The Red Cell Membrane

"After being frequently urged to write upon this subject, and as often declining to do it, from apprehension of my own inability, I am at length compelled to take up the pen, however unqualified I may still feel myself for the task. " William Withering, M. D. ' I have yet to find a description or a quote that better summanzes my initial ambivalence towards embarking on such an endeavor as partici­ pating in putting together this monograph. The impetus for The Red-Cell has been a simple, genuine Membrane: A Model for Solute Transport desire to bring together an authoritative account of the' 'state of the art and knowledge" in the red-ceIl-membrane transport field. In particular, it seems important to emphasize the pivotal role the red cell has played for several decades in the discovery and the elucidation of mechanisms of plasma-membrane transport processes. It is only with such knowledge that we can hope to push ahead and make progress in this exciting, multifaceted area. Eventually, one hopes to not only further our knowledge of red cells, but apply the newly gained insights to any other of the plasma membrane. cell with the common denominator In this compendium of reviews, the reader will find that the term model will take on a variety of gists and meanings. In some chapters, the red cell has been chosen as a model membrane solely on the basis of its preeminent design and simplicity.

Inhaltsangabe1. Introduction.- Why Red Cells?.- 1. Introduction.- 2. Transport Systems in Mature Red Cells.- 2.1. Transport of Inorganic Ions.- 2.2. Transport of Organic Molecules.- 2.3. Comparative Aspects.- 2.4. Conclusion.- 3. Advantages of Red Cells.- 4. Conclusion.- References.- Need and Applications of Integrated Red Cell Models.- 1. Introduction.- 2. General Considerations.- 2.1. Purpose and Requirements of an Integrated Red-Cell Model.- 2.2. Components of an Integrated Red-Cell Model.- 2.3. The Computation Strategy.- 3. Examples.- 3.1. Computing a Reference Steady State for a Reticulocyte.- 3.2. Experimental Test of Predictions of the Behavior of K-Permeabilized Red Cells.- References.- 2. Biochemistry and Biophysics.- Molecular Structure of the Na,K,-ATPase.- 1. Introduction.- 2. The Subunits and Their Function.- 2.1. ?-Subunit.- 2.2. ?-Subunit.- 2.3. ?-Subunit.- 3. The Structure of the ?-Subunit.- 3.1. Molecular Weight.- 3.2. Isoforms.- 3.3. ?-Subunit in the Red Blood Cell.- 3.4. Primary Structure.- 3.5. Secondary and Tertiary Structure.- 4. The Structure of the ?-Subunit.- 4.1. Molecular Weight.- 4.2. Primary Structure.- 4.3. Secondary and Tertiary Structure.- 5. Stoichiometry.- 5.1. Mass Ratios.- 5.2. Chemical Cross-Linking Studies.- 5.3. Functional Unit.- 6. Structure-Function Relationships.- 6.1. Amino-Terminal Domain.- 6.2. Conformational Transitions and Ion Binding.- 6.3. ATP Binding and Hydrolysis.- 6.4. Binding of Cardiac Glycosides.- 7. Summary.- References.- Enzymatic and Functional Aspects of Na+/K+ Transport.- 1. Introduction.- 2. Modes of Pump Behavior and Their Enzymic Correlates.- 2.1. Na/Na Exchange, K/K Exchange, Uncoupled Na+ Efflux and Uncoupled K+ Efflux.- 2.2. Affinities of Cations and the Role of Protons.- 3. Are There Characteristics of the Na,K-ATPase Unique to Red Cells?.- 3.1. Effects of Temperature.- 3.2. Interactions with Ouabain.- 3.3. Intracellular Ca2+.- 3.4. Membrane-Bound Glycolytic Enzymes and Their Interactions with Na,K-ATPase via 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