In the past few years, the scientific community has witnessed rapid and significant progress in the study of ion channels. Technological advance ment in biophysics, molecular biology, and immunology has been greatly accelerated, making it possible to conduct experiments that were deemed very difficult if not impossible in the past. For example, patch-clamp tech niques can now be used to measure ionic currents generated by almost any type of cell, thereby allowing us to analyze single-channel events. It is now possible to incorporate purified ion channel components into lipid bilayers to reconstitute an "excitable membrane." Gene cloning and monoclonal antibody techniques provide us with new approaches to the study of the molecular structure 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, have been shown to alter the ion channel function. For certain pesticides such as pyrethroids and DDT, sodium channels are clearly the major target site. Many diseases of excitable tissues are known to be associated with, if not caused by, dysfunction of ion channels; these include cardiac ar rhythmias, angina pectoris, cystic fibrosis, myotonia, and epilepsies, to men tion only a few. Channel dysfunction can now be studied due to theoretical and technological developments in this area.
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Dateigröße
ISBN-13
978-1-4615-7305-0 (9781461573050)
DOI
10.1007/978-1-4615-7305-0
Schweitzer Klassifikation
1 Channel Protein Engineering: An Approach to the Identification of Molecular Determinants of Function in Voltage-Gated and Ligand-Regulated Channel Proteins.- 1. The Question.- 2. The Approach.- 3. The Voltage-Sensitive Sodium Channel.- 4. The Nicotinic Acetylcholine Receptor.- 5. Other Channel Proteins.- 6. Concluding Remarks.- 7. References.- 2 The Role of Nonprotein Domains in the Function and Synthesis of Voltage-Gated Sodium Channels.- 1. Introduction.- 2. Purification and Physicochemical Characterization of Sodium Channels from Electric Organ.- 3. Possible Roles of Nonprotein Domains in the Function of Sodium Channels.- 4. Functional Consequences of Manipulating Nonprotein Domains in Purified Sodium Channels.- 5. Acquisition of Nonprotein Domains during Biosynthesis.- 6. Conclusion.- 7. References.- 3 The Gating Current of the Node of Ranvier.- 1. Introduction.- 2. The Charge-Voltage Relation.- 3. The Time Constants ?on and ?off.- 4. Charge Immobilization.- 5. The Chemical Nature of the Gating Particles.- 6. The Effect of Local Anesthetics.- 7. Comparison between Gating Current and Sodium Current.- 8. References.- 4 The Inactivation of Sodium Channels in the Node of Ranvier and Its Chemical Modification.- 1. Introduction.- 2. Inactivation.- 3. Modifiers of Both Activation and Inactivation.- 4. Modifiers of Inactivation Alone.- 5. Modifiers as Chemical Probes of Channel Protein.- 6. Summary and Conclusions.- 7. References.- 5 ATP-Activated Channels in Excitable Cells.- 1. Introduction.- 2. A Family of Nonselective Cation Channels.- 3. ATP-Activated Potassium Channels in Atrial Cells.- 4. Modulation of Voltage-Dependent and Other Channels.- 5. Summary and Conclusions.- 6. References.- 6 Regulation of the ATP-Sensitive Potassium Channel.- 1. Introduction.- 2.Regulation of the ATP-Sensitive K+ Channel by Nucleotides.- 3. The ATP-Sensitive K+ Channel Is the Receptor for Sulfonylureas.- 4. Phosphorylation of the ATP-Sensitive K+ Channel by Kinase C.- 5. Regulation of the ATP-Sensitive K+ Channel in ? Cells by Hormonal Peptides.- 6. Cardiac ATP-Sensitive K+ Channels Are Activated by Cromakalim (BRL 34915).- 7. What Are ATP-Sensitive K+ Channels Regulating?.- 8. References.- 7 Analytical Diffusion Models for Membrane Channels.- 1. Introduction.- 2. Derivation of One-Ion Channel Diffusion Theory.- 3. Channel States and Transition Rates.- 4. Electrodiffusion Interpretation of Transition Rates.- 5. Transition Rates as Mean First Passage Times.- 6. Standard Results.- 7. Discussion.- 8. Appendix: Comparison of One-Ion Diffusion Model with Traditional Chemical Kinetics.- 9. Symbols.- 10. References.
