Chemical and Molecular Basis of Nerve Activity

Preface Preface to First Edition Chapter I Physical Events during Nerve Activity A. Electrical Manifestations B. The Membrane Theory C. Ion Movements D. Heat Production E. Temperature Coefficient Chapter II Problems of Mechanisms Underlying Nerve Activity A. Necessity of Correlating Physical Events with Chemical Reactions B. Principles and Difficulties of Approach C. Hypothesis of Neurohumoral Transmission Chapter III Physiologically Significant Features of Acetylcholinesterase A. Specificity B. Occurrence in Conducting Tissues and Concentration C. Localization D. Rate of Hydrolysis of Acetylcholine E. Coincidence of High Enzyme Activity and Beginning of Function during Growth F. Free Energy Change of Acetylcholine Hydrolysis Chapter IV Inseparability of Conduction and Activity of Acetylcholinesterase A. Competitive Inhibitors B. Action of Competitive Inhibitors on ConductionChapter V Sequence of Energy Transformations A. Electric Fish B. The Concentration of Acetylcholinesterase in Electric Organs C. Phosphorylated Compounds as Source of Energy D. Discovery of Choline Acetylase E. Occurrence and Concentration of Choline Acetylase F. Depolarizing (Electrogenic) Action of Acetylcholine G. Role of Acetylcholine in Sensory Endings Chapter VI Tentative Picture of the Role of the Acetylcholine System in the Permeability Change Chapter VII Mechanism of Reactions Catalyzed by Acetylcholinesterase A. Molecular Forces Acting between Substrates and Enzyme B. The Hydrolytic Process Chapter VIII Nerve Gases, Insecticides, and Antidotes A. Mechanism of Inhibition by Organophosphorus Compounds B. Efficiency of an Antidote on the Basis of Molecular Complementarity C. Biochemical and Pharmacological Aspects of PAM Action Chapter IX Properties of Choline Acetylase A. Test System B. Specificity Chapter X Action of Acetylcholine on the Receptor in Intact Cells A. Difference between Tertiary and Quaternary Nitrogen Derivatives in Their Reactions with Esterase and Acetylase B. Evidence for the Existence of a Receptor C. Receptor Activators and Inhibitors Chapter XI Isolated Single Electroplax Preparation A. Method of Separating Two Pools of Fluid by a Single Electroplax B. Effects of Acetylcholine and Analog Compounds C. Ion Flux D. Isolation of the Receptor Protein in Solution Chapter XII Effects of Lipid-soluble Quaternary Ammonium Ions on Conduction A. Depolarizing Action on Axons and Electroplax B. Response of Striated MuscleChapter XIII The Complex Nature of the Permeability Change Chapter XIV Synaptic Transmission I. Reevaluation of the Original Neurohumoral Transmitter Theory A. Permeability Barrier Surrounding the Axon B. Curare C. The Origin of Acetylcholine Found in Perfusion Fluids Chapter XV Synaptic Transmission II. Localization of Cholinesterase at Junctions A. Chemical Determinations B. Histochemical Data Chapter XVI Synaptic Transmission III. Differences between Axon and Synapse A. Structure B. Electrical Signs; the End Plate Potential C. The Site of Drug Action D. Ion Movements and Permeability Changes at Junctions E. Significance of Acetylcholine Appearance in Junctional Perfusates F. Present State of the Problem Concluding Remarks References Supplement I Properties and Function of the Proteins of the Acetylcholine Cycle in Excitable Membranes I. Cell Membranes A. General Properties B. Excitable Membranes II. Role of the AcCh Cycle in Control of Ion Permeability A. Role of Acetylcholine in the Excitable Membrane; The Acetylcholine Cycle B. Macromolecular Conformation and Ca2+ Ions III. Proteins Processing Acetylcholine A. AcCh-Esterase B. AcCh-Receptor C. Choline O-Acetyltransferase (Choline Acetylase) D. Storage Site IV. Experimental Basis for the Direct Link of the AcCh Cycle with Electrical Activity A. Effects of Specific Inhibitors of AcCh-Esterase on Electrical Activity of Axons B. Problem of Minimum Requirements of AcCh-Esterase Activity for Electrical Activity C. Effects of Specific Inhibitors on the AcCh-Receptor in Electrical Activity D. Involvement of Other Proteins in Excitability E. Parallelism between Chemical Action on the AcCh-Receptor of Isolated Membrane Fragments of the Electroplax of Electrophorus and the Electrical Stimulation of their Intact Membrane F. Basic Excitation Units V. Role of the AcCh Cycle at Junctions A. Observations that Led to the Assumption of AcCh as a Neurohumoral Transmitter B. Evidence Supporting a Similar Role of AcCh Cycle in Pre- and Postsynaptic Junctional Membranes C. Alternative Interpretation of the Function of AcCh at Junctions VI. Concluding Remarks: Concepts and Axioms in Science Reviews by the Author Since 1959 Supplement II Toward a Molecular Model of Bioelectricity I. Introduction II. Biomembrane Electrochemistry III. Stationary Membrane Potentials IV. Transient Changes of Membrane Potentials A. Threshold Behavior B. Stimulus Characteristics C. Propagation of Local Activity D. Refractory Phases E. Time Constants V. Proteins Involved in Excitation VI. Impedance and Heat Changes A. Impedance Changes B. Heat Changes VII. The Cholinergic System and Excitability A. Localization of the AcCh System B. The Barrier Problem C. Electrogenic Aspects of the AcCh System D. Control Function of AcCh VIII. The Integral Model A. Key Processes B. Basic Excitation Unit C. Translocation Flux of AcCh D. Field Dependence of AcCh Storage E. Relaxation of AcCh Translocation Fluxes F. The AcCh Control Cycle IX. Summary References to Supplements I and II Index