The Cholinergic Synapse by Victor P. WhittakerThe Cholinergic Synapse by Victor P. Whittaker

The Cholinergic Synapse

byVictor P. Whittaker

Paperback | December 6, 2011

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One of the most impressive works of scholarship in the field of experimental pharmacology has been the Heffter-Heubner Handbuch der experimentellen Pharmakologie, internationalized some years ago under the title Handbook 0/ Experimental Pharmacology and kept up to date by a series of numbered Ergiin­ zungswerke or supplementary volumes which have now replaced in importance the original Handbuch. These volumes constitute a valuable and continuously up­ dated multi author review series of topics important in modern pharmacology and allied sciences. The Editorial Board of the Handbook invited me 2 years ago to undertake, as subeditor, the preparation of a new volume entitled The Cholinergic Synapse. A previous volume in this series, vol. 15, Cholinesterases and Anticholinesterase Agents, edited by GEORGE KOELLE, was published in 1963 and was far wider in scope than its title suggested: it was, in fact an authoritative summing up of the whole subject of cholinergic function and still has some value today as an account of the state of the art as it was at that time. Since then another excellent review, of a specific cholinergic synapse, has appeared in this series: this was vol. 42, Neuromuscular Junction, edited by ELEANOR ZAIMIS and published in 1976. A third volume, vol. 53, Pharmacology o/Ganglionic Transmission, which appeared in 1980 and was edited by D. A. KHARKEVICH, includes important aspects of autonomic cholinergic function.
Title:The Cholinergic SynapseFormat:PaperbackDimensions:762 pages, 24.2 × 17 × 0.07 inPublished:December 6, 2011Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:3642732224

ISBN - 13:9783642732225

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Table of Contents

I. Model Cholinergic Systems.- 1: Model Cholinergic Systems: An Overview.- A. The Value of Model Systems.- B. Pros and Cons of Selected Model Systems.- I. Cephalopod Optic Lobe.- II. Electric Organs.- III. Myenteric Plexus-Longitudinal Muscle Preparation.- IV. Ganglion Preparations.- V. Mammalian Central Nervous System Preparations.- VI. Amphibian and Mammalian Voluntary Muscle.- References.- 2: Model Cholinergic Systems: The Electromotor System of Torpedo.- A. Embryology.- B. Components of the Electromotor System.- I. Electric Lobe.- II. Axons.- III. Electric Organ.- C. Conclusions.- References.- 3: Model Cholinergic Systems: The Avian Ciliary Ganglion.- A. Introduction.- B. Anatomy.- C. Electrophysiology and Biochemistry.- I. Chemical and Electrical Components in Synaptic Transmission.- II. Presence of Neuropeptides and its Implications.- III. Presence of Presynaptic ACh Receptors.- IV. Postsynaptic Receptor Heterogeneity.- V. Regulation of ACh Synthesis.- D. Cell and Tissue Culture.- E. Concluding Remarks.- References.- II. Biology of the Cholinergic Synapse.- 4: Phylogeny of the Cholinergic Synapse.- A. Introduction.- B. Variation at the Synaptic Level.- I. Parameters Considered.- II. Synthesis of ACh.- III. Termination of the Action of ACh.- IV. Characteristics of ACh Receptors.- C. Qualitative and Quantitative Changes in Cholinergic Innervation.- I. Qualitative Changes.- II. Quantitative Changes.- D. Conclusions.- References.- 5: Development of the Cholinergic Synapse: Role of Trophic Factors.- A. Introduction.- B. Parasympathetic Ciliary Neurons.- I. Ciliary Ganglion as a Model System.- II. Necessity of Trophic Factors for the Survival and Growth of Ciliary Neurons In Vitro.- III. Developmental Regulation of Survival Activity for Ciliary Neurons.- IV. Characterization of Ciliary Neuron Survival Factors.- V. Factors Affecting the Growth and Development of Ciliary Neurons In Vitro.- VI. Factors Stimulating Neurite Growth in Ciliary Neuron Cultures.- C. Spinal Cord Neurons.- I. Greater Complexity of the System.- II. Survival Factors for Spinal Cord Neurons.- III. Factors Stimulating ChAT Activity in Spinal Cord Cultures.- IV. Factors Stimulating Neurite Growth in Spinal Cord Cultures.- D. Sympathetic Neurons.- I. Evidence for a Cholinergic Subpopulation.- II. Induction of Cholinergic Transmitter Status in Sympathetic Neurons.- III. Characterization of the Cholinergic-Specifying Factor.- E. Conclusions.- References.- III. Molecular Components of the Cholinergic System.- 6: Estimation of Acetylcholine and Choline and Analysis of Acetylcholine Turnover Rates In Vivo.- A. Introduction.- B. Preparation of Samples for ACh and Choline Analysis.- I. General Requirements for Measurement of ACh and Choline.- II. Extraction of ACh and Choline from Tissues, Subcellular Fractions and Perfusates.- III. Preservation of ACh and Choline Post-Mortem.- C. Analysis of ACh and Choline.- I. Bioassay.- II. Chemical Techniques Before 1972, Excluding Radioenzymatic and Gas Chromatographic (GC) Assays.- III. Radioenzymatic Assays.- IV. GC and GCMS Analyses.- V. New Developments Since 1978.- D. Methods for Measuring ACh Turnover.- I. General Considerations.- II. Non-isotopic Methods.- III. Isotopic Methods.- E. Concluding Remarks.- References.- 7: Choline Acetyltransferase and the Synthesis of Acetylcholine.- A. Introduction.- B. Choline Acetyltransferase.- I. The Enzyme Molecule.- II. Catalytic Action.- III. Cellular and Subcellular Localization.- C. Supply of Substrates.- I. Acetylcoenzyme A.- II. Choline.- III. Source of Choline for ACh Synthesis.- D. Regulation of ACh Synthesis.- I. Kinetic Considerations.- II. Regulatory Factors.- References.- 8a: Vertebrate Cholinesterases: Structure and Types of Interaction.- A. Introduction.- B. Duality of ChEs: AChE and BuChE.- C. Molecular Forms of ChEs: The Value and Limitations of a General Scheme and a Nomenclature for Their Quaternary Structure.- D. Electric Organs of Fish: A Privileged Source of AChE for Biochemical Studies.- E. Quaternary Structure and Interactions of Asymmetric Forms.- I. Electrophorus.- II. Torpedo.- III. Asymmetric AChE Forms from Other Species, BuChE Asymmetric Forms, Hybrid AChE-BuChE Asymmetric Forms.- IV. Ionic Interactions.- V. Asymmetric AChE Forms and the Basal Lamina.- F. Physiochemical Properties of Globular Forms.- I. Solubility and Hydrophobicity: Operational Definition of Amphiphilic Molecules.- II. Solubility of ChE Globular Forms: Soluble and Detergent-Soluble Fractions.- III. Non-amphiphilic or Hydrophilic Globular Forms.- IV. Membrane-Bound, Intracellular and Extracellular Amphiphilic Forms.- V. Interactions with Detergent Micelles.- VI. Dimeric Forms Containing a Hydrophobic Glycolipid Anchor.- VII. Structure of G4 Forms Containing a Distinct Hydrophobic Subunit.- VIII. Solubilization Artefacts, Modifications of the Solubilized Forms.- IX. Catalytic Activity and Hydrophobic Interactions.- X. Thermal Stability.- G. Variability of the Catalytic Subunits.- I. Catalytic Subunits of AChE and BuChE in Vertebrates: Analysis by SDS-PAGE.- II. Specificity of Inhibitory Antibodies and Peptide Toxins.- III. Comparison Between Catalytic Subunits of Different AChE Fractions Within a Given Species.- IV. Heterogeneity of AChE Globular Forms in Non-denaturing Electrophoresis.- V. Binding of Lectins and Heterogeneity of Glycosylation of AChE Molecules.- H. Immunochemical Studies.- I. Immunochemical Cross-Reactivity Between AChE and BuChE.- II. Interspecific Cross-Reactivity.- III. Immunochemical Differences Between AChE Fractions Within a Given Organism.- I. Molecular-Biological Studies.- I. Characterization of AChE mRNAs and Their Translation Products.- II. Characterization of AChE cDNA Clones.- III. Primary Structures of ChEs.- J. Conclusions.- References.- 8b: Cholinesterases: Tissue and Cellular Distribution of Molecular Forms and Their Physiological Regulation.- A. Introduction.- B. Tissue Distribution of ChE Molecular Forms.- I. General Considerations.- II. Distribution of AChE Molecular Forms at Neuromuscular Junctions.- III. Ganglionic Synapses of the Autonomic Nervous System.- C. Subcellular Distribution of AChE Molecular Forms in Muscle and Nerve Cells.- I. Determination of Endo- and Ectocellular Enzyme Activities.- II. Distribution of Molecular Forms in Ecto- and Endocellular Compartments.- D. Biosynthesis and Renewal of AChE Molecular Forms.- I. In Vitro Studies.- II. Nervous Tissue and Muscle In Vivo.- E. Intracellular Transport and Secretion of AChE Molecular Forms.- I. Intracellular Transport.- II. Secretion.- F. Regulation of the Synthesis of AChE by Muscle and Nerve Cells During Development In Vivo and In Vitro.- I. Evolution of AChE Activity and Molecular Forms in Muscle and Nerve Cells During Embryogenesis.- II. Relationship Between Synthesis of A Forms and Innervation of Muscle and Nerve Cells In Vivo.- III. Regulation of the Synthesis of A Forms by Muscle and Nerve Cells In Vitro.- IV. Localization of AChE on Muscle Membranes.- G. Non-cholinergic Functions of ChEs.- I. Adult Tissues: New Substrates for ChEs.- II. "Embryonic ChE": A Cholinergic Function in the Absence of Innervation?.- H. Effects of Peptides on ChEs.- I. Effect on the Activity of AChE.- II. Effect on the Synthesis of ChE.- I. ChEs in Pathological States and Their Evolution with Aging.- I. Muscular Dystrophy.- II. Human Pathology.- III. AChE and the Prenatal Diagnosis of Neural Tube Defects.- IV. Aging.- J. Conclusion.- References.- 9: Structure and Function of the Nicotinic Acetylcholine Receptor.- A. Introduction and Scope.- B. Structure of the nAChR.- I. Primary Structure.- II. Secondary Structure and Topography.- III. Tertiary Structure.- IV. Quaternary Structure.- V. Functional Domains.- VI. Conformations.- VII. Classification of ACh Receptors According to Structure.- C. Molecular Genetics.- I. Structure of nAChR Genes.- II. nAChR Gene Expression and Processing.- D. Function of the nAChR.- I. Ligand Binding.- II. Channel Gating.- III. Modulation of Binding and Response.- IV. Molecular Mechanism of Function.- References.- 10: Muscarinic Acetylcholine Receptors.- A. Introduction.- I. Two Main Types of ACh Receptor.- II. Biochemistry of mAChRs.- III. Localization of mAChRs.- B. Assays of Muscarinic Receptors and Muscarinic Ligands.- I. Binding Studies.- II. Assay of Muscarinic Agonist and Antagonist Actions.- III. Muscarinic Agonist Effects in Intact Animals.- C. Clinical Application of Muscarinic Drugs.- I. Therapeutic Uses of Muscarinic Drugs.- II. Acute Poisoning with Muscarinic Agonists.- III. Acute Poisoning with Muscarinic Antagonists.- References.- IV. Cellular Organization of the Cholinergic System.- 11: Cholinergic Synaptic Vesicles.- A. Introduction.- B. Isolation of Cholinergic Synaptic Vesicles.- C. General Properties.- D. Vesicle Core.- I. Constituents of the Core.- II. ACh and ATP.- III. Metal Ions.- IV. pH and Membrane Potential.- V. Proteoglycan.- VI. Peptides.- E. Vesicle Membrane.- I. Composition.- II. Membrane Lipids.- III. Polypeptide Composition.- IV. Vesicular Proteins.- F. Vesicular Transport Systems.- I. Types of System Present.- II. Vesicular Proton Pump.- III. Vesicular Uptake of Ca2+.- IV. Vesicular Uptake of Opioid Peptides.- V. Vesicular Uptake of ATP.- VI. Vesicular Uptake of ACh.- G. Dynamic Properties of Synaptic Vesicles.- I. Morphological Alterations on Nerve Stimulation.- II. Biochemical Alterations on Nerve Stimulation.- III. Mechanism of Exocytosis.- IV. Gated Release of ACh.- V. Life-Cycle of the Synaptic Vesicle.- References.- 12: Isolation of Cholinergic Nerve Terminals.- A. Introduction.- B. Historical Aspects.- C. Heterogeneous Mammalian Nerve-Terminal Preparations.- D. Heterogeneous Non-mammalian Nerve Terminals.- E. Purely Cholinergic Nerve-Terminal Preparations from Electric Organs.- I. Types of Preparation Available.- II. Purity and Functional State of Electromotor Synaptosome Preparations.- III. Presynaptic Plasma Membranes.- F. Affinity Purification of Mammalian Cholinergic Nerve Terminals.- I. Separation Procedure.- II. Characteristics of the Preparation.- G. Summary.- References.- 13: Axonal Transport in Cholinergic Neurons.- A. Introduction.- B. General Protein Transport in Cholinergic Nerves.- C. Transport of Distinctive Components of the Cholinergic Neuron.- I. Acetylcholine.- II. Acetylcholinesterase.- III. Choline Acetyltransferase.- IV. Cholinergic Synaptic Vesicle-Associated Proteins.- D. Interpretation of the Transport of Cholinergic-Specific Substances in the Context of General Axonal Protein Transport.- References.- 14: The High-Affinity Choline Uptake System.- A. Introduction.- B. Characteristics of HACU.- I. Tissue and Site Specificity.- II. Physiological Significance.- III. Structure-Activity Relationship Studies.- IV. Bioenergetics of Uptake.- V. Possible Role of Sialocompounds, Lipids and Steroids.- C. Identification of the HACU System.- I. Criteria for Identification.- II. Attempted Identification of Presynaptic Plasma Membrane Components and Their Modification.- III. Binding of Hemicholinium-3.- IV. Labelling with Covalent Probes.- V. Reconstitution of Choline Uptake Activity.- D. Areas for Future Investigation.- I. Functional Ligands and Components.- II. Arrangement of Transport System in the Membrane.- III. Isolation of Transport System.- IV. Possible Role of Lipids.- V. Conformational Changes of the Transporter Associated with Choline Uptake.- References.- 15: Cholinergic-Specific Antigens.- A. Introduction.- I. General Strategy.- II. The Problem of Unwanted Antibodies.- III. Complement Lysis Test.- B. Surface Antigens Specific for Cholinergic Nerve Terminals.- I. Identification of Cholinergic-Specific Gangliosides.- II. Applications of Anti-Chol-1 Antisera.- III. Possible Functional Significance of Chol-1.- IV. Complement-Mediated Lysis of Synaptosomes Induced by Anti-ChAT Antisera.- C. Synaptic Vesicle Proteoglycans.- I. From Torpedo marmorata.- II. From Other Torpedine Fish.- References.- 16: Cholinergic False Transmitters.- A. Definition and Structural Requirements.- I. Definition.- II. Adrenergic System.- III. Cholinergic System.- B. Differential Labelling of Transmitter Pools by False Transmitters.- I. Electric Organ.- II. Mammalian Preparations.- C. Conclusions.- References.- 17: Cholinergic Co-transmitters.- A. Introduction.- I. Scope of the Chapter: ATP and Neuropeptides.- II. Terminology.- III. Criteria to Be Satisfied.- B. ATP as a Neuroactive Compound.- I. ATP and Its Derivatives in Neuronal Function.- II. ATP in Chromaffin Granules.- III. ATP in the Cholinergic System of Torpedo.- IV. ATP in Mammalian Cholinergic Systems.- V. The Concept of Independent Purinergic Terminals.- VI. Must ATP Be Reckoned as a Cholinergic Co-transmitter?.- C. Evidence for Co-localization of Certain Neuropeptides and ACh.- I. Discovery of Neuropeptides.- II. Discovery of Co-localization.- III. Histochemical and Cytochemical Evidence for Co-localization.- IV. Cell-Biological and Biochemical Evidence.- V. Physiological and Pharmacological Evidence.- VI. Consequences of Coexistence of ACh and Neuropeptides.- References.- V. Peripheral Cholinergic Synapses.- 18: The Neuromuscular Junction.- A. Introduction.- B. Quantal Basis of Transmitter Release.- A. Classes of Quanta.- I. Bell-mEPPs and Skew- (sub-)mEPPS.- II. Schwann-Cell mEPPs.- III. Giant mEPPs and Doublet mEPPs.- IV. Slow Skew-mEPPs.- B. Subunit Hypothesis of the Quantum of Transmitter Release.- C. Morphological Correlates of Bell-mEPPs and Skew-mEPPs.- E Concluding Remarks.- References.- 19: The Electromotor Synapse.- A. Introduction.- B. Gross Physiology.- C. Physiology of Single Electrocytes.- D. Microphysiology of Transmission at the EMJ.- I. Extracellular Electroplaque Currents.- II. Intracellular Electroplaque Potentials.- III. Quantal Analysis of Electroplaque Potentials.- E. Conclusions.- References.- 20: The Autonomic Cholinergic Neuroeffector Junction.- A. Introduction.- B. Release of ACh.- I. Resting Release.- II. Electrically Evoked Release.- III. Release of Vasoactive Intestinal Peptide as a Co-transmitter in Cholinergic Nerves.- C. Modulation of ACh Release by Muscarinic Autoreceptors.- I. Prejunctional Autoreceptors.- II. Soma-Dendritic Autoreceptors.- D. Effects of ACh on Effector Organs: Mediation Through Subtypes of mAChRs.- References.- VI. Central Cholinergic Systems.- 21: Central Cholinergic Pathways: The Biochemical Evidence.- A. Introduction.- B. Biochemical Markers.- C. Preparation of Tissue.- I. Single Cell Preparations.- II. Microdissection from Freeze-Dried Sections.- III. Micropunches from Frozen Sections.- IV. Micropunches from Fresh Tissue.- V. Lesions.- D. Distribution of Cholinergic Markers in the Brain.- E. Localization of Cholinergic Pathways in the Brain.- I. Olfactory Bulb.- II. Cerebral Cortex.- III. Hippocampal Region.- IV. Amygdaloid Complex.- V. Striatum.- VI. Thalamus.- VII. Habenulo-Interpeduncular System.- VIII. Hypothalamus.- IX. Cerebellum.- X. Brain Stem.- XI. Spinal Cord.- XII. Retina.- References.- 22: Central Cholinergic Pathways: The Histochemical Evidence.- A. Introduction.- B. Techniques.- I. Immunohistochemistry for ChAT.- II. AChE Histochemistry.- III. Ancillary Techniques.- C. Central Cholinergic Systems.- I. Cholinergic Cell Groups.- II. Cholinergic Pathways.- D. Conclusions.- References.- 23: Central Cholinergic Transmission: The Physiological Evidence.- A. Introduction.- B. Nicotinic Synapses.- I. Characteristics of Peripheral Synapses.- II. Central Nicotinic Synapses.- C. Muscarinic Synapses.- I. General Considerations.- II. Forebrain Cholinergic System.- D. Conclusions.- References.- VII. Neuropathology of Cholinergic Transmission.- 24: The Cholinergic System in Aging.- A. The Process of Aging of Cholinergic Synapses: Hypotheses and Facts.- B. Aging of the Neuromuscular Junction.- I. Skeletal Muscle of Rodents.- II. Avian Iris NMJ.- C. ACh Synthesis and Metabolism in Brains of Aging Animals.- D. Cholinergic Receptors and Their Pharmacology.- E. Experimental Models of Dementia and Aging Based on Chemical Lesions of Cholinergic Systems.- F. Brain Transplants into ACh-Deficient Animals.- G. Cholinergic Deficits in Normal Aging and in Alzheimer's Disease.- References.- 25: Disorders of Cholinergic Synapses in the Peripheral Nervous System.- A. Introduction.- B. Presynaptic Disorders of the Neuromuscular Junction.- I. Lambert-Eaton Myasthenic Syndrome.- II. Intoxication with Botulinum Toxin in Man.- III. Other Toxins Acting on Presynaptic Terminals.- IV. Congenital Myasthenia.- C. Postsynaptic Disorders of the Neuromuscular Junction.- I. Myasthenia Gravis (Acquired Autoimmune Myasthenia).- II. Congenital Myasthenia.- III. Inhibition of AChE.- IV. Snake Neurotoxins.- D. Disorders of the Peripheral Somatic Nervous System.- I. Neuropathies with Predominant Motor Fibre Dysfunction and Motoneuron Disorders.- II. Amyotrophic Lateral Sclerosis.- E. Autonomic Neuropathies.- I. Clinical Tests for Autonomic Involvement.- II. Cholinergic Autonomic Dysfunction in Diabetes Mellitus.- III. Acute Pandysautonomia.- IV. Animal Models of Autonomic Neuropathy.- V. Generalized Smooth Muscle Disease with Intestinal Pseudoobstruction.- F. Glossary.- References.- 26: Central Cholinergic Neuropathologies.- A. Introduction.- B. Pathological Processes.- I. Disposing Factors.- II. Metabolic.- III. Genetic.- IV. Neuronal Loss of Unknown Cause.- V. Environmental Poisons and Infective Agents.- C. Central Cholinergic Neuropathies.- I. Alzheimer's Disease.- II. Down's Syndrome.- III. Parkinson's Disease.- IV. Huntington's Chorea.- V. Motoneuron Disease.- D. Conclusion.- References.