Excitatory Amino Acid Transmission in Health and Disease

by Balazs, Robert; Bridges, Richard J.; Cotman, Carl W.

• ISBN13: 9780195150025
• ISBN10: 0195150023
• Format: Hardcover
• Copyright: 2005-09-28
• Publisher: Oxford University Press

Summary

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). It regulates normal CNS function, is a major participant in pathology, and serves learning, memory, and higher cognitive functions. The 12 chapters of this book provide the first comprehensivecoverage of all the major features of glutamate as excitatory neurotransmitter. The book begins with a valuable historical backdrop. Building from a chapter on the common structure of glutamate receptors, several others cover the major ionotropic receptors, their structure, function, andpharmacology. A follow-up chapter discusses the metabotropic receptors that are directly coupled to second messenger metabolism. A central theme of the book is the capacity of the excitatory amino acid system to contribute to the diverse array of signaling systems in the CNS as a direct result ofthe large assortment of receptors (including, for the ionotropic receptors, various subunits) the combination of which determine distinct functional properties. A recent development in the field discussed in several chapters is the biochemical characterization of a supermolecular protein complex,the post-synaptic density, that makes the unique structure of excitatory synapses. This complex subserves the experience-dependent modulation of synaptic strength and synaptic plasticity, and gives the synapse the capacity to change dynamically in both structure and receptor composition. Drawingon the individual properties of the receptors, transporters, and functional architecture of the synapse, the concluding chapters describe the functional integration of these components in the more complex physiological processes of plasticity and pathology. Recognition that the regulation ofexcitatory amino acid receptor activity underlies the pathology of many neurological diseases, including stroke, Alzheimer's disease and schizophrenia, has opened up an exciting frontier that will allow the translation of our understanding of these basic mechanisms into new concepts of pathology andnew therapeutic strategies. This book will be invaluable for neuroscientists, pharmacologists, neurologists, and psychiatrists, and for their students and trainees.

Table of Contents

Overview and Perspective	1	(13)
Applications of L-Glutamate Potently Depolarize Central Nervous System Neurons	2	(2)
Demonstrations of Calcium-Dependent Glutamate Release	4	(1)
Identification of Agonists and Antagonists with Which to Delineate the Three Ionotropic Receptor Classes	5	(2)
Participation of Excitatory Amino Acid Ionotropic Receptors in Excitotoxicity	7	(1)
Participation of NMDA Receptors in Long-Term Potentiation	8	(1)
Cloning of the Ionotropic Glutamate Receptors	9	(1)
Delineation of Metabotropic Glutamate Receptors	10	(1)
Postsynaptic Molecular Organization at the Excitatory Synapse	11	(1)
Structural Changes Underlying Gating of iGluR Channels and Activation of mGluRs	12	(1)
Future Directions	12	(2)
Ionotropic Glutamate Receptors: General Characteristics	14	(22)
Posttranscriptional Modifications	20	(3)
Structure of the Ionotropic Glutamate Receptors	23	(13)
AMPA Receptors	36	(20)
Molecular Structure, Properties, and Regulation	36	(5)
Distribution of AMPA Receptors	41	(5)
AMPA Receptor Pharmacology	46	(8)
Therapeutic Applications	54	(2)
Kainate Receptors	56	(21)
Molecular Structure and Subunit Composition	57	(5)
Single-Channel Conductance and Desensitization	62	(1)
Distribution	63	(3)
Pharmacology	66	(5)
Synaptic Role of Kainate Receptors	71	(4)
Therapeutic Applications	75	(2)
NMDA Receptors	77	(34)
Unique Role of NMDA Receptors in Excitatory Transmission	77	(1)
Molecular Characterization	78	(12)
Posttranslational Modifications: Phosphorylation and Dephosphorylation	90	(3)
Molecular Interactions of NMDA Receptors Relevant for Signal Transduction	93	(1)
Desensitization	94	(1)
Anatomical Distribution	95	(3)
Pharmacology	98	(8)
Modulation of NMDA Receptor Expression in Gene-Targeted Mice	106	(3)
Therapeutic Applications	109	(2)
Delta Glutamate Receptors	111	(4)
Delta2 Glutamate Receptors	111	(3)
Delta1 Glutamate Receptors	114	(1)
Metabotropic Glutamate Receptors	115	(52)
mGluRs Are Members of the G Protein-Coupled Receptor Superfamily	115	(1)
Molecular Characterization of mGluRs	116	(5)
Distribution of mGluRs	121	(8)
Effects of mGluRs on Neurotransmission	129	(9)
Effect of mGluRs on Ion Channels	138	(5)
Regulation of Plasma Membrane Ion Channels and Intracellular Calcium Stores by Group I mGluRs: Critical Role of Homer Family Proteins	143	(1)
Regulation of mGluRs	144	(5)
Pharmacology	149	(18)
Glutamate Transporters	167	(23)
Cellular Excitatory Amino Acid Transporters	167	(18)
Vesicular Glutamate Transporters	185	(5)
Molecular Organization of Glutamate Receptors in the Postsynaptic Density	190	(17)
The NMDA Receptor within the PSD Complex	193	(7)
Shank Represents a Core for the Association of Glutamate Receptors in the PSD Complex	200	(1)
AMPA Receptors within the PSD Complex	201	(4)
Kainate Receptors within the PSD Complex	205	(1)
Metabotropic Glutamate Receptors within the PSD Complex	206	(1)
Trafficking of Glutamate Receptors	207	(19)
AMPA Receptor Trafficking	207	(9)
Kainate Receptor Trafficking	216	(1)
NMDA Receptor Trafficking	217	(6)
Metabotropic Glutamate Receptor Trafficking	223	(3)
Excitatory Amino Acid Transmission and Synaptic Plasticity	226	(43)
Long-Term Potentiation	227	(20)
Long-Term Depression	247	(9)
Developmental Plasticity	256	(7)
Trophic Effects of Excitatory Amino Acids	263	(6)
Glutamate and Glutamate Receptors in Neurological Diseases	269	(40)
Excitotoxicity	270	(7)
Ischemic Stroke	277	(3)
Alzheimer's Disease and the Role of Glutamatergic Synaptic Transmission	280	(6)
Parkinson's Disease	286	(4)
Schizophrenia	290	(6)
Amyotrophic Lateral Sclerosis	296	(3)
Epilepsy	299	(5)
Nociception	304	(1)
Anxiety	305	(4)
Bibliography	309	(46)
Index	355