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Current Topics in Membranes

CURRENT TOPICS IN MEMBRANES, VOLUME 81

Cell Volume Regulation

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CONTENTS

CONTRIBUTORS

PREFACE

1 - General Principles of Cell Volume Regulation

One - Water Homeostasis and Cell Volume Maintenance and Regulation

1. INTRODUCTION

2. WHOLE BODY WATER HOMEOSTASIS

2.1 Blood Pressure

2.2 The Kidney and Blood Pressure

2.3 Hypovolemia and Tubuloglomerular Feedback Mechanism

2.4 Urinary Concentrating Mechanism

2.5 Circumventricular Organ, Hypothalamus and Vasopressin

2.6 Back to the Relationship Between Na+ and Water

3. CELL VOLUME HOMEOSTASIS

3.1 Isosmotic Cell Volume Maintenance

3.1.1 Epithelial Transport

3.1.2 Neurotransmission

3.1.3 Cell Cycle

3.1.4 Apoptosis

3.1.5 Cell Migration

3.2 Anisosmotic Cell Volume Regulation

3.2.1 The Osmotic Equilibration Phase

3.2.2 Cell Response to Hypotonicity

3.2.2.1 Volume-Activated K+ Channels

3.2.2.2 Volume-Activated Cl− Channels

3.2.2.3 KCl Cotransporters

3.2.3 Cell Response to Hypertonicity

3.2.3.1 Short Term – Regulatory Volume Increase

3.2.3.1.1 The Na+/H+ and Cl−/HCO3− Exchangers

3.2.3.1.2 The NaK2Cl Cotransporter

3.2.3.2 Long Term – Accumulation of Organic Osmolytes

ACKNOWLEDGMENTS

REFERENCES

Two - Search for Upstream Cell Volume Sensors: The Role of Plasma Membrane and Cytoplasmic Hydrogel

1. INTRODUCTION

2. CELL VOLUME-SENSING BY THE PLASMA MEMBRANE

2.1 Plasma Membrane Stretch: Role of Intracellular Ca2+

2.2 Signaling Within Space-Limited Membrane Domains: Role of Cortical Cytoskeleton and Polyphosphoinositides

3. CELL VOLUME SENSING BY THE CYTOPLASM

3.1 Three-Dimensional Cytoskeleton

3.2 Macromolecular Crowding

3.3 Osmosensing Properties of the Cytoplasmic Hydrogel

4. DELAYED VOLUME SENSORS: ROLE OF ELEVATED [NA+]I/[K+]I RATIO

5. CONCLUSIONS AND PERSPECTIVE

ACKNOWLEDGMENTS

REFERENCES

Three - Cytoskeletal Contribution to Cell Stiffness Due to Osmotic Swelling; Extending the Donnan Equilibrium

1. INTRODUCTION

2. MODELING

3. EQUILIBRIUM OF CHEMICAL POTENTIAL AND OSMOTIC PRESSURE DUE TO FIXED CHARGE

4. MECHANICAL EQUILIBRIUM

5. NUMERICAL RESULTS

6. SUMMARY

7. DISCUSSION

REFERENCES

Four - Membrane Stiffening in Osmotic Swelling: Analysis of Membrane Tension and Elastic Modulus

1. INTRODUCTION

1.1 Basic Considerations: Low Extensibility and Limits of Membrane Stretch before Lysis

1.2 Membrane Unfolding during Cell Swelling

2. MEMBRANE TENSION

2.1 Theoretical Basis and Experimental Approaches of Measuring Membrane Tension

2.2 Osmotic Swelling has Little or No Effect on Membrane Tension

3. ELASTIC PROPERTIES

3.1 Theoretical Basis and Experimental Approaches of Measuring Membrane and Cellular Elastic Modulus

3.2 Osmotic Swelling has Differential Effects on Membrane and Cellular Elastic Moduli

4. CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

Five - Molecular Identities and ATP Release Activities of Two Types of Volume-Regulatory Anion Channels, VSOR and M ...

1. INTRODUCTION

2. TWO TYPES OF VOLUME-REGULATORY ANION CHANNELS: VSOR AND MAXI-CL

2.1 Roles of VSOR and Maxi-Cl in Cell Volume Regulation

2.2 Properties and Activation Mechanisms of VSOR

2.3 Properties and Activation Mechanisms of Maxi-Cl

3. MOLECULAR IDENTITIES OF VSOR

3.1 False Positive Candidates Proposed Previously for VSOR

3.2 Molecules Recently Identified as the Core Component of VSOR

3.3 Missing Components or Subcomponents yet Unidentified for VSOR

4. MOLECULAR IDENTITIES OF MAXI-CL

4.1 False Positive Candidates Suggested Previously for Maxi-Cl

4.2 Molecules Recently Identified as the Core Component of Maxi-Cl

4.3 Missing Components or Subcomponents yet Unidentified for Maxi-Cl

5. ATP RELEASE ACTIVITIES OF VSOR AND MAXI-CL

5.1 Channel-Mediated ATP Release

5.2 VSOR-Mediated ATP Release

5.3 Maxi-Cl-Mediated ATP Release

6. CONCLUSIONS AND FUTURE DIRECTIONS

ABBREVIATIONS

ACKNOWLEDGMENTS

REFERENCES

Six - Molecular Biology and Physiology of Volume-Regulated Anion Channel (VRAC)

1. INTRODUCTION

2. LRRC8 HETEROMERS AS VRAC

2.1 Identification of SWELL1 (LRRC8A) by Genome-Wide RNAi Screen

2.2 LRRC8 Heteromers as Essential Components of VRAC

2.3 LRRC8 Heteromers Form the VRAC Channel Pore

2.4 LRRC8 Subunit Compositions Determine Key VRAC Properties

2.5 VRAC as the Conducting Channel for Large Organic Compounds: Amino Acids, Cancer Drugs and Antibiotics

3. PHYSIOLOGICAL ROLE OF SWELL1 AND VRAC

3.1 Role of SWELL1 and VRAC in the Immune System

3.2 Role of SWELL1 and VRAC in Metabolism

3.3 Role of VRAC in Apoptosis and Cancer Drug Resistance

4. FUTURE STUDIES OF VRAC

4.1 Structural and Molecular Basis of VRAC Permeation, Activation and Regulation

4.2 Role of SWELL1 and VRAC in the Brain Physiology and Disease

4.3 Contribution of LRRC8 Subunits to VRAC Physiology and Beyond

ACKNOWLEDGMENTS

REFERENCES

2 - Regulation of Intracellular Chloride and Water Homeostasis

Seven - Role of WNK Kinases in the Modulation of Cell Volume

1. INTRODUCTION

2. PRINCIPLES OF CELL VOLUME REGULATION

2.1 RVI

2.2 RVD

2.3 The SLC12 Family of Cation-Chloride Cotransporters

2.4 Regulation of Cation Chloride Cotransporters During RVI and RVD by Protein Phosphorylation

3. WITH NO LYSINE KINASES (WNKS)

4. THE WNK KINASES AS INTRACELLULAR CHLORIDE SENSORS

4.1 L-WNK1 Kinase as an Intracellular Chloride Sensor

4.2 WNK4 Kinase as an Intracellular Chloride Sensor

4.3 WNK3 Kinase Is Not Sensitive to Intracellular Chloride Concentration

5. WNKS AND CELL VOLUME REGULATION

5.1 WNK1 Kinase Is Regulated by Hyperosmotic Stress

5.2 WNK3 Kinase and Cell Volume Regulation

5.3 Perspective

REFERENCES

Eight - Intracellular Macromolecules in Cell Volume Control and Methods of Their Quantification

1. INTRODUCTION

2. THE COMPONENTS OF CELL VOLUME AND THE MAIN RELATIONSHIPS

3. METHODS FOR MEASUREMENT OF W, AT, AND AS (NON-QPI)

3.1 Non-optical Methods

3.2 Optical Methods: Fluorescence

3.3 Other Optical Methods

4. QUANTITATIVE PHASE IMAGING (QPI)

4.1 The Principle of QPI

4.2 Interferometric Methods

4.3 Common-Path Methods

4.4 Propagation-Based Methods

4.5 Spatially Resolved Refractive Index Measurements

5. BIOLOGICAL QUESTIONS

5.1 Heterogeneity of Refractive Index

5.2 Long-term Volume Maintenance

5.3 Apoptotic Shrinkage

6. CONCLUSION

SYMBOLS

ABBREVIATIONS

ACKNOWLEDGMENTS

REFERENCES

3 - Cell Volume Regulation in the Airways

Nine - Slippery When Wet: Airway Surface Liquid Homeostasis and Mucus Hydration

1. INTRODUCTION

1.1 Airway Anatomy

1.2 Epithelial Heterogeneity

1.3 Transcellular and Paracellular Transport in the Airways

1.4 Submucosal Glands

2. AIRWAY SURFACE LIQUID (ASL) COMPOSITION

3. AIRWAY SURFACE LIQUID VOLUME REGULATION

3.1 K+ Channels

3.2 The Epithelial Na+ Channel (ENaC)

3.3 The Cystic Fibrosis Transmembrane Regulator (CFTR)

3.4 Ca2+-Activated Cl− Channels/TMEM16A

3.5 SLC26 Exchangers

3.6 Aquaporins

3.7 ASL Volume Regulators

3.8 SPLUNC1 as a Soluble Mediator of ASL Volume

3.9 Switching From a Secretory to an Absorptive State

4. PH HOMEOSTASIS OF THE ASL

4.1 Role of pH in Mucin Expansion

5. CF LUNG DISEASE

5.1 CF Genetics

5.2 The CF Dehydration Hypothesis

5.3 ASL Acidification as the Initial Event in CF Lung Disease

6. CONCLUSIONS

REFERENCES

Ten - Physiology of the Gut: Experimental Models for Investigating Intestinal Fluid and Electrolyte Transport

1. INTRODUCTION

1.1 Transport Problems

1.2 The Small Intestine

2. EPITHELIAL ION AND FLUID SECRETION

2.1 CFTR Anion Channels and Cystic Fibrosis

3. INTESTINAL ION AND FLUID TRANSPORT

3.1 Absorption

3.2 Secretion

3.3 Coupling of Physiologic Fluid Absorption With Pathophysiologic Fluid Secretion

4. MODEL SYSTEMS FOR STUDYING INTESTINAL ION TRANSPORT

4.1 Intestinal Loops

4.2 Everted Sacs

4.3 Ussing Chambers

4.4 Monolayers

4.5 3-D Cultures

4.6 Human Mini-Intestines

5. A “SWELL” ING ASSAY

5.1 Enteroid Swelling

5.2 LMTK2 and Swelling

5.3 CFTR, Cystic Fibrosis and Swelling

5.4 3-D Goes 2-D

6. SUMMARY

SUPPLEMENTARY DATA

REFERENCES

4 - Cell Volume Regulation in the Brain

Eleven - Cell Volume Control in Healthy Brain and Neuropathologies

1. COMMON AND UNIQUE ASPECTS OF OSMOTIC BALANCE WITHIN THE CNS

1.1 Common Mechanisms of Regulatory Volume Decrease (RVD)

1.2 Generic Mechanisms of Regulatory Volume Increase (RVI)

1.3 Donnan Cell Swelling

1.4 The Peculiarities of Cell Volume Regulation in the Brain

2. RVD IN THE CNS CELLS

2.1 Neuronal RVD and Its Ionic Mechanisms

2.2 Astrocytic RVD and Swelling-Activated Ion Channels

3. RVI IN THE CNS CELLS

4. CELL VOLUME CHANGES DURING NORMAL BRAIN FUNCTIONING

5. A SPECIAL CASE FOR ASTROCYTIC SWELLING AND CELL VOLUME CONTROL

5.1 Water Permeability and Aquaporin Channels

5.2 Neurotransmitter Uptake

5.3 K+ Buffering and Donnan Swelling

5.4 Ammonia Uptake and Metabolism

5.5 SUR1/TRPM4 Non-selective Cation Channels

5.6 NKCC1 Activity

5.7 Na+-Bicarbonate Cotransporters and Other Emerging Mechanisms

6. FAILURE OF CELL VOLUME CONTROL IN BRAIN PATHOLOGIES

6.1 Hyponatremia

6.2 Epilepsy

6.3 Hepatic Encephalopathy

6.4 Stroke

7. VRAC AS A VILLAIN IN NEUROPATHOLOGIES

8. THE EVOLVING UNDERSTANDING OF VRAC IDENTITY: PROGRESS AND PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

Twelve - Cytotoxic Swelling of Sick Excitable Cells – Impaired Ion Homeostasis and Membrane Tension Homeostasis in ...

1. MEMBRANE INJURY. NA+-LOADING. SWELLING DEATH. OR NOT?

2. MEMBRANE TENSION HOMEOSTASIS AND MEMBRANE FRAGILITY

2.1 The Concept of Membrane Tension Homeostasis

2.2 Intersecting Homeostatic Processes as Seen in Vicious Feedback Loops

3. SAFEGUARDING THE BILAYER – TENSION BUFFERING

3.1 Tension Buffering in Sarcolemma – Caveolae

3.2 Tension Buffering in Neurons – Open Question

3.2.1 Neuron-Specific Requirements

3.2.2 Neuronal Pre-stress

3.2.3 Neuronal Tension Buffering at a Snail's Pace

4. MAMMALIAN NEURON OSMORESISTIVITY REVISITED

5. DONNAN THE ELEPHANT (IN THE SICK EXCITABLE ROOM)

6. CYTOTOXIC SWELLING OF SKELETAL MUSCLE

6.1 Swelling of Muscle Fibers in Duchenne MD

6.2 Nav Channel Gating in Bleb-Damaged Membrane

6.3 Nav Leak and the Na/K Pump Response in Dystrophic Muscle

7. EXCITOTOXIC INSULTS STIFFEN NEURONS. THEN THEY SWELL, BLEB, SOFTEN, DIE

8. CYTOTOXIC SWELLING OF NEURONS

8.1 Excitotoxic Swelling of Cortical Neurons – The “Missing” Cl−-Leak Identified

8.2 Beading of Dendrites During SD Differs From Cytotoxic Swelling of the Soma

9. MODELING EXCITOTOXIC SWELLING IN NEURONS

9.1 Accurate Depiction of Mild Injury Is the Goal

9.2 Modeling Sick Excitable Cells That Leak Both Cl− and Na+

9.3 Bifurcation Plots Are to Homeostatic Modeling What Gels Are to Biochemistry

9.4 What Is “Ionic Excitability”?

9.5 Modeling Volume Changes of SD-Associated Cytotoxic Swelling

10. MECHANISTIC MODEL FOR EXCITOTOXIC NEURONAL SWELLING DURING SD

11. CONCLUSION: IH AND MTH WORKING TOGETHER

REFERENCES

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