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Kainate receptors

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Abstract

Kainate receptors form a family of ionotropic glutamate receptors that appear to play a special role in the regulation of the activity of synaptic networks. This review first describes briefly the molecular and pharmacological properties of native and recombinant kainate receptors. It then attempts to outline the general principles that appear to govern the function of kainate receptors in the activity of synaptic networks under physiological conditions. It subsequently describes the way that kainate receptors are involved in synaptic integration, synaptic plasticity, the regulation of neurotransmitter release and the control of neuronal excitability, and the manner in which they might play an important role in synaptogenesis and synaptic maturation. These functions require the proper subcellular localization of kainate receptors in specific functional domains of the neuron, necessitating complex cellular and molecular trafficking events. We show that our comprehension of these mechanisms is just starting to emerge. 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.

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References

  • Aarts M, Liu Y, Liu L, Besshoh S, Arundine M, Gurd JW, Wang YT, Salter MW, Tymianski M (2002) Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions. Science 298:846–850

    Article  PubMed  CAS  Google Scholar 

  • Agrawal S, Evans R (1986) The primary afferent depolarizing action of kainate in the rat. Br J Pharmacol 87:345–355

    PubMed  CAS  Google Scholar 

  • Alberdi E, Sanchez-Gomez MV, Torre I, Domercq M, Perez-Samartin A, Perez-Cerda F, Matute C (2006) Activation of kainate receptors sensitizes oligodendrocytes to complement attack. J Neurosci 26:3220–3228

    Article  PubMed  CAS  Google Scholar 

  • Ali AB (2003) Involvement of post-synaptic kainate receptors during synaptic transmission between unitary connections in rat neocortex. Eur J Neurosci 17:2344–2350

    Article  PubMed  Google Scholar 

  • Ali AB, Rossier J, Staiger JF, Audinat E (2001) Kainate receptors regulate unitary IPSCs elicited in pyramidal cells by fast-spiking interneurons in the neocortex. J Neurosci 21:2992–2999

    PubMed  CAS  Google Scholar 

  • Alle H, Geiger JR (2006) Combined analog and action potential coding in hippocampal mossy fibers. Science 311:1290–1293

    Article  PubMed  CAS  Google Scholar 

  • Alt A, Weiss B, Ogden AM, Knauss JL, Oler J, Ho K, Large TH, Bleakman D (2004) Pharmacological characterization of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro. Neuropharmacology 46:793–806

    Article  PubMed  CAS  Google Scholar 

  • Awatramani GB, Price GD, Trussell LO (2005) Modulation of transmitter release by presynaptic resting potential and background calcium levels. Neuron 48:109–121

    Article  PubMed  CAS  Google Scholar 

  • Bah J, Quach H, Ebstein RP, Segman RH, Melke J, Jamain S, Rietschel M, Modai I, Kanas K, Karni O, Lerer B, Gourion D, Krebs MO, Etain B, Schurhoff F, Szoke A, Leboyer M, Bourgeron T (2004) Maternal transmission disequilibrium of the glutamate receptor GRIK2 in schizophrenia. Neuroreport 15:1987–1991

    Article  PubMed  CAS  Google Scholar 

  • Bahn S, Volk B, Wisden W (1994) Kainate receptor gene expression in the developing rat brain. J Neurosci 14:5525–5547

    PubMed  CAS  Google Scholar 

  • Bahring R, Bowie D, Benveniste M, Mayer ML (1997) Permeation and block of rat GluR6 glutamate receptor channels by internal and external polyamines. J Physiol (Lond) 502:575–589

    Article  CAS  Google Scholar 

  • Bannister NJ, Benke TA, Mellor J, Scott H, Gurdal E, Crabtree JW, Isaac JT (2005) Developmental changes in AMPA and kainate receptor-mediated quantal transmission at thalamocortical synapses in the barrel cortex. J Neurosci 25:5259–5271

    Article  PubMed  CAS  Google Scholar 

  • Barbon A, Barlati S (2000) Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1. Cytogenet Cell Genet 88:236–239

    Article  PubMed  CAS  Google Scholar 

  • Barbon A, Vallini I, Barlati S (2001) Genomic organization of the human GRIK2 gene and evidence for multiple splicing variants. Gene 274:187–197

    Article  PubMed  CAS  Google Scholar 

  • Begni S, Popoli M, Moraschi S, Bignotti S, Tura GB, Gennarelli M (2002) Association between the ionotropic glutamate receptor kainate 3 (GRIK3) ser310ala polymorphism and schizophrenia. Mol Psychiatry 7:416–418

    Article  PubMed  CAS  Google Scholar 

  • Ben-Ari Y, Cossart R (2000) Kainate, a double agent that generates seizures: two decades of progress. Trends Neurosci 23:580–587

    Article  PubMed  CAS  Google Scholar 

  • Ben-Ari Y, Cherubini E, Corradetti R, Gaiarsa JL (1989) Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol (Lond) 416:303–325

    CAS  Google Scholar 

  • Bernard A, Ferhat L, Dessi F, Charton G, Represa A, Ben-Ari Y, Khrestchatisky M (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. Eur J Neurosci 11:604–616

    Article  PubMed  CAS  Google Scholar 

  • Best N, Sundstrom LE, Mitchell J, Wheal HV (1996) Pre-exposure to subtoxic levels prevents kainic acid lesions in organotypic hippocampal slice cultures: effects of kainic acid on parvalbumin-immunoreactive neurons and expression of heat shock protein 72 following the induction of tolerance. Eur J Neurosci 8:1209–1219

    Article  PubMed  CAS  Google Scholar 

  • Bettler B, Mulle C (1995) AMPA and kainate receptors. Neuropharmacology 34:123–139

    Article  PubMed  CAS  Google Scholar 

  • Bettler B, Boulter J, Hermans-Borgmeyer I, O’Shea-Greenfield A, Deneris ES, Moll C, Borgmeyer U, Hollmann M, Heinemann S (1990) Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron 5:583–595

    Article  PubMed  CAS  Google Scholar 

  • Bischofberger J, Geiger JR, Jonas P (2002) Timing and efficacy of Ca2+ channel activation in hippocampal mossy fiber boutons. J Neurosci 22:10593–10602

    PubMed  CAS  Google Scholar 

  • Bortolotto ZA, Clarke VR, Delany CM, Parry MC, Smolders I, Vignes M, Ho KH, Miu P, Brinton BT, Fantaske R, Ogden A, Gates M, Ornstein PL, Lodge D, Bleakman D, Collingridge GL (1999) Kainate receptors are involved in synaptic plasticity. Nature 402:297–301

    Article  PubMed  CAS  Google Scholar 

  • Bowie D (2002) External anions and cations distinguish between AMPA and kainate receptor gating mechanisms. J Physiol (Lond) 539:725–733

    Article  CAS  Google Scholar 

  • Bowie D, Mayer ML (1995) Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron 15:453–462

    Article  PubMed  CAS  Google Scholar 

  • Bowie D, Garcia EP, Marshall J, Traynelis SF, Lange GD (2003) Allosteric regulation and spatial distribution of kainate receptors bound to ancillary proteins. J Physiol (Lond) 547:373–385

    Article  CAS  Google Scholar 

  • Breustedt J, Schmitz D (2004) Assessing the role of GLUK5 and GLUK6 at hippocampal mossy fiber synapses. J Neurosci 24:10093–10098

    Article  PubMed  CAS  Google Scholar 

  • Bureau I, Bischoff S, Heinemann SF, Mulle C (1999) Kainate receptor-mediated responses in the CA1 field of wild-type and GluR6-deficient mice. J Neurosci 19:653–663

    PubMed  CAS  Google Scholar 

  • Bureau I, Dieudonne S, Coussen F, Mulle C (2000) Kainate receptor-mediated synaptic currents in cerebellar golgi cells are not shaped by diffusion of glutamate. Proc Natl Acad Sci USA 97:6838–6843

    Article  PubMed  CAS  Google Scholar 

  • Burnashev N, Zhou Z, Neher E, Sakmann B (1995) Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes. J Physiol (Lond) 485:403–418

    CAS  Google Scholar 

  • Casassus G, Mulle C (2002) Functional characterization of kainate receptors in the mouse nucleus accumbens. Neuropharmacology 42:603–611

    Article  PubMed  CAS  Google Scholar 

  • Castillo PE, Malenka RC, Nicoll RA (1997) Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature 388:182–186

    Article  PubMed  CAS  Google Scholar 

  • Chergui K, Bouron A, Normand E, Mulle C (2000) Functional GluR6 kainate receptors in the striatum: indirect downregulation of synaptic transmission. J Neurosci 20:2175–2182

    PubMed  CAS  Google Scholar 

  • Cho K, Francis JC, Hirbec H, Dev K, Brown MW, Henley JM, Bashir ZI (2003) Regulation of kainate receptors by protein kinase C and metabotropic glutamate receptors. J Physiol (Lond) 548:723–730

    Article  CAS  Google Scholar 

  • Christensen JK, Paternain AV, Selak S, Ahring PK, Lerma J (2004) A mosaic of functional kainate receptors in hippocampal interneurons. J Neurosci 24:8986–8993

    Article  PubMed  CAS  Google Scholar 

  • Clarke VR, Ballyk BA, Hoo KH, Mandelzys A, Pellizzari A, Bath CP, Thomas J, Sharpe EF, Davies CH, Ornstein PL, Schoepp DD, Kamboj RK, Collingridge GL, Lodge D, Bleakman D (1997) A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature 389:599–603

    Article  PubMed  CAS  Google Scholar 

  • Contractor A, Swanson GT, Sailer A, O’Gorman S, Heinemann SF (2000) Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. J Neurosci 20:8269–8278

    PubMed  CAS  Google Scholar 

  • Contractor A, Swanson G, Heinemann SF (2001) Kainate receptors are involved in short- and long-term plasticity at mossy fiber synapses in the hippocampus. Neuron 29:209–216

    Article  PubMed  CAS  Google Scholar 

  • Contractor A, Sailer AW, Darstein M, Maron C, Xu J, Swanson GT, Heinemann SF (2003) Loss of kainate receptor-mediated heterosynaptic facilitation of mossy-fiber synapses in KA2–/– mice. J Neurosci 23:422–429

    PubMed  CAS  Google Scholar 

  • Cossart R, Esclapez M, Hirsch JC, Bernard C, Ben-Ari Y (1998) GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nat Neurosci 1:470–478

    Article  PubMed  CAS  Google Scholar 

  • Cossart R, Epsztein J, Tyzio R, Becq H, Hirsch J, Ben-Ari Y, Crepel V (2002) Quantal release of glutamate generates pure kainate and mixed AMPA/kainate EPSCs in hippocampal neurons. Neuron 35:147–159

    Article  PubMed  CAS  Google Scholar 

  • Coussen F, Normand E, Marchal C, Costet P, Choquet D, Lambert M, Mege RM, Mulle C (2002) Recruitment of the kainate receptor subunit glutamate receptor 6 by cadherin/catenin complexes. J Neurosci 22:6426–6436

    PubMed  CAS  Google Scholar 

  • Coussen F, Perrais D, Jaskolski F, Sachidhanandam S, Normand E, Bockaert J, Marin P, Mulle C (2005) Co-assembly of two GluR6 kainate receptor splice variants within a functional protein complex. Neuron 47:555–566

    Article  PubMed  CAS  Google Scholar 

  • Cui C, Mayer ML (1999) Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. J Neurosci 19:8281–8291

    PubMed  CAS  Google Scholar 

  • Cunha RA, Malva JO, Ribeiro JA (2000) Pertussis toxin prevents presynaptic inhibition by kainate receptors of rat hippocampal [(3)H]GABA release. FEBS Lett 469:159–162

    Article  PubMed  CAS  Google Scholar 

  • Darstein M, Petralia RS, Swanson GT, Wenthold RJ, Heinemann SF (2003) Distribution of kainate receptor subunits at hippocampal mossy fiber synapses. J Neurosci 23:8013–8019

    PubMed  CAS  Google Scholar 

  • Delaney AJ, Jahr CE (2002) Kainate receptors differentially regulate release at two parallel fiber synapses. Neuron 36:475–482

    Article  PubMed  CAS  Google Scholar 

  • DeVries SH, Schwartz EA (1999) Kainate receptors mediate synaptic transmission between cones and “Off” bipolar cells in a mammalian retina. Nature 397:157–160

    Article  PubMed  CAS  Google Scholar 

  • Diguet E, Fernagut PO, Normand E, Centelles L, Mulle C, Tison F (2004) Experimental basis for the putative role of GluR6/kainate glutamate receptor subunit in Huntington’s disease natural history. Neurobiol Dis 15:667–675

    Article  PubMed  CAS  Google Scholar 

  • Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61

    PubMed  CAS  Google Scholar 

  • Dolman NP, Troop HM, More JC, Alt A, Knauss JL, Nistico R, Jack S, Morley RM, Bortolotto ZA, Roberts PJ, Bleakman D, Collingridge GL, Jane DE (2005) Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors. J Med Chem 48:7867–7881

    Article  PubMed  CAS  Google Scholar 

  • Dominguez E, Iyengar S, Shannon HE, Bleakman D, Alt A, Arnold BM, Bell MG, Bleisch TJ, Buckmaster JL, Castano AM, Del Prado M, Escribano A, Filla SA, Ho KH, Hudziak KJ, Jones CK, Martinez-Perez JA, Mateo A, Mathes BM, Mattiuz EL, Ogden AM, Simmons RM, Stack DR, Stratford RE, Winter MA, Wu Z, Ornstein PL (2005) Two prodrugs of potent and selective GluR5 kainate receptor antagonists active in three animal models of pain. J Med Chem 48:4200–4203

    Article  PubMed  CAS  Google Scholar 

  • Eder M, Becker K, Rammes G, Schierloh A, Azad SC, Zieglgansberger W, Dodt HU (2003) Distribution and properties of functional postsynaptic kainate receptors on neocortical layer V pyramidal neurons. J Neurosci 23:6660–6670

    PubMed  CAS  Google Scholar 

  • Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S (1991) Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature 351:745–748

    Article  PubMed  CAS  Google Scholar 

  • Engel D, Jonas P (2005) Presynaptic action potential amplification by voltage-gated Na+ channels in hippocampal mossy fiber boutons. Neuron 45:405–417

    Article  PubMed  CAS  Google Scholar 

  • Engelman HS, MacDermott AB (2004) Presynaptic ionotropic receptors and control of transmitter release. Nat Rev Neurosci 5:135–145

    Article  PubMed  CAS  Google Scholar 

  • Epsztein J, Represa A, Jorquera I, Ben-Ari Y, Crepel V (2005) Recurrent mossy fibers establish aberrant kainate receptor-operated synapses on granule cells from epileptic rats. J Neurosci 25:8229–8239

    Article  PubMed  CAS  Google Scholar 

  • Everts I, Villmann C, Hollmann M (1997) N-glycosylation is not a prerequisite for glutamate receptor function but is essential for lectin modulation. Mol Pharmacol 52:861–873

    PubMed  CAS  Google Scholar 

  • Everts I, Petroski R, Kizelsztein P, Teichberg VI, Heinemann SF, Hollmann M (1999) Lectin-induced inhibition of desensitization of the kainate receptor GluR6 depends on the activation state and can be mediated by a single native or ectopic N-linked carbohydrate side chain. J Neurosci 19:916–927

    PubMed  CAS  Google Scholar 

  • Fisahn A, Contractor A, Traub RD, Buhl EH, Heinemann SF, McBain CJ (2004) Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations. J Neurosci 24:9658–9668

    Article  PubMed  CAS  Google Scholar 

  • Fisahn A, Heinemann SF, McBain CJ (2005) The kainate receptor subunit GluR6 mediates metabotropic regulation of the slow and medium AHP currents in mouse hippocampal neurones. J Physiol (Lond) 562:199–203

    Article  CAS  Google Scholar 

  • Fleck MW, Cornell E, Mah SJ (2003) Amino-acid residues involved in glutamate receptor 6 kainate receptor gating and desensitization. J Neurosci 23:1219–1227

    PubMed  CAS  Google Scholar 

  • Frerking M, Ohliger-Frerking P (2002) AMPA receptors and kainate receptors encode different features of afferent activity. J Neurosci 22:7434-7443

    PubMed  CAS  Google Scholar 

  • Frerking M, Malenka R, Nicoll R (1998) Synaptic activation of KARs on hippocampal interneurons. Nat Neurosci 1:479–486

    Article  PubMed  CAS  Google Scholar 

  • Frerking M, Petersen CC, Nicoll RA (1999) Mechanisms underlying kainate receptor-mediated disinhibition in the hippocampus. Proc Natl Acad Sci USA 96:12917–12922

    Article  PubMed  CAS  Google Scholar 

  • Fukushima T, Shingai R, Ogurusu T, Ichinose M (2003) Inhibition of willardiine-induced currents through rat GluR6/KA-2 kainate receptor channels by zinc and other divalent cations. Neurosci Lett 349:107–110

    Article  PubMed  CAS  Google Scholar 

  • Gallyas F Jr, Ball SM, Molnar E (2003) Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. J Neurochem 86:1414–1427

    Article  PubMed  CAS  Google Scholar 

  • Garcia EP, Mehta S, Blair LA, Wells DG, Shang J, Fukushima T, Fallon JR, Garner CC, Marshall J (1998) SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron 21:727–739

    Article  PubMed  CAS  Google Scholar 

  • Ghetti A, Heinemann SF (2000) NMDA-dependent modulation of hippocampal kainate receptors by calcineurin and Ca(2+)/calmodulin-dependent protein kinase. J Neurosci 20:2766–2773

    PubMed  CAS  Google Scholar 

  • Gho M, King AE, Ben-Ari Y, Cherubini E (1986) Kainate reduces two voltage-dependent potassium conductances in rat hippocampal neurons in vitro. Brain Res 385:411–414

    Article  PubMed  CAS  Google Scholar 

  • Gregor P, O’Hara BF, Yang X, Uhl GR (1993) Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6. Neuroreport 4:1343–1346

    Article  PubMed  CAS  Google Scholar 

  • Grigorenko EV, Bell WL, Glazier S, Pons T, Deadwyler S (1998) Editing status at the Q/R site of the GluR2 and GluR6 glutamate receptor subunits in the surgically excised hippocampus of patients with refractory epilepsy. Neuroreport 9:2219–2224

    Article  PubMed  CAS  Google Scholar 

  • Gryder DS, Rogawski MA (2003) Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J Neurosci 23:7069–7074

    PubMed  CAS  Google Scholar 

  • Hayes DM, Braud S, Hurtado DE, McCallum J, Standley S, Isaac JT, Roche KW (2003) Trafficking and surface expression of the glutamate receptor subunit, KA2. Biochem Biophys Res Commun 310:8–13

    Article  PubMed  CAS  Google Scholar 

  • Henze DA, Urban NN, Barrionuevo G (2000) The multifarious hippocampal mossy fiber pathway: a review. Neuroscience 98:407–427

    Article  PubMed  CAS  Google Scholar 

  • Herb A, Burnashev N, Werner P, Sakmann B, Wisden W, Seeburg PH (1992) The KA-2 subunit of excitatory aminoacid receptor shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron 8:775–785

    Article  PubMed  CAS  Google Scholar 

  • Hirbec H, Francis JC, Lauri SE, Braithwaite SP, Coussen F, Mulle C, Dev KK, Couthino V, Meyer G, Isaac JT, Collingridge GL, Henley JM (2003) Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron 37:625–638

    Article  PubMed  CAS  Google Scholar 

  • Howe JR (1996) Homomeric and heteromeric ion channels formed from the kainate-type subunits GluR6 and KA2 have very small, but different, unitary conductances. J Neurophysiol 76:510–519

    PubMed  CAS  Google Scholar 

  • Huang YH, Dykes-Hoberg M, Tanaka K, Rothstein JD, Bergles DE (2004) Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cells. J Neurosci 24:103–111

    Article  PubMed  CAS  Google Scholar 

  • Huettner (1990) Glutamate receptor channels in rat DRG neurons-activation by kainate and quisqualate and blockade of desensitization by Con-A. Neuron 5:255–266

    Article  PubMed  CAS  Google Scholar 

  • Huettner JE (2003) Kainate receptors and synaptic transmission. Prog Neurobiol 70:387–407

    Article  PubMed  CAS  Google Scholar 

  • Huettner JE, Stack E, Wilding TJ (1998) Antagonism of neuronal kainate receptors by lanthanum and gadolinium. Neuropharmacology 37:1239–1247

    Article  PubMed  CAS  Google Scholar 

  • Hwang SJ, Pagliardini S, Rustioni A, Valtschanoff JG (2001) Presynaptic kainate receptors in primary afferents to the superficial laminae of the rat spinal cord. J Comp Neurol 436:275–289

    Article  PubMed  CAS  Google Scholar 

  • Izzi C, Barbon A, Kretz R, Sander T, Barlati S (2002) Sequencing of the GRIK1 gene in patients with juvenile absence epilepsy does not reveal mutations affecting receptor structure. Am J Med Genet 114:354–359

    Article  PubMed  Google Scholar 

  • Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, Gillberg C, Leboyer M, Bourgeron T (2002) Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 7:302–310

    Article  PubMed  CAS  Google Scholar 

  • Jaskolski F, Coussen F, Nagarajan N, Normand E, Rosenmund C, Mulle C (2004) Subunit composition and alternative splicing regulate membrane delivery of kainate receptors. J Neurosci 24:2506–2515

    Article  PubMed  CAS  Google Scholar 

  • Jaskolski F, Coussen F, Mulle C (2005a) Subcellular localization and trafficking of kainate receptors. Trends Pharmacol Sci 26:20–26

    Article  PubMed  CAS  Google Scholar 

  • Jaskolski F, Normand E, Mulle C, Coussen F (2005b) Differential trafficking of GluR7 kainate receptor subunit splice variants. J Biol Chem 280:22968–22976

    Article  PubMed  CAS  Google Scholar 

  • Jiang L, Xu J, Nedergaard M, Kang J (2001) A kainate receptor increases the efficacy of GABAergic synapses. Neuron 30:503–513

    Article  PubMed  CAS  Google Scholar 

  • Kaminski RM, Banerjee M, Rogawski MA (2004) Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology 46:1097–1104

    Article  PubMed  CAS  Google Scholar 

  • Kamiya H, Ozawa S, Manabe T (2002) Kainate receptor-dependent short-term plasticity of presynaptic Ca2+ influx at the hippocampal mossy fiber synapses. J Neurosci 22:9237–9243

    PubMed  CAS  Google Scholar 

  • Kerchner GA, Wang GD, Qiu CS, Huettner JE, Zhuo M (2001a) Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism. Neuron 32:477–488

    Article  PubMed  CAS  Google Scholar 

  • Kerchner GA, Wilding TJ, Li P, Zhuo M, Huettner JE (2001b) Presynaptic kainate receptors regulate spinal sensory transmission. J Neurosci 21:59–66

    PubMed  CAS  Google Scholar 

  • Kerchner GA, Wilding TJ, Huettner JE, Zhuo M (2002) Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn. J Neurosci 22:8010–8017

    PubMed  CAS  Google Scholar 

  • Khalilov I, Hirsch J, Cossart R, Ben-Ari Y (2002) Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors. J Neurophysiol 88:523–527

    PubMed  CAS  Google Scholar 

  • Kidd FL, Isaac JT (1999) Developmental and activity-dependent regulation of kainate receptors at thalamocortical synapses. Nature 400:569–573

    Article  PubMed  CAS  Google Scholar 

  • Kidd FL, Coumis U, Collingridge GL, Crabtree JW, Isaac JT (2002) A presynaptic kainate receptor is involved in regulating the dynamic properties of thalamocortical synapses during development. Neuron 34:635–646

    Article  PubMed  CAS  Google Scholar 

  • Ko S, Zhao MG, Toyoda H, Qiu CS, Zhuo M (2005) Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice. J Neurosci 25:977–984

    Article  PubMed  CAS  Google Scholar 

  • Köhler M, Burnashev N, Sakmann B, Seeburg P (1993) Determinants of Ca++ permeability in both TMA and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron 10:491–500

    Article  PubMed  Google Scholar 

  • Kortenbruck G, Berger E, Speckmann EJ, Musshoff U (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. Neurobiol Dis 8:459–468

    Article  PubMed  CAS  Google Scholar 

  • Lauri SE, Bortolotto ZA, Bleakman D, Ornstein PL, Lodge D, Isaac JT, Collingridge GL (2001a) A critical role of a facilitatory presynaptic kainate receptor in mossy fiber LTP. Neuron 32:697–709

    Article  PubMed  CAS  Google Scholar 

  • Lauri SE, Delany C, VR JC, Bortolotto ZA, Ornstein PL, J TRI, Collingridge GL (2001b) Synaptic activation of a presynaptic kainate receptor facilitates AMPA receptor-mediated synaptic transmission at hippocampal mossy fibre synapses. Neuropharmacology 41:907–915

    Article  PubMed  CAS  Google Scholar 

  • Lauri SE, Bortolotto ZA, Bleakman D, Ornstein PL, Lodge D, Isaac JT, Collingridge GL (2001c) A critical role of a facilitatory presynaptic kainate receptor in mossy fiber LTP. Neuron 32:697–709

    Article  PubMed  CAS  Google Scholar 

  • Lauri SE, Bortolotto ZA, Nistico R, Bleakman D, Ornstein PL, Lodge D, Isaac JT, Collingridge GL (2003) A role for Ca2+ stores in kainate receptor-dependent synaptic facilitation and LTP at mossy fiber synapses in the hippocampus. Neuron 39:327–341

    Article  PubMed  CAS  Google Scholar 

  • Lauri SE, Segerstrale M, Vesikansa A, Maingret F, Mulle C, Collingridge GL, Isaac JT, Taira T (2005) Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus. J Neurosci 25:4473–4484

    Article  PubMed  CAS  Google Scholar 

  • Lee CJ, Kong H, Manzini MC, Albuquerque C, Chao MV, MacDermott AB (2001) Kainate receptors expressed by a subpopulation of developing nociceptors rapidly switch from high to low Ca2+ permeability. J Neurosci 21:4572–4581

    PubMed  CAS  Google Scholar 

  • Lerma J (2003) Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci 4:481–495

    Article  PubMed  CAS  Google Scholar 

  • Li H, Rogawski MA (1998) GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro. Neuropharmacology 37:1279–1286

    Article  PubMed  CAS  Google Scholar 

  • Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo M (1999) Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 397:161–164

    Article  PubMed  CAS  Google Scholar 

  • Liu QS, Xu Q, Arcuino G, Kang J, Nedergaard M (2004) Astrocyte-mediated activation of neuronal kainate receptors. Proc Natl Acad Sci USA 101:3172–3177

    Article  PubMed  CAS  Google Scholar 

  • Lomeli H, Wisden W, Köhler M, Keinanen K, Sommer B, Seeburg PH (1992) High-affinity kainate and domoate receptors in rat brain. FEBS Lett 307:139–143

    Article  PubMed  CAS  Google Scholar 

  • London ED, Coyle JT (1979) Specific binding of [3H]kainic acid to receptor sites in rat brain. Mol Pharmacol 15:492–505

    PubMed  CAS  Google Scholar 

  • Loscher W, Lehmann H, Behl B, Seemann D, Teschendorf HJ, Hofmann HP, Lubisch W, Hoger T, Lemaire HG, Gross G (1999) A new pyrrolyl-quinoxalinedione series of non-NMDA glutamate receptor antagonists: pharmacological characterization and comparison with NBQX and valproate in the kindling model of epilepsy. Eur J Neurosci 11:250–262

    Article  PubMed  CAS  Google Scholar 

  • MacDonald ME, Vonsattel JP, Shrinidhi J, Couropmitree NN, Cupples LA, Bird ED, Gusella JF, Myers RH (1999) Evidence for the GluR6 gene associated with younger onset age of Huntington’s disease. Neurology 53:1330–1332

    PubMed  CAS  Google Scholar 

  • Mah SJ, Cornell E, Mitchell NA, Fleck MW (2005) Glutamate receptor trafficking: endoplasmic reticulum quality control involves ligand binding and receptor function. J Neurosci 25:2215–2225

    Article  PubMed  CAS  Google Scholar 

  • Marchal C, Mulle C (2004) Postnatal maturation of mossy fibre excitatory transmission in mouse CA3 pyramidal cells: a potential role for kainate receptors. J Physiol (Lond) 561:27–37

    Article  CAS  Google Scholar 

  • Martin S, Henley JM (2004) Activity-dependent endocytic sorting of kainate receptors to recycling or degradation pathways. EMBO J 23:4749–4759

    Article  PubMed  CAS  Google Scholar 

  • Mathern GW, Pretorius JK, Kornblum HI, Mendoza D, Lozada A, Leite JP, Chimelli L, Born DE, Fried I, Sakamoto AC, Assirati JA, Peacock WJ, Ojemann GA, Adelson PD (1998) Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients. Neurobiol Dis 5:151–176

    Article  PubMed  CAS  Google Scholar 

  • Mayer ML (2005) Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron 45:539–552

    Article  PubMed  CAS  Google Scholar 

  • Mayer ML, Ghosal A, Dolman NP, Jane DE (2006) Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. J Neurosci 26:2852–2861

    Article  PubMed  CAS  Google Scholar 

  • Mehta S, Wu H, Garner CC, Marshall J (2001) Molecular mechanisms regulating the differential association of kainate receptor subunits with SAP90/PSD-95 and SAP 97. J Biol Chem 276:16092–16099

    Article  PubMed  CAS  Google Scholar 

  • Melyan Z, Wheal HV, Lancaster B (2002) Metabotropic-mediated kainate receptor regulation of IsAHP and excitability in pyramidal cells. Neuron 34:107–114

    Article  PubMed  CAS  Google Scholar 

  • Melyan Z, Lancaster B, Wheal HV (2004) Metabotropic regulation of intrinsic excitability by synaptic activation of kainate receptors. J Neurosci 24:4530–4534

    Article  PubMed  CAS  Google Scholar 

  • Min MY, Melyan Z, Kullmann DM (1999) Synaptically released glutamate reduces gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus via kainate receptors. Proc Natl Acad Sci USA 96:9932–9937

    Article  PubMed  CAS  Google Scholar 

  • Moghaddam B (2003) Bringing order to the glutamate chaos in schizophrenia. Neuron 40:881–884

    Article  PubMed  CAS  Google Scholar 

  • Monaghan D, Cotman C (1982) The distribution of [3H]-kainic acid binding sites in rat CNS as determined by autoradiography. Brain Research 252:91–100

    Article  PubMed  CAS  Google Scholar 

  • More JC, Nistico R, Dolman NP, Clarke VR, Alt AJ, Ogden AM, Buelens FP, Troop HM, Kelland EE, Pilato F, Bleakman D, Bortolotto ZA, Collingridge GL, Jane DE (2004) Characterisation of UBP296: a novel, potent and selective kainate receptor antagonist. Neuropharmacology 47:46–64

    Article  PubMed  CAS  Google Scholar 

  • Mott DD, Washburn MS, Zhang S, Dingledine RJ (2003) Subunit-dependent modulation of kainate receptors by extracellular protons and polyamines. J Neurosci 23:1179–1188

    PubMed  CAS  Google Scholar 

  • Mulle C, Sailer A, Perez-Otano I, Dickinson-Anson H, Castillo PE, Bureau I, Maron C, Gage FH, Mann JR, Bettler B, Heinemann SF (1998) Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature 392:601–605

    Article  PubMed  CAS  Google Scholar 

  • Mulle C, Sailer A, Swanson GT, Brana C, O’Gorman S, Bettler B, Heinemann SF (2000) Subunit composition of kainate receptors in hippocampal interneurons. Neuron 28:475–484

    Article  PubMed  CAS  Google Scholar 

  • Nadler J (1978) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271:676–677

    Article  PubMed  CAS  Google Scholar 

  • Nadler JV (2003) The recurrent mossy fiber pathway of the epileptic brain. Neurochem Res 28:1649–1658

    Article  PubMed  CAS  Google Scholar 

  • Nakazawa K, Quirk MC, Chitwood RA, Watanabe M, Yeckel MF, Sun LD, Kato A, Carr CA, Johnston D, Wilson MA, Tonegawa S (2002) Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297:211–218

    Article  PubMed  CAS  Google Scholar 

  • Nanao MH, Green T, Stern-Bach Y, Heinemann SF, Choe S (2005) Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid. Proc Natl Acad Sci USA 102:1708–1713

    Article  PubMed  CAS  Google Scholar 

  • Naur P, Vestergaard B, Skov LK, Egebjerg J, Gajhede M, Kastrup JS (2005) Crystal structure of the kainate receptor GluR5 ligand-binding core in complex with (S)-glutamate. FEBS Lett 579:1154–1160

    Article  PubMed  CAS  Google Scholar 

  • Nvue R, Gorianov V, Best N, Sundstrom LE, Pringle AK (2004) Time window and pharmacological characterisation of kainate-mediated preconditioning in organotypic rat hippocampal slice cultures. Neurosci Lett 367:365–368

    Article  PubMed  CAS  Google Scholar 

  • O’Neill MJ, Bond A, Ornstein PL, Ward MA, Hicks CA, Hoo K, Bleakman D, Lodge D (1998) Decahydroisoquinolines: novel competitive AMPA/kainate antagonists with neuroprotective effects in global cerebral ischaemia. Neuropharmacology 37:1211–1222

    Article  PubMed  CAS  Google Scholar 

  • O’Neill MJ, Bogaert L, Hicks CA, Bond A, Ward MA, Ebinger G, Ornstein PL, Michotte Y, Lodge D (2000) LY377770, a novel iGlu5 kainate receptor antagonist with neuroprotective effects in global and focal cerebral ischaemia.Neuropharmacology 39:1575–1588

    Article  PubMed  CAS  Google Scholar 

  • Park Y, Jo J, Isaac JT, Cho K (2006) Long-term depression of kainate receptor-mediated synaptic transmission. Neuron 49:95–106

    Article  PubMed  CAS  Google Scholar 

  • Partin KM, Patneau DK, Winters CA, Mayer ML, Buonanno A (1993) Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 11:1069–1082

    Article  PubMed  CAS  Google Scholar 

  • Paternain A, Morales M, Lerma J (1995) Selective antagonism of AMPA receptor unmasks kainate receptor-mediated responses in hippocampal neurons. Neuron 14:185–189

    Article  PubMed  CAS  Google Scholar 

  • Paternain AV, Rodriguez-Moreno A, Villarroel A, Lerma J (1998) Activation and desensitization properties of native and recombinant kainate receptors. Neuropharmacology 37:1249–1259

    Article  PubMed  CAS  Google Scholar 

  • Paternain AV, Herrera MT, Nieto MA, Lerma J (2000) GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors. J Neurosci 20:196–205

    PubMed  CAS  Google Scholar 

  • Paternain AV, Cohen A, Stern-Bach Y, Lerma J (2003) A role for extracellular Na+ in the channel gating of native and recombinant kainate receptors. J Neurosci 23:8641-8648

    PubMed  CAS  Google Scholar 

  • Patneau DK, Mayer ML, Jane DE, Watkins JC (1992)Activation and desensitization of AMPA/kainate receptors by novel derivatives of willardiine.J Neurosci 12:595–606

    PubMed  CAS  Google Scholar 

  • Pedregal C, Collado I, Escribano A, Ezquerra J, Dominguez C, Mateo AI, Rubio A, Baker SR, Goldsworthy J, Kamboj RK, Ballyk BA, Hoo K, Bleakman D (2000) 4-Alkyl- and 4-cinnamylglutamic acid analogues are potent GluR5 kainate receptor agonists. J Med Chem 43:1958–1968

    Article  PubMed  CAS  Google Scholar 

  • Pei DS, Wang XT, Liu Y, Sun YF, Guan QH, Wang W, Yan JZ, Zong YY, Xu TL, Zhang GY (2006) Neuroprotection against ischaemic brain injury by a GluR6-9c peptide containing the TAT protein transduction sequence. Brain 129:465–479

    Article  PubMed  Google Scholar 

  • Petralia R, Wang Y, Wenthold R (1994) Histological and ultrastructural localization of the kainate receptor subunits KA2, and GluR6/7, in the rat central nervous system using selective antipeptide antibodies. J Comp Neurol 349:85–110

    Article  PubMed  CAS  Google Scholar 

  • Pinheiro PS, Rodrigues RJ, Rebola N, Xapelli S, Oliveira CR, Malva JO (2005a) Presynaptic kainate receptors are localized close to release sites in rat hippocampal synapses. Neurochem Int 47:309–316

    Article  PubMed  CAS  Google Scholar 

  • Pinheiro PS, et al (2005b) Soc Neurosci Abstr

  • Procter MJ, Houghton AK, Faber ES, Chizh BA, Ornstein PL, Lodge D, Headley PM (1998) Actions of kainate and AMPA selective glutamate receptor ligands on nociceptive processing in the spinal cord. Neuropharmacology 37:1287–1297

    Article  PubMed  CAS  Google Scholar 

  • Raymond LA, Blackstone CD, Huganir RL (1993) Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase. Nature 361:637–641

    Article  PubMed  CAS  Google Scholar 

  • Ren Z, Riley NJ, Garcia EP, Sanders JM, Swanson GT, Marshall J (2003a) Multiple trafficking signals regulate kainate receptor KA2 subunit surface expression. J Neurosci 23:6608–6616

    PubMed  Google Scholar 

  • Ren Z, Riley NJ, Needleman LA, Sanders JM, Swanson GT, Marshall J (2003b) Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal. J Biol Chem 278:52700–52709

    Google Scholar 

  • Rodriguez-Moreno A, Lerma J (1998) Kainate receptor modulation of GABA release involves a metabotropic function. Neuron 20:1211–1218

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Moreno A, Herreras O, Lerma J (1997) Kainate receptors presynaptically downregulate GABAergic inhibition in the rat hippocampus. Neuron 19:893–901

    Article  PubMed  CAS  Google Scholar 

  • Rozas JL, Paternain AV, Lerma J (2003) Noncanonical signaling by ionotropic kainate receptors. Neuron 39:543–553

    Article  PubMed  CAS  Google Scholar 

  • Rubinsztein DC, Leggo J, Chiano M, Dodge A, Norbury G, Rosser E, Craufurd D (1997) Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease. Proc Natl Acad Sci USA 94:3872–3876

    Article  PubMed  CAS  Google Scholar 

  • Ruiz A, Sachidhanandam S, Utvik JK, Coussen F, Mulle C (2005) Distinct subunits in heteromeric kainate receptors mediate ionotropic and metabotropic function at hippocampal mossy fiber synapses. J Neurosci 25:11710–11718

    Article  PubMed  CAS  Google Scholar 

  • Sakai R, Swanson GT, Shimamoto K, Green T, Contractor A, Ghetti A, Tamura-Horikawa Y, Oiwa C, Kamiya H (2001) Pharmacological properties of the potent epileptogenic amino acid dysiherbaine, a novel glutamate receptor agonist isolated from the marine sponge Dysidea herbacea. J Pharmacol Exp Ther 296:650–658

    PubMed  CAS  Google Scholar 

  • Sakimura K, Morita T, Kushiya E, Mishina M (1992) Primary structure and expression of the gamma 2 subunit of the glutamate receptor channel selective for kainate. Neuron 8:267–274

    Article  PubMed  CAS  Google Scholar 

  • Salin P, Scanziani M, Malenka R, Nicoll R (1996) Distinct short-term plasticity at two excitatory synapses in the hippocampus. Proc Natl Acad Sci USA 93:13304–13309

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Gomez MV, Matute C (1999) AMPA and kainate receptors each mediate excitotoxicity in oligodendroglial cultures. Neurobiol Dis 6:475–485

    Article  PubMed  CAS  Google Scholar 

  • Sander T, Janz D, Ramel C, Ross CA, Paschen W, Hildmann T, Wienker TF, Bianchi A, Bauer G, Sailer U, et al (1995) Refinement of map position of the human GluR6 kainate receptor gene (GRIK2) and lack of association and linkage with idiopathic generalized epilepsies. Neurology 45:1713–1720

    PubMed  CAS  Google Scholar 

  • Sander T, Hildmann T, Kretz R, Furst R, Sailer U, Bauer G, Schmitz B, Beck-Mannagetta G, Wienker TF, Janz D (1997) Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene (GRIK1) polymorphism. Am J Med Genet 74:416–421

    Article  PubMed  CAS  Google Scholar 

  • Sanders JM, Ito K, Settimo L, Pentikainen OT, Shoji M, Sasaki M, Johnson MS, Sakai R, Swanson GT (2005) Divergent pharmacological activity of novel marine-derived excitatory amino acids on glutamate receptors. J Pharmacol Exp Ther 314:1068–1078

    Article  PubMed  CAS  Google Scholar 

  • Savinainen A, Garcia EP, Dorow D, Marshall J, Liu YF (2001) Kainate receptor activation induces mixed lineage kinase-mediated cellular signaling cascades via post-synaptic density protein 95. J Biol Chem 276:11382–11386

    Article  PubMed  CAS  Google Scholar 

  • Schiffer HH, Swanson GT, Heinemann SF (1997) Rat GluR7 and a carboxy-terminal splice variant, GluR7b, are functional kainate receptor subunits with a low sensitivity to glutamate. Neuron 19:1141–1146

    Article  PubMed  CAS  Google Scholar 

  • Schmitz D, Frerking M, Nicoll RA (2000) Synaptic activation of presynaptic kainate receptors on hippocampal mossy fiber synapses. Neuron 27:327–338

    Article  PubMed  CAS  Google Scholar 

  • Schmitz D, Mellor J, Nicoll RA (2001) Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science 291:1972–1976

    Article  PubMed  CAS  Google Scholar 

  • Schmitz D, Mellor J, Breustedt J, Nicoll RA (2003) Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation. Nat Neurosci 6:1058–1063

    Article  PubMed  CAS  Google Scholar 

  • Semyanov A, Kullmann DM (2001) Kainate receptor-dependent axonal depolarization and action potential initiation in interneurons. Nat Neurosci 4:718–723

    Article  PubMed  CAS  Google Scholar 

  • Shibata H, Joo A, Fujii Y, Tani A, Makino C, Hirata N, Kikuta R, Ninomiya H, Tashiro N, Fukumaki Y (2001) Association study of polymorphisms in the GluR5 kainate receptor gene (GRIK1) with schizophrenia. Psychiatr Genet 11:139–144

    Article  PubMed  CAS  Google Scholar 

  • Shibata H, Shibata A, Ninomiya H, Tashiro N, Fukumaki Y (2002) Association study of polymorphisms in the GluR6 kainate receptor gene (GRIK2) with schizophrenia. Psychiatry Res 113:59–67

    Article  PubMed  CAS  Google Scholar 

  • Shibata H, Aramaki T, Sakai M, Ninomiya H, Tashiro N, Iwata N, Ozaki N, Fukumaki Y (2006) Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia. Psychiatry Res 141:39–51

    Article  PubMed  CAS  Google Scholar 

  • Shuang M, Liu J, Jia MX, Yang JZ, Wu SP, Gong XH, Ling YS, Ruan Y, Yang XL, Zhang D (2004) Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios. Am J Med Genet [B] Neuropsychiatr Genet 131:48–50

    Article  Google Scholar 

  • Simmons RM, Li DL, Hoo KH, Deverill M, Ornstein PL, Iyengar S (1998) Kainate GluR5 receptor subtype mediates the nociceptive response to formalin in the rat. Neuropharmacology 37:25–36

    Article  PubMed  CAS  Google Scholar 

  • Small B, Thomas J, Kemp M, Hoo K, Ballyk B, Deverill M, Ogden AM, Rubio A, Pedregal C, Bleakman D (1998) LY339434, a GluR5 kainate receptor agonist. Neuropharmacology 37:1261–1267

    Article  PubMed  CAS  Google Scholar 

  • Smolders I, Bortolotto ZA, Clarke VR, Warre R, Khan GM, O’Neill MJ, Ornstein PL, Bleakman D, Ogden A, Weiss B, Stables JP, Ho KH, Ebinger G, Collingridge GL, Lodge D, Michotte Y (2002) Antagonists of GLU(K5)-containing kainate receptors prevent pilocarpine-induced limbic seizures. Nat Neurosci 5:796–804

    PubMed  CAS  Google Scholar 

  • Sommer B, Burnashev N, Verdoorn TA, Keinänen K, Sakmann B, Seeburg PH (1992) A glutamate receptor with high affinity for domoate and kainate. EMBO J 11:1651–1656

    PubMed  CAS  Google Scholar 

  • Standley S, Roche KW, McCallum J, Sans N, Wenthold RJ (2000) PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron 28:887–898

    Article  PubMed  CAS  Google Scholar 

  • Sun W, Kang Y, Kim IH, Kim EH, Rhyu IJ, Kim HJ, Kim H (2006) Inhibition of rat brain inositol 1,4,5-trisphosphate 3-kinase A expression by kainic acid.Neurosci Lett 392:181–186

    Article  PubMed  CAS  Google Scholar 

  • Swanson GT, Feldmeyer D, Kaneda M, Cull-Candy SG (1996) Effect of RNA editing and subunit co-assembly single-channel properties of recombinant kainate receptors. J Physiol (Lond) 492:129–142

    CAS  Google Scholar 

  • Swanson GT, Green T, Heinemann SF (1998) Kainate receptors exhibit differential sensitivities to (S)-5-iodowillardiine. Mol Pharmacol 53:942–949

    PubMed  CAS  Google Scholar 

  • Swanson GT, Green T, Sakai R, Contractor A, Che W, Kamiya H, Heinemann SF (2002) Differential activation of individual subunits in heteromeric kainate receptors. Neuron 34:589–598

    Article  PubMed  CAS  Google Scholar 

  • Takago H, Nakamura Y, Takahashi T (2005) G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held. Proc Natl Acad Sci USA 102:7368–7373

    Article  PubMed  CAS  Google Scholar 

  • Tashiro A, Dunaevsky A, Blazeski R, Mason CA, Yuste R (2003) Bidirectional regulation of hippocampal mossy fiber filopodial motility by kainate receptors: a two-step model of synaptogenesis. Neuron 38:773–784

    Article  PubMed  CAS  Google Scholar 

  • Telfeian AE, Federoff HJ, Leone P, During MJ, Williamson A (2000) Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous nonsynaptic bursting in vitro. Neurobiol Dis 7:362–374

    Article  PubMed  CAS  Google Scholar 

  • Traynelis SF, Wahl P (1997) Control of rat GluR6 glutamate receptor open probability by protein kinase A and calcineurin. J Physiol (Lond) 503:513–531

    Article  CAS  Google Scholar 

  • Valluru L, Xu J, Zhu Y, Yan S, Contractor A, Swanson GT (2005) Ligand binding is a critical requirement for plasma membrane expression of heteromeric kainate receptors. J Biol Chem 280:6085–6093

    Article  PubMed  CAS  Google Scholar 

  • Vignes M, Collingridge GL (1997) The synaptic activation of kainate receptors. Nature 388:179–182

    Article  PubMed  CAS  Google Scholar 

  • Vissel B, Royle GA, Christie BR, Schiffer HH, Ghetti A, Tritto T, Perez-Otano I, Radcliffe RA, Seamans J, Sejnowski T, Wehner JM, Collins AC, O’Gorman S, Heinemann SF (2001) The role of RNA editing of kainate receptors in synaptic plasticity and seizures. Neuron 29:217–227

    Article  PubMed  CAS  Google Scholar 

  • Vivithanaporn P, Yan S, Swanson GT (2006) Intracellular trafficking of KA2 kainate receptors mediated by interactions with coatomer protein complex I (COPI) and 14-3-3 chaperone systems. J Biol Chem 281:15475–15484

    Article  PubMed  CAS  Google Scholar 

  • Wang LY, Taverna FA, Huang XP, MacDonald JF, Hampson DR (1993) Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase. Science 259:1173–1175

    Article  PubMed  CAS  Google Scholar 

  • Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 21:165–204

    Article  PubMed  CAS  Google Scholar 

  • Werner P, Voigt M, Keinänen K, Wisden W, Seeburg PH (1991) Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature 351:742–744

    Article  PubMed  CAS  Google Scholar 

  • Wilding TJ, Huettner JE (1996) Antagonist pharmacology of kainate- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring receptors. Mol Pharmacol 49:540–546

    PubMed  CAS  Google Scholar 

  • Wilding TJ, Huettner JE (2001) Functional diversity and developmental changes in rat neuronal kainate receptors. J Physiol (Lond) 532:411–421

    Article  CAS  Google Scholar 

  • Wilding TJ, Chai YH, Huettner JE (1998) Inhibition of rat neuronal kainate receptors by cis-unsaturated fatty acids. J Physiol (Lond) 513:331–339

    Article  CAS  Google Scholar 

  • Wilding TJ, Zhou Y, Huettner JE (2005) Q/R site editing controls kainate receptor inhibition by membrane fatty acids. J Neurosci 25:9470–9478

    Article  PubMed  CAS  Google Scholar 

  • Wilson GM, Flibotte S, Chopra V, Melnyk BL, Honer WG, Holt RA (2006) DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling. Hum Mol Genet 15:743–749

    Article  PubMed  CAS  Google Scholar 

  • Wisden W, Seeburg P (1993) A complex mosaic of high-affinity kainate receptors in rat brain. J Neurosci 13:3582–3598

    PubMed  CAS  Google Scholar 

  • Wong LA, Mayer ML (1993) Differential modulation by cyclothiazide and concanavalin A of desensitization at native alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- and kainate-preferring glutamate receptors. Mol Pharmacol 44:504–510

    PubMed  CAS  Google Scholar 

  • Wong LA, Mayer ML, Jane DE, Watkins JC (1994) Willardiines differentiate agonist binding sites for kainate- versus AMPA-preferring glutamate receptors in DRG and hippocampal neurons. J Neurosci 14:3881–3897

    PubMed  CAS  Google Scholar 

  • Wu LJ, Zhao MG, Toyoda H, Ko SW, Zhuo M (2005) Kainate receptor-mediated synaptic transmission in the adult anterior cingulate cortex. J Neurophysiol 94:1805–1813

    Article  PubMed  CAS  Google Scholar 

  • Yan S, Sanders JM, Xu J, Zhu Y, Contractor A, Swanson GT (2004) A C-terminal determinant of GluR6 kainate receptor trafficking. J Neurosci 24:679–691

    Article  PubMed  CAS  Google Scholar 

  • Youn DH, Randic M (2004) Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit. J Physiol (Lond) 555:683–698

    Article  CAS  Google Scholar 

  • Yue KT, MacDonald JF, Pekhletski R, Hampson DR (1995) Differential effects of lectins on recombinant glutamate receptors. Eur J Pharmacol 291:229–235

    Article  PubMed  CAS  Google Scholar 

  • Zerangue N, Schwappach B, Jan YN, Jan LY (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22:537–548

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Zhang D, McQuade JS, Behbehani M, Tsien JZ, Xu M (2002) c-fos regulates neuronal excitability and survival. Nat Genet 30:416–420

    Article  PubMed  CAS  Google Scholar 

  • Zhou LM, Gu ZQ, Costa AM, Yamada KA, Mansson PE, Giordano T, Skolnick P, Jones KA (1997) (2S,4R)-4-methylglutamic acid (SYM 2081): a selective, high-affinity ligand for kainate receptors. J Pharmacol Exp Ther 280:422–427

    PubMed  CAS  Google Scholar 

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We are grateful to David Perrais and Neil Davies for careful reading of the manuscript.

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Correspondence to Christophe Mulle.

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The work performed in the lab of C. Mulle was supported by grants from the Centre National de la Recherche Scientifique, by the French Ministry of Research and by the EU commission (contracts QLRT-2000-02089 and 2005-511995).

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Pinheiro, P., Mulle, C. Kainate receptors. Cell Tissue Res 326, 457–482 (2006). https://doi.org/10.1007/s00441-006-0265-6

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