Has the neuromuscular junction been over-exposed or is it perhaps already a closed book? I asked myself this at a recent International Congress when an American colleague complained that the Journal of Physiology had articles on nothing but the neuromuscular junction, while another colleague asked why I was editing a volume on a subject about which everything was already known. It is worrying to think that these views may be shared by other people. I hope that this volume will convince my two colleagues and other readers that the neuromuscular junction is very much alive and continues to attract the interest of many workers from a variety of fields; strange as it may seem, the synapse between a motor nerve ending and muscle fibre, with its relatively simple architecture, is one of the most inter­ esting sites in the body-I do hope we have done it justice. The various chapters of this volume present a cross section of knowledge as viewed by a group of 13 individuals, actively engaged in research. Multi-author volumes such as this are frequently criticised on the grounds that chapters or sec­ tions overlap. I believe that such criticium is only valid where the overlap is repetitious. Where it results in the reader having available discussions of material from differing stand-points, overlap becomes a valuable feature of this type of publication.

Inhalt

Introductory Chapter The Neuromuscular Junction: Areas of Uncertainty.- Neuromuscular Block by Prolonged Depolarisation.- Desensitisation.- The Clinical Picture.- The Presence of Other Drugs.- The Importance of the Drug Structure and that of the Acetylcholine Receptor.- Pre-Synaptic or Post-Synaptic Action?.- Closing Remarks.- References.- 1 The Anatomy and Pathology of the Neuromuscular Junction.- A. Introduction.- B. Normal Muscle.- I. The Motor Unit.- II. Pattern of Innervation and Distribution of Motor End-Plates.- III. The Structure of the Neuromuscular Junction.- 1. Axon Terminals.- 2. Experimental Modifications of the Structure of the Axon Terminal.- 3. Transmitter Release and Synaptic Vesicles.- 4. The Postsynaptic Region.- 5. The Localization of Cholinesterase.- 6. The Basement Membrane.- 7. The Localization of Acetylcholine Receptors.- C. Development, Growth, and Plasticity of the Neuromuscular Junction.- 1. Development of the Neuromuscular Junction.- 2. Development in Tissue Culture.- 3. Structural Denervation.- D. The Neuromuscular Junction in Disorders of Transmission.- 1. Myasthenia Gravis.- 2. The Myasthenic Syndrome.- 3. Hereditary Motor End-Plate Disease in the Mouse.- 4. The Effects of Botulinum Toxin.- 5. The Effects of Tetanus Toxin.- E. The Neuromuscular Junction in Disorders of the Muscle Fibre.- F. Conclusion.- References.- 2 Neurochemistry of Cholinergic Terminals.- A. Introduction.- B. Methods for Extracting and Measuring Acetylcholine.- 1. Preparation of Tissues for Extraction of ACh.- 2. Extraction of ACh.- 3. Assay of ACh.- C. Acetylcholine Synthesis.- 1. Choline Acetyltransferase: its Location and Physical Properties.- 2. Choline Acetyltransferase: its Chemistry, Substrates, and Inhibitors.- 3. Choline Acetyltransferase: its Kinetics.- 4. Supply of Acetyl Groups for ACh Synthesis.- 5. Supply of Choline for ACh Synthesis.- 6. Transport of Choline.- 7. Inhibitors of Choline Transport.- 8. ACh Uptake.- 9. Control of ACh Synthesis.- D. Acetylcholine Storage.- 1. Brain.- 2. Ganglion.- 3. Skeletal Muscle.- 4. Electric Organ.- 5. Other Tissues.- E. Acetylcholine Release.- 1. Correlation of Neurochemical and Electrophysiological Data.- 2. ACh Content: Vesicles vs. Quanta.- 3. Is ACh Released from the Nerve-Terminal Cytoplasm?.- 4. Is Release of ACh Regenerative?.- 5. Calcium and ACh Release.- 6. Neurotoxins and ACh Release.- 7. Drugs and ACh Release.- 8. Cyclic Nucleotides, Prostaglandins and ACh Release.- 9. Contractile Proteins, Microtubules and Microfilaments.- 10. Are Quanta Released by Exocytosis?.- F. Acetylcholine Turnover.- 1. Tissue ACh Turnover during Rest and Activity.- 2. Preferential Release of Newly Synthesized ACh.- 3. ACh Turnover in Relation to Changes in Ultrastructure.- 4. ACh Turnover as Studied by Cell Fractionation Techniques.- 5. Transfer of ACh between Pools or Compartments.- 6. A Tentative Model for ACh Storage and Metabolism.- G. Removal of Acetylcholine.- 1. Enzymatic Destruction.- 2. ACh Uptake.- 3. Diffusion from the Synaptic Cleft.- H. Axonal Transport of Materials Related to Cholinergic Transmission.- 1. Acetylcholinesterase.- 2. Choline Acetyltransferase.- 3. Acetylcholine.- 4. Other Materials.- 5. Effects of Agents that Block Axonal Transport.- 6. A Note on Other Trophic Influences Mediated by Cholinergic Nerves.- I. Prolonged Neurochemical Changes Resulting from Synaptic Activity.- 1. Causes of Synaptic Plasticity.- 2. Post-Tetanic Potentiation.- 3. Enzyme Induction.- 4. Possible Contribution by Glial Elements.- References.- 3 Transmission of Impulses from Nerve to Muscle.- A. Introduction.- B. The Muscle Fibre and the Action of Acetylcholine.- I. Some Relevant Properties of Muscle Fibres.- 1. The Membrane Potential and its Measurement.- 2. Factors Influencing the Membrane Potential.- II. The End-Plate Potential.- 1. Introduction.- 2. General Characteristics of the Permeability Change Caused by the Transmitter.- 3. The Representation of Transmitter Action in Electrical Terms.- 4. The Influence of the Non-Synaptic Membrane on the Response to Acetylcholine.- III. The Ion Selectivity of the Permeability Change Produced by the Transmitter.- 1. The Voltage Clamp Technique.- 2. The End-Plate Current.- 3. Relative Contribution of Different Ions to the Conductance Increase.- 4. Characteristics of the Additional Ion Channels.- 5. Evidence on Ion Selectivity from the Use of Radio-Isotopes.- IV. Localization of Acetylcholine Receptors.- 1. Introduction.- 2. The Ionophoretic Method of Drug Application.- 3. Evidence on Receptor Distribution from Ionophoretic Experiments.- 4. Other Electrophysiological Evidence on the Distribution of Receptors.- 5. Evidence on Receptor Distribution from Experiments with Labelled Antagonists.- 6. Denervated Muscle.- 7. Characteristics of Acetylcholine Receptors in Denervated Muscle.- V. The Interaction between Acetylcholine and its Receptors.- 1. Classical Models of Receptor Action.- 2. The "Allosteric" Model of the Receptor.- 3. New Evidence on Receptor Action: Acetylcholine "Noise".- 4. The Response to Prolonged Application of Depolarizing Agents.- VI. Modification of Transmitter Action.- 1. Competitive Antagonism.- 2. Evidence for Competition between Curare Alkaloids and Acetylcholine.- 3. Other Agents which Influence Transmitter Action.- C. Pre-Synaptic Events.- I. Introduction.- II. Miniature End-Plate Potentials.- 1. Occurrence.- 2. Amplitudes of Miniature End-Plate Potentials.- 3. Abnormal Miniature End-Plate Potentials.- 4. The Rate of Spontaneous Release.- 5. External Recording of Spontaneous Discharge.- III. Evidence for the Quantal Nature of Evoked Transmitter Release.- 1. Intracellular Recording: Counts of "Failures".- 2. Evidence from Extracellular Recording: Counts of Quanta.- 3. Amplitude Distribution of Responses.- 4. Variance of the Amplitude Distribution.- 5. Evidence that Fluctuations in Transmitter Release Reflect Variations in the Number of Quanta Released Rather than in the Amount of Transmitter per Quantum during Facilitation and Depression.- 6. Quantal Nature of Transmitter Release Evoked by Presynaptic Depolarization without Action Potentials.- IV. Physical and Statistical Models for Quantal Release.- V. The Calcium Hypothesis.- VI. Estimating Values of the Quantal Content.- 1. Methods.- 2. Estimates of Normal Quantal Contents.- 3. Errors in Quantal Content Estimates in the Presence of Drugs.- VII. Studies on Evoked Release of Transmitter.- 1. Methods of Evoking Release.- 2. Relationship between the Various Methods of Evoking Release.- VIII. Factors Affecting Evoked Transmitter Release.- 1…