Kainate receptors coming of age: milestones of two decades of research
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Two decades have passed since the first report of the cloning of a kainate-type glutamate receptor (KAR) subunit. The intervening years have seen a rapid growth in our understanding of the biophysical properties and function of KARs in the brain. This research has led to an appreciation that KARs play very distinct roles at synapses relative to other members of the glutamate-gated ion channel receptor family, despite structural and functional commonalities. The surprisingly diverse and complex nature of KAR signaling underlies their unique impact upon neuronal networks through their direct and indirect effects on synaptic transmission, and their prominent role in regulating cell excitability. This review pieces together highlights from the two decades of research subsequent to the cloning of the first subunit, and provides an overview of our current understanding of the role of KARs in the CNS and their potential importance to neurological and neuropsychiatric disorders.
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At either presynaptic or postsynaptic location, kainate receptors can have metabotropic (G-protein coupled) actions to suppress or facilitate both glutamate or GABA release.
“At either location, they can have metabotropic (G-protein coupled) actions to suppress or facilitate both glutamate or GABA release (Contractor et al., 2011;Marshall et al., 2018).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Contractor et al., 2011
The diversity of roles played by kainate receptors in the CNS, including extensive excitatory, inhibitory, ionotropic, and metabotropic activities, provides a wide range of possible functions upon which natural selection can act.
“The diversity of roles played by kainate receptors in the CNS, including extensive excitatory, inhibitory, ionotropic, and metabotropic activities (Contractor et al., 2011), provides a wide range of possible functions upon which natural selection can act.”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Contractor et al., 2011
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Self-citationKainate receptor-mediated heterosynaptic facilitation in the amygdala
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Subunit Composition and Alternative Splicing Regulate Membrane Delivery of Kainate Receptors
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Self-citationSubcellular localization and trafficking of kainate receptors
Jaskolski, F., Coussen, F., & Mulle, C. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.11.008 · Cited by 101 · see citing works
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Self-citationAMPA Receptors and Kainate Receptors Encode Different Features of Afferent Activity
Frerking, M. E., & Ohliger-Frerking, P. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-17-07434.2002 · Cited by 99 · see citing works
Characterisation of UBP296: a novel, potent and selective kainate receptor antagonist
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Activation of Kainate Receptors Sensitizes Oligodendrocytes to Complement Attack
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Molecular Basis of Kainate Receptor Modulation by Sodium
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Palmitoylation of the GluR6 kainate receptor.
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Functional GluR6 Kainate Receptors in the Striatum: Indirect Downregulation of Synaptic Transmission
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Crystal structure of the kainate receptor GluR5 ligand‐binding core in complex with (S)‐glutamate
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Antagonism of recombinant and native GluK3-containing kainate receptors
Perrais, D., Pinheiro, P. S., Jane, D. E., & Mulle, C. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.08.002 · Cited by 83 · see citing works
Self-citationCoassembly of Two GluR6 Kainate Receptor Splice Variants within a Functional Protein Complex
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Self-citationGluR6/KA2 Kainate Receptors Mediate Slow-Deactivating Currents
Barberis, A., Sachidhanandam, S., & Mulle, C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1204-08.2008 · Cited by 81 · see citing works
Self-citationRole of Glutamate Autoreceptors at Hippocampal Mossy Fiber Synapses
Kwon, H., & Castillo, P. E. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.045 · Cited by 80 · see citing works
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Synaptic activation of kainate receptors gates presynaptic CB1 signaling at GABAergic synapses
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Self-citationAssessing the Role of GLUK5and GLUK6at Hippocampal Mossy Fiber Synapses
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Structural aspects of AMPA receptor activation, desensitization and deactivation
Hansen, K. B., Yuan, H., & Traynelis, S. F. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.03.014 · Cited by 62 · see citing works
A Role for Extracellular Na+in the Channel Gating of Native and Recombinant Kainate Receptors
Paternain, A. V., Cohen, A., Stern-Bach, Y., & Lerma, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-25-08641.2003 · Cited by 60 · see citing works
A C-Terminal Determinant of GluR6 Kainate Receptor Trafficking
Yan, S., Sanders, J. M., Xu, J., Zhu, Y., Contractor, A., & Swanson, G. T. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4985-03.2004 · Cited by 58 · see citing works
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Kamboj, R. K., Schoepp, D. D., Nutt, S. L., Shekter, L. R., Korczak, B. M., True, R. A., Rampersad, V., Zimmerman, D. M., & Wosnick, M. A. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.62010001.x · Cited by 53 · see citing works
Segerstråle, M., Juuri, J., Lanore, F., Piepponen, P. T., Lauri, S. E., Mulle, C., & Taira, T. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4856-09.2010 · Cited by 50 · see citing works
Self-citationKRIP6: A novel BTB/kelch protein regulating function of kainate receptors
Laezza, F., Wilding, T. J., Sequeira, S. M., Coussen, F., Zhang, X. Z., Robinson-Hill, R. M., Mulle, C., Huettner, J. E., & Craig, A. M. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.12.003 · Cited by 50 · see citing works
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External Ions Are Coactivators of Kainate Receptors
Wong, A. Y. C., Fay, A.-M. L., & Bowie, D. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0301-06.2006 · Cited by 49 · see citing works
Kainate Receptors and Pain: From Dorsal Root Ganglion to the Anterior Cingulate Cortex
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Ion‐dependent gating of kainate receptors
Bowie, D. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.178863 · Cited by 43 · see citing works
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Inhibition of Kainate Receptors Reduces the Frequency of Hippocampal Theta Oscillations
Huxter, J. R., Zinyuk, L. E., Roloff, E. V. L., Clarke, V. R. J., Dolman, N. P., More, J. C. A., Jane, D. E., Collingridge, G. L., & Muller, R. U. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3954-06.2007 · Cited by 36 · see citing works
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Association study of polymorphisms in the GluR6 kainate receptor gene (GRIK2) with schizophrenia
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Profilin II Regulates the Exocytosis of Kainate Glutamate Receptors
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Ionotropic Glutamate Receptors
Bleakman, D., Alt, A. J., Lodge, D., Monaghan, D. T., Jane, D. E., & Nisenbaum, E. S. (2007) · doi:10.1002/9780470101001.hcn010 · Cited by 6 · see citing works
A Role for SNAP25 in Internalization of Kainate Receptors and Synaptic Plasticity
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Characterisation of UBP296: a novel, potent and selective kainate receptor antagonist
More, J. R. (2004) · Neuropharmacology · doi:10.1016/s0028-3908(04)00066-8 · Cited by 5 · see citing works
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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Self-citationLTP requires a reserve pool of glutamate receptors independent of subunit type
Granger, A. J., Shi, Y., Lu, W., Cerpas, M., & Nicoll, R. A. (2013) · Nature · doi:10.1038/nature11775 · Cited by 313 · see citing works
Transsynaptic modulation of kainate receptor functions by C1q-like proteins
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Distinct functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1
Straub, C., Hunt, D. L., Yamasaki, M., Kim, K. S., Watanabe, M., Castillo, P. E., & Tomita, S. (2011) · Nature Neuroscience · doi:10.1038/nn.2837 · Cited by 133 · see citing works
Approaches and Limitations in the Investigation of Synaptic Transmission and Plasticity
Glasgow, S. D., McPhedrain, R., Madranges, J. F., Kennedy, T. E., & Ruthazer, E. S. (2019) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2019.00020 · Cited by 100 · see citing works
Glutamate receptors in domestication and modern human evolution
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Self-citationMarshall, J. J., Xu, J., & Contractor, A. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.1788-17.2018 · Cited by 30 · see citing works
Self-citationTurk, E., Scholtens, L. H., & van den Heuvel, M. P. (2016) · Human Brain Mapping · doi:10.1002/hbm.23141 · Cited by 27 · see citing works
Gurung, S., Evans, A. J., Wilkinson, K. A., & Henley, J. M. (2018) · Journal of Cell Science · doi:10.1242/jcs.222273 · Cited by 26 · see citing works
- Authors
- Contractor, A., Mulle, C., & Swanson, G. T.
- Affiliations
- Northwestern University (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Contractor, Anis
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 34
- Issue
- 3
- Pages
- 154-163
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC3051042
- OpenAlex
- W2138295391
- Cited by
- 292
- References
- 155
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 16 · 2023: 17 · 2022: 14 · 2021: 27 · 2020: 15 · 2019: 23 · 2018: 16 · 2017: 23 · 2016: 28 · 2015: 16 · 2014: 24 · 2013: 25 · 2012: 20
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Centre National de la Recherche Scientifique
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS044322, R01NS058894, R01NS071952)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- kainate receptors, glutamate-gated ion channels, synaptic transmission, neuronal excitability, neuronal networks, neurological disorders, neuropsychiatric disorders, ion channel biophysics
- MeSH terms
- Animals, Disease Models, Animal, Humans, Neurosciences, Drug Delivery Systems, Kainic Acid Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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