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…mehr
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.
1. General Characteristics of Neuronal Acetylcholine Receptors.- 1.1. Structure and Functions of Interneuronal Cholinergic Synapses.- 1.2. Localization of Acetylcholine Receptors on the Neuronal Surface.- 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.- 2.3. 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.- 3.4. 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.- 4.2. Classification of Ganglion-Blocking Agents according to Classical Characteristics of Their Blocking Effects.- 4.3. Pharmacological Specificity of Neuronal Nicotinic Acetylcholine Receptors.- 4.4. Conclusions.- 5. Molecular Mechanisms Underlying the Effects of Ganglion-Blocking Agents.- 5.1. Open-Channel Block.- 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.- 5.6. 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.- 6.3. Conclusions.- 7. The Relation of Nicotinic Receptor Open-Channel Blockade to Blockade of Synaptic Transmission.- 7.1. Theoretical Predictions of Synaptic Transmission Blockade as Caused by Blockade of the Open Channel in Postsynaptic Receptors.- 7.2. Mechanisms Underlying Selectivity in Drug-Induced Blockade of Synaptic Transmission.- 7.3. Selectivity of Open-Channel Blockade in Postsynaptic Receptors Other Than Nicotinic Receptors in Autonomic Ganglia.- 7.4. Conclusions.- 8. Recognition Center of Muscarinic Acetylcholine Receptor.- 8.1. Stoichiometry of Interactions of Agonists and Antagonists with the Muscarinic Acetylcholine Receptor.- 8.2. Functional Organization and Chemical Structure of the Muscarinic Acetylcholine Receptor Recognition Center.- 8.3. Conclusions.- 9. Mechanisms Underlying Muscarinic Postsynaptic Response.- 9.1. General Properties of Muscarinic Response.- 9.2. Ionic Mechanisms Underlying Muscarinic Depolarization.- 9.3. Mechanisms Underlying Muscarinic Hyperpolarization.- 9.4. Ionic Mechanisms Underlying Activities of Muscarinic Acetylcholine Receptors of Various Subtypes.- 9.5. Coupling of Muscarinic Acetylcholine Receptors with Ionic Channels Involved in the Generation of Postysynaptic Response.- 9.6. Conclusions.- 10. Mechanisms of Muscarinic Regulation of Neuronal Electrical Activity.- 10.1. Regulation of Action Potential Characteristics.- 10.2. Effect of Muscarinic Postsynaptic Response on Neuronal Electrical Activity.- 10.3. Conclusions.- 11. Effects of Noncholinergic Transmitters on Neuronal Acetylcholine Receptors.- 11.1. Effects on Nicotinic Acetylcholine Receptors.- 11.2. Effects on Muscarinic Acetylcholine Receptors.- 11.3. Conclusions.- References.
1. General Characteristics of Neuronal Acetylcholine Receptors.- 1.1. Structure and Functions of Interneuronal Cholinergic Synapses.- 1.2. Localization of Acetylcholine Receptors on the Neuronal Surface.- 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.- 2.3. 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.- 3.4. 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.- 4.2. Classification of Ganglion-Blocking Agents according to Classical Characteristics of Their Blocking Effects.- 4.3. Pharmacological Specificity of Neuronal Nicotinic Acetylcholine Receptors.- 4.4. Conclusions.- 5. Molecular Mechanisms Underlying the Effects of Ganglion-Blocking Agents.- 5.1. Open-Channel Block.- 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.- 5.6. 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.- 6.3. Conclusions.- 7. The Relation of Nicotinic Receptor Open-Channel Blockade to Blockade of Synaptic Transmission.- 7.1. Theoretical Predictions of Synaptic Transmission Blockade as Caused by Blockade of the Open Channel in Postsynaptic Receptors.- 7.2. Mechanisms Underlying Selectivity in Drug-Induced Blockade of Synaptic Transmission.- 7.3. Selectivity of Open-Channel Blockade in Postsynaptic Receptors Other Than Nicotinic Receptors in Autonomic Ganglia.- 7.4. Conclusions.- 8. Recognition Center of Muscarinic Acetylcholine Receptor.- 8.1. Stoichiometry of Interactions of Agonists and Antagonists with the Muscarinic Acetylcholine Receptor.- 8.2. Functional Organization and Chemical Structure of the Muscarinic Acetylcholine Receptor Recognition Center.- 8.3. Conclusions.- 9. Mechanisms Underlying Muscarinic Postsynaptic Response.- 9.1. General Properties of Muscarinic Response.- 9.2. Ionic Mechanisms Underlying Muscarinic Depolarization.- 9.3. Mechanisms Underlying Muscarinic Hyperpolarization.- 9.4. Ionic Mechanisms Underlying Activities of Muscarinic Acetylcholine Receptors of Various Subtypes.- 9.5. Coupling of Muscarinic Acetylcholine Receptors with Ionic Channels Involved in the Generation of Postysynaptic Response.- 9.6. Conclusions.- 10. Mechanisms of Muscarinic Regulation of Neuronal Electrical Activity.- 10.1. Regulation of Action Potential Characteristics.- 10.2. Effect of Muscarinic Postsynaptic Response on Neuronal Electrical Activity.- 10.3. Conclusions.- 11. Effects of Noncholinergic Transmitters on Neuronal Acetylcholine Receptors.- 11.1. Effects on Nicotinic Acetylcholine Receptors.- 11.2. Effects on Muscarinic Acetylcholine Receptors.- 11.3. Conclusions.- References.
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