- Principles and Models of Biological Transport

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TABLE OF CONTENTS
CHAPTER 1. EQUILIBRIUM THERMODYNAMICS. Introduction
1.1 Chemical Potentials and Activities
1.1.1 Thermodynamic Preliminaries. The Electrochemical Potential
1.1.2 The Interphase Equilibrium Condition
1.1.3 Electrochemical Potentials in Terms of Measurable Solution Variables:
Introduction, and the Effect of Electrostatic Potential
1.1.4 The Gibbs-Duhem Equation
1.1.5 Dependence of the Chemical Potential on Pressure
1.1.6 Dependence of the Chemical Potential on Composition
1.1.7 Units
1.1.8 Activity and Activity Coefficient
1.2 Ion Equilibrium across Membranes
1.2.1 The Nernst Equilibrium
1.2.2 Origin of the Nernst Potential
1.2.3 Specific Ion Electrodes
1.2.4 Activity Coefficient Considerations
1.2.5 The Donnan Equilibrium
1.3 Chemical Equilibrium
Problems
CHAPTER 2. FREE DIFFUSION. Introduction
2.1 Free Diffusion of Nonelectrolytes
2.1.1 The Teorell Equation
2.1.2 Integration of the Teorell Equation; Fick's First Law; Solute Permeability
2.1.3 Unstirred Layers
2.1.4 Applications of Solution Theory
2.1.5 Fick's Second Law and Convective Diffusion
2.1.6 Justification of the Steady-State Assumption: Time Scales in Biological
Transport
2.2 Free Diffusion of Electrolytes
2.2.1 Differences between Electrolyte and Nonelectrolyte Diffusion
2.2.2 The Electrodiffusion Equation
2.2.3 Integration of the Electrodiffusion Equation
2.2.4 Some Special Cases
Equilibrium
Uniform Composition
Diffusion Potential of a Bi-Ionic System
Active and Passive Exchange with a Closed Compartment
Equal Total Concentrations on the Two Sides of the Membrane: The
Constant-Field Equation
2.2.5 Ionic Permeability and the Resting Potential of the Cell
2.2.6 Charged Membranes
2.2.7 Limitations of the Electrodiffusion Equation and Its Solutions
Problems
CHAPTER 3. THE CELL. Introduction
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3.1 Overview
3.2 The Structure of an Animal Cell
3.2.1 Composition and Structure of the Plasma Membrane
Heterogeneity of Cell Membranes
The Mosaic Model of the Plasma Membrane
The Glycocalyx and Surface Charge
3.2.2 The Internal Structure of the Cell
3.3 Metabolism: The Production of ATP
3.4 Intracellular Transport
3.4.1 Intracellular Diffusion
3.4.2 Protein Transport
Transport into the Nucleus
Transport into the Mitochondrion
3.4.3 Vesicular Transport
Endocytosis
Exocytosis, Secretion and Transcytosis
3.5 Cellular Motility and Locomotion
3.5.1 Actin-Based Movement and Chemotaxis
3.5.2 Cilia and Flagella
Problems
CHAPTER 4. FACILITATED DIFFUSION: CHANNELS AND CARRIERS. Introduction
4.1 Mechanisms of Channels and Carriers
4.1.1 Hallmarks of Mediated Transport
4.1.2 Ion Selectivity of Channels
4.1.3 Energetics of Ion Selectivity, and Steric Effects
4.1.4 Ion Selectivity of Channels: Summary
4.1.5 The Structure of Ion Channels: Selectivity Filters, Gates, and Energy
Profiles
4.1.6 Regulation of the Gating Process
4.1.7 Classification of Ion Channels. Aquaporins and Gap Junctions
4.1.8 Carrier Models
4.1.9 Carriers and Channels: Convergences and Differences
4.2 Kinetics of Facilitated Transport
4.2.1 Models of Ion Channel Transport: Overview
4.2.2 Energy Barrier and Binding Models of Channel Transport
Ionic Independence: Absolute Rate Theory
Saturable Channels: Kinetic Analysis
4.2.3 The Patch Clamp and Two Applications
Acetylcholine Receptor Channel Kinetics
Voltage and Current Sensitivity of a Voltage-Activated Sodium Channel
4.2.4 Stochastic Properties of Channels: Membrane Noise Analysis
4.2.5 The Simplest Model of Carrier Transport: Assumptions
4.2.6 The Simplest Model of Carrier Transport: Equations
4.2.7 Monosaccharide Transport in the Erythrocyte
4.2.8 More Complex Carrier Models
4.2.9 Exchangers and Cotransporters
4.3 Inhibition of Facilitated Transport
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4.3.1 Inhibition of Channel Transport: Channel Block
4.3.2 Inhibition of Carrier Transport
Problems
CHAPTER 5. ACTIVE TRANSPORT. Introduction
5.1 Active Transport: General Considerations
5.1.1 Metabolic Coupling and Affinity
5.1.2 Classification of Active Transport Processes
5.1.3 Identification of Active Transport Processes
5.2 Mechanisms of Active Transport
5.2.1 Scalar Active Transport: Overview
5.2.2 Primary Scalar Transport
5.2.3 Secondary Scalar Transport
Cotransport
Countertransport
5.2.4 Vectorial Active Transport, the Curie Theorem and Substrate
Activation
5.2.5 Sodium-Potassium Exchange
5.2.6 Pump Selectivity and Other Properties Shared with Passive Carriers
5.3 Kinetics of Active Transport
5.3.1 A Simple Secondary Scalar Transport Model: Assumptions
5.3.2 A Simple Secondary Scalar Transport Model: Equations
5.3.3 More Complex Symport Models; the Sodium-Glucose Transporter
5.3.4 Primary Scalar Transport
5.3.5 Flux Equations for Primary Scalar Transport
5.3.6 Relation between the Coupling Parameter Γ and the Affinity of the
Metabolic Reaction
5.3.7 Vectorial Active Transport and the Nature of Na-K Exchange
5.3.8 Pumps and Leaks
Problems
CHAPTER 6. NONEQUILIBRIUM THERMODYNAMICS. Introduction
6.1 The Basic Phenomenological Equations
6.1.1 Conjugate Forces and Fluxes
6.1.2 Phenomenological Coefficients and Linear Thermodynamics
6.1.3 Frictional Interpretation of the Phenomenological Equations
6.1.4 A Cautionary Note before Proceeding
6.2 Nonequilibrium Thermodynamic Description of Passive Transport
6.2.1 Setting the Stage
6.2.2 The Chemical Potential of the Solvent
6.2.3 A New Set of Forces and Fluxes; Osmotic Pressure
6.2.4 The Kedem-Katchalsky Equations
6.2.5 Physical Significance of the Reflection Coefficient: Semipermeable
Membranes and the Osmometer, Steric Effects and Sieving
6.2.6 Osmotic Pressure of Solutions; Donnan Osmotic Pressure; Osmotic
Effects on Cells
6.2.7 Passive Transport of Multiple Nonelectrolytes
6.2.8 Passive Transport of Electrolytes: Electrokinetic Phenomena
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6.3 Nonequilibrium Thermodynamic Description of Active Transport
6.3.1 Definition of Active Transport
6.3.2 Coupling between Nonconjugate Forces and Fluxes
6.3.3 Nonequilibrium Thermodynamics of Motor Proteins and ATP Synthase
6.4 Limitations of Nonequilibrium Thermodynamics
6.4.1 Closeness to Equilibrium: A Limitation Intrinsic to Linearized
Nonequilibrium Thermodynamics
6.4.2 The Concentration Dependence of the Phenomenological Coefficients
6.4.3 Closeness to Equilibrium in Biological Systems
6.4.4 The Information Content of Nonequilibrium Thermodynamics
6.4.5 Approximations in the Derivation of the Kedem-Katchalsky Equations
Problems
CHAPTER 7. MODELS OF TRANSPORT ACROSS CELL MEMBRANES. Introduction
7.1 Transport Across the Lipid Bilayer of Cell Membranes
7.1.1 Evidence for Nonelectrolyte Diffusion Across the Lipid Bilayer
7.1.2 A Simple Model of Transbilayer Diffusion
7.1.3 Potential Barriers in the Bilayer
7.2 Models of Transport Through Pores
7.2.1 Classification of Pore Transport Models
7.2.2 Hydraulic Conductivity of a Pore
7.2.3 Hindered Diffusion; Solute Permeability as a Probe of Pore Radius
7.2.4 Other Factors Affecting Estimated Pore Size; The Equivalent Pore
7.2.5 Hindered Convection (Sieving); the Reflection Coefficient as a Probe of
Pore Radius
7.2.6 Combined Diffusion and Convection through Pores
7.2.7 Single-File Transport through Pores
7.2.8 The Permeability Ratio of Larger Pores
7.3 Electrical Analogs
7.3.1 Equivalent Circuit for the Passive Flux of a Single Ion
7.3.2 Equivalent Circuit for the Passive Transport of Multiple Ions
7.3.3 The Electrical Analog of a Rheogenic Pump
7.3.4 Some Final Remarks
Problems
CHAPTER 8. REGULATION AND FEEDBACK. Introduction
8.1 Regulation of Transport
8.1.1 Receptor-Mediated Second Messenger Systems: Cyclic AMP and
Antidiuretic Hormone
8.1.2 Direct Hormonal Regulation without an Extracellular Receptor:
Aldosterone
8.1.3 Calcium-Based Regulation
Maintenance of a Low Cytosolic Calcium Concentration
Calcium Signaling
Calcium Handling in Cells and Compartmental Analysis
8.2 Feedback in Transport Systems: Insulin
8.3 Regulation by Transport
8.3.1 Regulation of Cell Volume
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8.3.2 Regulation of Cell pH
Problems
Appendix 8.1 Nonequilibrium Binding in Compartmental Analysis
CHAPTER 9. EXCITABLE CELLS. Introduction
9.1 Nerve
9.1.1. The Resting Neuron
9.1.2. The Action Potential: Electrical Aspects
The Membrane Action Potential: Resting State
Hodgkin and Huxley's Equations for the Dependence of Conductance on
Membrane Potential
Excitation of the Membrane Action Potential
The Propagating Action Potential: Cable Theory
The Role of Myelin
9.1.3. The Action Potential: Molecular Aspects
Hodgkin and Huxley's Channel Model
More Recent Models of the Potassium and Sodium Channels of Nerve
9.1.4. Synaptic Transmission
9.2 Muscle
9.2.1. The Resting Muscle Fiber
9.2.2. Excitation and Excitation-Contraction Coupling
Neuromuscular Transmission and Excitation: the Acetylcholine Receptor
Excitation-Contraction Coupling
9.2.3. Molecular Mechanisms of Muscle Contraction
Problems
CHAPTER 10. EPITHELIAL TRANSPORT. Introduction
10.1 Organization of Epithelial and Endothelial Cell Layers and Some Consequences
10.1.1 The Organization of Epithelial and Endothelial Cell Layers
10.1.2 The Pathways across Leaky and Tight Epithelia
10.1.3 Transport in a Parallel Path System
10.1.4 Coupling of Transepithelial Water Flow to Active Ion Transport
The Curran Model
The Standing Gradient Model
The Sodium Recirculation Model
The Cotransporter Hypothesis
10.1.5 The Effect of Unstirred Layers on Transepithelial Diffusion and Osmosis:
Concentration Polarization
10.1.6 Electrical Analogs of Cell Layers
10.2 Examples of Epithelial and Endothelial Function
10.2.1 Absorption
Absorption of Sugars in the Small Intestine
Transport of Water and Sodium in the Proximal Tubule of the Kidney
Transport of Water and Sodium in the Distal Tubule of the Kidney
10.2.2 Secretion
10.2.3 Filtration
Problems
Appendix 10.1 Convection, Diffusion and Mass Addition in Channel Geometries
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CHAPTER 11. GAS TRANSPORT. Introduction
11.1 Partial Pressure and the Equations for Gas Flux
11.2 Overview of the Gas Transport Process
11.3 Gas Exchange in the Lung
11.4 Oxygen Transport in the Blood
11.5 Transport from Red Blood Cells to Tissue
11.5.1 Reaction-Diffusion Processes
11.5.2 The Krogh Tissue Cylinder
11.5.3 Modifications to the Basic Krogh Model
11.5.4 Beyond the Krogh Cylinder
Problems
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