Beschreibung
Among the different types of receptors for neurotransmitters, nicotinic acetyl choline receptors were the first to be studied systematically; at present they are very well characterized. This is due to the discovery of two very convenient objects that are endowed with nicotinic acetylcholine receptors - the skeletal muscle and the electric organ. The large size of skeletal muscle fibers, which simplifies the intra cellular recording of transmembrane potentials and currents, played a crucial role in obtaining the fIrst quantitative estimates of the activity of acetylcholine receptors and the kinetics of their interaction with ligands. On the other hand, the extremely high content of receptor protein in the electric organ tissue - two orders higher than in muscle tissue - rendered it highly suitable for studying the biochemistry of recep tors. The combination of pharmacological, electrophysiological, and biochemical approaches resulted in rapid progress in the investigation of acetylcholine receptors. Nicotinic acetylcholine receptors are also present in the neurons of autonomic ganglia, in the central nervous system of vertebrates, and in the ganglion neurons of invertebrates. Although each of these three types of receptors has its own pharma cological specificity, some of their properties are common and differ from those in the acetylcholine receptors of skeletal muscle and electric organ. One of these differences is that neuronal nicotinic receptors usually coexist in the same nerve cell with other receptors, e. g., muscarinic, serotoninergic, or peptidergic.
Autorenporträt
Inhaltsangabe1. General Characteristics of Neuronal Acetylcholine Receptors.- 1.1. Structure and Functions of Interneuronal Cholinergic Synapses.- 1.1.1. Autonomic Ganglia of Vertebrates.- 1.1.2. Central Nervous System of Vertebrates.- 1.1.3. The Ganglia of Invertebrates.- 1.2. Localization of Acetylcholine Receptors on the Neuronal Surface.- 1.2.1. Binding of Labeled Antagonists.- 1.2.1.1. Nicotinic Receptors.- 1.2.1.2. Muscarinic Receptors.- 1.2.2. Distribution of Sensitivity to Acetylcholine and to Acetylcholine Agonists on the Neuronal Surface.- 1.2.2.1. Nicotinic Receptors.- 1.2.2.2. Muscarinic Receptors.- 1.2.2.3. Acetylcholine Receptors in the Neurons of Invertebrate Ganglia.- 1.3. Biochemical Properties, Molecular Structure, and Functional Organization of an Acetylcholine Receptor.- 1.4. Conclusions.- 2. Recognition Center of the Neuronal Nicotinic Acetylcholine Receptor.- 2.1. Stoichiometry in the Agonist-Receptor Interaction.- 2.2. Functional Organization and Chemical Structure of the Recognition Center.- 2.2.1. Anionic Site.- 2.2.2. Esterophilic Area.- 2.2.3. Functional Organization of the Recognition Center.- 2.2.4. Chemical Structure of the Recognition Center.- 2.3. Localization of the Recognition Center in the Acetylcholine Receptor Molecule.- 2.4. Conclusions.- 3. Ionic Channel of the Nicotinic Acetylcholine Receptor.- 3.1. Channel Ionic Selectivity and Energy Profile.- 3.2. Channel Conductance.- 3.3. Channel Kinetics.- 3.3.1. Sequential Model.- 3.3.2. Synaptic Current Decay.- 3.3.3. Acetylcholine-Induced Current Fluctuations.- 3.3.4. Relaxation of Acetylcholine-Induced Current Caused by Membrane Voltage Step.- 3.3.5. Kinetics of Single Acetylcholine-Activated Channels.- 3.3.6. Voltage Dependence of Channel Kinetics.- 3.4. Localization of Ionic Channel in Acetylcholine Receptor Molecule.- 3.5. Conclusions.- 4. General Characteristics of the Effects Produced by Blocking Agents in Neuronal Acetylcholine Receptors.- 4.1. Relationship between Chemical Structure and Ganglion-Blocking Activity.- 4.1.1. Mono-Quaternary Ammonium Compounds.- 4.1.2. Tertiary and Secondary Amines.- 4.1.3. Bis-Quaternary Ammonium Compounds.- 4.2. Classification of Ganglion-Blocking Agents according to Classical Characteristics of Their Blocking Effects.- 4.3. Pharmacological Specificity of Neuronal Nicotinic Acetylcholine Receptors.- 4.3.1. Neurons of Autonomic Ganglia.- 4.3.2. Molluscan Neurons.- 4.4. Conclusions.- 5. Molecular Mechanisms Underlying the Effects of Ganglion-Blocking Agents.- 5.1. Open-Channel Block.- 5.1.1. Effect of Ganglion-Blocking Agents on Integrated Activity of Nicotinic Acetylcholine-Sensitive Channels Recorded from the Whole Cell.- 5.1.2. Effect of Ganglion-Blocking Agents on the Acetylcholine-Induced Current in Strongly Depolarized Membrane.- 5.1.3. Effect of Ganglion-Blocking Agents on the Activity of a Single Acetylcholine-Sensitive Channel.- 5.2. Blocking of Recognition Center.- 5.3. Blocking of Closed Ionic Channel.- 5.4. The Mechanism for a Block by Tubocurarine.- 5.5. The Mechanism for a Block by Neurotoxins.- 5.5.1. Variability of the Effects Produced by ?-Toxins in Neuronal Nicotinic Acetylcholine Receptors.- 5.5.2. Binding of Neurotoxins to Neuronal Nicotinic Acetylcholine Receptors without Causing Their Blocking.- 5.5.3. Effects Produced on Neuronal Nicotinic Acetylcholine Receptors by Snake Venom Components Ineffective in Other Acetylcholine Receptors.- 5.5.4. Possible Functional Significance of the Sites That Bind Neurotoxins without Affecting Synaptic Transmission.- 5.5.5. The Effects of a Neurotoxin Obtained from Mollusc.- 5.6. Conclusions.- 6. Localization and Possible Functional Significance of the Sites in the Neuronal Nicotinic Acetylcholine Receptor Interacting with Blocking Agents.- 6.1. Localization of the Sites Interacting with Blocking Agents in the Receptor Molecule.- 6.2. Possible Functional Significance of Sites in the Ionic Channel of the Nicotinic Acetylcholine Receptor That Bind Blocking Agents.- 6.
