechanisms were resolved: an ER retention signal at Arg-896 in the GluK1-2b splice variant controls surface expression via phosphorylation at Thr-898; Ser741 was identified as the critical residue conferring GluK1 selectivity for the agonist ATPA; and GluK1 in the BLA was shown to modulate interneuron excitability and anxiety-related behavior.

    Evidence Mutagenesis with surface biotinylation; oocyte electrophysiology of point mutants; BLA recordings in knockout mice with behavioral assays

    PMID:12091575 PMID:12488532 PMID:14527949 PMID:17245443

    Open questions at the time
    • Kinase responsible for Thr-898 phosphorylation not identified
    • Whether ER retention mechanism operates in all neuron types unknown
  8. 2005 High

    Crystal structures of the GluK1 ligand-binding domain revealed a 40% larger binding cavity than AMPA receptors, with Ser741 mediating an interdomain water network and a novel dimer interface, providing the atomic basis for kainate receptor agonist selectivity and explaining prior mutagenesis results.

    Evidence X-ray crystallography at 1.95 Å resolution with multiple ligands

    PMID:15710405 PMID:15721240

    Open questions at the time
    • Full-length receptor structure not available
    • No structural insight into desensitization or heteromeric assemblies
  9. 2005 High

    Genetic dissociation of GluK1 versus GluK2 functions showed that GluK1 loss increases susceptibility to kainate-induced epileptiform activity and reduces inflammatory/capsaicin pain responses without affecting fear memory, defining subunit-specific behavioral roles.

    Evidence GluK1 and GluK2 knockout mice with gamma oscillation recordings, pain assays, and fear conditioning

    PMID:15509753 PMID:15673679

    Open questions at the time
    • Compensatory changes in knockout mice not assessed
    • Circuit mechanism linking GluK1 loss to increased seizure susceptibility not fully explained
  10. 2006 High

    A novel antagonist binding mechanism was revealed structurally—GluK1-selective antagonists UBP302/UBP310 do not contact E723, causing hyperextension of the binding core—while presynaptic GluK1 on spinal inhibitory terminals was shown to facilitate GABA/glycine release.

    Evidence X-ray crystallography of antagonist complexes; spinal cord slice electrophysiology with GluK1 knockout mice

    PMID:16540562 PMID:16948848

    Open questions at the time
    • Whether the hyperextended conformation represents the resting or a distinct inhibited state is unclear
    • Mechanism coupling presynaptic GluK1 activation to vesicle release not defined
  11. 2008 Medium

    GluK1 was found to signal metabotropically on myelinated axons through a pertussis toxin-sensitive G-protein/PLC/IP3 pathway coupled to nNOS, and GluK1-mediated neuroprotection against ischemia was linked to enhanced GABA release that attenuates NMDA receptor signaling via Src kinase inhibition.

    Evidence Confocal Ca²⁺ imaging and co-immunoprecipitation in dorsal column axons; in vivo ischemia model with antisense knockdown and pharmacology

    PMID:18678878 PMID:19224531

    Open questions at the time
    • nNOS interaction demonstrated by single co-IP without reciprocal validation
    • Neuroprotection pathway characterized in a single lab
    • Whether axonal metabotropic signaling occurs at physiological glutamate concentrations unknown
  12. 2011 High

    NETO2 was identified as an auxiliary subunit that profoundly slows GluK1 desensitization and promotes surface/synaptic targeting, while NETO1 accelerates desensitization, establishing auxiliary proteins as major determinants of GluK1 gating diversity.

    Evidence Patch-clamp in heterologous cells and transfected hippocampal neurons with immunofluorescence

    PMID:21593317

    Open questions at the time
    • Stoichiometry of NETO-GluK1 complexes unknown
    • Whether NETO proteins differentially affect heteromeric versus homomeric GluK1 receptors not tested
  13. 2015 High

    GluK1 was shown to be selectively incorporated into silent synapses (lacking AMPA receptors) in a NETO-dependent manner, with NETO-driven synaptic targeting mechanistically separable from surface trafficking; simultaneously, GluK1 was found to directly activate Goα via its C-terminal domain, establishing dual ionotropic/metabotropic signaling.

    Evidence Null-background hippocampal CA1 neuron rescue system with lentiviral expression; proteomics, BRET assays, and co-IP validated in GluK1 knockout mice

    PMID:25834043 PMID:26720915

    Open questions at the time
    • Downstream effectors of Goα activated by GluK1 not identified
    • Whether metabotropic and ionotropic signaling occur at the same synapses is unknown
    • Molecular mechanism selecting GluK1 for silent synapses not defined
  14. 2018 High

    The cleaved signal peptide of GluK1 was discovered to interact in trans with the amino-terminal domain to repress forward trafficking, revealing a unique post-cleavage regulatory mechanism that limits GluK1 surface and synaptic expression.

    Evidence Chimeric receptor strategies with EPSC recordings in hippocampal CA1 neurons

    PMID:30451858

    Open questions at the time
    • How the cleaved signal peptide is retained and recycled is unknown
    • Whether this mechanism is regulated by neuronal activity not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length receptor structure (especially of heteromeric assemblies), the identity of downstream effectors of GluK1-Goα metabotropic signaling, the kinase(s) regulating ER exit via Thr-898 phosphorylation, and how GluK1 is selectively excluded from AMPA receptor-containing synapses at the molecular level.
  • No full-length GluK1 cryo-EM or crystal structure available
  • Goα pathway downstream of GluK1 activation uncharacterized
  • Kinase for Thr-898 not identified
  • Molecular basis for silent synapse selectivity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0005215 transporter activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-112316 Neuronal System 9 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2
Partners
GNAO1GRIA5GRIK2GRIK3NETO1NETO2NOS1
Complex memberships
GluK1 homomeric kainate receptorGluK1/GluK2 heteromeric kainate receptorGluK1/KA-2 heteromeric kainate receptor

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 GluR5 (GRIK1) encodes a glutamate receptor subunit that forms homomeric ion channels when expressed in Xenopus oocytes, responding weakly to L-glutamate; it shares ~40-41% amino acid identity with AMPA/kainate receptor subunits GluR1-4, placing it in a distinct kainate receptor subfamily. Xenopus oocyte expression, electrophysiology, cDNA cloning Neuron High 1977421
1996 RNA editing at the Q/R site of GluR5 pre-mRNA requires base pairing with an intronic editing site complementary sequence (ECS) located up to 1900 nucleotides distal to the Q/R site; double-stranded RNA adenosine deaminase preferentially targets the Q/R site adenosine when coexpressed in HEK293 cells. Minigene transfection in PC-12 cells, HEK293 coexpression, transcript analysis Proceedings of the National Academy of Sciences of the United States of America High 8700852
1997 GluR5 subunit-containing kainate receptors regulate GABAergic inhibitory synaptic transmission in hippocampal CA1, as shown by selective agonist ATPA and antagonist LY294486; this modulation of inhibition could contribute to kainate's epileptogenic effects. Hippocampal slice electrophysiology, selective pharmacological tools (ATPA agonist, LY294486 antagonist) Nature High 9335499
1997 A single amino acid residue N721 in GluR6 (and its GluR5 counterpart) controls both AMPA sensitivity and domoate deactivation rates; residue A689 in GluR6 controls kainate desensitization rates, as revealed by chimeric and point-mutant receptors. Patch-clamp analysis of chimeric GluR5-GluR6 receptors and point mutants expressed in Xenopus oocytes/HEK cells, ligand binding Neuron High 9354337
1997 GluR5 and KA-2 subunits co-assemble to form heteromeric kainate receptor channels in trigeminal ganglion neurons; native KA receptor channels in TG neurons resemble recombinant GluR5(R)/KA-2 channels in pharmacological properties, desensitization, rectification, ion permeability, and single-channel conductance. RT-PCR, patch-clamp electrophysiology of acutely dissociated TG neurons, comparison with recombinant receptors in heterologous cells The Journal of neuroscience Medium 9254673
1998 Activation of GluR5-containing kainate receptors on hippocampal CA1 interneurons generates inward current and repetitive action potential firing, causing a massive increase in tonic GABAergic inhibition of pyramidal neuron somata and apical dendrites; electrical stimulation of excitatory afferents produces kainate receptor-mediated EPSCs and action potentials in interneurons. Whole-cell patch-clamp in hippocampal slices, selective GluR5 agonist ATPA and antagonist LY293558 Nature neuroscience High 10196544
1998 GluR5 subunits contribute to a kainate receptor that presynaptically depresses excitatory synaptic transmission in both CA1 and CA3 hippocampal regions, as demonstrated by ATPA-induced depression of EPSPs/EPSCs and increased paired-pulse facilitation. Field and whole-cell recordings in hippocampal slices, selective GluR5 agonist ATPA and antagonist LY294486 Neuropharmacology High 9849664
1998 GluR5 kainate receptor-mediated synaptic transmission occurs in the basolateral amygdala (BLA), where high-frequency stimulation of external capsule evokes GluR5-dependent synaptic currents that are inwardly rectifying and blocked by LY293558. Intracellular and whole-cell voltage-clamp recordings in BLA slices, selective AMPA and kainate receptor antagonists Neuropharmacology High 9849665
1999 GluR5, GluR6, and GluR7 kainate receptor subunits coassemble promiscuously to form heteromeric receptors; GluR5/GluR6 heteromers exhibit reduced desensitization and faster recovery from desensitization compared to homomeric GluR5; GluR7 coassembly with GluR6 markedly decreases agonist response amplitude. Coexpression in Xenopus oocytes with selective GluR5 agonists and rectification analysis of edited/unedited Q/R-site subunit combinations The Journal of neuroscience High 10493729
1999 RNA editing of the Q/R site in GluR5 reduces kainate receptor current density by ~6-fold in dorsal root ganglion sensory neurons; GluR5(R) knock-in mice (encoding arginine at Q/R site) show reduced DRG kainate current density without altered thermal/chemical pain responses. Embryonic stem cell knock-in transgenesis, patch-clamp in acutely isolated DRG neurons from mutant mice The Journal of neuroscience High 10516295
2000 GluR5 and GluR6 subunits coassemble into heteromeric kainate receptors in hippocampal GABAergic interneurons; >80% of receptors in co-transfected single HEK293 cells are GluR5/GluR6 heteromers, exhibiting different desensitization and gating properties from homomeric GluR6. Double in situ hybridization in hippocampal slices, patch-clamp electrophysiology in co-transfected HEK293 cells, selective agonist ATPA The Journal of neuroscience High 10627597
2003 Cell surface expression of GluR5-2b is regulated by a novel endoplasmic reticulum retention signal in the alternatively spliced C-terminal domain; a critical arginine (Arg-896) and surrounding residues mediate ER retention, and phosphorylation-mimicking mutation of Thr-898 promotes ER exit and surface expression. Mutagenesis, heterologous cell transfection, cell surface biotinylation, immunofluorescence in neurons The Journal of biological chemistry High 14527949
2003 Topiramate at low concentrations (IC50 ~0.5 µM) selectively inhibits postsynaptic GluR5 kainate receptor-mediated synaptic currents in BLA principal neurons; it reduces miniature EPSC amplitude without affecting frequency, indicating postsynaptic block. Whole-cell voltage-clamp recordings in rat BLA slices, miniature EPSC analysis, paired-pulse experiments The Journal of neuroscience High 12904467
2003 GluR5 activation selectively depolarizes inhibitory interneurons in the basolateral amygdala, increasing GABA release and tonic GABA current in the BLA; GluR5 genetic deletion or local antagonist injection increases anxiety-like behavior. Whole-cell recordings in BLA slices, GluR5 knockout mice, local antagonist microinjection, behavioral tests Journal of neurophysiology / PloS one High 12091575 17245443
2005 Crystal structures of GluR5 and GluR6 ligand binding cores reveal that GluR5 ligand binding cavity is 40% larger than GluR2; extensive interdomain contacts between domains 1 and 2 of GluR5 (absent in AMPA receptors) contribute to high-affinity kainate complex stability; agonist selectivity is determined by steric occlusion within the binding cavity. X-ray crystallography of ligand binding cores in complex with glutamate, 4-methylglutamate, kainate, and quisqualate Neuron High 15721240
2005 Crystal structure of GluR5 ligand binding core with (S)-glutamate reveals 26° domain closure; Ser741 stabilizes an interdomain water network and forms an interdomain bridge; GluR5-S1S2 forms a novel dimer interface distinct from GluR2. X-ray crystallography at 1.95 Å resolution FEBS letters High 15710405
2003 GluR5 selectivity for the agonist ATPA is controlled by Ser741 in GluR5 (vs. Met722 in GluR1); Ser741 stabilizes the active conformation induced by bulky 5-position isoxazole substituents, as demonstrated by mutagenesis. Two-electrode voltage clamp in Xenopus oocytes, site-directed mutagenesis of GluR5 and GluR1 Molecular pharmacology High 12488532
2004 GluR5 and GluR6 kainate receptor subunits play distinct roles in hippocampal gamma oscillations: GluR5 ablation increases susceptibility to kainate-induced oscillations/epileptiform activity, while GluR6 ablation prevents them; GluR5-containing KARs on interneuron axons and GluR6-containing KARs in somatodendritic regions underlie distinct network functions. Kainate receptor knockout mice, field potential recordings, computational network modeling The Journal of neuroscience High 15509753
2005 GluR5 knockout mice show significantly reduced responses to capsaicin- and inflammation-induced pain but not fear memory, while GluR6 knockouts show reduced fear memory but not pain responses, demonstrating that distinct KAR subtypes control nociception versus fear. GluR5 and GluR6 knockout mice, behavioral pain and fear-memory assays, lateral amygdala synaptic recordings The Journal of neuroscience High 15673679
2006 Crystal structures of GluR5 ligand binding core with selective antagonists UBP302 and UBP310 reveal a novel binding mechanism: antagonists do not contact E723 (unlike all previously solved agonist/antagonist complexes), causing hyperextension of the binding core and a 22 Å extension of ion channel linkers compared to the glutamate-bound form. X-ray crystallography of GluR5-S1S2 complexes with antagonists, radiolabel displacement assays, whole-cell electrophysiology The Journal of neuroscience High 16540562
2008 GluR5 activation in myelinated dorsal column axons increases intraaxonal Ca2+ via both ionotropic and metabotropic (pertussis toxin-sensitive G-protein/PLC-dependent) signaling involving IP3-dependent Ca2+ release; GluR5 co-immunoprecipitates with nNOS and colocalizes with nNOS clusters on internodal axons. Confocal Ca2+ imaging in dorsal column axons, pharmacological dissection, co-immunoprecipitation, immunohistochemistry Annals of neurology Medium 19224531
2008 GluR5-containing KAR activation in vivo exerts neuroprotection against ischemia-reperfusion by facilitating Ca2+-dependent GABA release from interneurons; released GABA activates postsynaptic GABA-A receptors, which attenuates NMDA receptor tyrosine phosphorylation by inhibiting Src kinase activation and disrupting the NR2A-PSD-95-Src signaling module. In vivo ischemia-reperfusion model, patch-clamp recordings, co-immunoprecipitation, antisense oligodeoxynucleotides, selective pharmacological tools The Journal of biological chemistry Medium 18678878
2009 GluR5 kainate receptors regulate HPA axis stress responses differentially: GluR5 in the paraventricular nucleus tonically inhibits ACTH/corticosterone release, while GluR5 at the median eminence (co-localized with CRH) facilitates restraint-induced ACTH release. In situ hybridization, immunohistochemistry, intra-PVN and intra-median eminence pharmacological infusion, plasma hormone measurements Psychoneuroendocrinology Medium 19450932
2011 NETO2 profoundly slows desensitization of GluK1 (GluR5) kainate receptors and promotes plasma membrane localization and synaptic targeting of GluK1-containing receptors in hippocampal neurons; NETO1 increases GluK1 desensitization rate. These effects extend the temporal range of GluK1 gating by over an order of magnitude. Heterologous expression, patch-clamp electrophysiology, transfection of hippocampal neurons, immunofluorescence The Journal of neuroscience High 21593317
2015 Both NETO1 and NETO2 are auxiliary subunits that profoundly increase GluK1 surface expression and drive GluK1 to synapses in hippocampal CA1 neurons; synaptic targeting by NETO proteins is independent of their role in promoting surface trafficking; GluK1 is selectively incorporated into silent synapses (excluded from AMPA receptor-containing synapses); NETO2 slows GluK1 deactivation and desensitization, while NETO1 speeds desensitization. Hippocampal CA1 null-background system, lentiviral expression, whole-cell patch-clamp, EPSC recordings eLife High 26720915
2015 GluK1 C-terminal domain interacts with Goα subunit; GluK1 activates Go proteins as shown by BRET experiments; interaction was validated by in vitro and in vivo co-immunoprecipitation and was absent in GluK1-deficient mice, establishing GluK1 as a mediator of metabotropic (G-protein) as well as ionotropic signaling. Proteomics/mass spectrometry of GluK1 C-terminal interactome, co-immunoprecipitation, BRET assays, GluK1 knockout mice The Journal of neuroscience High 25834043
2018 The cleaved signal peptide of GluK1 interacts with the amino-terminal domain (ATD) in trans to repress forward trafficking (surface and synaptic expression) of GluK1; chimeric replacement of GluK1 signal peptide with that of GluK2 dramatically increases surface/synaptic expression, and this is suppressed by co-expression of the GluK1 signal peptide. Chimeric receptor strategy, EPSC recordings in hippocampal CA1 neurons, co-expression experiments Nature communications High 30451858
1998 Homomeric GluR5 receptors expressed in HEK293 cells exhibit striking inter-cell variability in desensitization kinetics (range 1.5 ms to 1.5 s for kainate), suggesting modulation of GluR5 gating by intracellular mechanisms; DRG neurons (likely homomeric GluR5) show biexponential recovery from desensitization similar to fast-desensitizing GluR5 cells. Patch-clamp electrophysiology in HEK293 cells and acutely isolated DRG neurons The Journal of physiology Medium 9824706
2009 GluR5 kainate receptor activation in the anterior cingulate cortex selectively facilitates GABAergic (not glutamatergic) transmission through somatodendritic (not presynaptic) GluR5 in a Ca2+-dependent, voltage-gated Ca2+ channel-dependent manner; endogenous GluR5 activation produces tonic GABA currents in ACC pyramidal neurons. Whole-cell recordings in ACC slices, selective GluR5 agonist/antagonist, GluR5 knockout mice Developmental neurobiology Medium 17443779
2006 GluR5-containing kainate receptors are located presynaptically on inhibitory GABAergic terminals in spinal substantia gelatinosa, where their activation facilitates the frequency (but not amplitude) of both GABAergic and glycinergic IPSCs; this effect is absent in GluR5 knockout mice. Whole-cell recordings in spinal cord slices, ATPA selective agonist, GluR5 knockout mice, miniature IPSC analysis Molecular pain High 16948848

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron 561 1977421
1997 A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature 343 9335499
1998 GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nature neuroscience 255 10196544
2005 Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron 225 15721240
2004 Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations. The Journal of neuroscience : the official journal of the Society for Neuroscience 176 15509753
2003 Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 161 12904467
2000 GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 158 10627597
2014 Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism. The American journal of psychiatry 156 24525690
1993 Selective distribution of kainate receptor subunit immunoreactivity in monkey neocortex revealed by a monoclonal antibody that recognizes glutamate receptor subunits GluR5/6/7. The Journal of neuroscience : the official journal of the Society for Neuroscience 148 8392536
1998 Kainate GluR5 receptor subtype mediates the nociceptive response to formalin in the rat. Neuropharmacology 146 9680256
2009 Arabidopsis protein kinases GRIK1 and GRIK2 specifically activate SnRK1 by phosphorylating its activation loop. Plant physiology 143 19339507
1996 Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. Proceedings of the National Academy of Sciences of the United States of America 134 8700852
2004 LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia : an international journal of headache 128 15196302
1998 The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus. Neuropharmacology 122 9849664
1999 Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 10493729
1995 Distribution of the excitatory amino acid receptor subunits GluR2(4) in monkey hippocampus and colocalization with subunits GluR5-7 and NMDAR1. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 7722624
1997 Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors. Neuron 109 9354337
1999 Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: evidence for independent developmental, pathological and cellular regulation. The European journal of neuroscience 108 10051761
1997 Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 9254673
2004 Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology 104 15111016
2006 Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 16540562
1996 Pharmacological discrimination of GluR5 and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisdoquinoline-3 carboxylic-acid. Molecular pharmacology 97 8609884
2005 Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 15673679
1994 Assessing the extent of RNA editing in the TMII regions of GluR5 and GluR6 kainate receptors during rat brain development. Journal of neurochemistry 89 7512622
2011 Synaptic targeting and functional modulation of GluK1 kainate receptors by the auxiliary neuropilin and tolloid-like (NETO) proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 21593317
2009 Glutamate receptors on myelinated spinal cord axons: II. AMPA and GluR5 receptors. Annals of neurology 83 19224531
1998 GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro. Neuropharmacology 83 9849665
2005 Crystal structure of the kainate receptor GluR5 ligand-binding core in complex with (S)-glutamate. FEBS letters 77 15710405
1997 Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene (GRIK1) polymorphism. American journal of medical genetics 77 9259378
2001 RNA editing at the Q/R site for the glutamate receptor subunits GLUR2, GLUR5, and GLUR6 in hippocampus and temporal cortex from epileptic patients. Neurobiology of disease 75 11442354
2007 Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice. PloS one 67 17245443
2001 GluR5,6,7 subunit immunoreactivity on apical pyramidal cell dendrites in hippocampus of schizophrenics and manic depressives. Hippocampus 63 11732702
1993 The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America 62 8419920
2010 The GluK1 (GluR5) Kainate/{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist LY293558 reduces soman-induced seizures and neuropathology. The Journal of pharmacology and experimental therapeutics 60 20962029
2009 Association of markers in the 3' region of the GluR5 kainate receptor subunit gene to alcohol dependence. Alcoholism, clinical and experimental research 57 19320626
1993 Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6. Neuroreport 56 8260617
2009 Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons. The Journal of pharmacology and experimental therapeutics 55 19417176
2003 Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal. The Journal of biological chemistry 54 14527949
2002 Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors. Journal of neurophysiology 54 12091575
2003 GluR5 kainate receptors, seizures, and the amygdala. Annals of the New York Academy of Sciences 52 12724156
2001 Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. Neuropharmacology 51 11077068
1997 The synaptic activation of the GluR5 subtype of kainate receptor in area CA3 of the rat hippocampus. Neuropharmacology 51 9517417
1999 Generation and analysis of GluR5(Q636R) kainate receptor mutant mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 10516295
2004 Behavioural effects of the novel AMPA/GluR5 selective receptor antagonist NS1209 after systemic administration in animal models of experimental pain. Neuropharmacology 48 15275824
2003 Glutamate receptor RNA editing: a molecular analysis of GluR2, GluR5 and GluR6 in human brain tissues and in NT2 cells following in vitro neural differentiation. Brain research. Molecular brain research 46 14559151
1998 Heterogeneity of homomeric GluR5 kainate receptor desensitization expressed in HEK293 cells. The Journal of physiology 44 9824706
1993 Organization and quantitative analysis of kainate receptor subunit GluR5-7 immunoreactivity in monkey hippocampus. Brain research 44 8252413
2001 Immunocytochemical localization of kainate-selective glutamate receptor subunits GluR5, GluR6, and GluR7 in the cat retina. Brain research 43 11164787
2004 Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit. The Journal of physiology 42 14724198
2002 Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso-quinoline-3-carboxylic ester: a prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine. Journal of medicinal chemistry 42 12238915
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2015 A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists. Toxicology and applied pharmacology 20 25689173
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2011 Binding and selectivity of the marine toxin neodysiherbaine A and its synthetic analogues to GluK1 and GluK2 kainate receptors. Journal of molecular biology 16 21893069
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