Cell and Tissue Research

, Volume 326, Issue 2, pp 457–482 | Cite as

Kainate receptors

  • Paulo Pinheiro
  • Christophe Mulle


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.


Synapse Glutamate receptors Synaptic plasticity Trafficking Excitotoxicity 



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


  1. 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 298:846–850PubMedCrossRefGoogle Scholar
  2. Agrawal S, Evans R (1986) The primary afferent depolarizing action of kainate in the rat. Br J Pharmacol 87:345–355PubMedGoogle Scholar
  3. 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 26:3220–3228PubMedCrossRefGoogle Scholar
  4. Ali AB (2003) Involvement of post-synaptic kainate receptors during synaptic transmission between unitary connections in rat neocortex. Eur J Neurosci 17:2344–2350PubMedCrossRefGoogle Scholar
  5. 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 21:2992–2999PubMedGoogle Scholar
  6. Alle H, Geiger JR (2006) Combined analog and action potential coding in hippocampal mossy fibers. Science 311:1290–1293PubMedCrossRefGoogle Scholar
  7. 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 46:793–806PubMedCrossRefGoogle Scholar
  8. Awatramani GB, Price GD, Trussell LO (2005) Modulation of transmitter release by presynaptic resting potential and background calcium levels. Neuron 48:109–121PubMedCrossRefGoogle Scholar
  9. 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 15:1987–1991PubMedCrossRefGoogle Scholar
  10. Bahn S, Volk B, Wisden W (1994) Kainate receptor gene expression in the developing rat brain. J Neurosci 14:5525–5547PubMedGoogle Scholar
  11. 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) 502:575–589CrossRefGoogle Scholar
  12. 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 25:5259–5271PubMedCrossRefGoogle Scholar
  13. Barbon A, Barlati S (2000) Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1. Cytogenet Cell Genet 88:236–239PubMedCrossRefGoogle Scholar
  14. Barbon A, Vallini I, Barlati S (2001) Genomic organization of the human GRIK2 gene and evidence for multiple splicing variants. Gene 274:187–197PubMedCrossRefGoogle Scholar
  15. 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 7:416–418PubMedCrossRefGoogle Scholar
  16. Ben-Ari Y, Cossart R (2000) Kainate, a double agent that generates seizures: two decades of progress. Trends Neurosci 23:580–587PubMedCrossRefGoogle Scholar
  17. Ben-Ari Y, Cherubini E, Corradetti R, Gaiarsa JL (1989) Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol (Lond) 416:303–325Google Scholar
  18. 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 11:604–616PubMedCrossRefGoogle Scholar
  19. 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 8:1209–1219PubMedCrossRefGoogle Scholar
  20. Bettler B, Mulle C (1995) AMPA and kainate receptors. Neuropharmacology 34:123–139PubMedCrossRefGoogle Scholar
  21. 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 5:583–595PubMedCrossRefGoogle Scholar
  22. Bischofberger J, Geiger JR, Jonas P (2002) Timing and efficacy of Ca2+ channel activation in hippocampal mossy fiber boutons. J Neurosci 22:10593–10602PubMedGoogle Scholar
  23. 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 402:297–301PubMedCrossRefGoogle Scholar
  24. Bowie D (2002) External anions and cations distinguish between AMPA and kainate receptor gating mechanisms. J Physiol (Lond) 539:725–733CrossRefGoogle Scholar
  25. Bowie D, Mayer ML (1995) Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron 15:453–462PubMedCrossRefGoogle Scholar
  26. 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) 547:373–385CrossRefGoogle Scholar
  27. Breustedt J, Schmitz D (2004) Assessing the role of GLUK5 and GLUK6 at hippocampal mossy fiber synapses. J Neurosci 24:10093–10098PubMedCrossRefGoogle Scholar
  28. 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 19:653–663PubMedGoogle Scholar
  29. 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 97:6838–6843PubMedCrossRefGoogle Scholar
  30. 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) 485:403–418Google Scholar
  31. Casassus G, Mulle C (2002) Functional characterization of kainate receptors in the mouse nucleus accumbens. Neuropharmacology 42:603–611PubMedCrossRefGoogle Scholar
  32. Castillo PE, Malenka RC, Nicoll RA (1997) Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature 388:182–186PubMedCrossRefGoogle Scholar
  33. Chergui K, Bouron A, Normand E, Mulle C (2000) Functional GluR6 kainate receptors in the striatum: indirect downregulation of synaptic transmission. J Neurosci 20:2175–2182PubMedGoogle Scholar
  34. 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) 548:723–730CrossRefGoogle Scholar
  35. Christensen JK, Paternain AV, Selak S, Ahring PK, Lerma J (2004) A mosaic of functional kainate receptors in hippocampal interneurons. J Neurosci 24:8986–8993PubMedCrossRefGoogle Scholar
  36. 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 389:599–603PubMedCrossRefGoogle Scholar
  37. 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 20:8269–8278PubMedGoogle Scholar
  38. 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 29:209–216PubMedCrossRefGoogle Scholar
  39. 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 23:422–429PubMedGoogle Scholar
  40. 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 1:470–478PubMedCrossRefGoogle Scholar
  41. 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 35:147–159PubMedCrossRefGoogle Scholar
  42. 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 22:6426–6436PubMedGoogle Scholar
  43. 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 47:555–566PubMedCrossRefGoogle Scholar
  44. Cui C, Mayer ML (1999) Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. J Neurosci 19:8281–8291PubMedGoogle Scholar
  45. Cunha RA, Malva JO, Ribeiro JA (2000) Pertussis toxin prevents presynaptic inhibition by kainate receptors of rat hippocampal [(3)H]GABA release. FEBS Lett 469:159–162PubMedCrossRefGoogle Scholar
  46. Darstein M, Petralia RS, Swanson GT, Wenthold RJ, Heinemann SF (2003) Distribution of kainate receptor subunits at hippocampal mossy fiber synapses. J Neurosci 23:8013–8019PubMedGoogle Scholar
  47. Delaney AJ, Jahr CE (2002) Kainate receptors differentially regulate release at two parallel fiber synapses. Neuron 36:475–482PubMedCrossRefGoogle Scholar
  48. DeVries SH, Schwartz EA (1999) Kainate receptors mediate synaptic transmission between cones and “Off” bipolar cells in a mammalian retina. Nature 397:157–160PubMedCrossRefGoogle Scholar
  49. 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 15:667–675PubMedCrossRefGoogle Scholar
  50. Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61PubMedGoogle Scholar
  51. 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 48:7867–7881PubMedCrossRefGoogle Scholar
  52. 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 48:4200–4203PubMedCrossRefGoogle Scholar
  53. 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 23:6660–6670PubMedGoogle Scholar
  54. 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 351:745–748PubMedCrossRefGoogle Scholar
  55. Engel D, Jonas P (2005) Presynaptic action potential amplification by voltage-gated Na+ channels in hippocampal mossy fiber boutons. Neuron 45:405–417PubMedCrossRefGoogle Scholar
  56. Engelman HS, MacDermott AB (2004) Presynaptic ionotropic receptors and control of transmitter release. Nat Rev Neurosci 5:135–145PubMedCrossRefGoogle Scholar
  57. 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 25:8229–8239PubMedCrossRefGoogle Scholar
  58. 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 52:861–873PubMedGoogle Scholar
  59. 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 19:916–927PubMedGoogle Scholar
  60. 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 24:9658–9668PubMedCrossRefGoogle Scholar
  61. 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) 562:199–203CrossRefGoogle Scholar
  62. Fleck MW, Cornell E, Mah SJ (2003) Amino-acid residues involved in glutamate receptor 6 kainate receptor gating and desensitization. J Neurosci 23:1219–1227PubMedGoogle Scholar
  63. Frerking M, Ohliger-Frerking P (2002) AMPA receptors and kainate receptors encode different features of afferent activity. J Neurosci 22:7434-7443PubMedGoogle Scholar
  64. Frerking M, Malenka R, Nicoll R (1998) Synaptic activation of KARs on hippocampal interneurons. Nat Neurosci 1:479–486PubMedCrossRefGoogle Scholar
  65. Frerking M, Petersen CC, Nicoll RA (1999) Mechanisms underlying kainate receptor-mediated disinhibition in the hippocampus. Proc Natl Acad Sci USA 96:12917–12922PubMedCrossRefGoogle Scholar
  66. 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 349:107–110PubMedCrossRefGoogle Scholar
  67. Gallyas F Jr, Ball SM, Molnar E (2003) Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. J Neurochem 86:1414–1427PubMedCrossRefGoogle Scholar
  68. 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 21:727–739PubMedCrossRefGoogle Scholar
  69. Ghetti A, Heinemann SF (2000) NMDA-dependent modulation of hippocampal kainate receptors by calcineurin and Ca(2+)/calmodulin-dependent protein kinase. J Neurosci 20:2766–2773PubMedGoogle Scholar
  70. 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 385:411–414PubMedCrossRefGoogle Scholar
  71. Gregor P, O’Hara BF, Yang X, Uhl GR (1993) Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6. Neuroreport 4:1343–1346PubMedCrossRefGoogle Scholar
  72. 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 9:2219–2224PubMedCrossRefGoogle Scholar
  73. Gryder DS, Rogawski MA (2003) Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J Neurosci 23:7069–7074PubMedGoogle Scholar
  74. 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 310:8–13PubMedCrossRefGoogle Scholar
  75. Henze DA, Urban NN, Barrionuevo G (2000) The multifarious hippocampal mossy fiber pathway: a review. Neuroscience 98:407–427PubMedCrossRefGoogle Scholar
  76. 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 8:775–785PubMedCrossRefGoogle Scholar
  77. 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 37:625–638PubMedCrossRefGoogle Scholar
  78. 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 76:510–519PubMedGoogle Scholar
  79. 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 24:103–111PubMedCrossRefGoogle Scholar
  80. Huettner (1990) Glutamate receptor channels in rat DRG neurons-activation by kainate and quisqualate and blockade of desensitization by Con-A. Neuron 5:255–266PubMedCrossRefGoogle Scholar
  81. Huettner JE (2003) Kainate receptors and synaptic transmission. Prog Neurobiol 70:387–407PubMedCrossRefGoogle Scholar
  82. Huettner JE, Stack E, Wilding TJ (1998) Antagonism of neuronal kainate receptors by lanthanum and gadolinium. Neuropharmacology 37:1239–1247PubMedCrossRefGoogle Scholar
  83. 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 436:275–289PubMedCrossRefGoogle Scholar
  84. 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 114:354–359PubMedCrossRefGoogle Scholar
  85. 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 7:302–310PubMedCrossRefGoogle Scholar
  86. 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 24:2506–2515PubMedCrossRefGoogle Scholar
  87. Jaskolski F, Coussen F, Mulle C (2005a) Subcellular localization and trafficking of kainate receptors. Trends Pharmacol Sci 26:20–26PubMedCrossRefGoogle Scholar
  88. Jaskolski F, Normand E, Mulle C, Coussen F (2005b) Differential trafficking of GluR7 kainate receptor subunit splice variants. J Biol Chem 280:22968–22976PubMedCrossRefGoogle Scholar
  89. Jiang L, Xu J, Nedergaard M, Kang J (2001) A kainate receptor increases the efficacy of GABAergic synapses. Neuron 30:503–513PubMedCrossRefGoogle Scholar
  90. Kaminski RM, Banerjee M, Rogawski MA (2004) Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology 46:1097–1104PubMedCrossRefGoogle Scholar
  91. 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 22:9237–9243PubMedGoogle Scholar
  92. 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 32:477–488PubMedCrossRefGoogle Scholar
  93. Kerchner GA, Wilding TJ, Li P, Zhuo M, Huettner JE (2001b) Presynaptic kainate receptors regulate spinal sensory transmission. J Neurosci 21:59–66PubMedGoogle Scholar
  94. Kerchner GA, Wilding TJ, Huettner JE, Zhuo M (2002) Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn. J Neurosci 22:8010–8017PubMedGoogle Scholar
  95. Khalilov I, Hirsch J, Cossart R, Ben-Ari Y (2002) Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors. J Neurophysiol 88:523–527PubMedGoogle Scholar
  96. Kidd FL, Isaac JT (1999) Developmental and activity-dependent regulation of kainate receptors at thalamocortical synapses. Nature 400:569–573PubMedCrossRefGoogle Scholar
  97. 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 34:635–646PubMedCrossRefGoogle Scholar
  98. 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 25:977–984PubMedCrossRefGoogle Scholar
  99. 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 10:491–500PubMedCrossRefGoogle Scholar
  100. 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 8:459–468PubMedCrossRefGoogle Scholar
  101. 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 32:697–709PubMedCrossRefGoogle Scholar
  102. 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 41:907–915PubMedCrossRefGoogle Scholar
  103. 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 32:697–709PubMedCrossRefGoogle Scholar
  104. 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 39:327–341PubMedCrossRefGoogle Scholar
  105. 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 25:4473–4484PubMedCrossRefGoogle Scholar
  106. 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 21:4572–4581PubMedGoogle Scholar
  107. Lerma J (2003) Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci 4:481–495PubMedCrossRefGoogle Scholar
  108. Li H, Rogawski MA (1998) GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro. Neuropharmacology 37:1279–1286PubMedCrossRefGoogle Scholar
  109. Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo M (1999) Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature 397:161–164PubMedCrossRefGoogle Scholar
  110. Liu QS, Xu Q, Arcuino G, Kang J, Nedergaard M (2004) Astrocyte-mediated activation of neuronal kainate receptors. Proc Natl Acad Sci USA 101:3172–3177PubMedCrossRefGoogle Scholar
  111. Lomeli H, Wisden W, Köhler M, Keinanen K, Sommer B, Seeburg PH (1992) High-affinity kainate and domoate receptors in rat brain. FEBS Lett 307:139–143PubMedCrossRefGoogle Scholar
  112. London ED, Coyle JT (1979) Specific binding of [3H]kainic acid to receptor sites in rat brain. Mol Pharmacol 15:492–505PubMedGoogle Scholar
  113. 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 11:250–262PubMedCrossRefGoogle Scholar
  114. 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 53:1330–1332PubMedGoogle Scholar
  115. Mah SJ, Cornell E, Mitchell NA, Fleck MW (2005) Glutamate receptor trafficking: endoplasmic reticulum quality control involves ligand binding and receptor function. J Neurosci 25:2215–2225PubMedCrossRefGoogle Scholar
  116. 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) 561:27–37CrossRefGoogle Scholar
  117. Martin S, Henley JM (2004) Activity-dependent endocytic sorting of kainate receptors to recycling or degradation pathways. EMBO J 23:4749–4759PubMedCrossRefGoogle Scholar
  118. 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 5:151–176PubMedCrossRefGoogle Scholar
  119. Mayer ML (2005) Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron 45:539–552PubMedCrossRefGoogle Scholar
  120. 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 26:2852–2861PubMedCrossRefGoogle Scholar
  121. 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 276:16092–16099PubMedCrossRefGoogle Scholar
  122. Melyan Z, Wheal HV, Lancaster B (2002) Metabotropic-mediated kainate receptor regulation of IsAHP and excitability in pyramidal cells. Neuron 34:107–114PubMedCrossRefGoogle Scholar
  123. Melyan Z, Lancaster B, Wheal HV (2004) Metabotropic regulation of intrinsic excitability by synaptic activation of kainate receptors. J Neurosci 24:4530–4534PubMedCrossRefGoogle Scholar
  124. 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 96:9932–9937PubMedCrossRefGoogle Scholar
  125. Moghaddam B (2003) Bringing order to the glutamate chaos in schizophrenia. Neuron 40:881–884PubMedCrossRefGoogle Scholar
  126. Monaghan D, Cotman C (1982) The distribution of [3H]-kainic acid binding sites in rat CNS as determined by autoradiography. Brain Research 252:91–100PubMedCrossRefGoogle Scholar
  127. 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 47:46–64PubMedCrossRefGoogle Scholar
  128. Mott DD, Washburn MS, Zhang S, Dingledine RJ (2003) Subunit-dependent modulation of kainate receptors by extracellular protons and polyamines. J Neurosci 23:1179–1188PubMedGoogle Scholar
  129. 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 392:601–605PubMedCrossRefGoogle Scholar
  130. 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 28:475–484PubMedCrossRefGoogle Scholar
  131. Nadler J (1978) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271:676–677PubMedCrossRefGoogle Scholar
  132. Nadler JV (2003) The recurrent mossy fiber pathway of the epileptic brain. Neurochem Res 28:1649–1658PubMedCrossRefGoogle Scholar
  133. 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 297:211–218PubMedCrossRefGoogle Scholar
  134. 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 102:1708–1713PubMedCrossRefGoogle Scholar
  135. 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 579:1154–1160PubMedCrossRefGoogle Scholar
  136. 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 367:365–368PubMedCrossRefGoogle Scholar
  137. 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 37:1211–1222PubMedCrossRefGoogle Scholar
  138. 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 39:1575–1588PubMedCrossRefGoogle Scholar
  139. Park Y, Jo J, Isaac JT, Cho K (2006) Long-term depression of kainate receptor-mediated synaptic transmission. Neuron 49:95–106PubMedCrossRefGoogle Scholar
  140. 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 11:1069–1082PubMedCrossRefGoogle Scholar
  141. Paternain A, Morales M, Lerma J (1995) Selective antagonism of AMPA receptor unmasks kainate receptor-mediated responses in hippocampal neurons. Neuron 14:185–189PubMedCrossRefGoogle Scholar
  142. Paternain AV, Rodriguez-Moreno A, Villarroel A, Lerma J (1998) Activation and desensitization properties of native and recombinant kainate receptors. Neuropharmacology 37:1249–1259PubMedCrossRefGoogle Scholar
  143. 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 20:196–205PubMedGoogle Scholar
  144. 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 23:8641-8648PubMedGoogle Scholar
  145. Patneau DK, Mayer ML, Jane DE, Watkins JC (1992)Activation and desensitization of AMPA/kainate receptors by novel derivatives of willardiine.J Neurosci 12:595–606PubMedGoogle Scholar
  146. 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 43:1958–1968PubMedCrossRefGoogle Scholar
  147. 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 129:465–479PubMedCrossRefGoogle Scholar
  148. 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 349:85–110PubMedCrossRefGoogle Scholar
  149. 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 47:309–316PubMedCrossRefGoogle Scholar
  150. Pinheiro PS, et al (2005b) Soc Neurosci AbstrGoogle Scholar
  151. 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 37:1287–1297PubMedCrossRefGoogle Scholar
  152. Raymond LA, Blackstone CD, Huganir RL (1993) Phosphorylation and modulation of recombinant GluR6 glutamate receptors by cAMP-dependent protein kinase. Nature 361:637–641PubMedCrossRefGoogle Scholar
  153. 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 23:6608–6616PubMedGoogle Scholar
  154. 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 278:52700–52709Google Scholar
  155. Rodriguez-Moreno A, Lerma J (1998) Kainate receptor modulation of GABA release involves a metabotropic function. Neuron 20:1211–1218PubMedCrossRefGoogle Scholar
  156. Rodriguez-Moreno A, Herreras O, Lerma J (1997) Kainate receptors presynaptically downregulate GABAergic inhibition in the rat hippocampus. Neuron 19:893–901PubMedCrossRefGoogle Scholar
  157. Rozas JL, Paternain AV, Lerma J (2003) Noncanonical signaling by ionotropic kainate receptors. Neuron 39:543–553PubMedCrossRefGoogle Scholar
  158. 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 94:3872–3876PubMedCrossRefGoogle Scholar
  159. 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 25:11710–11718PubMedCrossRefGoogle Scholar
  160. 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 296:650–658PubMedGoogle Scholar
  161. 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 8:267–274PubMedCrossRefGoogle Scholar
  162. 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 93:13304–13309PubMedCrossRefGoogle Scholar
  163. Sanchez-Gomez MV, Matute C (1999) AMPA and kainate receptors each mediate excitotoxicity in oligodendroglial cultures. Neurobiol Dis 6:475–485PubMedCrossRefGoogle Scholar
  164. 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 45:1713–1720PubMedGoogle Scholar
  165. 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 74:416–421PubMedCrossRefGoogle Scholar
  166. 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 314:1068–1078PubMedCrossRefGoogle Scholar
  167. 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 276:11382–11386PubMedCrossRefGoogle Scholar
  168. 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 19:1141–1146PubMedCrossRefGoogle Scholar
  169. Schmitz D, Frerking M, Nicoll RA (2000) Synaptic activation of presynaptic kainate receptors on hippocampal mossy fiber synapses. Neuron 27:327–338PubMedCrossRefGoogle Scholar
  170. Schmitz D, Mellor J, Nicoll RA (2001) Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science 291:1972–1976PubMedCrossRefGoogle Scholar
  171. 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 6:1058–1063PubMedCrossRefGoogle Scholar
  172. Semyanov A, Kullmann DM (2001) Kainate receptor-dependent axonal depolarization and action potential initiation in interneurons. Nat Neurosci 4:718–723PubMedCrossRefGoogle Scholar
  173. 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 11:139–144PubMedCrossRefGoogle Scholar
  174. 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 113:59–67PubMedCrossRefGoogle Scholar
  175. 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 141:39–51PubMedCrossRefGoogle Scholar
  176. 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 131:48–50CrossRefGoogle Scholar
  177. 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 37:25–36PubMedCrossRefGoogle Scholar
  178. 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 37:1261–1267PubMedCrossRefGoogle Scholar
  179. 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 5:796–804PubMedGoogle Scholar
  180. 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 11:1651–1656PubMedGoogle Scholar
  181. 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 28:887–898PubMedCrossRefGoogle Scholar
  182. 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 392:181–186PubMedCrossRefGoogle Scholar
  183. 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) 492:129–142Google Scholar
  184. Swanson GT, Green T, Heinemann SF (1998) Kainate receptors exhibit differential sensitivities to (S)-5-iodowillardiine. Mol Pharmacol 53:942–949PubMedGoogle Scholar
  185. 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 34:589–598PubMedCrossRefGoogle Scholar
  186. 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 102:7368–7373PubMedCrossRefGoogle Scholar
  187. 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 38:773–784PubMedCrossRefGoogle Scholar
  188. 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 7:362–374PubMedCrossRefGoogle Scholar
  189. Traynelis SF, Wahl P (1997) Control of rat GluR6 glutamate receptor open probability by protein kinase A and calcineurin. J Physiol (Lond) 503:513–531CrossRefGoogle Scholar
  190. 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 280:6085–6093PubMedCrossRefGoogle Scholar
  191. Vignes M, Collingridge GL (1997) The synaptic activation of kainate receptors. Nature 388:179–182PubMedCrossRefGoogle Scholar
  192. 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 29:217–227PubMedCrossRefGoogle Scholar
  193. 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 281:15475–15484PubMedCrossRefGoogle Scholar
  194. 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 259:1173–1175PubMedCrossRefGoogle Scholar
  195. Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 21:165–204PubMedCrossRefGoogle Scholar
  196. 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 351:742–744PubMedCrossRefGoogle Scholar
  197. Wilding TJ, Huettner JE (1996) Antagonist pharmacology of kainate- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring receptors. Mol Pharmacol 49:540–546PubMedGoogle Scholar
  198. Wilding TJ, Huettner JE (2001) Functional diversity and developmental changes in rat neuronal kainate receptors. J Physiol (Lond) 532:411–421CrossRefGoogle Scholar
  199. Wilding TJ, Chai YH, Huettner JE (1998) Inhibition of rat neuronal kainate receptors by cis-unsaturated fatty acids. J Physiol (Lond) 513:331–339CrossRefGoogle Scholar
  200. Wilding TJ, Zhou Y, Huettner JE (2005) Q/R site editing controls kainate receptor inhibition by membrane fatty acids. J Neurosci 25:9470–9478PubMedCrossRefGoogle Scholar
  201. 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 15:743–749PubMedCrossRefGoogle Scholar
  202. Wisden W, Seeburg P (1993) A complex mosaic of high-affinity kainate receptors in rat brain. J Neurosci 13:3582–3598PubMedGoogle Scholar
  203. 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 44:504–510PubMedGoogle Scholar
  204. 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 14:3881–3897PubMedGoogle Scholar
  205. Wu LJ, Zhao MG, Toyoda H, Ko SW, Zhuo M (2005) Kainate receptor-mediated synaptic transmission in the adult anterior cingulate cortex. J Neurophysiol 94:1805–1813PubMedCrossRefGoogle Scholar
  206. Yan S, Sanders JM, Xu J, Zhu Y, Contractor A, Swanson GT (2004) A C-terminal determinant of GluR6 kainate receptor trafficking. J Neurosci 24:679–691PubMedCrossRefGoogle Scholar
  207. 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) 555:683–698CrossRefGoogle Scholar
  208. Yue KT, MacDonald JF, Pekhletski R, Hampson DR (1995) Differential effects of lectins on recombinant glutamate receptors. Eur J Pharmacol 291:229–235PubMedCrossRefGoogle Scholar
  209. 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 22:537–548PubMedCrossRefGoogle Scholar
  210. Zhang J, Zhang D, McQuade JS, Behbehani M, Tsien JZ, Xu M (2002) c-fos regulates neuronal excitability and survival. Nat Genet 30:416–420PubMedCrossRefGoogle Scholar
  211. 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 280:422–427PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.CNRS UMR 5091, Laboratoire “Physiologie Cellulaire de la Synapse”, Bordeaux Neuroscience InstituteUniversity of BordeauxBordeaux CedexFrance

Personalised recommendations