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Molecular Diversity, Structure, and Function of Glutamate Receptor Channels

  • Chapter
Pharmacology of Ionic Channel Function: Activators and Inhibitors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 147))

Abstract

In 1954, Hayashi noted the excitatory action of L-glutamate in the motor cortex. Extensive studies by Watkins and colleagues revealed structure and function relationships of excitatory amino acids and their derivatives (WATKINS and OLVERMAN 1981). Since then, cumulative evidence indicates that glutamate receptor (GluR) channels mediate most fast excitatory synaptic transmission in the vertebrate central nervous system. The development of selective agonists and antagonists led to the classification of G1uR channels into Nmethyl-D-aspartate (NMDA) and non-NMDA subtypes. Subsequently, the non-NMDA subtype was further subdivided into the α-amino-3-hydroxy-5methyl-4-isoxazole propionic acid (AMPA) and kainate subtypes. It is becoming clear that some of the most important functions of the nervous system, such as synaptic plasticity and synapse formation, critically depend on G1uR channels and that neurological damage caused by a variety of pathological states can result from exaggerated activation of GluR channels. In 1989, Hollmann et al. cloned the first member of G1uR channel subunit genes. Successful cloning and targeting of G1uR channel subunit genes have made it possible to study the molecular and functional diversity of GluR channel families and their physiological roles in brain function.

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References

  • Akazawa C, Shigemoto R, Bessho Y, Nakanishi S, Mizuno N (1994) Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J Comp Neurol 347:150–160

    Article  PubMed  CAS  Google Scholar 

  • Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M (1993) Selective expression of the glutamate receptor channel 82 subunit in cerebellar Purkinje cells. Biochem Biophys Res Commun 197:1267–1276

    Article  PubMed  CAS  Google Scholar 

  • Ascher P, Nowak L (1988) The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol 399:247–266

    PubMed  CAS  Google Scholar 

  • Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RG (1995) Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature 378:182–186

    Article  PubMed  CAS  Google Scholar 

  • Barria A, Muller D, Derkach V, Griffith LC, Soderling TR (1997) Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science 276(5321):2042–2045

    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 

  • Bettler B, Egebjerg J, Sharma G, Pecht G, Hermans-Borgmeyer I, Moll C, Stevens CF, Heinemann S (1992) Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit. Neuron 8:257–265

    Article  PubMed  CAS  Google Scholar 

  • Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  • Bochet P, Audinat E, Lambolez B, Crépel F, Rossier J, Iino M, Tsuzuki K, Ozawa S (1994) Subunit composition at the single-cell level explains functional properties of a glutamate-gated channel. Neuron 12:383–388

    Article  PubMed  CAS  Google Scholar 

  • Boulter J, Hollmann M, O’Shea-Greenfield A, Hartley M, Deneris ES, Heinemann S (1990) Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249:1033–1037

    Article  PubMed  CAS  Google Scholar 

  • Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alphal-syntrophin mediated by PDZ domains. Cell 84:757–767

    Article  PubMed  CAS  Google Scholar 

  • Brose N, Gasic GP, Vetter DE, Sullivan JM, Heinemann SF (1993) Protein chemical characterization and immunocytochemical localization of the NMDA receptor subunit NMDA R1. J Biol Chem 268:22663–22671

    PubMed  CAS  Google Scholar 

  • Brusa R, Zimmermann F, Koh DS, Feldmeyer D, Gass P, Seeburg PH, Sprengel R (1995) Early-onset epilepsy and postnatal lethality associated with an editing-deficient GIuR-B allele in mice. Science 270:1677–80

    Article  PubMed  CAS  Google Scholar 

  • Buller AL, Larson HC, Schneider BE, Beaton JA, Morrisett RA, Monaghan DT (1994) The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition. J. Neurosci. 14:5471–5484

    PubMed  CAS  Google Scholar 

  • Burnashev N, Schoepfer R, Monyer H, Ruppersberg JP, Günther W, Seeburg PH, Sakmann B (1992) Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor. Science 257:1415–1419

    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. Journal of Physiology 485:403–18

    PubMed  CAS  Google Scholar 

  • Carmignoto G, Vicini S (1992) Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science 258:1007–1011 Caddy KW, Biscoe TJ (1979) Structural and quantitative studies on the normal C3Hand Lurcher mutant mouse. Phil Trans R Soc Lond B 287:167–201

    Google Scholar 

  • Cheng SS, Heinz N (1997) Massive loss of mid-and hindbrain neurons during embryonic development of homozygous Lurcher mice. J Neurosci 17:2400–2407

    PubMed  CAS  Google Scholar 

  • Ciabarra AM, Sullivan JM, Gahn, LG, Pecht G, Heinemann S, Sevarino KA (1995) Cloning and characterization of x-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J Neurosci 15:6498–6508

    PubMed  CAS  Google Scholar 

  • Cline HT, Debski EA, Constantine-Paton M (1987) N-methyl-D-aspartate receptor antagonist desegregates eye-specific stripes. Proc Natl Acad Sci USA 84:4342–4345

    Article  PubMed  CAS  Google Scholar 

  • Das S, Sasaki YF, Rothe T, Premkumar LS, Takasu M, Crandall JE, Dikkes P, Conner DA, Rayudu PV, Cheung Wing, Chen H-SV, Lipton SA, Nakanishi N (1998) Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3 A. Nature 393:377–381.

    Article  PubMed  CAS  Google Scholar 

  • Davis S, Butcher SP, Morris RGM (1992) The NMDA receptor antagonist D-2amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro. J Neurosci 12:21–34

    PubMed  CAS  Google Scholar 

  • Dong H, O’Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL (1997) GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature 386:279–284

    Article  PubMed  CAS  Google Scholar 

  • Ebralidze AK, Rossi DJ, Tonegawa S, Slater NT (1996) Modification of NMDA receptor channels and synaptic transmission by targeted disruption of the NR2 C gene. J Neurosci 16:5014–5025

    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 

  • Ehlers MD, Tingley WG, Huganir RL (1995) Regulated subcellular distribution of the NR1 subunit of the NMDA receptor. Science 269:1734–1737

    Article  PubMed  CAS  Google Scholar 

  • Ehlers MD, Zhang S, Bernhadt JP, Huganir RL (1996) Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 84:745–755

    Article  PubMed  CAS  Google Scholar 

  • Farrant M, Feldmeyer D, Takahashi T, Cull-Candy SG (1994) NMDA-receptor channel diversity in the developing cerebellum. Nature 368:335–339

    Article  PubMed  CAS  Google Scholar 

  • Flint AC, Maisch US, Weishaupt JH, Kriegstein AR, Monyer H (1997) NR2 A Subunit Expression Shortens NMDA Receptor Synaptic Currents in Developing Neo-cortex. J Neurosci 17:2469–2476.

    PubMed  CAS  Google Scholar 

  • Forrest D, Yuzaki M, Soares HD, Ng L, Luk DC, Sheng M, Stewart CL, Morgan JI, Connor JA, Curran T (1994) Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death. Neuron 13:325–338

    Article  PubMed  CAS  Google Scholar 

  • Funabiki K, Mishina M, Hirano T (1995) Retarded vestibular compensation in the mutant mice deficient of 82 glutamate receptor subunit. NeuroReport 7:189–192

    PubMed  CAS  Google Scholar 

  • Gallo V, Upso LM, Hayes WP, Vyklicky L, Winters CA, Buonanno A (1992) Molecular cloning and developmental analysis of a new glutamate receptor isoform in cerebellum. J Neurosci 12:1010–1023

    PubMed  CAS  Google Scholar 

  • Gibb AJ, Colquhoun D (1991) Glutamate activation of a single NMDA receptor-channel produces a cluster of channel openings. Proc R Soc B 243:39–45

    Article  PubMed  CAS  Google Scholar 

  • Gibb AJ, Colquhoun D (1992) Activation of N-methyl-D-aspartate receptors by L-glutamate in cells dissociated from adult rat hippocampus. J Physiol 456:143–179

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Hestrin S (1992) Developmental regulation of NMDA receptor-mediated synaptic currents at a central synapse. Nature 357:686–689

    Article  PubMed  CAS  Google Scholar 

  • Hirai H, Kirsch J, Laube B, Betz H, Kuhse J (1996) The glycine binding site of the Nmethyl-D-aspartate receptor subunit NR1: identification of novel determinants of co-agonist potentiation in the extracellular M3–M4 loop region. Proc Natl Acad Sci USA 93(12):6031–6

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, O’Shea-Greenfield A, Rogers SW, Heinemann S (1989) Cloning by functional expression of a member of the glutamate receptor family. Nature 342:643–648

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, Hartley M, Heinemann S (1991) Ca’ permeability of KA-AMPA-gated glutamate receptor channels depends on subunit composition. Science 252:851853

    Google Scholar 

  • Hollmann M, Boulter J, Maron C, Beasley L, Sullivan J, Pecht G, Heinemann S (1993) Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor. Neuron 10:943–954

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, Maron C, Heinemann S (1994) N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GIuR1. Neuron 13:1331–1343

    Article  PubMed  CAS  Google Scholar 

  • Hsueh YP, Kim E, Sheng M (1997) Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95. Neuron 18:803–814

    Article  PubMed  CAS  Google Scholar 

  • Hume RI, Dingledine R, Heinemann SF (1991) Identification of a site in glutamate receptor subunits that controls calcium permeability. Science 253:1028–1031

    Article  PubMed  CAS  Google Scholar 

  • Iino M, Ozawa S, Tsuzuki K (1990) Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurons. J Physiol 424:151–165

    PubMed  CAS  Google Scholar 

  • Ikeda K, Nagasawa M, Mori H, Araki K, Sakimura K, Watanabe M, Inoue Y, Mishina M (1992) Cloning and expression of the £4 subunit of the NMDA receptor channel. FEBS Lett 313:34–38

    Article  PubMed  CAS  Google Scholar 

  • Ikeda K, Araki K, Takayama C, Inoue Y, Yagi T, Aizawa S, Mishina M (1995) Reduced spontaneous activity of mice defective in the £4 subunit of the NMDA receptor channel. Mol Brain Res 33:61–71

    Article  PubMed  CAS  Google Scholar 

  • Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Sudhof TC (1997) Binding of neuroligins to PSD-95. Science 277:1511–1515

    Article  PubMed  CAS  Google Scholar 

  • Ishii T, Moriyoshi K, Sugihara H, Sakurada K, Kadotani H, Yokoi M, Akazawa C, Shigemoto R, Mizuno N, Masu M, Nakanishi S (1993) Molecular characterization of the family of the N-methyl-o-aspartate receptor subunits. J Biol Chem 268: 2836–2843

    PubMed  CAS  Google Scholar 

  • Ito I, Futai K, Katagiri H, Watanabe M, Sakimura K, Mishina M, Sugiyama H (1997) Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor el or e2 subunit. J Physiol 500:401–408

    PubMed  CAS  Google Scholar 

  • Jia Z, Agopyan N, Miu P, Xiong Z, Henderson J, Gerlai R, Taverna FA, Velumian A, MacDonald J, Carlen P, Abramow-Newerly W, Roder J (1996) Enhanced LTP in mice deficient in the AMPA receptor G1uR2. Neuron 17:945–956

    Article  PubMed  CAS  Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531

    Article  PubMed  CAS  Google Scholar 

  • Jonas P, Racca C, Sakmann B, Seeburg PH, Monyer H (1994) Differences in calcium permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential G1uR-B subunit expression. Neuron 12:1281–1289

    Article  PubMed  CAS  Google Scholar 

  • Kashiwabuchi N, Ikeda K, Araki K, Hirano T, Shibuki K, Takayama C, Inoue Y, Kutsuwada T, Yagi T, Kang Y, Aizawa S, Mishina M (1995) Impairment of motor coordination, Purkinje cell synapse formation and cerebellar long-term depression in GIuR52 mutant mice. Cell 81:245–252

    Article  PubMed  CAS  Google Scholar 

  • Keinänen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B Seeburg PH (1990) A family of AMPA-selective glutamate receptors. Science 249:556–560

    Article  PubMed  Google Scholar 

  • Kendrick SJ, Lynch DR, Pritchett DB (1996) Characterization of glutamate binding sites in receptors assembled from transfected NMDA receptor subunits. J Neurochem 67:608–616

    Article  PubMed  CAS  Google Scholar 

  • Kim E, Cho K-O, Rothschild A, Sheng M (1996) Heteromultimerization and NMDA receptor-clustering activity of chapsyn-110, a member of the PSD-95 family of proteins. Neuron 17:103–113

    Article  PubMed  CAS  Google Scholar 

  • Kim E, Naisbitt S, Hsueh YP, Rao A, Rothschild A, Craig AM, Sheng M (1997) GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J Cell Biol 136:669678

    Google Scholar 

  • Kim J-H, Liao D, Lau L-F, Huganir RL (1998) SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 20:683–691

    Article  PubMed  CAS  Google Scholar 

  • Kiyama Y, Manabe T, Sakimura K, Kawakami F, Mori H, Mishina M (1998) Increased thresholds for LTP and contextual learning in mice lacking the GluRel subunit of the NMDA receptor channel. J Neurosci 18:6704–6712

    PubMed  CAS  Google Scholar 

  • Kleckner NW, Dingledine R (1988) Requirement for glycine in activation of NMDAreceptors expressed in Xenopus oocytes. Science 241:835–837

    Article  PubMed  CAS  Google Scholar 

  • Kleinschmidt A, Bear MF, Singer W (1987) Blockade of “NMDA” receptors disrupts experience-dependent plasticity of kitten striate cortex. Science 238:355–358

    Article  PubMed  CAS  Google Scholar 

  • Köhr G, Eckardt S, Lüddens H, Monyer H, Seeburg PH (1994) NMDA receptor chan nels: subunit-specific potentiation by reducing agents. Neuron 12:1031–1040

    Article  PubMed  Google Scholar 

  • Köhr G, Seeburg PH (1996) Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family. J Physiol 492:445–52

    PubMed  Google Scholar 

  • Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995) Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269:1737–40

    Article  PubMed  CAS  Google Scholar 

  • Kuner T, Wollmuth LP, Karlin A, Seeburg PH, Sakmann B (1996) Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines. Neuron 17:343–352

    Article  PubMed  CAS  Google Scholar 

  • Kurihara H, Hashimoto K, Kano M, Takayama C, Sakimura K, Mishina M, Inoue Y, Watanabe M (1997) Impaired parallel fiber-Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor 52 subunit. J Neurosci 15:9613–9623

    Google Scholar 

  • Kupper J, Ascher P, Neyton J (1996) Probing the pore region of recombinant N-methylD-aspartate channels using external and internal magnesium block. Proc Natl Acad Sci USA 93:8648–8653

    Article  PubMed  CAS  Google Scholar 

  • Kupper J, Ascher P, Neyton J (1998) Internal Mg’ block of recombinant NMDA channels mutated within the selectivity filter and expressed in Xenopus oocytes. J Physiol 507:1–12

    Article  PubMed  CAS  Google Scholar 

  • Kuryatov A, Laube B, Betz H, Kuhse J (1994) Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins. Neuron 12:1291–1300

    Article  PubMed  CAS  Google Scholar 

  • Kutsuwada T, Kashiwabuchi N, Mori H, Sakimura K, Kushiya E, Araki K, Meguro H, Masaki H, Kumanishi T, Arakawa M, Mishina M (1992) Molecular diversity of the NMDA receptor channel. Nature 358:36–41

    Article  PubMed  CAS  Google Scholar 

  • Kutsuwada T, Sakimura K, Manabe T, Takayama C, Katakura N, Kushiya E, Natsume R, Watanabe M, Inoue Y, Yagi T, Aizawa S, Arakawa M, Takahashi T, Nakamura Y, Mori H, Mishina M (1996) Impairment of suckling response, trigeminal neuronal pattern formation and hippocampal LTD in NMDA receptor s2 subunit mutant mice. Neuron 16:333–344

    Article  PubMed  CAS  Google Scholar 

  • Landsend AS, Amiry-Moghaddam M, Matsubara A, Bergersen L, Usami S, Wenthold RJ, Ottersen OP (1997) Differential localization of S glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. J Neurosci 17:834–842

    PubMed  CAS  Google Scholar 

  • Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (1997) Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit. Neuron 18:493–503

    Article  PubMed  CAS  Google Scholar 

  • Laurie DJ, Seeburg PH (1994) Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA. J Neurosci 14:3180–3194

    PubMed  CAS  Google Scholar 

  • Li Y, Erzurumlu RS, Chen C, Jhaveri S, Tonegawa S (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76:427–437

    Article  PubMed  CAS  Google Scholar 

  • Lin JW,Wyszynski M, Madhavan R, Sealock R, Kim JU, Sheng M (1998) Yotiao: a novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1. J Neurosci 18:2017–2027

    PubMed  CAS  Google Scholar 

  • Lomeli H, Sprengel R, Laurie DJ, Köhr G, Herb A, Seeburg PH, Wisden W (1993) The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett 315:318–322

    Article  PubMed  CAS  Google Scholar 

  • Lynch DR, Anegawa NJ, Verdoorn T, Pritchett DB (1994) N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents. Mol Pharmacol 45:540–545

    PubMed  CAS  Google Scholar 

  • Masood K, Wu C, Brauneis U, Weight FF (1993) Differential ethanol sensitivity of recombinant N-methyl-D-aspartate receptor subunits. Mol Pharmacol 45:324329

    Google Scholar 

  • Mayer ML, Westbrook GL (1987) Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurons, J Physiol 394:501

    PubMed  CAS  Google Scholar 

  • Meguro H, Mori H, Araki K, Kushiya E, Kutsuwada T, Yamazaki M, Kumanishi T, Arakawa M, Sakimura K, Mishina M (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357:70–74

    Article  PubMed  CAS  Google Scholar 

  • Mishina M, Sakimura K, Mori H, Kushiya E, Harabayashi M, Uchino S, Nagahari K (1991) A single amino acid residue determines the Ca’ permeability of AMPAselective glutamate receptor channels. Biochem Biophys Res Commun 180:813821

    Article  Google Scholar 

  • Mishina M, Mori H, Araki K, Kushiya E, Meguro H, Kutsuwada T, Kashiwabuchi N, Ikeda K, Nagasawa M, Yamazaki M, Masaki M, Yamakura T, Morita T, Sakimura K (1993) Molecular and functional diversity of the NMDA receptor channel. Ann NY Acad Sci 707:136–152

    Article  PubMed  CAS  Google Scholar 

  • Monaghan DT, Olverman HJ, Nguyen L, Watkins JC, Cotman CW (1988) Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine. Proc Natl Acad Sci USA 85:9836–9840

    Article  PubMed  CAS  Google Scholar 

  • Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217–1221

    Article  PubMed  CAS  Google Scholar 

  • Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529–540

    Article  PubMed  CAS  Google Scholar 

  • Moon IS, Apperson ML, Kennedy MB (1994) The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc Natl Acad Sci USA 91:3954–3958

    Article  PubMed  CAS  Google Scholar 

  • Mori H, Masaki H, Yamakura T, Mishina M (1992) Identification by mutagenesis of a Mgt+-block site of the NMDA receptor channel. Nature 358:673–675

    Article  PubMed  CAS  Google Scholar 

  • Mori H, Yamakura T, Masaki H, Mishina M (1993) Involvement of the carboxyl-terminal region in modulation by TPA of the NMDA receptor channel. NeuroReport 4:519–522

    Article  PubMed  CAS  Google Scholar 

  • Mori H, Mishina M (1995) Structure and function of the NMDA receptor channel. Neuropharmacology 34:1219–1237

    Article  PubMed  CAS  Google Scholar 

  • Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354:31–37

    Article  PubMed  CAS  Google Scholar 

  • Morris RGM, Anderson E, Lynch GS, Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319:774–776

    Article  PubMed  CAS  Google Scholar 

  • Mulle C, Sailer A, Pérez-Otaño 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 G1uR6-deficient mice. Nature 392:601–605

    Article  PubMed  CAS  Google Scholar 

  • Müller T, Möller T, Berger T, Schnitzer J, Kettenmann H (1992) Calcium entry through kainate receptors and resulting potassium-channel blockade in Bergmann glial cells. Science 256:1563–1566

    Article  PubMed  Google Scholar 

  • Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau L-F, Veh RW, Huganir RL, Gundelfinger ED, Garner CC (1996) SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo. Neuron 17:255–265

    Article  PubMed  Google Scholar 

  • Nagasawa M, Sakimura K, Mori KJ, Bedell MA, Copeland NG, Jenkins NA, Mishina M (1996) Gene structure and chromosomal localization of the mouse NMDA receptor channel subunits. Mol Brain Res 36:1–11

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi N, Shneider NA, Axel R (1990) A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties. Neuron 5:569–581

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi N, Axel R, Shneider NA (1992) Alternative splicing generates functionally distinct N-methyl-D-aspartate receptors. Proc Natl Acad Sci USA 89:85528556

    Google Scholar 

  • O’Hara PJ, Sheppard PO, Thogersen H, Venezia D, Haldemann BA, McGrane V, Houamed KM, Thomsen C, Gilbert TL, Mulvihill ER (1993) The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron 11:41–52

    Article  PubMed  Google Scholar 

  • Perkel DJ, Hestrin S, Sah P, Nicoll RA (1990) Excitatory synaptic currents in Purkinje cells. Proc R Soc Lond B 241:116–121

    Article  CAS  Google Scholar 

  • Phillips RJS (1960) “Lurcher”, new gene in linkage group XI of the house mouse. J Genet 57:35–42

    Article  Google Scholar 

  • Quinlan JE, Davies J (1985) Excitatory and inhibitory responses of Purkinje cells, in the rat cerebellum in vivo, induced by excitatory amino acids. Neurosci Lett 60:39–46

    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 361:637–41

    Article  PubMed  CAS  Google Scholar 

  • Roche KW, Raymond LA, Blackstone C, Huganir RL (1994) Transmembrane topology of the glutamate receptor subunit GluR6. J Biol Chem 269:11679–11682

    PubMed  CAS  Google Scholar 

  • Roche KW, O’Brien RJ, Mammen AL, Bernhardt J, Huganir RL (1996) Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16:1179–1188

    Article  PubMed  CAS  Google Scholar 

  • Rogers SW, Andrews PI, Gahring LC, Whisenand T, Cauley K, Crain B, Hughes TE, Heinemann SF, McNamara JO (1994) Autoantibodies to glutamate receptor G1uR3 in Rasmussen’s encephalitis. Science 265:648–651

    Article  PubMed  CAS  Google Scholar 

  • Sakimura K, Bujo H, Kushiya E, Araki K, Yamazaki M, Yamazaki M, Meguro H, Warashina A, Numa S, Mishina M (1990) Functional expression from cloned cDNAs of glutamate receptor species responsive to kainate and quisqualate. FEBS Lett 272:73–80

    Article  PubMed  CAS  Google Scholar 

  • Sakimura K, Morita T, Kushiya E, Mishina M (1992) Primary structure and expression of the y2 subunit of the glutamate receptor channel selective for kainate. Neuron 8:267–274

    Article  PubMed  CAS  Google Scholar 

  • Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H, Mishina M (1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor el subunit. Nature 373:151–155

    Article  PubMed  CAS  Google Scholar 

  • Sakurada K, Masu M, Nakanishi S (1993) Alteration of Ca’ permeability and sensitivity to Mg’ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor. J Biol Chem 268:410–415

    PubMed  CAS  Google Scholar 

  • Saucier D, Cain DP (1995) Spatial learning without NMDA receptor-dependent long-term potentiation. Nature 378:186–189

    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 

  • Seeburg PH (1993) The molecular biology of mammalian glutamate receptor channels. Trends Neurosci 16:359–365

    Article  PubMed  CAS  Google Scholar 

  • Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (1994) Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 368:144–147

    Article  PubMed  CAS  Google Scholar 

  • Sommer B, Keinänen K, Verdoorn TA, Wisden W, Burnashev N, Herb A, Köhler M, Takagi T, Sakmann B, Seeburg PH (1990) Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science 249:1580–1585

    Article  PubMed  CAS  Google Scholar 

  • Sommer B, Köhler M, Sprengel R, Seeburg PH (1991) RNA editing in the brain controls a determinant of ion flow in glutamate-gated channels. Cell 67:11–19

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Standaert DG, Testa CM, Young AB, Penny JB Jr (1994) Organization of N-methyl-Daspartate glutamate receptor gene expression in the basal ganglia of the rat. J Comp Neurol 343:1–16

    Article  PubMed  CAS  Google Scholar 

  • Stern P, Béhé P, Schoepfer R, Colquhoun D (1992) Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proc R Soc Lond B 250:271–277

    Article  CAS  Google Scholar 

  • Sucher NJ, Akbarian S, Chi CL, Leclerc CL, Awobuluyi M, Deitcher DL, Wu MK, Yuan JP, Jones EG, Lipton SA (1995) Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. J Neurosci 15:6509–6520

    PubMed  CAS  Google Scholar 

  • Sugihara H, Moriyoshi K, Ishii T, Masu M, Nakanishi S (1992) Structures and properties of seven isoforms of the NMDA receptor generated by alternative splicing. Biochem . Biophys Res Commun 185:826–832

    Article  CAS  Google Scholar 

  • Sullivan JM, Traynelis SF, Chen H-SV, Escobar W, Heinemann SF, Lipton SA (1994) Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor. Neuron 13:929–936

    Article  PubMed  CAS  Google Scholar 

  • Swanson GT, Kamboj SK, Cull-Candy SG (1997) Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. J Neurosci 17:58–69

    PubMed  CAS  Google Scholar 

  • Takahashi T, Feldmeyer D, Suzuki N, Onodera K, Cull-Candy SG, Sakimura K, Mishina M (1996) Functional correlation of NMDA receptor e subunits expression with the properties of single-channel and synaptic currents in the developing cerebellum. J Neurosci 16:4376–4382

    PubMed  CAS  Google Scholar 

  • Takayama C, Nakagawa S, Watanabe M, Mishina M, Inoue Y (1996) Developmental changes in expression and distribution of the glutamate receptor channel 82 subunit according to the Purkinje cell maturation. Dev Brain Res 92:147–155

    Article  CAS  Google Scholar 

  • Takeuchi M, Hata Y, Hirao K, Toyoda A, Irie M, Takai Y (1997) SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J Biol Chem 272:11943–11951

    Article  PubMed  CAS  Google Scholar 

  • Taverna FA, Wang L-Y, MacDonald JF, Hampson DR (1994) A transmembrane model for an ionotropic glutamate receptor predicted on the basis of the location of asparagine-linked oligosaccharides. J Biol Chem 269:14159–14164

    PubMed  CAS  Google Scholar 

  • Tingley WG, Roche KW, Thompson AK, Huganir RL (1993) Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain. Nature 364:70–73

    Article  PubMed  CAS  Google Scholar 

  • Tingley WG, Huganir RL (1994) Generation of antibodies specific for phosphorylated NMDA receptors. Soc Neurosci Abstr 20:1466

    Google Scholar 

  • Traynelis SF, Hartley M, Heinemann SF (1995) Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines. Science 268:873–876

    Article  PubMed  CAS  Google Scholar 

  • Tsien JZ, Huerta PT, Tonegawa S (1996) The essential role of hippocampal CAl NMDA receptor-dependent synaptic plasticity in spatial memory. Cell 87:1327–1338

    Article  PubMed  CAS  Google Scholar 

  • Tsuzuki K, Mochizuki S, lino M, Mori H, Mishina M, Ozawa S (1994) Ion permeation properties of the cloned mouse e2/Ç1 NMDA receptor channel. Mol Brain Res 26:37–46

    Article  PubMed  CAS  Google Scholar 

  • Verdoorn TA, Burnashev N, Monyer H, Seeburg PH, Sakmann B (1991) Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252:1715–1718

    Article  PubMed  CAS  Google Scholar 

  • Wang LY, Taverna FA, Huang XP, MacDonald JF, Hampson DR (1993) Phosphorylation and modulation of a kainate receptor (G1uR6) by cAMP-dependent protein kinase. Science 259(5098):1173–1175

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Inoue Y, Sakimura K, Mishina M (1992) Developmental changes in distribution of NMDA receptor channel subunit mRNAs. NeuroReport 3:1138–1140

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Inoue Y, Sakimura K, Mishina M (1993) Distinct distributions of five Nmethyl-D-aspartate receptor channel subunit mRNAs in the forebrain. J Comp Neurol 338:377–390

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Mishina M, Inoue Y (1994a) Distinct spatiotemporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum. J Comp Neurol 343:513–519

    Article  Google Scholar 

  • Watanabe M, Mishina M, Inoue Y (1994b) Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem. J Comp Neurol 343:520–531

    Article  Google Scholar 

  • Watkins JC, Olverman HJ (1981) Agonists and antagonists for excitatory amino acidreceptors. Trends Neurosci 10:265–272

    Article  Google Scholar 

  • Werner P, Voight 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 

  • Wo ZG, Oswald RE (1994) Transmembrane topology of two kainate receptor subunits revealed by N-glycosylation. Proc Natl Acad Sci USA 91:7154–7158

    Article  PubMed  CAS  Google Scholar 

  • Wollmuth LP, Kuner T, Seeburg PH, Sakmann B (1996) Differential contribution of the NR1- and NR2A-subunits to the selectivity filter of recombinant NMDA receptor channels. J Physiol 491:779–797

    PubMed  CAS  Google Scholar 

  • Wollmuth LP, Kuner T, Sakmann G (1998a) Adjacent asparagines in the NR2-subunit of the NMDA receptor channel control the voltage-dependent block by extracellular Mg’. J Physiol 506:13–32

    Article  Google Scholar 

  • Wollmuth LP, Kuner T, Sakmann B (1998b) Intracellular Mg’ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel. J Physiol 506:33–52

    Article  Google Scholar 

  • Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (1997) Competitive binding of a-actinin and calmodulin to the NMDA receptor. Nature 385: 439–442

    Article  PubMed  CAS  Google Scholar 

  • Yamakura T, Mori H, Masaki H, Shimoji K, Mishina M (1993) Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists. NeuroReport 4:687–690

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki M, Mori H, Araki K, Mori KJ, Mishina M (1992) Cloning, expression and modulation of a mouse NMDA receptor subunit. FEBS Lett 300:39–45

    Article  PubMed  CAS  Google Scholar 

  • Yu XM, Askalan R, Keil GJ II, Salter MW (1997) NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275:674–8

    Article  PubMed  CAS  Google Scholar 

  • Zuo J, De Jager PL, Takahashi KA, Jiang W, Linden DJ, Heintz N (1997) Neurodegeneration in Lurcher mice caused by mutation in 82 glutamate receptor gene. Nature 388:769–773

    Article  PubMed  CAS  Google Scholar 

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  1. M. Mishina
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Editors and Affiliations

  1. Saitama Medical School, 38 Morohongo, Moroyama Iruma-Gun, Saitama, 350-0495, Japan

    Makato Endo M.D., Ph.D.

  2. Department of Pharmacology II Graduate School of Medicine and Faculty of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Yoshihisa Kurachi

  3. Department of Molecular Neurobiology and Pharmacology School of Medicine, University of Tokyo, Hongo 7-3-1, Bukyo-ku, Tokyo, 113-0033, Japan

    Masayoshi Mishina

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Mishina, M. (2000). Molecular Diversity, Structure, and Function of Glutamate Receptor Channels. In: Endo, M., Kurachi, Y., Mishina, M. (eds) Pharmacology of Ionic Channel Function: Activators and Inhibitors. Handbook of Experimental Pharmacology, vol 147. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57083-4_16

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  • DOI: https://doi.org/10.1007/978-3-642-57083-4_16

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