Physiology of Membrane Disorders

I: The Nature of Biological Membranes.- 1: The Anatomy of Biological Interfaces.- 1. Introduction.- 2. Models of Membrane Structure.- 3. Membrane Junctions.- 4. Certain Specialized Membranes.- 5. Artificial Membrane-Protein Interactions.- 6. Membrane Fluidity.- 7. Mechanisms of Protein-Lipid Interaction.- 8. Mueller-Rudin Bilayer Membranes.- 9. Freeze-Fracture-Etch Studies of Membranes.- 10. Summary.- References.- 2: Dynamics of Lipids in Biomembranes.- 1. The Molecular Organization of Lipids in Biomembranes.- 2. Molecular Structure of Membrane Lipids.- 3. Molecular Motions in Bilayers.- 4. Interactions between Lipids in Bilayers.- 5. Summary.- References.- 3: Membrane Proteins: Structure and Arrangement in the Membrane.- 1. Introduction.- 2. Protein Composition of Membranes.- 3. Types of Membrane Proteins.- 4. Extrinsic Proteins.- 5. Intrinsic Proteins.- 6. Types of Intrinsic Membrane Proteins.- 7. The Structure of the Intramembrane Portion.- 8. The Quaternary Structure of Intrinsic Proteins.- 9. Summary.- References.- II: Methods for Studying Membranes.- 4: The Nature and Limitations of Electron Microscopic Methods in Biology.- 1. Introduction.- 2. The Conventional Transmission Electron Microscope.- 3. Specimen Preparation.- 4. Embedding.- 5. Sectioning.- 6. Positive Staining.- 7. Negative Staining.- 8. Low Dose Electron Microscopy.- 9. The Freeze-Fracture-Etch Technique.- 10. Summary.- References.- 5: Isolation and Characterization of Biological Membranes.- 1. Introduction.- 2. Methods for Dissociating and Separating Cells.- 3. Isolation of Plasma Membranes.- 4. Assessment of Purification.- 5. Expression of Data.- 6. Functional Properties of Plasma Membranes.- 7. Pathological Considerations.- 8. Summary.- References.- 6: Ultraviolet Absorption, Circular Dichroism, and Optical Rotatory Dispersion in Biomembrane Studies.- 1. General Considerations.- 2. Distortions and Corrections for Suspensions.- 3. Purple Membrane as a Sample Calculation.- 4. Summary.- References.- 7: Mathematical Models of Membrane Transport Processes.- 1. Introduction.- 2. Diffusion.- 3. Osmosis.- 4. Ionic Diffusion.- 5. Facilitated Diffusion.- 6. Summary.- References.- 8: Tracers in the Study of Membrane Processes.- 1. Introduction.- 2. Tracers and Problems in the Use of Tracers.- 3. Isotope Effects.- 4. Compartmental Systems and Compartmental Analysis.- 5. A Fundamental Theorem for Steady State Systems.- 6. Applications in the Study of Membrane Processes.- 7. Summary.- References.- 9: Principles of Water and Nonelectrolyte Transport across Membranes.- 1. Introduction.- 2. Diffusion as a Permeation Mechanism.- 3. Activation Energy for Diffusion: Measurement and Significance.- 4. Convection.- 5. Osmosis.- 6. Water and Nonelectrolyte Membrane Permeation Mechanisms.- 7. Summary.- References.- 10: Principles of Electrical Methods for Studying Membrane Movements of Ions.- 1. Introduction.- 2. Steady State Characteristics of Biological Membranes.- 3. Non-Steady-State Electrical Properties of Membranes.- 4. Fluctuation Analysis of Electrical Properties of Membranes.- 5. Summary.- References.- 11: Lipid Bilayer Membranes: Their Permeability Properties as Related to Those of Cell Membranes.- 1. Introduction.- 2. Planar Bilayer Membranes.- 3. Reconstitution of Biological Transport Systems in Lipid Bilayers.- 4. Summary.- References.- III: General Problems in Membrane Biology.- 12: Ion Selectivity in Membrane Permeation.- 1. Introduction.- 2. The Patterns of Ion Selectivity Observed for Biological and Model Systems.- 3. How Is Ion Discrimination Inferred from Electrical Measurements on Membranes?.- 4. Origins of Ion Selectivity.- 5. Summary.- References.- 13: Electrically Neutral Ion Transport in Biomembranes.- 1. Introduction.- 2. Electrically Silent Ion Pair Transport.- 3. Ion Pair Transport in Erythrocytes.- 4. Ion Pair Formation with Membrane Components.- 5. Summary.- References.- 14: Na and K Transport in Red Blood Cells.- 1. Introduction.- 2. Intracellular Solutes and Water.- 3. Donnan and "Double Donnan" Equilibrium.- 4. Membrane Potential.- 5. Active Transport.- 6. Stoichiometry of Na, K Pumping.- 7. Modes of Na, K Pump Operation.- 8. Ionic Discrimination by the Na, K Pump.- 9. Ouabain and the Na, K Pump.- 10. Molecular Mechanism of the Na,K Pump.- References.- 15: Ion-Coupled Transport across Biological Membranes.- 1. Introduction.- 2. Ion-Coupled Transport Processes.- 3. The Ion Gradient Hypothesis.- 4. Some Incompletely Resolved Problems.- 5. The Current Status.- 6. Summary.- References.- 16: The Provision of Cellular Metabolic Energy for Active Ion Transport.- 1. Introduction.- 2. Relationship of Ion Transport to Glycolysis and Oxidative Metabolism.- 3. ATP as the Major Link between Metabolism and Active Ion Transport.- 4. Transport Coupled to Metabolism by Mechanisms Which May Not Involve ATP.- 5. Regulation of Rates of Ion Transport and Metabolism.- 6. Summary.- References.- 17: Regulation of Cellular Volume.- 1. Introduction.- 2. Historical Perspective.- 3. The Gibbs-Donnan Equilibrium.- 4. The "Double Donnan" Hypothesis and Cellular Volume Regulation.- 5. Replacement of Intracellular Potassium by Sodium without Cellular Swelling.- 6. Regulation of Cellular Volume in Media Containing Cardiac Glycosides.- 7. The Specificity of Sodium in Cellular Volume Regulation.- 8. Cellular Volume Regulation by Means Other than the Cardiac Glycoside-Sensitive Na,K-ATPase.- 9. The Regulation of Volume in Cells Exposed to Anisosmotic Media.- 10. The Relationship between the Regulation of Cellular Volume and Transepithelial Sodium Transport.- 11. Summary and Conclusions.- References.- 18: Cell-to-Cell Communication: Permeability, Formation, Genetics, and Functions of the Cell-Cell Membrane Channel.- 1. Introduction.- 2. Permeability and Size of the Junctional Membrane Channel.- 3. Regulation of Channel Permeability by Ca2+.- 4. Formation of Junctional Membrane Channels.- 5. Genetics of the Junctional Membrane Channel.- 6. Functions of the Junctional Channels.- References.- 19: Genes and Membranes.- 1. Introduction.- 2. Criteria for Establishing that Differences in Membrane Properties Are Genetically Determined.- 3. Information that Can Be Gained from Biochemical and Physiological Studies on Membrane Mutants.- 4. Information that Can Be Gained from Genetic Analysis.- 5. Summary.- References.- 20: Membrane Immunology and Permeability Functions.- 1. Introduction.- 2. Membrane Immunology and Cation Transport in Erythrocyte Mutants.- 3. Immunology of Membrane Transport Proteins.- 4. Toward a Physiological Basis of Immune Cytolysis.- 5. Summary and Conclusion.- References.- 21: The Interaction of Hormones with Biological Membranes.- 1. Introduction.- 2. Hormone Interaction with Receptors.- 3. Chemical Composition of Membrane Receptors for Hormones.- 4. Self-Regulation of Membrane Content of Receptors.- 5. Translation of Hormone-Receptor Interactions into Biological Function.- 6. Disorders of Membrane Receptors.- 7. Other Classes of Hormone and Transmitter Receptors.- 8. Summary.- References.- 22: Modification of Membrane Function by Drugs.- 1. Introduction.- 2. Drugs Affecting Excitation Phenomena.- 3. Drugs Affecting Transport Mechanisms.- 4. Drugs Affecting Coupling Mechanisms of Membranes.- 5. Summary.- References.- IV: Transport Events in Specialized Cells, Tissues, and Organs.- 23: Processing of Exportable Proteins: Structure-Function Correlates and Role of Cellular Membranes.- 1. Introduction.- 2. Functional and Structural Considerations of the Secretory Process.- 3. Summary of Transport Steps.- 4. Membrane Interactions and Dynamics in the Secretory Process.- 5. Summary.- References.- 24: Lactose Transport in Escherichia coli.- 1. Introduction.- 2. Discovery.- 3. Substrates for Transport.- 4. Accumulation of Nonmetabolized Galactosides.- 5. Entry of o-Nitrophenylgalactoside.- 6. Induction of the Transport System.- 7. Affinity of Substrates for the Carrier.- 8. Exchange Diffusion.- 9. Counterflow.- 10. Steady State Accumulation: "Diffusion" versus Carrier.- 11. Identification of the Lactose Transport Protein.- 12. Energy Coupling.- 13. Membrane Vesicles.- 14. Binding Studies.- 15. Energy-Uncoupled Mutants.- 16. Lactose-Proton Cotransport.- 17. Summary.- References.- 25: Some General Properties of Excitable Tissues.- 1. Introduction.- 2. Osmotic Equilibrium in an Animal Cell.- 3. Signal Transmission.- 4. The Action Potential: What It Does.- 5. The Action Potential: How It Works.- 6. Reconstructing the Action Potential from Voltage Clamp Data.- 7. Summary.- References.- 26: Ion Movements in Skeletal Muscle in Relation to the Activation of Contraction.- 1. Introduction.- 2. The Ultrastructure of the Tubular System in Skeletal Muscle Fibers.- 3. Electrical Properties of the Surface and Tubular Membrane.- 4. Inward Spread of Excitation.- 5. Cellular Ca Movements Related to the Activation of Contraction.- 6. Summary.- References.- 27: Excitable Tissues: The Heart.- 1. Multicellular Structure of the Heart.- 2. Electrical Activity in Different Regions of the Heart.- 3. Ionic Basis and Function of Electrical Activity.- 4. Control of Cardiac Activity by Neurotransmitters.- 5. Summary.- References.- 28: Ion and Water Transport in Gastric Mucosa.- 1. Introduction.- 2. Histology.- 3. Ion Transport across the Secretory and Nutrient Membranes of the Tubular Cells.- 4. Water Transport.- 5. Summary.- References.- 29: Ion Transport by Gastric Mucosa.- 1. H+ Transport.- 2. Cl? Transport by Intact Mucosa.- 3. Conductance Pathways.- 4. Morphological Changes.- 5. Summary.- References.- 30: The Uptake of Lipids into the Intestinal Mucosa.- 1. Chemical Species of Lipids That Are Involved during Fat Absorption.- 2. The Barriers to Lipid Absorption in the Intestine.- 3. Characteristics of the Intestinal Microvillus Membrane Barrier to Lipid Absorption.- 4. Characteristics of the Intestinal Unstirred Water Layer Barrier to Lipid Absorption.- 5. Characteristics of Fatty Acid and Cholesterol Absorption in the Intestine.- 6. Role of Bile Acid Micelles in Facilitating Lipid Absorption in the Intestine.- 7. Summary Description of the Process of Lipid Uptake.- References.- 31: The Regulation of Glomerular Filtration Rate in Mammalian Kidneys.- 1. Introduction.- 2. Ultrastructural Considerations.- 3. Basic Characteristics of the Filtration Process.- 4. Determination of the Filtration Coefficient.- 5. Quantitative Description of Intraglomerular Dynamics.- 6. Physiological Regulation of Glomerular Filtration Rate.- 7. Intrarenal Distribution of Glomerular Filtration Rate.- 8. Summary.- References.- 32: The Proximal Nephron.- 1. Introduction.- 2. Distribution of Transport Functions along the Proximal Tubule.- 3. Electrophysiological Considerations.- 4. Sodium Chloride and Sodium Bicarbonate Transport.- 5. Some Unresolved Problems.- 6. Summary.- References.- 33: Transport Characteristics of the Loop of Henle.- 1. Introduction.- 2. Anatomy.- 3. Experimental Observations.- 4. Functional Role of the Loop of Henle in the Concentration of Urine.- 5. Summary.- References.- 34: Transport Functions of the Distal Convoluted Tubule.- 1. Introduction: General Properties of the Distal Convoluted Tubule.- 2. Transepithelial Net Movements of Solutes and Water.- 3. Electrophysiological Considerations.- 4. Mechanisms of Transport.- 5. Summary.- References.- 35: The Collecting Duct.- 1. Introduction.- 2. Morphologic Considerations.- 3. Methods of Study.- 4. Ion Transport by the Collecting Duct.- 5. Effects of Antidiuretic Hormone on Transport Events in Collecting Duct.- 6. Comparison of ADH Effects in Collecting Tubules and Amphibian Epithelia.- 7. The Mechanism of c-AMP Action.- 8. Summary.- References.- 36: Renal Hemodynamic Factors and the Regulation of Sodium Excretion.- 1. Introduction.- 2. Peritubular Capillary Regulation of Tubular Reabsorption.- 3. Mechanisms Involved in Hemodynamically Mediated Alterations in Sodium Transport.- 4. Intrarenal Distribution of Glomerular Filtration Rate and Blood Flow.- 5. Differences in Transport Characteristics of Superficial and Juxtamedullary Nephrons.- 6. Summary.- References.- V: Clinical Disorders of Membrane Transport Processes.- 37: Disorders of Ion Transport in Red Blood Cells.- 1. Introduction.- 2. Energetic and Ultrastructural Determinants of Permeability and Transport.- 3. Selective Na Leak: The Ion Pair Hypothesis.- 4. The Interaction of Membrane Pumps with the Glycolytic Pathway.- 5. Pump-Leak Relationships.- 6. Mechanisms of Red Blood Cell Destruction.- 7. Systemic Membrane Disorders Manifest in Red Blood Cells.- 8. Summary.- References.- 38: Inherited Membrane Disorders of Muscle: Duchenne Muscular Dystrophy and Myotonic Muscular Dystrophy.- 1. Introduction.- 2. Myotonic Muscular Dystrophy.- 3. Duchenne Muscular Dystrophy.- 4. Summary.- References.- 39: Disorders of Muscle Membranes: The Periodic Paralyses.- 1. Introduction.- 2. Clinical Features.- 3. Hypokalemic Periodic Paralysis.- 4. Hyperkalemic Periodic Paralysis.- 5. Normokalemic Periodic Paralysis.- 6. Summary.- References.- 40: The Anatomical Basis for Cardiac Rhythm and Conduction.- 1. Introduction.- 2. The Sinus Node.- 3. Internodal Pathways.- 4. The Atrioventricular Node.- 5. The Bundle of His.- 6. The Bundle Branches.- 7. Significance of Intercellular Junctional Differences in Sinus Node, AV Node, and His Bundle.- 8. Effect of Diseases and Pathological States on Cell Junctions in the Conduction System and the Potential Physiological Significance of Such Changes.- 9. Special Consideration of the Calcium Dependence of Undifferentiated Regions and of Calcium Independence of Gap Junctions.- 10. Summary.- References.- 41: Cholera Toxin, Adenylate Cyclase and the Process of Active Secretion in the Small Intestine: The Pathogenesis of Diarrhea in Cholera.- 1. Introduction.- 2. Cholera Toxin, c-AMP, and the Intestinal Secretory Process.- 3. Effects of Cholera Toxin on Adenylate Cyclase.- 4. Summary.- References.- 42: Malabsorption Syndromes.- 1. Introduction.- 2. Process of Normal Fat Digestion and Absorption.- 3. Normal Enterohepatic Circulation of Bile Acids.- 4. Process of Normal Carbohydrate and Protein Digestion and Absorption.- 5. Tests of Intestinal Digestive and Absorptive Function.- 6. Diseases Affecting the Normal Absorptive Mechanisms.- 7. Summary.- References.- 43: Mechanisms of Calcium Absorption: A Reappraisal.- 1. Introduction.- 2. Regulation of Calcium Absorption.- 3. Sites of Calcium Absorption.- 4. Mechanisms of Calcium Absorption.- 5. Passive and Facilitated Diffusion versus Active Transport.- 6. The Role of Vitamin D.- 7. Calcium Binding Protein.- 8. Clinical Disorders Associated with Alterations in Calcium Absorption.- 9. Summary.- References.- 44: Cystic Fibrosis.- 1. Introduction.- 2. Clinical Features.- 3. Prognosis.- 4. Genetics.- 5. Pathogenesis.- 6. Animal Models.- 7. Conclusions.- 8. Summary.- References.- 45: Uremia: Strategies in the Search for Toxins.- 1. General Features of the Uremic State.- 2. Examples of Altered Cellular Transport in Uremia.- 3. The Search for Toxins.- 4. Production of a Unique Toxin-Guanidines.- 5. Accelerated Production of a Normal Substance-Natriuretic Hormone.- 6. Retention of a Normal Metabolic Product-Aryl Acids.- 7. Summary.- References.- 46: Disorders of Glomerular Filtration.- 1. Introduction.- 2. Definitions.- 3. General Concepts.- 4. Experimental Methods.- 5. Specific Biologic Mechanisms for Reduction in GFR.- 6. Summary.- References.- 47: Cellular Defects in Urinary Acidification and Renal Tubular Acidosis.- 1. Introduction.- 2. Transport Processes and Functional Organization of Urinary Acidification.- 3. Disorders of Acidification in Different Nephron Segments.- 4. Cellular Defects in Bicarbonate Reab sorption.- 5. Defects in the Formation of Transepithelial Acid-Base Gradients.- 6. Defects in Acid Excretion without Impairment of Gradient Formation.- 7. Clinical Spectrum and Associated Disorders of Electrolyte Transport.- 8. Summary.- References.- 48: Cystinosis and the Fanconi Syndrome.- 1. Introduction.- 2. Historical Resume.- 3. Clinical and Pathological Features.- 4. Chemistry and Metabolism of Cystine.- 5. Other Causes of the Fanconi Syndrome.- 6. Treatment.- 7. Prevention of Cystinosis through Antenatal Diagnosis.- 8. Summary.- References.- 49: Renal Tubular Defects in Phosphate and Amino Acid Transport.- 1. Introduction.- 2. Defects in Phosphate Transport Processes.- 3. Aminoacidurias.- 4. Summary.- References.- 50: The Polyuric Syndromes.- 1. Introduction.- 2. Antidiuretic Hormone.- 3. Regulation of Hormone Release.- 4. Urinary Concentrating and Diluting Processes.- 5. ADH and Water Permeation.- 6. Classification and Description of Polyuric Syndromes.- 7. Pathogenesis of Symptomatology.- 8. Diagnostic and Therapeutic Considerations.- 9. Summary.- References.- 51: Ischemia and Disturbances in Cell Volume Regulation.- 1. Introduction.- 2. Cell Volume and Ischemia.- 3. Responses to in Vivo Alterations in Extracellular Fluid Tonicity.- 4. Summary.- References.