strategies.
vi Preface
Contents
1 OVERVIEW AND PERSPECTIVE, 1
Applications of L-Glutamate Potently Depolarize Central Nervous System
Neurons, 2
Demonstrations of Calcium-Dependent Glutamate Release, 4
Identification of Agonists and Antagonists with Which to Delineate the
Three Ionotropic Receptor Classes, 5
Participation of Excitatory Amino Acid Ionotropic Receptors in
Excitotoxicity, 7
Participation of NMDA Receptors in Long-Term Potentiation, 8
Cloning of the Ionotropic Glutamate Receptors, 9
Delineation of Metabotropic Glutamate Receptors, 10
Postsynaptic Molecular Organization at the Excitatory Synapse, 11
Structural Changes Underlying Gating of iGluR Channels and Activation
of mGluRs, 12
Future Directions, 12
2 IONOTROPIC GLUTAMATE RECEPTORS:
GENERAL CHARACTERISTICS, 14
Posttranscriptional Modifications, 20
Structure of the Ionotropic Glutamate Receptors, 23
3 AMPA RECEPTORS, 36
Molecular Structure, Properties, and Regulation, 36
Distribution of AMPA Receptors, 41
AMPA Receptor Pharmacology, 46
Therapeutic Applications, 54
4 KAINATE RECEPTORS, 56
Molecular Structure and Subunit Composition, 57
Single-Channel Conductance and Desensitization, 62
Distribution, 63
Pharmacology, 66
Synaptic Role of Kainate Receptors, 71
Therapeutic Applications, 75
5 NMDA RECEPTORS, 77
Unique Role of NMDA Receptors in Excitatory Transmission, 77
Molecular Characterization, 78
Posttranslational Modifications: Phosphorylation and
Dephosphorylation, 90
Molecular Interactions of NMDA Receptors Relevant for Signal
Transduction, 93
Desensitization, 94
Anatomical Distribution, 95
Pharmacology, 98
Modulation of NMDA Receptor Expression in Gene-Targeted Mice, 106
Therapeutic Applications, 109
6 DELTA GLUTAMATE RECEPTORS, 111
Delta2 Glutamate Receptors, 111
Delta1 Glutamate Receptors, 114
7 METABOTROPIC GLUTAMATE RECEPTORS, 115
mGluRs Are Members of the G Protein–Coupled Receptor
Superfamily, 115
Molecular Characterization of mGluRs, 116
Distribution of mGluRs, 121
Effects of mGluRs on Neurotransmission, 129
Effect of mGluRs on Ion Channels, 138
Regulation of Plasma Membrane Ion Channels and Intracellular
Calcium Stores by Group I mGluRs: Critical Role of Homer
Family Proteins, 143
Regulation of mGluRs, 144
Pharmacology, 149
8 GLUTAMATE TRANSPORTERS, 167
Cellular Excitatory Amino Acid Transporters, 167
Vesicular Glutamate Transporters, 185
9 MOLECULAR ORGANIZATION OF GLUTAMATE RECEPTORS IN
THE POSTSYNAPTIC DENSITY, 190
The NMDA Receptor within the PSD Complex, 193
Shank Represents a Core for the Association of Glutamate Receptors in
the PSD Complex, 200
AMPA Receptors within the PSD Complex, 201
Kainate Receptors within the PSD Complex, 205
Metabotropic Glutamate Receptors within the PSD Complex, 206
10 TRAFFICKING OF GLUTAMATE RECEPTORS, 207
AMPA Receptor Trafficking, 207
Kainate Receptor Trafficking, 216
NMDA Receptor Trafficking, 217
Metabotropic Glutamate Receptor Trafficking, 223
11 EXCITATORY AMINO ACID TRANSMISSION AND SYNAPTIC
PLASTICITY, 226
Long-Term Potentiation, 227
Long-Term Depression, 247
Developmental Plasticity, 256
Trophic Effects of Excitatory Amino Acids, 263
12 GLUTAMATE AND GLUTAMATE RECEPTORS IN
NEUROLOGICAL DISEASES, 269
Excitotoxicity, 270
Ischemic Stroke, 277
Alzheimer’s Disease and the Role of Glutamatergic Synaptic
Transmission, 280
Parkinson’s Disease, 286
Schizophrenia, 290
Amyotrophic Lateral Sclerosis, 296
Epilepsy, 299
Nociception, 304
Anxiety, 305
Bibliography, 309
Index, 355



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