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Vol. 51, Issue 1, 7-62, March 1999
Department of Pharmacology, Emory University School of
Medicine, Atlanta, Georgia
I. Introduction
II. Gene Families
III. Receptor Structure
A. Transmembrane Topology
B. Subunit Stoichiometry
C. Ligand-Binding Sites Located in a Hinged Clamshell-like Gorge
IV. RNA Modifications That Promote Molecular Diversity
A. Alternative Splicing
B. Editing of AMPA and Kainate Receptors
V. Post-translational Modifications
A. Phosphorylation of AMPA and Kainate Receptors
B. Serine/Threonine Phosphorylation of NMDA Receptors
C. Tyrosine Phosphorylation of NMDA Receptors
D. Glycosylation, Proteolysis, and Covalently Bound Lipids
VI. Receptor Activation and Desensitization
A. Agonists
B. Competitive Antagonists: New Developments
C. Noncompetitive Antagonists
D. Uncompetitive Blockers
E. Antagonists with Unknown Mechanism
F. Glutamate Receptor Kinetics
G. Molecular Determinants of AMPA Receptor Deactivation and
Desensitization
H. Molecular Determinants of Kainate Receptor Deactivation and
Desensitization
I. Molecular Determinants of NMDA Receptor Deactivation and
Desensitization
VII. Endogenous Allosteric Modulators
A. Extracellular Zinc
B. Reduction and Oxidation of Extracellular Cysteine Residues
C. Extracellular Protons
D. Extracellular Polyamines
VIII. Molecular Determinants of Ion Permeation
A. Pore Diameter
B. Unitary Sublevel Conductances
C. Ionic Selectivity
IX. Molecular Determinants of Channel Block
A. External Mg2+ Block of NMDA Receptors
B. Internal Mg2+ Block of NMDA Receptors
C. Internal Polyamine Block of AMPA and Kainate Receptors
X. Molecular Composition of the Pore
A. Outer Vestibules
B. Narrow Constriction and Selectivity Filter
XI. Association of Glutamate Receptors with Intracellular Proteins
A. AMPA Receptors
B. NMDA Receptors: Signaling Molecules and Proteins Lacking PDZ
Domains
C. NMDA Receptors: PDZ Domain-Containing Proteins
D. Kainate Receptors
XII. Genetic Regulation of Receptor Expression
A. Transcriptional Control
B. Translational Control
XIII. Therapeutic Potential: Clinical Trials
A. Ischemic Stroke
B. Neuropathic Pain
C. Parkinson's Disease
D. Cognitive Enhancement
XIV. Outlook
Acknowledgments
References
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Y. H. Huang, Y. Lin, T. E. Brown, M.-H. Han, D. B. Saal, R. L. Neve, R. S. Zukin, B. A. Sorg, E. J. Nestler, R. C. Malenka, et al. CREB Modulates the Functional Output of Nucleus Accumbens Neurons: A CRITICAL ROLE OF N-METHYL-D-ASPARTATE GLUTAMATE RECEPTOR (NMDAR) RECEPTORS J. Biol. Chem., February 1, 2008; 283(5): 2751 - 2760. [Abstract] [Full Text] [PDF]
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K. Erreger and S. F. Traynelis Zinc inhibition of rat NR1/NR2A N-methyl-D-aspartate receptors J. Physiol., February 1, 2008; 586(3): 763 - 778. [Abstract] [Full Text] [PDF]
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 N. R. Stephens, Z. Qi, and E. P. Spalding Glutamate Receptor Subtypes Evidenced by Differences in Desensitization and Dependence on the GLR3.3 and GLR3.4 Genes Plant Physiology, February 1, 2008; 146(2): 529 - 538. [Abstract] [Full Text] [PDF]
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W. Zhang, Y. Cho, E. Lolis, and J. R. Howe Structural and Single-Channel Results Indicate That the Rates of Ligand Binding Domain Closing and Opening Directly Impact AMPA Receptor Gating J. Neurosci., January 23, 2008; 28(4): 932 - 943. [Abstract] [Full Text] [PDF]
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S. Panicker, K. Brown, and R. A. Nicoll Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GluR2-lacking mouse PNAS, January 22, 2008; 105(3): 1032 - 1037. [Abstract] [Full Text] [PDF]
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V. Biou, S. Bhattacharyya, and R. C. Malenka Endocytosis and recycling of AMPA receptors lacking GluR2/3 PNAS, January 22, 2008; 105(3): 1038 - 1043. [Abstract] [Full Text] [PDF]
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K. S. Vikman, B. K. Rycroft, and M. J. Christie Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat J. Physiol., January 15, 2008; 586(2): 515 - 527. [Abstract] [Full Text] [PDF]
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S. Zhang, L. Edelmann, J. Liu, J. E. Crandall, and M. A. Morabito Cdk5 Regulates the Phosphorylation of Tyrosine 1472 NR2B and the Surface Expression of NMDA Receptors J. Neurosci., January 9, 2008; 28(2): 415 - 424. [Abstract] [Full Text] [PDF]
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G. Tong, H. Takahashi, S. Tu, Y. Shin, M. Talantova, W. Zago, P. Xia, Z. Nie, T. Goetz, D. Zhang, et al. Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons J Neurophysiol, January 1, 2008; 99(1): 122 - 132. [Abstract] [Full Text] [PDF]
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D. C. Wrighton, E. J. Baker, P. E. Chen, and D. J. A. Wyllie Mg2+ and memantine block of rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes J. Physiol., January 1, 2008; 586(1): 211 - 225. [Abstract] [Full Text] [PDF]
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P. E. Chen, M. T. Geballe, E. Katz, K. Erreger, M. R. Livesey, K. K. O'Toole, P. Le, C. J. Lee, J. P. Snyder, S. F. Traynelis, et al. Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes J. Physiol., January 1, 2008; 586(1): 227 - 245. [Abstract] [Full Text] [PDF]
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A. J. Milnerwood and L. A. Raymond Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load J. Physiol., December 15, 2007; 585(3): 817 - 831. [Abstract] [Full Text] [PDF]
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D.-T. Lin and R. L. Huganir PICK1 and Phosphorylation of the Glutamate Receptor 2 (GluR2) AMPA Receptor Subunit Regulates GluR2 Recycling after NMDA Receptor-Induced Internalization J. Neurosci., December 12, 2007; 27(50): 13903 - 13908. [Abstract] [Full Text] [PDF]
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C. Villmann and C.-M. Becker On the Hypes and Falls in Neuroprotection: Targeting the NMDA Receptor Neuroscientist, December 1, 2007; 13(6): 594 - 615. [Abstract] [PDF]
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C. Madry, I. Mesic, H. Betz, and B. Laube The N-Terminal Domains of both NR1 and NR2 Subunits Determine Allosteric Zn2+ Inhibition and Glycine Affinity of N-Methyl-D-aspartate Receptors Mol. Pharmacol., December 1, 2007; 72(6): 1535 - 1544. [Abstract] [Full Text] [PDF]
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M. Renzi, M. Farrant, and S. G. Cull-Candy Climbing-fibre activation of NMDA receptors in Purkinje cells of adult mice J. Physiol., November 15, 2007; 585(1): 91 - 101. [Abstract] [Full Text] [PDF]
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P. M. Paez, V. Spreuer, V. Handley, J.-M. Feng, C. Campagnoni, and A. T. Campagnoni Increased Expression of Golli Myelin Basic Proteins Enhances Calcium Influx into Oligodendroglial Cells J. Neurosci., November 14, 2007; 27(46): 12690 - 12699. [Abstract] [Full Text] [PDF]
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Y. Xia, S. Nawy, and R. C. Carroll Activity-Dependent Synaptic Plasticity in Retinal Ganglion Cells J. Neurosci., November 7, 2007; 27(45): 12221 - 12229. [Abstract] [Full Text] [PDF]
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M. T.-W. Ho, K. A. Pelkey, L. Topolnik, R. S. Petralia, K. Takamiya, J. Xia, R. L. Huganir, J.-C. Lacaille, and C. J. McBain Developmental Expression of Ca2+-Permeable AMPA Receptors Underlies Depolarization-Induced Long-Term Depression at Mossy Fiber CA3 Pyramid Synapses J. Neurosci., October 24, 2007; 27(43): 11651 - 11662. [Abstract] [Full Text] [PDF]
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C. Piochon, T. Irinopoulou, D. Brusciano, Y. Bailly, J. Mariani, and C. Levenes NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell J. Neurosci., October 3, 2007; 27(40): 10797 - 10809. [Abstract] [Full Text] [PDF]
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D. Hatakeyama, H. Aonuma, E. Ito, and K. Elekes Localization of Glutamate-like Immunoreactive Neurons in the Central and Peripheral Nervous System of the Adult and Developing Pond Snail, Lymnaea stagnalis Biol. Bull., October 1, 2007; 213(2): 172 - 186. [Abstract] [Full Text] [PDF]
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K. Erreger, M. T. Geballe, A. Kristensen, P. E. Chen, K. B. Hansen, C. J. Lee, H. Yuan, P. Le, P. N. Lyuboslavsky, N. Micale, et al. Subunit-Specific Agonist Activity at NR2A-, NR2B-, NR2C-, and NR2D-Containing N-Methyl-D-aspartate Glutamate Receptors Mol. Pharmacol., October 1, 2007; 72(4): 907 - 920. [Abstract] [Full Text] [PDF]
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A. Limon, J. M. Reyes-Ruiz, F. Eusebi, and R. Miledi Properties of GluR3 receptors tagged with GFP at the amino or carboxyl terminus PNAS, September 25, 2007; 104(39): 15526 - 15530. [Abstract] [Full Text] [PDF]
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M. J. Laster, Y. Zhang, E. I. Eger II, D. Shnayderman, and J. M. Sonner Alterations in Spinal, but Not Cerebral, Cerebrospinal Fluid Na+ Concentrations Affect the Isoflurane Minimum Alveolar Concentration in Rats Anesth. Analg., September 1, 2007; 105(3): 661 - 665. [Abstract] [Full Text] [PDF]
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H. Hald, P. Naur, D. S. Pickering, D. Sprogoe, U. Madsen, D. B. Timmermann, P. K. Ahring, T. Liljefors, A. Schousboe, J. Egebjerg, et al. Partial Agonism and Antagonism of the Ionotropic Glutamate Receptor iGLuR5: STRUCTURES OF THE LIGAND-BINDING CORE IN COMPLEX WITH DOMOIC ACID AND 2-AMINO-3-[5-tert-BUTYL-3-(PHOSPHONOMETHOXY)-4-ISOXAZOLYL]PROPIONIC ACID J. Biol. Chem., August 31, 2007; 282(35): 25726 - 25736. [Abstract] [Full Text] [PDF]
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P. T. Atlason, M. L. Garside, E. Meddows, P. Whiting, and R. A. J. McIlhinney N-Methyl-D-aspartate (NMDA) Receptor Subunit NR1 Forms the Substrate for Oligomeric Assembly of the NMDA Receptor J. Biol. Chem., August 31, 2007; 282(35): 25299 - 25307. [Abstract] [Full Text] [PDF]
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T. Chernova, J. R. Steinert, C. J. Guerin, P. Nicotera, I. D. Forsythe, and A. G. Smith Neurite Degeneration Induced by Heme Deficiency Mediated via Inhibition of NMDA Receptor-Dependent Extracellular Signal-Regulated Kinase 1/2 Activation J. Neurosci., August 8, 2007; 27(32): 8475 - 8485. [Abstract] [Full Text] [PDF]
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