Basic Epithelial Ion Transport Principles and Function: Ion Channels and Transporters of Epithelia in Health and Disease - Vol. 1 [1, 2 ed.] 9783030527792, 9783030527808

Table of contents :
Preface to Second Edition—Volume 1
Volume 1: Basic Epithelial Ion Transport Principles and Function
Preface
Contents
About the Editors
Chapter 1: Techniques of Epithelial Transport Physiology
1.1 Introduction
1.2 The Road to Epithelial Transport: How Did Epithelial Ion Transport Begin?
1.2.1 Early Research in Epithelial Transport
1.3 Radioisotopes and Radioisotopic Tracers Studies
1.3.1 Early Pioneer Researchers in Radioactivity
1.3.2 Taking Radioisotopes Tracers into Chemistry and Biology: George de Hevesy
1.4 The Epithelial Cell Begins to Open Up: Hans H. Ussing, the `Black Box´, the Ussing Chamber, and Isc
1.4.1 Ussing´s Early Years in Preparation for His Chamber
1.4.2 The Ussing Chamber and the Short-Circuit Technique
1.5 The Micropuncture Technique
1.5.1 Historical Aspects of the Micropuncture Technique
1.5.2 The Micropuncture Technique
1.5.3 Advantages and Limitations of the Micropuncture Technique
1.5.4 The Future of the Micropuncture Technique
1.6 Isolated Perfused Kidney Tubule: Maurice Burg
1.6.1 Maurice Burg´s Scientific Training
1.6.2 Development of the Isolated Perfused Tubule Preparation
1.6.3 Advances in Renal Physiology with the Isolated Perfused Kidney Tubule
1.7 In Vivo and In Vitro Intestinal Techniques and the Everted Intestinal Sac Technique: Gerald Wiseman
1.7.1 In Vivo Techniques
1.7.2 In Vitro Techniques
1.7.3 The Historical Perspective of the Everted Sac Preparation: Gerald Wiseman
1.7.4 Advantages and Disadvantages of the Everted Sac Preparation
1.8 Brush Border Membrane Vesicles
1.8.1 Transition from the Epithelial Membrane to Membrane Vesicles
1.8.2 Advantages and Disadvantages to the Brush Border Membrane Vesicle Technique
1.9 Additional Techniques Used in Epithelial Transport Physiology
1.9.1 Site-Directed Mutagenesis and Polymerase Chain Reaction
1.9.1.1 Oligonucleotide-Based Site-Directed Mutagenesis (SDM)
1.9.1.2 Polymerase Chain Reaction
1.9.2 Fluctuation (Noise Analysis) Analyses and Epithelia Ion Channels
1.10 Human Genome Project and the Physiology and Pathophysiology of Epithelia
1.10.1 Impact of the HGP on Epithelial Diseases
1.11 Conclusions
References
Chapter 2: Principles of Epithelial Transport
2.1 Introduction
2.2 What Are Epithelia?
2.2.1 Epithelial Anatomy
2.2.2 Evolution and Developmental Biology of Epithelia
2.2.3 Functional Classification of Epithelia
2.3 Epithelial Transport
2.3.1 Transcellular vs. Paracellular Transport
2.3.2 Energy for Membrane Transport
2.3.3 Protein-Mediated Transport
2.3.4 Transporter Terminology
2.3.5 Conventions for Drawing Transport
2.3.6 Transepithelial Transport
2.3.7 Transepithelial Potential Differences
2.3.8 Flow Down Gradients
2.4 Teaching Epithelial Transport
References
Chapter 3: Establishment and Maintenance of Epithelial Polarization
3.1 Introduction
3.2 Major Molecular Determinants of Polarity
3.2.1 The aPKC Protein Kinases
3.2.2 The Small Signal-Transducing GTPases
3.2.3 Par3 and Par6: Scaffold Proteins of the PAR Complex
3.2.4 Crumbs and the Scaffold Proteins of the CRUMBS Complex
3.2.5 The Scaffold Proteins of the SCRIBBLE Complex
3.2.6 The Phosphatidyl-Phosphoinositols
3.3 Co-ordination of the Molecular Interactions That Prescribe the Apical-Basolateral Axis
3.3.1 Initialization of Axis Formation
3.3.2 SCRIBBLE Complex Function
3.3.3 The Microtubule Cytoskeleton Directs Cargo to Apical and Basolateral Membranes
3.4 The Horizontal Axis of Polarization
3.4.1 Establishment of Planar Cell Polarity in Epithelial Sheets
3.4.2 Points of Intersection Between the Two Plains of Polarization
3.5 Outputs of Polarization
3.5.1 Tissue Morphogenesis
3.5.2 Mitotic Spindle Orientation
3.5.3 Formation of the Basement Lamina
3.5.4 Transepithelial Solute Transport
3.6 Conclusions
References
Chapter 4: Mathematical Modeling of Epithelial Ion Transport
4.1 Introduction
4.1.1 Model Exchange and Reproducible Science
4.2 Epithelial Cell Modeling
4.2.1 State Equations
4.2.2 Buffer Pairs and pH Equilibrium
4.2.3 Electroneutrality Constraints
4.2.4 Model Specialisation
4.2.4.1 Water Fluxes
4.2.4.2 Convective Solute Fluxes
4.2.4.3 Passive Solute Fluxes
4.2.5 Electrodiffusive Fluxes
4.2.5.1 Active Solute Fluxes
4.2.5.2 Total Membrane Solute Fluxes
4.3 Computational Simulation
4.4 Transporter Modeling
References
Chapter 5: Molecular Mechanisms of Apical and Basolateral Sorting in Polarized Epithelial Cells
5.1 General Organization of Secretory and Endocytic Pathways
5.2 Sorting to the Apical Membrane
5.2.1 Apical Sorting Signals
5.2.2 GPI Anchors
5.2.3 Glycan-Dependent Sorting Signals
5.2.4 Peptide-Based Sorting Signals
5.2.5 Apical Sorting Mechanisms
5.3 Sorting to the Basolateral Membrane
5.3.1 Basolateral Sorting Signals and Adaptors
5.3.2 AP-1B Expression in the Kidneys
5.3.3 Autosomal Recessive Hypercholesterolemia Protein (ARH) Expression in the Kidneys
5.3.4 Mechanisms of AP-1B-Mediated Basolateral Sorting
5.3.5 Basolateral Sorting of Transporters
5.4 Retention at the Cell Surface Through Interaction with PDZ Domains
5.5 Sorting of Multi-subunit Transporters
5.6 Challenges to the Field
References
Chapter 6: Membrane Protein Structure and Folding
6.1 Protein Folding and Biosynthesis
6.1.1 Physical Regulation of Protein Folding and Structure
6.1.2 Thermodynamic and Kinetic Regulation of Protein Folding
6.1.3 Protein Folding in the Cellular Environment
6.1.4 Protein Insertion in the Biosynthetic Pathway
6.1.5 Transmembrane Protein Sequences
6.2 Transmembrane Protein Structure
6.2.1 The History of Crystallography
6.2.2 Biological Application of X-Ray Diffraction
6.2.3 Approaches to Membrane Protein Structure Determination
6.2.4 X-Ray Determination of Membrane Protein Structures
6.2.5 Cryo-electron Microscopy Determination of Membrane Protein Structures
6.3 Biological Insights Derived from Transmembrane Protein Structures
6.3.1 ABC Transporters
6.3.2 NBD Structure
6.3.3 NBD-NBD Dimerization and Function
6.3.4 TMD Structure
6.3.5 TMD-NBD Interactions
6.4 Cystic Fibrosis, CFTR Folding and Structure, and Therapeutic Developments
6.4.1 CFTR Folding
6.4.1.1 Full-Length CFTR Folding Studies
6.4.1.2 Folding Studies of NBD1
6.4.1.3 Folding Rescue and Therapeutic Strategies
6.4.2 Structural Biology of CFTR
6.4.2.1 Structures of NBD1
6.4.2.2 Structures of NBD2
6.4.2.3 Full-Length CFTR
6.5 Conclusions
References
Chapter 7: Epithelial Ion Channel Folding and ER-Associated Degradation (ERAD)
7.1 Introduction
7.2 Protein Folding in the Endoplasmic Reticulum
7.2.1 The Role of Molecular Chaperones in Protein Folding
7.2.2 The Role of the Chaperone-Like Lectins in Protein Folding
7.3 Endoplasmic Reticulum-Associated Degradation
7.3.1 Recognition of ERAD Substrates
7.3.2 Ubiquitination of ERAD Substrates
7.3.3 Retrotranslocation of ERAD Substrates
7.3.4 Degradation by the 26S Proteasome
7.4 Epithelial Ion Channels and Transporters Subject to ER Protein Quality Control
7.4.1 The Na,K-ATPase
7.4.1.1 Assembly and ER-Associated Degradation of the Na,K-ATPase
7.4.1.2 The Roles of Chaperones in Na,K-ATPase Regulation
7.4.2 The Epithelial Sodium Channel
7.4.2.1 Posttranslational Modifications of ENaC
7.4.2.2 Regulation of ENaC by ERAD
7.4.2.3 ENaC Channel Assembly and ER Exit
7.4.3 Other Epithelial Ion Channels and Transporters Regulated by ERAD
7.4.3.1 Renal Outer Medullary Potassium Channel
7.4.3.2 Thiazide-Sensitive Sodium Chloride Cotransporter
7.4.3.3 V2 Vasopressin Receptor
7.4.3.4 Aquaporin-2
7.4.3.5 Polycystin-2
7.4.3.6 The Sodium-Potassium Chloride Cotransporter-2
7.5 Conclusions and Future Directions
References
Chapter 8: Fundamentals of Epithelial Cl- Transport
8.1 Introduction
8.2 Active Cl- Transport
8.3 Cl- Transport Regulation
8.3.1 Cholera
8.3.2 Crypts Are the Site of Intestinal Fluid Secretion
8.4 Initial Cell Models for Cl- Transport
8.5 Cl- Conductances
8.5.1 Apical Cl- Conductances
8.5.2 Cystic Fibrosis Transmembrane Conductance Regulator
8.5.2.1 CFTR Pharmacology and Potential Therapeutic Applications
8.6 Apical Cl-/HCO3- Exchangers
8.7 Evidence for a Na+/K+/2Cl- Cotransporter
8.8 Evidence for a Basolateral Membrane K+ Channel
8.8.1 Identification of the cAMP- and Ca2+-Activated Basolateral Membrane K+ Channels
8.8.2 KCa3.1 Is the Ca2+-Activated Basolateral Membrane K+ Channel
8.8.3 KCNQ1 (Kv7.1)/KCNE3 (Mirp2) Is the cAMP-Activated Basolateral Membrane K+ Channel
8.9 Conclusion: An Extensive Cell Model
References
Chapter 9: Fundamentals of Epithelial Na+ Absorption
9.1 Introduction
9.2 General Concepts of Sodium Absorption in Epithelia
9.2.1 Basic Principles of Sodium Transport
9.2.2 Cytosolic Diffusion
9.2.3 Maintenance of Membrane Potential
9.2.4 Mechanisms of Na+ Transport Across the Plasma Membrane
9.2.4.1 Active Transcellular Transport
9.2.4.2 Passive Paracellular Transport
9.2.5 Methods of Na+ Transport Measurement
9.3 Sodium Homeostasis and Its Role in the Kidney
9.3.1 Role of Sodium Reabsorption in the Passive Diffusion of Water, Urea, and Other Solutes
9.3.2 Sodium Absorption in Different Nephron Segments
9.3.2.1 Proximal Tubule (PT)
9.3.2.2 The Loop of Henle
9.3.2.3 Distal Convoluted Tubule
9.3.2.4 Connecting Tubule and Collecting Duct
9.3.3 Physiological Regulation of Na+ Absorption
9.3.4 Tubulo-Glomerular Feedback (TGF) Mechanisms
9.3.5 Pharmacological Control of Na+ Absorption
9.3.5.1 Loop Diuretics
9.3.5.2 Thiazide Diuretics
9.3.5.3 Amiloride and Its Analogs
9.3.5.4 Mineralocorticoid Receptors (MR) Antagonists
9.3.5.5 SGLT Inhibitors
9.4 Sodium Balance and Its Role in Other Organs
9.4.1 Sodium Absorption in the Lung
9.4.2 Sodium Absorption in the Gastrointestinal and Endocrine Systems
9.5 Sodium Transport in Epithelia and Human Diseases
9.6 Final Conclusions
References
Chapter 10: Physiologic Influences of Transepithelial K+ Secretion
10.1 Introduction
10.2 Pathways for Transepithelial K+ Secretion
10.2.1 Cellular Mechanisms for Transepithelial K+ Flow
10.2.1.1 Electrogenic Na+ Absorption
10.2.1.2 Electrogenic Cl- Secretion
10.2.2 Transport Proteins Supporting Transcellular K+ Secretion
10.2.3 Paracellular K+ Flow
10.3 Physiologic Contributions of Transepithelial K+ Secretion
10.3.1 Potassium Excretion
10.3.1.1 Cellular K+ Secretory Mechanisms
Dependence on Na+ Absorption
Dependence on Basolateral Membrane Na+\K+\2Cl--Cotransporter
10.3.1.2 Interactions with Ammonium
10.3.2 Epithelial K+ Gradients Supporting Sensory Physiology
10.3.2.1 Balance and Hearing in the Inner Ear
10.3.2.2 Olfactory Sensation
10.3.3 Transport Cofactor
10.3.3.1 Gastric Acid Secretion
10.3.3.2 Pancreatic Acinar Enzyme Release
10.3.3.3 Na+Cl- Absorption
10.3.3.4 Cl- Secretion
10.3.4 Apical Fluid Composition
10.4 Signaling Pathways for Transepithelial K+ Secretion
10.5 Summary
References
Chapter 11: Volume Regulation in Epithelia
11.1 Introduction
11.2 Concepts in Cell Volume and Electrolyte Homeostasis
11.2.1 Application of the van´t Hoff Law
11.2.2 Cell Water Homeostasis Depends on Metabolic Energy
11.2.3 Isoosmotic and Aniso-osmotic Cell Volume Regulation
11.2.4 ``Cross Talk´´ Between Membrane Domains of Transporting Epithelia
11.3 Osmotic Permeability of Epithelial Cell Membranes
11.4 Cell Volume Response to Osmotic Challenges in Extrarenal Epithelia
11.4.1 Amphibian Skin
11.4.1.1 Principal Cells
11.4.1.2 Mitochondria-Rich Cells
11.4.2 Gallbladder
11.4.3 Small Intestine
11.4.3.1 Intestinal Crypt Cells
11.4.3.2 Intestinal Villus Cells
11.4.4 Upper Airways
11.4.5 Exocrine Glands
11.4.6 Teleost Gill and Opercular Epithelium
11.4.7 Intestine of European Eel
11.5 Cell Volume Response to Osmotic Challenges in Renal Epithelia
11.5.1 Kidney Proximal Tubules
11.5.2 Cortical Collecting Tubule
11.5.3 Medullary and Papillary Portions of Mammalian Nephron
11.6 Epithelial Cell Volume as a Signal for Regulating Isoosmotic Transport
11.7 Molecular Identity of Channels and Transporters Involved in Epithelial Cell Volume Regulation
11.7.1 Chloride Channels
11.7.1.1 Activation and Modulation of Chloride Channels
11.7.2 Potassium Channels
11.7.2.1 Large Conductance or Maxi-(BK) K+ Channel
11.7.2.2 RVD-Mediating Intermediate Conductance (IK) Channels
11.7.2.3 The Two-Pore Domain K+ (K2P) Channel KCNK5
11.7.2.4 KCNQ Channels
11.7.3 Na+/H+ Exchangers
11.7.4 Na+-K+-2Cl- Cotransporters (NKCC)
11.7.4.1 NKCC1
11.7.4.2 NKCC2
Activation by Cell Shrinkage
11.8 Putative Sensors of Cell Volume and Cell Volume Changes
11.8.1 Integrins and Other Receptors
11.8.2 Transient Receptor Potential (TRP) Channels
11.8.3 Phospholipases of the Phospholipase 2 (PLA2) Family
11.8.4 Cytoskeleton
11.9 Signal Transduction in Response to Cell Volume
11.9.1 Free Intracellular Ca2+ Concentration
11.9.2 Role of ATP Release
11.9.3 Mitogen-Activated Protein Kinases (MAPKs)
11.9.4 With No Lysine Kinases (WNKs) and Ste20-Related Kinases
References
Chapter 12: Fundamentals of Bicarbonate Secretion in Epithelia
12.1 Introduction
12.1.1 Overview
12.1.2 Cellular Acid/Base Homeostasis
12.1.2.1 Sodium Hydrogen Exchangers (NHEs, SLC9)
12.1.2.2 Sodium Bicarbonate Cotransporters (NBCs and NDCBEs, SLC4)
12.1.2.3 Classical Anion Exchangers (AE, SLC4)
12.1.2.4 Promiscuous Anion Exchangers
12.1.2.5 Anion Channels
12.1.2.6 Vacuolar H+-ATPase and H+/K+-ATPase
12.1.2.7 Carbonic Anhydrases
12.1.3 Vectorial Bicarbonate Transport
12.2 Pancreas
12.2.1 The Prototype of a Bicarbonate Secretor Is a Complex Gland: Integrated Function and Morphology
12.2.2 HCO3- and H+ Transporters in Pancreatic Ducts
12.2.2.1 CFTR and Cl-/HCO3- Exchangers
12.2.2.2 Calcium-Activated Cl- channels
12.2.2.3 NBCs, NHEs, and Carbonic Anhydrases
12.2.2.4 Proton Pumps
12.2.2.5 K+ Channels
12.2.2.6 Aquaporins and NKCC1
12.2.3 Integrating Ion Channels and Transporters to Pancreatic Ducts
12.2.4 Regulation of Pancreatic Duct Secretion
12.2.4.1 Purinergic Signaling
12.2.4.2 Bile Acids
12.2.4.3 Synergistic Intracellular Signaling: Calcium, cAMP, and Cell Volume
12.3 Salivary Glands
12.3.1 Salivary Glands: Heterogenous Structures and Functions
12.3.2 Ion Channels and Transporters in Salivary Gland Acini
12.3.3 Ion Channels and Transporters in Salivary Gland Ducts
12.3.4 Salivary Glands Can Secrete Very High Bicarbonate and/or Potassium: Where and When?
12.3.5 Regulation of Salivary Gland Secretion
12.4 Hepatobiliary System
12.4.1 Hepatobiliary System: Concerted Action of Several Types of Epithelial Cells
12.4.2 Canalicular Bile Salt-Independent Flow Generated by Hepatocytes
12.4.3 Intrahepatic Biliary Duct System: Ion Transport in Cholangiocytes
12.4.4 Gallbladder Epithelium
12.4.5 Regulation of Bile Formation
12.4.5.1 Purinergic Signaling
12.4.5.2 Bile Acids
12.5 Duodenum
12.6 Renal Intercalated Cells
12.7 Choroid Plexus Epithelium
12.7.1 Basic Secretory Machinery
12.7.2 Luminal HCO3- Extrusion
12.7.3 Other Acid/Base Transporters of Consequence for HCO3- Secretion
12.7.4 Model for Bicarbonate Secretion by the Choroid Plexus
12.7.5 Regulation of CP Bicarbonate Secretion
12.8 Conclusions and Perspectives
References
Chapter 13: MicroRNA Regulation of Channels and Transporters
13.1 Introduction
13.1.1 Background and History of miRNAs
13.1.2 MiRNA Biogenesis
13.2 General miRNA Function
13.3 Regulation of miRNAs
13.4 Role of miRNAs in Channel Physiology
13.5 MiRNAs as Components of Feedback Regulation
13.6 MiRNAs in RAAS Signaling
13.6.1 Renin
13.6.2 Angiotensin
13.6.3 Aldosterone
13.7 Aldosterone Regulated miRNAs
13.8 MiRNAs in Vasopressin Signaling
13.9 Conclusions
References

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