The Red Cell Membrane

Compartmentalized ATP.- 4. Functional Variants of the Na,K-ATPase: Sodium Pump Behavior in Genetically Dimorphic Sheep Red Blood Cells.- 5. Conclusion.- References.- The (Ca2+ + Mg2+)-ATPase: Purification and Reconstitution.- 1. Introduction.- 2. Purification of (Ca2+ + Mg2+)-ATPase.- 2.1. Early Attempts.- 2.2. Calmodulin-Affinity Chromatography.- 3. Kinetic Properties of the Purified Enzyme.- 3.1. Requirement for Phospholipids.- 3.2. Calmodulin-Insensitive Forms.- 4. Reconstitution of (Ca2+ + Mg2+)-ATPase.- 4.1. Early Attempts.- 4.2. Principle of the Methods.- 4.3. Characterization of the Proteoliposomes.- 4.4. Properties of the Reconstituted Enzyme.- 4.5. Mechanism of Ca2+ Transport.- 5. Summary and Conclusions.- References.- Catalytic Mechanisms of the Ca-Pump ATPase.- 1. Introduction.- 2. The Main Properties of the Transport of Ca2+ and the Hydrolysis of ATP by the Ca-Pump ATPase.- 2.1. Transport of Ca2+.- 2.2. Hydrolysis of ATP.- 2.3. Elementary Steps of ATP Hydrolysis.- 2.4. Phosphatase Activity of the Ca-Pump ATPase.- 2.5. Activators of the Ca-Pump ATPase.- 2.6. Inhibitors of the Ca-Pump ATPase.- 3. Summary and Conclusions.- References.- Regulation of the Plasma Membrane Ca2+-Pump.- 1. Introduction.- 2. Does the RBC Need a Regulated Ca2+-Pump?.- 3. ATP as a Regulator of the Ca2+ -Pump.- 4. Calmodulin as a Regulator of the Ca2+-Pump.- 5. Anti-CaM Drugs as Modifiers of the Ca2+-Pump.- 6. Lipids as Regulators of the Ca2+-Pump.- 7. Mechanically Induced Ca2+ Permeation as a Regulator of the Ca2+-Pump.- 8. Diseases as Modifiers of the Ca2+-Pump.- 9. RBCs as Models for Ca2+ Transport.- 10. Summary.- References.- The Anion Transport Protein: Structure and Function.- 1. Introduction.- 2. Structural Domains.- 2.1. Cytoplasmic Domain.- 2.2. Membrane Domain.- 3. The Anion Transport Pathway.- 3.1. Minimum Structure Required for Transport.- 3.2. Extracellular Aspect: The Stilbenedisulfonate Site.- 3.3. Role of Amino Groups in Anion Transport.- 3.4. Histidine Modification.- 3.5. Arginine Residues and Carboxyl Groups.- 3.6. Other Amino Acid Residues.- 3.7. Transport-Related Conformational Changes.- 4. Oligomeric Structure.- 5. Transport Activities of Band 3 Other than Cl-HCO3 Exchange.- 5.1. Anion Selectivity.- 5.2. Proton Transport.- 5.3. Anion Conductance.- 5.4. Postulated Water Transport.- 6. Band 3-Related Proteins in Nonerythroid Cells.- 6.1. Stilbenedisulfonate-Inhibitable Anion Transport Processes.- 6.2. Na-Independent Cl-HCO3 Exchange in Nonerythroid Cells.- 6.3. Acid-Secreting Epithelia.- 6.4. Cells Not Involved in Net Acid or Base Secretion.- References.- Kinetics of Anion Transport.- 1. Introduction.- 1.1. Functions of Anion Exchange.- 1.2. Basic Transport Characteristics.- 2. Models for Tightly Coupled Anion Exchange.- 2.1. Comparison of Ping-Pong and Simultaneous Models.- 2.2. Evidence for the Ping-Pong Model.- 3. Nature of the Transporting Conformational Change.- 3.1. Kinds of Conformational Change.- 3.2. Conformational Distribution and Asymmetry.- 4. Noncompetitive Inhibitors as Probes of Conformation.- 4.1. Effects of Transport Site Orientation.- 4.2. Effects of Substrate Binding.- 4.3. Asymmetry of Chloride-Loaded Sites.- 5. Transport Mechanism: Thin Barrier Vs Zipper.- 6. Net Anion Transport.- 6.1. Involvement of Capnophorin.- 6.2. Mechanism of Net Anion Transport.- 6.3. Rates of Slippage, Diffusion, and Exchange.- 7. Relation to Other Transport Systems.- References.- Ca2+-Activated Potassium Channels.- 1. Introduction.- 2. Some Experimental Points.- 3. Properties of Ca2+ -Dependent K+ Transport.- 3.1. Mechanisms of Activation.- 3.2. Selectivity and Kinetics.- 3.3. Inhibitors.- 3.4. Regulation of the Activity.- 3.5. All or Nothing Behavior.- 3.6. Molecular Substrate.- 4. Summary.- References.- Amino Acid Flux Across the Human Red Cell Plasma Membrane.- 1. Introduction.- 2. Na+-Independent Flux.- 2.1. L System.- 2.2. Ly System.- 2.3. T System.- 3. Na+-Dependent Flux.- 3.1. ASC System.- 3.2. Gly System.- 4. Nature of the Amino-Acid Transport Binding Sites.- 5. Function of Red-Cell Amino-Acid Transport.- 6. Conclusions and Summary.- References.- Hexose Transport Across Human Erythrocyte Membranes.- 1. Introduction.- 2. Perspective.- 3. Catalytic Properties of Human Red-Cell Sugar Transport.- 4. Models for Sugar Transport.- 5. Interpretation of Transport Data.- 5.1. Testing the One-Site Carrier.- 5.2. Testing the Two-Site Carrier.- 5.3. Conclusions.- 6. A One- or Two-Site Transport Mechanism?.- 6.1. Transport Studies.- 6.2. Ligand Binding Studies.- 6.3. Fluorescence Quenching Studies.- 6.4. Conclusions.- 7. Factors Influencing Transport.- 7.1. Compartmentalization of Intracellular Glucose.- 7.2. Transport in Fresh, Outdated, and Metabolically Depleted Human Blood.- 7.3. Sugar Transport in Red-Cell Ghosts and Effects of ATP.- 7.4. Inconsistencies.- 7.5. Conclusions.- 8. Summary.- 8.1. The Mechanism of Sugar Transport.- 8.2. Regulation of Sugar Transport.- 8.3. Sugar Transport in Other Cell Types.- References.- Chloride-Dependent Cation Transport in Human Erythrocytes.- 1. Introduction.- 2. The NaKCl Cotransport System.- 2.1. Transport Modalities and Substrate Kinetics for Na, K, and Cl.- 2.2. Inhibitor Sensitivity and Binding.- 2.3. Effect of Variation in Cell Volume In Vitro.- 2.4. Intracellular Energy Sources and Other Ligands.- 2.5. Role in the Human Red Cell: Net Flux Measurements and Regulation.- 3. Loop Diuretic-Insensitive Chloride-Dependent K Fluxes.- 3.1. Other Signals Switching on KCl Cotransport.- 4. Summary and Conclusions.- References.- 3. Pharmacology.- Pharmacological Modification of the Red Cell Ca2+-Pump.- 1. Introduction.- 2. Red-Cell Preparations to Study Molecular Drug Action.- 2.1. Intact Red Cells.- 2.2. Reversibly Hemolyzed Ghosts.- 2.3. White-Ghost Membrane Fragments.- 2.4. Inside-Out Vesicularized Membrane Fragments.- 3. Drugs that Modulate the Ca2+ -Pump.- 3.1. Inhibitors.- 3.2. Activators of the Ca2+-Pump.- 4. Conclusions and Outlook.- References.- Irreversible Modification of the Anion Transporter.- 1. Introduction.- 1.1. Physiological Aspects.- 1.2. Structure and Function.- 2. Functional Groups Identified by Acid-Base Titration.- 2.1. Extracellular Titration.- 2.2. Effects of Substrate Ions.- 2.3. Effects of Transport Coupled Conformational Changes.- 2.4. Summary.- 3. Modification of Arginine Residues.- 3.1. Phenylglyoxal Modification of the Transport System.- 3.2. Characterization of the Exofacial Modification.- 3.3. Instantaneous Reversible Phenylglyoxal Inhibition.- 3.4. PG Inactivation and Inhibitor Binding.- 3.5. Summary.- 4. Selectivity of Arginine Modification.- 4.1. Localization of the Exofacial Essential Arginine Groups.- 4.2. Modification from the Intracellular Side.- 4.3. Summary.- 5. Modification of Carboxyl Groups.- 5.1. Inactivation of Anion Transport by Carbodiimides.- 5.2. Stimulation by Nucleophile Reaction.- 5.3. Inactivation and Stilbene Disulfonate Binding.- 5.4. Extracellular Titration After Modification.- 5.5. Summary.- 6. Identification of Functional Important Carboxyl Group(s).- 6.1. Carbodiimide-Modified Carboxyl Groups.- 6.2. Modification with Woodward's Reagent K.- 6.3. Summary.- 7. Transport Pathway Models.- 7.1. The Exofacial Substrate and Inhibitor Binding "Sites".- 7.2. Translocation Models.- 7.3. Possible Location and Function of the Modified Groups.- 7.4. Summary.- References.- Drug Actions on Potassium Fluxes in Red Cells.- 1. Introduction.- 2. Chemically Induced Potassium Transport in Red Cells.- 2.1. General Increase in the Cation Permeability of the Red Cell Membrane-SH Group Reagents.- 2.2. Alkali Ion Transport Mediated by Ionophores.- 2.3. Selective Increase in the Potassium Permeability-The Role of Intracellular Calcium.- 2.4. Potassium-Chloride Cotransport Induced by NEM.- 3. Inhibitors of "Nonpump" Potassium Transport Pathways in Red Cells.- 3.1. Inhibitors of the Ca2+-Induced K+ Transport.- 3.2. Inhibitors of the Na+/K+/Cl- Cotransport.- 3.3. Inhibitors of the K+/Cl- Cotransport.- 4. Summary and Conclusions.- References.- 4. Pathophysiology.- Membrane Lipid Changes in the Abnormal Red Cell.- 1. Introduction.- 2. Lipid Compostition of Erythrocyte Plasma Membrane in Normal and Abnormal Conditions.- 2.1. Lipid Composition of the Normal Erythrocyte Plasma Membrane.- 2.2. Lipid Composition of the Abnormal Erythrocyte Plasma Membrane.- 3. Conclusions.- References.- Calcium Fluxes in Pathologically Altered Red Cells.- 1. Introduction.- 2. Tools for Study of Calcium Flux.- 2.1. Active Ca2+ Transport.- 2.2. Passive Ca2+ Flux.- 2.3. Cellular Calcium Homeostasis.- 2.4. Ionized Cellular Calcium.- 2.5. Some Pitfalls.- 3. Sickle Cell Anemia.- 3.1. Ca2+ Homeostasis.- 3.2. Endocytic Vacuoles.- 4. ?-Thalassemia.- 5. Glucose-6-Phosphate Dehydrogenase Deficiency.- 5.1. Effect of Oxidant Drugs.- 5.2. Favism.- 6. Hereditary Spherocytosis.- 7. Malaria.- 8. Cystic Fibrosis.- 8.1. (Ca2+ + Mg2+)-ATPase.- 8.2. Ca2+ Fluxes.- 9. Hypertension.- 10. Affective Disorders.- 11. Other Diseases.- 11.1. Ca2+ Uptake.- 11.2. Active Ca2+ Transport.- 12. Summary and Conclusions.- References.- Mechanisms of Red Cell Dehydration in Sickle Cell Anemia: Application of an Integrated Red Cell Model.- 1. Introduction.- 1.1. Cation and Water Content of Dense SS Cells.- 1.2. Life Cycle of Dense SS Cells In Vivo.- 1.3. Pathophysiological Significance of Dense SS Cells.- 2. Mechanisms of Red-Cell Dehydration.- 2.1. Activation of the Calcium-Dependent K Channel in SS Cells.- 2.2. Role of the Na-Pump in SS Cell Dehydration.- 2.3. Possible Role of K:Cl Cotransport in SS Cell Dehydration.- References.