Main description:

Omnis cellula e cellula, "every cell from a cell," was dogma to the 19th century cellular physiologist and the cornerstone of Virchow's Cellular pathologie. "Spread out a cell into a layer and you will find that, in ceasing to be a cell, it has ceased to act as such," wrote the British 1 physiologist G . R. Lewes more than a century age. "The cell remains vital as long as its wall remains intact . . . " keeping its content "pure and clear" and thus preserving the "vital principle" within, echoed Claude 2 Bernard a few years later. The notion of the cell membrane as a pro tecting envelope held sway until it became clear that it could not account for the "coalescence" of poorly differentiated embryonic "vesicles" and for their transformation into "cell-like structures" capable of auto regulation and yet subject to what the grandfather of one of us defined as the "federal obligations imposed by the whole organism. ,,3 A new concept was needed, and soon the membrane was described as a structure capable of uniting as well as separating adjacent cells. Morphologic evidence for this dual function was obtained several years later when the electron microscope revealed the existence of tight and gap junc tions which, acting as intercellular bonds and channels, allowed the cells to communicate with one another and thus coordinate their biologic activities.

Contents:

Preface.- Contributors.- 1. The Molecular Structure and Gating of Calcium Channels.- Multiplicity of Voltage-Dependent Calcium Channels.- Structure of a Skeletal Muscle L-Type Calcium Channel.- The Roles of D HP-Binding Proteins in Skeletal Muscle.- Homologous Calcium Channels.- Gating of Voltage-Dependent Calcium Channels.- Structure-Function Relationships of VDCCs.- Regulation of Calcium Channels.- Conclusion.- 2. Calcium Signals in Cell Proliferation, Differentiation, and Death.- Cell Cycle Signals.- Liver Regeneration.- Keratinocytes.- 3. Role of Calcium in Stimulus-Secretion Coupling in Exocrine Glands.- Requirement for Calcium in Exocrine Secretion.- Calcium Entry, Release, and Efflux Mechanisms.- Cellular Mechanisms Involved in Agonist-Stimulated Increases in Intracellular Calcium in Exocrine Cells.- Summary and Conclusions.- 4. Calcium Channels, the Pancreatic Islet, and Endocrine Secretion.- Ion Channels in ss Cells.- Calcium Channels in a Cells.- Conclusions.- 5. Calcium Channels in Cells of the Anterior Pituitary.- General Properties of Calcium Channels in Pituitary Cells.- Calcium Channels in Pituitary Lactotrophs.- Calcium Channels in Somatotrophs.- Calcium Channels in Corticotrophs and Thyrotrophs.- Calcium Channels in Gonadotrophs.- Conclusion.- 6. Role of Calcium in the Secretion of Atrial Natriuretic Peptide.- The Langendorff Preparation.- Isolated Atrial Preparations.- Cardiomyocytes in Culture.- 7. Intracellular Ca2+ and Insulin Action: Possible Role in the Pathogenesis of Syndrome X.- Physiologic Regulation of the Intracellular Calcium Concentration.- The Role of [Ca2+]i in Insulin Action and Insulin Resistance.- Abnormal [Ca2+]i Homeostasis in Diabetes.- Abnormal [Ca2+]i Homeostasis in Hypertension and Obesity.- Abnormal [Ca2+]i and Syndrome X.- High [Ca2+]i and Atherosclerosis.- Conclusions.- 8. [Ca2+]i and Contraction of Arterial Smooth Muscle.- Regulation of Myoplasmic [Ca2+].- Regulation of Myosin Light Chain Phosphorylation ([Ca2+]i Sensitivity).- Regulation of Contractile Force (The Latch Phenomenon).- Conclusion.- 9. Autoimmunity Against the Nicotinic Acetylcholine Receptor and the Presynaptic Calcium Channel at the Neuromuscular Junction.- Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: A Brief History.- The Autoantigen in MG: Structure of the Nicotinic Acetylcholine Receptor.- The Autoantigen in LEMS: Structure and Function of the co-Conotoxin-Sensitive VOCC.- The Effectors of Myasthenic Symptoms: Autoantibodies Against Membrane Proteins Involved in the Cholinergic Transmission.- B and T Epitopes on the AChR Molecule.- Pathogenetic Mechanisms in MG.- Pathogenetic Mechanisms of LEMS.- Possible Similarities in the Pathogenesis of LEMS and MG.- 10. Clinical Pharmacology of Calcium Channels.- Classification of Plasmalemmal Calcium Channels.- Classification of Calcium Channel Modulators.- Clinical Profile and Tissue Selectivity.- Basis for Tissue Selectivity of L-Channel Antagonists.- Clinical Use of Ca2+ Antagonists.- Conclusion.- 11. Hormonal Modulation of Sodium Pump Activity: Identification of Second Messengers.- Adrenal Glomerulosa Cells.- Heart.- Skeletal Muscle.- Liver.- HeLa Cells Transfected with the 5-HT1A Receptor.- Platelets.- Neurons.- Kidney.- Rat Brain Synaptosomes.- Adipocytes.- Summary.- 12. Endogenous Regulation of Sodium Pump Activity.- Volume Expansion and Sodium Pump Inhibitor.- Sodium Pump Inhibitor and Hypertension.- Cellular Mechanisms Linking Hypertension, Fluid Balance, and the Sodium Pump.- The Search for an Endogenous Digitalis-Like Factor (EDLF).- Possible Sources of Endogenous Digitalis-Like Factor.- Sodium Pump Inhibition in the Clinical Setting.- Conclusion.- 13. Structure, Gating, and Clinical Implications of the Potassium Channel.- An Approach to the Study of Potassium Channels.- Biophysical Properties.- Different Types of Potassium Channel Conductance.- Clinical Implications.- Conclusions.- 14. Potassium Channels in Skeletal Muscle.- Ionic Channels in Skeletal Muscle.- Involvement of Potassium Channels in Selected Muscle Diseases.- Conclusions.- 15. The Role of Potassium Ions in the Control of Heart Function.- Permeability.- Rectification.- The Delayed Rectifier (IKdr).- The Inward Rectifier (IKir).- The Transient Outward Current (IKto).- The Calcium-Dependent Potassium Current (IKCa).- The [ATP] i-Dependent Potassium Current (IKATP).- The ACh-Sensitive Potassium Current (IKACh).- The Na-Dependent Potassium Current (IKNa).- The Arachidonic Acid-Activated Potassium Current (IKAA).- The Plateau-Potential Potassium Current (IKP).- Summary.- 16. Nonrenal Potassium Homeostasis: Hypokalemia and Potassium Depletion - Role of Skeletal Muscle Potassium-Pump (Na+,K+ -ATPase).- Body Potassium Homeostasis.- Skeletal Muscles and Potassium Homeostasis.- Rapid Regulation of the Na,K Pump in Skeletal Muscle.- Long-Term Regulation of the Na,K Pump in Skeletal Muscle.- Etiology of Hypokalemia and Potassium Depletion.- Methods for the Assessment of Hypokalemia and Potassium-Depletion.- Consequences of Hypokalemia and Potassium Depletion.- Therapy of Hypokalemia and Potassium Depletion.- Conclusion.- 17. The Clinical Pharmacology of Potassium Channels.- Role of Potassium Channels in Cell Function.- Potassium-Channel Subtypes.- Hypoglycemic Sulphonylureas.- Class III Anti-Arrhythmics.- Drug Design Based on the Structure of Potassium-Channel Toxins.- Potassium-Channel Openers.- Conclusion.- 18. Ion Transport in Vascular Smooth Muscle and the Pathogenesis of Hypertension.- Ion Transport in Vascular Smooth Muscle and How This Relates to Contraction.- Pathophysiologic Changes in the Vasculature in Essential Hypertension.- Conclusion.- 19. Calcium Ion Homeostasis in the Aging Brain: Regulation of Voltage-Dependent Calcium Channels.- Calcium Ion Homeostasis at the Neuronal Level.- Calcium and the Aging Nervous System.- VDCC and Brain Aging.- Functional Expression of VDCC During Aging.- Conclusions.- 20. Interactions of Ethanol with Ion Channels: Possible Implications for Mechanisms of Intoxication and Dependence.- Ethanol and Cellular Calcium Mechanisms.- ET-OH and Na+,K+-ATPase (NKA).- ET-OH and the Na+ Channel.- ET-OH and NMD A-Activated Ion Current.- ET-OH Interaction with GABA-Induced Chloride Current.- ET-OH and 5-HT-3 Receptor.- Conclusions.- 21. Structure and Function of Receptor-Mediated Chloride Channels in the Central Nervous System.- The GABAA Receptor-Mediated CI~ Channel.- Glycine Receptor-Mediated CI~ Channels.- Conclusions.- 22. Characterization of Ion Channels in the Central Nervous System: Insights from Radioligand Binding, Autoradiography, and In Situ Hybridization Histochemistry.- Classes of Ion Channels and Their Roles in the CNS.- Techniques for the Detection of Ion Channels in the CNS.- Studies of Ion Channel/Receptor Recognition Sites Using Radioligands.- Neuroanatomic Localization of Ion Channel/Receptors by In Vitro Autoradiography.- Cellular and Anatomic Localization of Ion Channel/Receptor Expression by In Situ Hybridization Histochemistry.- Studies of Ion Channel Receptor Proteins in Human Brain and Clinical Applications of Ion Channel Research.- Future Developments.- 23. Chloride Channels in Cystic Fibrosis.- Historical Perspective.- CI~ Channels in Epithelia.- Respiratory System.- Intestinal Tract.- Sweat Gland.- Future Considerations.- 24. Cyclic Nucleotide-Activated Channels.- Transduction-Excitation Coupling in Sensory Systems.- Ion Permeation Through Cyclic Nucleotide-Activated Channels.- Structure of Cyclic Nucleotide-Activated Channels.- 25. Transport Systems for Arsenic, Antimony, and Cadmium Ions Encoded by Bacterial Plasmids.- Plasmid-Encoded Transport of Oxyanions of Arsenic and Antimony.- Plasmid-Mediated Cadmium Resistance in Staphylococcus aureus.- Cadmium, Zinc, and Cobalt Resistance in Alcaligenes eutrophus.- Conclusion.