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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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