1;Preface;5 1.1;References;7 2;Contents;8 3;Contributors;10 4;Neurotransmitter Release;14 4.1;1 Principles of Neurotransmitter Release;15 4.2;2 Very Short History of the Analysis of Neurotransmitter Release;18 4.3;3 Basic Mechanisms of Release by Exocytosis;20 4.4;3.1 Rab-Proteins and Rab-Effectors;21 4.5;3.2 SNARE Proteins;21 4.6;3.3 SM Proteins;24 4.7;3.4 Mechanism of SNARE and SM Protein Catalyzed Fusion;24 4.8;4 Mechanism of Ca2+-Triggering: Ca2+-Channels, Ca2+- Buffering, and Synaptotagmin;25 4.9;4.1 Ca2+- Dynamics;25 4.10;4.2 Synaptotagmins as Ca2+- Sensors for Fast Neurotransmitter Release;26 4.11;5 Regulation of Release Beyond Ca2+-Triggering;29 4.12;5.1 Acetylcholine-Receptor-Mediated Ca2+- Influx into Presynaptic Nerve Terminals;29 4.13;5.2 Ca2+- Channel Modulation by Presynaptic Receptors;30 4.14;5.3 Presynaptic Long-Term Plasticity Mediated by cAMP- Dependent Protein Kinase A ( PKA);30 4.15;6 Ca2+-Induced Exocytosis of Small Dense-Core Vesicles and LDCVs;31 4.16;7 Presynaptic Drug Targets;32 4.17;References;32 5;Pharmacology of Neurotransmitter Release: Measuring Exocytosis;35 5.1;1 Electrophysiological Detection of Secretion 1.1 Electrical Detection of Neurotransmitter Release Using Postsynaptic Ionotropic Receptors;36 5.2;1.2 Detection of Probability of Neurotransmitter Release;38 5.3;1.3 Studying Synaptic Vesicle Recycling Using Electrophysiological Techniques;40 5.4;1.4 Detection of Neurotransmitter Secretion Through Amperometric Recordings;41 5.5;1.5 Detection of Membrane Fusion via Presynaptic Capacitance Measurements;42 5.6;2 Fluorescent Visualization of Synaptic Vesicle Fusion and Recycling 2.1 Optical Detection of Neurotransmitter Release;43 5.7;2.2 Functional Analysis of Exocytosis and Vesicle Recycling Using Styryl Dyes;44 5.8;2.3 Detection of Synaptic Vesicle Exocytosis and Endocytosis Using pHluorin- Tagged Synaptic Vesicle Proteins;48 5.9;2.4 Comparison of Styryl Dye Imaging and pHluorin-Based Visualization of Exo- Endocytosis;49 5.10;3 Biochemical Approaches to Measuring Neurotransmitter Release;50 5.11;References;52 6;Presynaptic Calcium Channels: Structure, Regulators, and Blockers;56 6.1;1 Subtypes and Physiological Functions of Calcium Channels;57 6.2;2 Molecular Structure of Voltage-Gated Calcium Channels;60 6.3;3 Consequences of Calcium Channel Gene Knockout;62 6.4;4 Calcium Channelopathies Involving P/Q-Type Calcium Channel a1 Subunits;64 6.5;5 Calcium Channel Pharmacology 5.1 Peptide Blockers;65 6.6;5.2 Small Organic Compounds Blocking N-type Channels;66 6.7;6 Regulation by G Protein-Coupled Receptors;67 6.8;7 Regulation of Calcium Channels by Synaptic Proteins;70 6.9;8 Regulation of Presynaptic Calcium Channel Activity by Protein Kinases;72 6.10;9 Feedback Regulation by Calcium Binding Proteins;73 6.11;10 Summary;75 6.12;References;75 7;Pharmacology of Neurotransmitter Transport into Secretory Vesicles;87 7.1;1 Introduction: Neurotransmitter Recycling;88 7.2;2 H+ Electrochemical Gradient 2.1 Vacuolar H+- ATPase;90 7.3;2.2 Chloride Channels;92 7.4;2.3 Ionophores;92 7.5;3 Vesicular Transport Proteins 3.1 Vesicular Monoamine Transporters (VMAT1 and VMAT2);93 7.6;3.2 Vesicular Acetylcholine Transporter (VAChT);99 7.7;3.3 Vesicular GABA and Glycine Transporter (VGAT);101 7.8;3.4 Vesicular Glutamate Transporters (VGLUT1-3);102 7.9;3.5 Other Transporters on Vesicles;106 7.10;4 Conclusions;107 7.11;References;108 8;Core Proteins of the Secretory Machinery;117 8.1;1 SNAREs;118 8.2;1.1 Structure of the Neuronal SNAREs;119 8.3;Qa Qb Qc R;120 8.4;Syntaxin 1A SNAP-25;120 8.5;Synaptobrevin 2;120 8.6;Neuronal SNARE-core complex;120 8.7;1.2 Assembly and Disassembly of SNAREs: Mechanistic Considerations;122 8.8;2 Sec1/Munc18 (SM) Proteins;125 8.9;2.1 SM Protein Interactions with SNAREs;126 8.10;2.2 Munc18-1-an Oddity among the SM Proteins?;126 8.11;3 Synaptotagmins 3.1 Synaptotagmin Family;127 8.12;3.2 Synaptotagmin 1 as Ca2+- Sensor for Fast Neurotransmitter Release;128 8.13;3.3 Molecular Mechanism of Synap