Ion Channels, Softcover reprint of the original 1st ed. 1988
Volume 1
Ion Channels Series, Vol. 1

A wealth of information has been accumulated about the function of ion channels of excitable cells since the extensive and pioneering voltage clamp studies by Hodgkin, Huxley, and Katz 36 years ago. The study of ion chan­ nels has now reached a stage at which a quantum jump in progress is antici­ pated. There are many good reasons for this. Patch clamp techniques origi­ nally developed by Neher and Sakmann 12 years ago have made it possible to study the function of ion channels in a variety of cells. Membrane ionic currents can now be recorded practically from many types of cells using the whole-cell patch clamp technique. The opening and closing of individual ion channels can be analyzed using the single-channel patch clamp method. Techniques have also been developed to incorporate purified ion channels into lipid bilayers to reconstitute an "excitable membrane. " Advanced tech­ niques developed in molecular biology, genetics, and immunology, such as gene cloning and the use of monoclonal antibodies, are now being applied to the study of ion channels. A variety of drugs have now been found or are suspected to interact with ion channels to exert therapeutic effects. In addition to the classical exam­ ples, as represented by local anesthetics, many other drugs, including cal­ cium antagonists, psychoactive drugs, cardiac drugs, and anticonvulsants, shown to alter ion channel function. For certain pesticides such as have been pyrethroids and DDT, sodium channels are clearly the major target site.

1 Fluorescence Spectroscopy to Probe the Structure and Cellular Dynamics of Ion Channels.- 1. Introduction.- 2. Methods, Principles, and Utility of Fluorescence Spectroscopy.- 2.1 Principles of Fluorescence.- 3. Selection, Design, and Utilization of Ion Channel Probes.- 3.1. Chemical Requirements.- 3.2. Spectroscopic Requirements.- 3.3. Preparation and Characterization of Fluorescent Ion Channel Probes.- 4. Fluorescence Spectroscopy of the Voltage-Dependent Na + Channel.- 4.1. Molecular Environment and Conformational Fluctuations of the Voltage-Dependent Na+ Channel Receptor Sites.- 4.2. Structural Mapping of the Na+ Channel by Fluorescence Resonance Energy Transfer: Molecular Organization of the Channel Receptor Sites.- 5. Cellular Mapping of Na+ Channels in Excitable Tissues.- 5.1. Use of Fluorescent Neurotoxin Probes.- 5.2. Localization of Na+ Channels by Fluorescence Microscopy.- 5.3. Regionalization and Lateral Mobility of Voltage-Dependent Na+ Channels.- 5.4. Localization and Mobility of Other Ion Channels in Nerve and Muscle.- 6. Conclusion.- 7. References.- 2 M Currents.- 1. Prologue.- 2. M Current.- 3. M-Current Kinetics.- 4. Physiological Function.- 4.1. Contribution of IM to the Resting Membrane Potential.- 4.2. Control of Membrane Potential Change.- 4.3. Control of Excitability.- 5. Pharmacology of M Current.- 5.1. Cholinergic Agonists.- 5.2. Receptors.- 5.3. Peptides.- 5.4. Nucleotides.- 5.5. K-Channel Blockers.- 5.6. Organic K-Channel Blockers.- 5.7. Transduction Mechanisms for IM Inhibition.- 6. Synaptic Inhibition of M Current.- 6.1. Frog Sympathetic Neurons.- 6.2. Slow epsp.- 6.3. Late Slow epsp.- 6.4. Mammalian Sympathetic Neurons.- 6.5. Hippocampal Neurons.- 6.6. Functional Effects of IM-Driven Synaptic Potentials.- 7. Future Work.- 8. References.- 3 Macromolecular Sites for Specific Neurotoxins and Drugs on Chemosensitive Synapses and Electrical Excitation in Biological Membranes.- 1. Introduction.- 2. Voltage and Patch Clamping.- 3. Impact of Neurotoxins in Molecular Pharmacology.- 3.1. The Sodium Channel.- 3.2. The Potassium Channel.- 3.3. The Nicotinic Acetylcholine Receptor/Channel Complex.- 4. The Histrionicotoxins.- 4.1. History.- 4.2. Effect of the Histrionicotoxins on Sodium and Potassium Channels.- 4.3. Effect of the Histrionicotoxins on the Nicotinic AChR.- 4.4. Comparative Effects of the Histrionicotoxins in Dendrobatid and Rana Frogs.- 5. Summary.- 6. References.- 4 Developmental Changes in Acetylcholine Receptor Channel Properties of Vertebrate Skeletal Muscle.- 1. Introduction.- 2. Materials and Methods.- 2.1. Experimental Animals.- 2.2. Electrophysiological Techniques.- 3. Results.- 3.1. Two Types of ACh Receptor Channels in the Adult Animal.- 3.2. Two Types of ACh Receptor Channels in the Young Animal.- 3.3. Two Types of ACh Receptor Channels in Cultured Muscle Cells.- 3.4. Developmental Changes of ACh Receptor Channel Kinetics.- 3.5. Correlation between Channel Conversion and Other Developmental Changes.- 4. Discussion.- 5. Postscript.- 6. References.- 5 Intracellular ATP and Cardiac Membrane Currents.- 1. Introduction.- 2. Techniques for the Single Cardiac Cell.- 2.1. Single Cardiac Cell Preparation.- 2.2. Single Channel Recordings.- 2.3. Intracellular Microinjection and Whole-Cell Current Recording.- 2.4. Whole-Cell Voltage Clamp and Internal Dialysis.- 3. Whole-Cell Current and Intracellular ATP Level.- 3.1. ATP Level and the Membrane Current.- 3.2. Effects of Other Nucleotides and Related Substances.- 4. ATP-Sensitive K Channel.- 4.1. Conductance Properties.- 4.2. Kinetic Properties.- 4.3. Nature of the ATP-Binding Site.- 4.4. Contribution to the Whole-Cell Current.- 5. Effects of ATP on Other K Channels.- 6. Conclusion.- 7. References.- 6 Calcium Antagonist Receptors.- 1. Introduction.- 2. Radioreceptor Binding Studies.- 2.1. Dihydropyridine Ligands.- 2.2. Phenylalkylamine Ligands.- 2.3. Other Ligands.- 3. Atypical Actions of Calcium Antagonists.- 3.1. Nonspecific Actions of Calcium Antagonists.- 3.2. Atypical Calcium Antagonists.- 4. The Relation of Calcium Antagonist Receptors to Voltage-Sensitive Calcium Channels.- 4.1. Experimental Design.- 4.2. Experimental Findings.- 5. Future Developments in Calcium Antagonist Receptors.- 6. References.- 7 The Amiloride-Blockable Sodium Channel of Epithelial Tissue.- 1. Introduction.- 2. Na+ Uptake at the Apical Membrane.- 2.1. Na+ Channel “Self-Inhibition”.- 2.2. Amiloride Block of the Apical Na+ Conductance.- 2.3. Regulation of Apical Na+ Channel.- 3. A6 Cells as a Model for Kidney Distal Tubule.- 3.1. Problems with Native Tissues.- 3.2. A6 Cell Origin and Properties.- 3.3. Additional Advantages of A6 Cells.- 4. Single Na + Channel Activity.- 4.1. Different Subtypes of Na+ Channels.- 4.2. Differences between Single Channel and Macroscopic Measurements.- 4.3. Patch-Clamp Studies of Na +-Transporting Cells.- 4.4. Does Na + Channel Conductance Saturate?.- 5. A Model for the Regulation of Apical Na+ Permeability.- 6. Future Work.- 7. References.- 8 Ionic Channels in Ocular Epithelia.- 1. Introduction.- 2. Low-Noise Methods and Glass Considerations.- 2.1. Noise Performance.- 2.2. Comments on Glass.- 3. General Approach to Channel Identification.- 4. Selectivity.- 4.1. Experimental Characterization of Channel Types.- 4.2. Identification of Channels: Practical Problems.- 4.3. Need for Accurate Reversal Potential Measurements.- 4.4. Errors from Artifactual Offset Potentials.- 5. Current-Voltage Relations.- 6. Kinetics of Gating.- 6.1. Difficulties in Estimating Kinetics.- 6.2. Channel Density.- 6.3. Kinetics in Patches with Several Channels.- 6.4. Patches with Different Channel Types.- 7. Characterization of Blockers.- 8. Channel Types Observed in Ocular Epithelia.- 8.1. Nonselective Cation Channels.- 8.2. Anion Channels.- 8.3. Sodium Channels.- 8.4. Calcium Channels.- 8.5. Potassium Channels.- 8.6. Channel Types in Different Cells and Species.- 8.7. Summary of Diversity.- 9. References.