Genomes and Genes
kainic acid receptors
Summary: A class of ionotropic glutamate receptors characterized by their affinity for KAINIC ACID.
- Maingret F, Lauri S, Taira T, Isaac J. Profound regulation of neonatal CA1 rat hippocampal GABAergic transmission by functionally distinct kainate receptor populations. J Physiol. 2005;567:131-42 pubmed..Thus kainate receptors are strategically located to play a critical role in shaping early hippocampal network activity and by virtue of this have a key role in hippocampal development. ..
- Dominguez E, Iyengar S, Shannon H, Bleakman D, Alt A, Arnold B, et al. Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain. J Med Chem. 2005;48:4200-3 pubmed..Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia. ..
- Lerma J. Kainate receptor physiology. Curr Opin Pharmacol. 2006;6:89-97 pubmed..However, the role of kainate receptors in other brain pathologies remains obscure. ..
- Coussen F, Mulle C. Kainate receptor-interacting proteins and membrane trafficking. Biochem Soc Trans. 2006;34:927-30 pubmed..This review summarizes our knowledge of the regulation of trafficking of kainate receptors and focuses on the identification and characterization of functions of interacting partners. ..
- Wilding T, Zhou Y, Huettner J. Q/R site editing controls kainate receptor inhibition by membrane fatty acids. J Neurosci. 2005;25:9470-8 pubmed..Inhibition of fully edited channels is equivalent at voltages from -70 to +40 mV and is noncompetitive, consistent with allosteric regulation of channel function. ..
- Epsztein J, Represa A, Jorquera I, Ben Ari Y, Crepel V. Recurrent mossy fibers establish aberrant kainate receptor-operated synapses on granule cells from epileptic rats. J Neurosci. 2005;25:8229-39 pubmed..Therefore, in addition to axonal rewiring, sprouting of mossy fibers induces a shift in the nature of glutamatergic transmission in granule cells that may contribute to the physiopathology of the dentate gyrus in epileptic animals. ..
- Zhang W, St Gelais F, Grabner C, Trinidad J, Sumioka A, Morimoto Tomita M, et al. A transmembrane accessory subunit that modulates kainate-type glutamate receptors. Neuron. 2009;61:385-96 pubmed publisher..The results show that NETO2 is a kainate receptor subunit with significant effects on glutamate signaling mechanisms in brain. ..
- Pinheiro P, Mulle C. Kainate receptors. Cell Tissue Res. 2006;326:457-82 pubmed..Finally, this review presents evidence that implicates kainate receptors in pathophysiological conditions such as epilepsy, excitotoxicity and pain, and that shows that these receptors represent promising therapeutic targets. ..
- Xu H, Wu L, Zhao M, Toyoda H, Vadakkan K, Jia Y, et al. Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. Mol Pain. 2006;2:29 pubmed..GluR5-containing KARs are thus important for spinal sensory transmission/modulation in the spinal cord. ..
- Barberis A, Sachidhanandam S, Mulle C. GluR6/KA2 kainate receptors mediate slow-deactivating currents. J Neurosci. 2008;28:6402-6 pubmed publisher..We propose, therefore, that the GluR6/KA2 gating features could contribute to the slow KAR-EPSC decay kinetics. ..
- Jane D, Lodge D, Collingridge G. Kainate receptors: pharmacology, function and therapeutic potential. Neuropharmacology. 2009;56:90-113 pubmed publisher..This potential has now been confirmed in dental pain and migraine in initial studies in man. ..
- Dolman N, Troop H, More J, Alt A, Knauss J, Nistico R, et al. Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors. J Med Chem. 2005;48:7867-81 pubmed..5-Iodo substitution of the uracil ring of 44a gave 45, which was found to have enhanced potency and selectivity for GLUK5. ..
- Huxter J, Zinyuk L, Roloff E, Clarke V, Dolman N, More J, et al. Inhibition of kainate receptors reduces the frequency of hippocampal theta oscillations. J Neurosci. 2007;27:2212-23 pubmed..In addition, the effects on cellular responses provide both insight into the mechanisms of theta pacing, and useful information for models of temporal coding. ..
- Fisahn A, Contractor A, Traub R, Buhl E, Heinemann S, McBain C. Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations. J Neurosci. 2004;24:9658-68 pubmed
- Brown J, Teriakidis A, Randall A. A pharmacological investigation of the role of GLUK5-containing receptors in kainate-driven hippocampal gamma band oscillations. Neuropharmacology. 2006;50:47-56 pubmed
- Puller C, Haverkamp S, Grünert U. OFF midget bipolar cells in the retina of the marmoset, Callithrix jacchus, express AMPA receptors. J Comp Neurol. 2007;502:442-54 pubmed..The presence of GluR5 clusters at S-cone pedicles indicates that in primate retinas OFF bipolar cells expressing kainate receptor subunits receive some S-cone input. ..
- Wu L, Zhao M, Toyoda H, Ko S, Zhuo M. Kainate receptor-mediated synaptic transmission in the adult anterior cingulate cortex. J Neurophysiol. 2005;94:1805-13 pubmed..Our results show that KA receptors contribute to synaptic transmission in adult ACC pyramidal neurons and provide a synaptic basis for the physiology and pathology of KA receptors in ACC-related functions. ..
- Lu C, Willcockson H, Phend K, Lucifora S, Darstein M, Valtschanoff J, et al. Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat superficial dorsal horn. J Comp Neurol. 2005;486:169-78 pubmed..As heteroreceptors in GABAergic terminals in the same laminae, on the other hand, presynaptic IGRs may have an opposite role and even contribute to central sensitization and hyperalgesia. ..
- Pinheiro P, Perrais D, Coussen F, Barhanin J, Bettler B, Mann J, et al. GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses. Proc Natl Acad Sci U S A. 2007;104:12181-6 pubmed
- Schiffer H, Heinemann S. Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:20-6 pubmed..068). Our findings imply that the GluR7 gene is a susceptibility factor in R-MDD and that the glutamatergic receptor system plays a critical role in the disease etiology. ..
- Santiago A, Rosa S, Santos P, Cristóvão A, Barber A, Ambrósio A. Elevated glucose changes the expression of ionotropic glutamate receptor subunits and impairs calcium homeostasis in retinal neural cells. Invest Ophthalmol Vis Sci. 2006;47:4130-7 pubmed..The results suggest that elevated glucose may alter glutamate neurotransmission and calcium homeostasis in the retina, which may have implications for the mechanisms of vision loss in DR. ..
- Youn D, Voitenko N, Gerber G, Park Y, Galik J, Randic M. Altered long-term synaptic plasticity and kainate-induced Ca2+ transients in the substantia gelatinosa neurons in GLU(K6)-deficient mice. Brain Res Mol Brain Res. 2005;142:9-18 pubmed..These results indicate that unique expression of kainate receptors subunits is important in regulating spinal synaptic plasticity and thereby processing of sensory information, including pain. ..
- Mayer M. Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron. 2005;45:539-52 pubmed..This, together with extensive interdomain contacts between domains 1 and 2 of GluR5 and GluR6, absent from AMPA receptors, likely contributes to the high stability of GluR5 and GluR6 kainate complexes. ..
- Goldin M, Epsztein J, Jorquera I, Represa A, Ben Ari Y, Crepel V, et al. Synaptic kainate receptors tune oriens-lacunosum moleculare interneurons to operate at theta frequency. J Neurosci. 2007;27:9560-72 pubmed..Such preferential processing of excitatory inputs via KA-Rs by distally projecting GABAergic microcircuits could provide a key role in theta band frequency oscillations. ..
- Isaac J, Mellor J, Hurtado D, Roche K. Kainate receptor trafficking: physiological roles and molecular mechanisms. Pharmacol Ther. 2004;104:163-72 pubmed..This review summarizes the current state of knowledge on this topic, focusing on the molecular mechanisms of kainate receptor trafficking and the potential for these mechanisms to regulate neuronal kainate receptor function. ..
- Fisahn A. Kainate receptors and rhythmic activity in neuronal networks: hippocampal gamma oscillations as a tool. J Physiol. 2005;562:65-72 pubmed
- Motazacker M, Rost B, Hucho T, Garshasbi M, Kahrizi K, Ullmann R, et al. A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. Am J Hum Genet. 2007;81:792-8 pubmed
- Bortolotto Z, Nistico R, More J, Jane D, Collingridge G. Kainate receptors and mossy fiber LTP. Neurotoxicology. 2005;26:769-77 pubmed..This form of LTP is triggered by the synaptic activation of kainate receptors. We also address the importance of Ca2+ availability in the extracellular environment and the release of Ca2+ from intracellular stores for this form of LTP. ..
- Cannella M, Gellera C, Maglione V, Giallonardo P, Cislaghi G, Muglia M, et al. The gender effect in juvenile Huntington disease patients of Italian origin. Am J Med Genet B Neuropsychiatr Genet. 2004;125B:92-8 pubmed..82). Our findings suggest the occurrence of a weaker effect of the paternal mutation on juvenile age at onset in our population, possibly amplified by other genetic factors, such as the TAA-triplet length in the GluR6 gene. ..
- Lerma J. Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci. 2003;4:481-95 pubmed
- Cunningham M, Davies C, Buhl E, Kopell N, Whittington M. Gamma oscillations induced by kainate receptor activation in the entorhinal cortex in vitro. J Neurosci. 2003;23:9761-9 pubmed..We propose that similar cellular and network mechanisms to those seen in the hippocampus generate and modulate persistent gamma oscillations in the entorhinal cortex. ..
- Robert A, Hyde R, Hughes T, Howe J. The expression of dominant-negative subunits selectively suppresses neuronal AMPA and kainate receptors. Neuroscience. 2002;115:1199-210 pubmed..If co-assembly of the mutant subunits with related native subunits is combinatorial, this level of suppression gives receptor half-lives of approximately 20 h. ..
- Frerking M, Ohliger Frerking P. AMPA receptors and kainate receptors encode different features of afferent activity. J Neurosci. 2002;22:7434-43 pubmed..Our results suggest that synaptically activated KARs have a strong influence on membrane potential and that AMPARs and KARs differ in their ability to encode temporal information. ..
- Chattopadhyay B, Ghosh S, Gangopadhyay P, Das S, Roy T, Sinha K, et al. Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India. Neurosci Lett. 2003;345:93-6 pubmed..Similar analysis with SCA2 patients indicated that RAI1 might explain about 13% of the variability in the age at onset. Specific alleles in GluR6 and CA150 locus were only observed in HD patients. ..
- Eder M, Becker K, Rammes G, Schierloh A, Azad S, Zieglgänsberger W, et al. Distribution and properties of functional postsynaptic kainate receptors on neocortical layer V pyramidal neurons. J Neurosci. 2003;23:6660-70 pubmed..Furthermore, it is feasible to assume that extrasynaptic KARs could be activated by a "spillover" of synaptically released glutamate, ambient glutamate in the CSF, or glutamate released from adjacent astrocytes. ..
- Clarke V, Collingridge G. Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices. Neuropharmacology. 2004;47:363-72 pubmed..However, LY382884 is less potent as an antagonist of the effects of ATPA on IPSPs compared to its depressant effect on EPSPs. ..
- Takahashi J, Giuliani F, Power C, Imai Y, Yong V. Interleukin-1beta promotes oligodendrocyte death through glutamate excitotoxicity. Ann Neurol. 2003;53:588-95 pubmed
- Kerchner G, Wilding T, Huettner J, Zhuo M. Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn. J Neurosci. 2002;22:8010-7 pubmed..These results highlight fundamental differences in KA receptor physiology between the two cell types and suggest possible strategies for the pharmacological modulation of nociception. ..
- Contractor A, Sailer A, Darstein M, Maron C, Xu J, Swanson G, et al. Loss of kainate receptor-mediated heterosynaptic facilitation of mossy-fiber synapses in KA2-/- mice. J Neurosci. 2003;23:422-9 pubmed..These results identify the KA2 subunit as a determinant of kainate receptor function at presynaptic and postsynaptic mossy-fiber kainate receptors. ..
- Harvey D, Calkins D. Localization of kainate receptors to the presynaptic active zone of the rod photoreceptor in primate retina. Vis Neurosci. 2002;19:681-92 pubmed
- Wosik K, Ruffini F, Almazan G, Olivier A, Nalbantoglu J, Antel J. Resistance of human adult oligodendrocytes to AMPA/kainate receptor-mediated glutamate injury. Brain. 2004;127:2636-48 pubmed..The apparent lack of glutamate receptor expression on human OLs and their resistance to AMPA/kainate toxicity should be considered when postulating mechanisms of tissue injury in multiple sclerosis. ..
- Braga M, Aroniadou Anderjaska V, Li H. The physiological role of kainate receptors in the amygdala. Mol Neurobiol. 2004;30:127-41 pubmed..Taken together, these findings have suggested a prominent role of GLUk5-containing kainate receptors in the regulation of neuronal excitability in the amygdala. ..
- Darstein M, Petralia R, Swanson G, Wenthold R, Heinemann S. Distribution of kainate receptor subunits at hippocampal mossy fiber synapses. J Neurosci. 2003;23:8013-9 pubmed
- Huettner J. Kainate receptors and synaptic transmission. Prog Neurobiol. 2003;70:387-407 pubmed..This review briefly addresses the properties of kainate receptors and considers in greater detail the physiological analysis of their contributions to synaptic transmission. ..
- Grünert U, Lin B, Martin P. Glutamate receptors at bipolar synapses in the inner plexiform layer of primate retina: light microscopic analysis. J Comp Neurol. 2003;466:136-47 pubmed..The NMDA receptor subunit NR1C2' was specifically colocalized with flat midget and DB3 axons. These findings suggest that rod and cone bipolar cell types contribute to multiple but distinct glutamate receptor pathways in primate retina. ..
- Youn D, Randic M. Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit. J Physiol. 2004;555:683-98 pubmed
- Caruso A, Di Giorgi Gerevini V, Castiglione M, Marinelli F, Tomassini V, Pozzilli C, et al. Testosterone amplifies excitotoxic damage of cultured oligodendrocytes. J Neurochem. 2004;88:1179-85 pubmed..We conclude that testosterone amplifies excitotoxic damage of oligodendrocytes acting at an early step of the death cascade triggered by AMPA/kainate receptors. ..
- Braga M, Aroniadou Anderjaska V, Xie J, Li H. Bidirectional modulation of GABA release by presynaptic glutamate receptor 5 kainate receptors in the basolateral amygdala. J Neurosci. 2003;23:442-52 pubmed
- Liu Q, Xu Q, Arcuino G, Kang J, Nedergaard M. Astrocyte-mediated activation of neuronal kainate receptors. Proc Natl Acad Sci U S A. 2004;101:3172-7 pubmed..By modulating the activity of interneurons, astrocytes may play a critical role in circuit function of hippocampus. ..
- Diguet E, Fernagut P, Normand E, Centelles L, Mulle C, Tison F. Experimental basis for the putative role of GluR6/kainate glutamate receptor subunit in Huntington's disease natural history. Neurobiol Dis. 2004;15:667-75 pubmed
- Christensen J, Paternain A, Selak S, Ahring P, Lerma J. A mosaic of functional kainate receptors in hippocampal interneurons. J Neurosci. 2004;24:8986-93 pubmed
- Guo W, Zou S, Tal M, Ren K. Activation of spinal kainate receptors after inflammation: behavioral hyperalgesia and subunit gene expression. Eur J Pharmacol. 2002;452:309-18 pubmed..These results suggest that a selective upregulation of kainate receptor subunit expression contributes to inflammatory hyperalgesia. ..
- More J, Nistico R, Dolman N, Clarke V, Alt A, Ogden A, et al. Characterisation of UBP296: a novel, potent and selective kainate receptor antagonist. Neuropharmacology. 2004;47:46-64 pubmed..These data provide further evidence for a role for GLUK5-containing kainate receptors in mossy fibre LTP. In conclusion, UBP296 is the most potent and selective antagonist of GLUK5-containing kainate receptors so far described. ..