Physiology and Pathology of Chloride Transporters and Channels in the Nervous System (eBook)

From Molecules to Diseases

F. Javier Alvarez-Leefmans, Eric Delpire (Herausgeber)

eBook Download: PDF

2009 | 1. Auflage
630 Seiten
Elsevier Science (Verlag)
978-0-08-092203-4 (ISBN)

Infos

The importance of chloride ions in cell physiology has not been fully recognized until recently, in spite of the fact that chloride (Cl-), together with bicarbonate, is the most abundant free anion in animal cells, and performs or determines fundamental biological functions in all tissues. For many years it was thought that Cl- was distributed in thermodynamic equilibrium across the plasma membrane of most cells. Research carried out during the last couple of decades has led to a dramatic change in this simplistic view. We now know that most animal cells, neurons included, exhibit a non-equilibrium distribution of Cl- across their plasma membranes. Over the last 10 to 15 years, with the growth of molecular biology and the advent of new optical methods, an enormous amount of exciting new information has become available on the molecular structure and function of Cl- channels and carriers. In nerve cells, Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control. Disruption of Cl- homeostasis in neurons underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation. This book is about how chloride ions are regulated and how they cross the plasma membrane of neurons. It spans from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases.

• The first comprehensive book on the structure, molecular biology, cell physiology, and role in diseases of chloride transporters / channels in the nervous system in almost 20 years
• Chloride is the most abundant free anion in animal cells. THis book summarizes and integrates for the first time the important research of the past two decades that has shown that Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control
• The first book that systematically discusses the result of disruption of Cl- homeostasis in neurons which underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation
• Spanning topics from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases
• Involves all of the leading researchers in the field
• Includes an extensive introductory section that covers basic thermodynamic and kinetics aspects of Cl- transport, as well as current methods for studying Cl- regulation, spanning from fluorescent dyes in single cells to knock-out models to make the book available for a growing population of graduate students and postdocs entering the field

Inhalt

Front Cover 1
Physiology and Pathology of Chloride Transporters and Channels in the Nervous System 4
Copyright Page 5
Contents 6
Preface 10
List of Contributors 12
PART I: OVERVIEW OF CHLORIDE TRANSPORTERS AND CHANNELS 14
Chapter 1 Chloride Channels: An Historical Perspective 16
I. INTRODUCTION 16
II. CHLORIDE "PASSIVITY" 16
III. ACTIVE CHLORIDE TRANSPORT 17
IV. TECHNICAL HURDLES TO STUDYING Cl[sup(–)] CHANNELS 18
V. THE CHLORIDE AWAKENING 19
VI. Cl[sup(–)] CHANNEL GENES 20
VII. STRUCTURE AND FUNCTION 21
VIII. DISEASES CAUSED BY DISORDERS OF Cl[sup(–)] CHANNELS AND TRANSPORTERS 22
IX. INTRACELLULAR Cl[sup(–)] CHANNELS 22
X. CHLORIDE MAY REGULATE PROTEIN FUNCTION 23
XI. OTHER FUNCTIONS OF Cl[sup(–)] CHANNELS 24
XII. CONCLUDING REMARKS 24
References 25
Chapter 2 Sodium-Coupled Chloride Cotransporters: Discovery and Newly Emerging Concepts 30
I. INTRODUCTION 30
II. LOCALIZATION AND REGULATION 31
III. FUNCTIONS OF THE Na[sup(+)]-COUPLED COTRANSPORTERS 32
IV. NKCC REGULATION 36
References 37
Chapter 3 Pathophysiology of the K[sup(+)]-Cl[sup(–)] Cotransporters: Paths to Discovery and Overview 40
I. THE EMERGENCE OF K[sup(+)]-Cl[sup(–)] COTRANSPORT AS A FUNCTIONAL TRANSPORT ENTITY 40
II. MOLECULAR IDENTIFICATION OF K[sup(+)]-Cl[sup(–)] COTRANSPORTERS 43
III. TISSUE DISTRIBUTION OF K[sup(+)]-Cl[sup(–)] COTRANSPORTER ISOFORMS 43
IV. TRANSPORT MODES, SELECTIVITY AND KINETICS 44
V. PHYSIOLOGICAL PROPERTIES, MODULATION AND REGULATION OF K[sup(+)]-Cl[sup(–)] COTRANSPORTERS 45
VI. PATHOLOGY AND K[sup(+)]-Cl[sup(–)] COTRANSPORTERS 48
VII. FUTURE PERSPECTIVES 50
Acknowledgements 51
References 51
Chapter 4 From Cloning to Structure, Function, and Regulation of Chloride-dependent and Independent Bicarbonate Transporters 56
I. INTRODUCTION 56
II. HISTORY OF ANION EXCHANGERS 57
III. MODES OF MEMBRANE ANION TRANSPORT – THEORETICAL 57
IV. THE FOCUS OF THE REVIEW 60
V. SLC4 ANION EXCHANGERS AND COTRANSPORTERS 60
VI. SLC26 ANION EXCHANGERS/TRANSPORTERS/CHANNELS 71
Acknowledgements 83
References 83
Chapter 5 Thermodynamics and Kinetics of Chloride Transport in Neurons: An Outline 94
I. INTRODUCTION 95
II. THERMODYNAMICS OF Cl[sup(–)] TRANSPORT 102
III. KINETICS OF CATION-Cl[sup(–)] COTRANSPORT 111
IV. CONCLUSIONS 117
Acknowledgements 117
References 117
PART II: CURRENT METHODS FOR STUDYING CHLORIDE REGULATION 122
Chapter 6 Chemical and GFP-based Fluorescent Chloride Indicators 124
I. INTRODUCTION 124
II. SMALL-MOLECULE CHLORIDE-SENSITIVE FLUORESCENT INDICATORS 125
III. Cl[sup(–)] SENSING MACROMOLECULAR CONJUGATES 128
IV. GREEN FLUORESCENT PROTEIN-BASED HALIDE INDICATORS 130
V. CONCLUSIONS 134
References 134
Chapter 7 Clomeleon, a Genetically Encoded Chloride Indicator 138
I. INTRODUCTION 138
II. PROPERTIES OF CLOMELEON 139
III. STRATEGIES FOR CLOMELEON EXPRESSION 142
IV. APPROACHES TO CLOMELEON IMAGING 144
V. APPLICATIONS OF CLOMELEON 145
VI. OUTLOOK: OPTIMIZING CLOMELEON IMAGING 150
References 150
Chapter 8 Gramicidin Perforated Patch 154
I. INTRODUCTION 154
II. APPLICATION OF GRAMICIDIN PERFORATED PATCH TO CNS NEURONS 155
III. CONCLUSIONS 158
References 159
Chapter 9 Measuring Electroneutral Chloride-dependent Ion Fluxes in Mammalian Cells and in Heterologous Expression Systems 162
I. INTRODUCTION 162
II. HETEROLOGOUS EXPRESSION SYSTEMS 163
III. TRACER VERSUS NON-TRACER FLUX MEASUREMENTS 164
IV. ELECTROCHEMICAL DRIVING FORCE OF ION FLUX 165
V. TECHNIQUES 165
VI. CONCLUSION 168
References 169
Chapter 10 Knockout Models of Cation-Chloride Cotransporters 172
I. INTRODUCTION 172
II. STRAIGHT KNOCKOUT VERSUS CONDITIONAL KNOCKOUT MOUSE MODELS 173
III. KNOCK-IN MOUSE MODELS 173
IV. TARGETING A GENE BY HOMOLOGOUS RECOMBINATION 174
V. KNOCKOUTS OF CATION-CHLORIDE COTRANSPORTERS 176
References 178
PART III: FROM CLONING TO STRUCTURE, FUNCTION AND REGULATION OF CHLORIDE TRANSPORTERS AND CHANNELS 180
Chapter 11 The NKCC and NCC Genes: An in Silico View 182
I. AN IN SILICO VIEW OF THE NKCC AND NCC GENES 183
II. THE SLC12A1 GENE ENCODING FOR Na[sup(+)]-K[sup(+)]-2Cl[sup(–)] COTRANSPORTER 2 (NKCC2) 190
III. THE SLC12A2 GENE ENCODING FOR Na[sup(+)]-K[sup(+)]-2Cl[sup(–)] COTRANSPORTER 1 (NKCC1) 203
IV. THE SLC12A3 GENE ENCODING FOR Na[sup(+)]-Cl[sup(–)] COTRANSPORTER (NCC) 208
Acknowledgements 216
References 216
Chapter 12 The CLC Family of Chloride Channels and Transporters 222
I. INTRODUCTION 222
II. GENERAL PROPERTIES OF THE CLC PROTEIN FAMILY 223
III. PHYSIOLOGY AND PATHOLOGY OF THE NEURONAL CLC PROTEINS 229
IV. OUTLOOK 238
References 238
Chapter 13 Calcium-activated Chloride Channels 246
I. INTRODUCTION 246
II. THE Cl[sup(–)] EQUILIBRIUM POTENTIAL IN DEVELOPMENT AND INJURY 249
III. EXPRESSION OF Cl[Sub(Ca)] CHANNELS IN DEVELOPMENT AND INJURY 251
IV. BIOPHYSICAL PROPERTIES OF Cl[Sub(Ca)] CHANNELS 252
V. REGULATION OF Cl[Sub(Ca)] CHANNELS BY KINASES AND PHOSPHATASES 258
VI. CLONING, STRUCTURE AND FUNCTION OF Cl[Sub(Ca)] CHANNELS 260
VII. CONCLUDING REMARKS 264
Acknowledgements 265
References 265
Chapter 14 GABA[sub(A)] Receptor Channels 270
I. INTRODUCTION 270
II. MOLECULAR BIOLOGY OF GABA[sub(A)] RECEPTORS 271
III. ASSEMBLY OF GABA[sub(A)] RECEPTORS 272
IV. SPATIAL AND TEMPORAL REGULATION OF GABA[sub(A)] RECEPTORS 274
V. STRUCTURE OF GABA[sub(A)] RECEPTORS 276
VI. BIOPHYSICAL AND KINETIC PROPERTIES OF GABA[sub(A)] RECEPTOR CHANNELS 278
VII. PHARMACOLOGICAL PROPERTIES OF GABA[sub(A)] RECEPTORS 283
VIII. MODES OF GABAergic INHIBITION 283
IX. INVOLVEMENT OF GABA[sub(A)] RECEPTORS IN EPILEPSY 285
Acknowledgements 287
References 287
Chapter 15 The Puzzles of Volume-activated Anion Channels 296
I. INTRODUCTION: ANION CHANNELS AND THEIR MULTIPLE FUNCTIONS 296
II. WHAT ARE VOLUME-ACTIVATED ANION CHANNELS (VAACS)? 298
III. WHICH VAACS ARE VOLUMESENSITIVE ORGANIC OSMOLYTE ANION CHANNELS (VSOACs)? 304
IV. WHAT ARE THE MOLECULAR IDENTITIES OF MAXI-ANION AND VSOR? 308
V. ADDENDUM: THOUGHTS ON WHETHER ClC-3 IS A Cl[sup(–)] CHANNEL OR A Cl[sup(–)]/H[sup(+)] ANTIPORTER 311
Acknowledgements 312
References 312
Chapter 16 The Sodium-dependent Chloride Cotransporters 320
I. INTRODUCTION 320
II. MOLECULAR BIOLOGY OF THE SODIUM-DEPENDENT CHLORIDE COTRANSPORTERS 321
III. FUNCTIONAL PROPERTIES 325
IV. STRUCTURE–FUNCTION RELATIONSHIPS 328
V. PHYSIOLOGICAL ROLES 332
VI. THE ROLE OF THE SODIUM-COUPLED CATION CHLORIDE COTRANSPORTERS IN INHERITED DISEASE 335
VII. POTENTIAL ROLE IN POLYGENIC DISEASES 337
Acknowledgements 338
References 338
Chapter 17 The Potassium-Chloride Cotransporters: from Cloning to Structure and Function 346
I. OVERVIEW OF THE K[sup(+)]-Cl[sup(–)] COTRANSPORTERS: A HISTORICAL PERSPECTIVE 346
II. MOLECULAR BIOLOGY OF THE K[sup(+)]-Cl[sup(–)] COTRANSPORTERS 348
III. STRUCTURE–FUNCTION STUDIES WITH THE K[sup(+)]-Cl[sup(–)] COTRANSPORTERS 354
IV. PHYSIOLOGICAL FUNCTION OF K[sup(+)]-Cl[sup(–)] COTRANSPORTER IN NEURONS 357
V. CONCLUDING REMARKS 364
Acknowledgements 365
References 365
Chapter 18 Regulation of Cation-Chloride Cotransporters 370
I. INTRODUCTION 370
II. REGULATION OF PROTEIN EXPRESSION AND ABUNDANCE 371
III. POST-TRANSLATIONAL PROCESSING 373
IV. MEMBRANE RETRIEVAL AND DEGRADATION 374
V. REGULATION OF TRANSPORT RATE 374
VI. CONCLUSIONS 387
References 388
PART IV: CATION-CHLORIDE COTRANSPORTERS IN NEURAL FUNCTION AND DYSFUNCTION 396
Chapter 19 GABA, Glycine and Cation-Chloride Cotransporters in Retinal Function and Development 398
I. INTRODUCTION 398
II. FUNCTION OF GABA, GLYCINE AND CHLORIDE COTRANSPORTERS IN THE ADULT RETINA 399
III. FUNCTION OF GABA, GLYCINE AND CATION-CHLORIDE COTRANSPORTERS IN RETINAL DEVELOPMENT 412
References 421
Chapter 20 Chloride-based Signal Amplification in Olfactory Sensory Neurons 426
I. ODOR-INDUCED CHLORIDE CURRENTS IN OLFACTORY SENSORY NEURONS 426
II. CALCIUM-ACTIVATED CHLORIDE CHANNELS IN OLFACTORY SENSORY CILIA 428
III. CHLORIDE ACCUMULATION IN OLFACTORY SENSORY NEURONS 432
IV. BEYOND THE NOSE 433
V. CONCLUSION 435
References 436
Chapter 21 Cochlear and Vestibular Function and Dysfunction 438
I. INTRODUCTION 438
II. SENSORY TRANSDUCTION 438
III. IONIC BASIS OF SENSORY TRANSDUCTION IN THE COCHLEA AND THE VESTIBULAR LABYRINTH 442
Acknowledgements 448
References 448
Chapter 22 Chloride Transporters in Presynaptic Inhibition, Pain and Neurogenic Inflammation 452
I. INTRODUCTION 453
II. THE CELLULAR AND MOLECULAR BASIS OF PRESYNAPTIC INHIBITION AND PAD 457
III. POSSIBLE ROLE OF NKCC1 IN PAIN, HYPERALGESIA AND NEUROGENIC INFLAMMATION 468
IV. Na[sup(+)]-K[sup(+)]-Cl[sup(–)] COTRANSPORTER EXPRESSION IN PERIPHERAL AXONS AND SCHWANN CELLS 472
V. CONCLUSIONS 477
Acknowledgements 477
References 477
Chapter 23 Modulation of Chloride Homeostasis by Microglia 484
I. INTRODUCTION 484
II. ALTERED CHLORIDE HOMEOSTASIS IN THE SPINAL DORSAL HORN AS A SUBSTRATE OF NEUROPATHIC PAIN 485
III. BDNF, A SIGNALING MOLECULE CONTROLLING KCC2 EXPRESSION 488
IV. MECHANISM OF BDNF-TRKB MEDIATED ALTERED CHLORIDE HOMEOSTASIS 489
V. MICROGLIA CONTROL NEUROTRANSMITTER-MEDIATED NEURONAL EXCITABILITY BY ALTERING ANION HOMEOSTASIS 491
VI. WHAT ACTIVATES MICROGLIA? 495
VII. THERAPEUTIC IMPLICATIONS 498
Acknowledgements 498
References 498
Chapter 24 Cation-Chloride Cotransporters as Pharmacological Targets in the Treatment of Epilepsy 502
I. INTRODUCTION 502
II. THE MAGNITUDE AND POLARITY OF GABAergic NEUROTRANSMISSION IS DETERMINED BY THE INTRANEURONAL CONCENTRATION OF Cl[sup(–)] 503
III. A DEVELOPMENTAL SWITCH IN CATION-CHLORIDE COTRANSPORTER EXPRESSION RENDERS GABA HYPERPOLARIZING DURING NEURONAL MATURATION 504
IV. THE ROLE OF NKCC1 IN NEONATAL SEIZURES 505
V. ROLE OF NKCC1 AND KCC2 IN TEMPORAL LOBE EPILEPSY AND SEIZURES FOLLOWING HYPOXIC-ISCHEMIC INJURY 507
VI. CATION-CHLORIDE COTRANSPORTERS AS THERAPEUTIC TARGETS FOR SEIZURES 509
References 511
Chapter 25 The Role of Cation-Chloride Transporters in Brain Ischemia 514
I. INTRODUCTION 514
II. Cl[sup(–)] TRANSPORTERS IN DISSOCIATED BRAIN CELLS FOLLOWING IN VITRO ISCHEMIA 515
III. Cl[sup(–)] TRANSPORTERS IN BRAIN SLICES FOLLOWING IN VITRO ISCHEMIA 521
IV. Cl[sup(–)] TRANSPORTERS FOLLOWING IN VIVO CEREBRAL ISCHEMIA 524
V. CONCLUSIONS 526
Acknowledgement 527
References 527
Chapter 26 Chloride Transport in Glioma Growth and Cell Invasion 532
I. INTRODUCTION 532
II. GLIOMAS AND THEIR LINEAGE 533
III. GLIOMA MIGRATION AND INVASION 534
IV. Cl[sup(–)] TRANSPORT AND CELL VOLUME REGULATION IN GLIOMA CELLS 534
V. CHANGES IN CELL VOLUME OF INVADING CELL REQUIRE Cl[sup(–)] EFFLUX VIA ClC CHANNELS 536
VI. MECHANISM OF CHLOROTOXIN ACTION ON GLIOMA INVASION 537
VII. CLINICAL USE OF CHLOROTOXIN 538
VIII. CELL VOLUME CHANGES ASSOCIATED WITH CELL PROLIFERATION 539
IX. CONCLUSIONS 541
Acknowledgements 541
References 542
Chapter 27 The Sodium-Potassium-Chloride Cotransporter, Human Cytomegalovirus and the Cell Cycle 544
I. INTRODUCTION 544
II. HCMV BASICS 545
III. HCMV PATHOLOGY 545
IV. BIOLOGY OF THE VIRUS 545
V. HCMV PARTIALLY ACTIVATES HOST CELL CYCLE 546
VI. HCMV AND OTHER HOST CELL ION TRANSPORTERS 547
VII. HCMV EFFECTS ON NKCC 549
VIII. NKCC AND THE NORMAL CELL CYCLE: POSSIBLE LINK TO EFFECT OF HCMV 552
IX. WHY IS NKCC "TARGETED" BY HCMV? 553
Acknowledgements 554
References 554
PART V: CATION-CHLORIDE COTRANSPORT IN CHOROID PLEXUS AND BLOOD–BRAIN BARRIER 558
Chapter 28 Chloride Transporters as Water Pumps: Elements in a New Model of Epithelial Water Transport 560
I. INTRODUCTION 560
II. WATER TRANSPORT BY COTRANSPORTERS 562
III. A MOLECULAR MODEL OF EPITHELIAL WATER TRANSPORT BASED UPON COTRANSPORTERS AND THEIR REGULATION 569
IV. ROLE OF COTRANSPORTERS AND UNIPORTERS IN A TIGHT EPITHELIUM, THE BLOOD–BRAIN BARRIER 574
V. CONCLUDING REMARKS 577
Acknowledgements 577
References 577
Chapter 29 Ion Transport in Choroid Plexus 582
I. INTRODUCTION TO THE CEREBROSPINAL FLUID AND THE CHOROID PLEXUSES 582
II. AN OVERVIEW OF CSF SECRETION BY THE CHOROID PLEXUSES 584
III. CATION CHANNELS AND CATION TRANSPORTERS EXPRESSION IN THE CHOROID PLEXUS 584
IV. HCO[sub(3)][sup(–)] TRANSPORTERS AND CSF SECRETION 586
V. A MODEL FOR CSF SECRETION: THE RELATIONSHIP BETWEEN Na[sup(+)], HCO[sub(3)][sup(–)] AND Cl[sup(–)] TRANSPORT IN THE CHOROID PLEXUS 587
VI. REMAINING QUESTIONS ABOUT THE MECHANISM OF CSF SECRETION: POTENTIAL ROLES FOR CATION-CHLORIDE COTRANSPORTERS 588
VII. THE EXPRESSION OF CATION-CHLORIDE COTRANSPORTERS (SLC12 FAMILY) IN CHOROID PLEXUS 589
VIII. FUNCTIONS OF CATION-CHLORIDE COTRANSPORTERS IN CHOROID PLEXUS EPITHELIAL CELLS 590
IX. CONCLUSIONS 593
References 593
Chapter 30 Ion and Water Transport across the Blood–Brain Barrier 598
I. INTRODUCTION 598
II. ION TRANSPORT OF THE BLOOD–BRAIN BARRIER 600
III. DISEASES OF THE BLOOD–BRAIN BARRIER 604
IV. CONCLUSIONS 615
References 615
Index 620
A 620
B 620
C 621
D 623
E 623
F 623
G 623
H 624
I 624
J 624
K 624
L 624
M 624
N 625
O 625
P 625
Q 626
R 626
S 627
T 629
V 629
W 630
X 630
Y 630

Produkt-Details

• Erscheint lt. Verlag: 22.8.2009
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Studium ► 2. Studienabschnitt (Klinik) ► Pathologie
• Themenwelt: Naturwissenschaften ► Biologie ► Humanbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zoologie
• Themenwelt: Technik
• ISBN-10: 0-08-092203-1 / 0080922031
• ISBN-13: 978-0-08-092203-4 / 9780080922034