Chloride Movements Across Cellular Membranes (eBook)

Front Cover 1
Chloride Movements Across Cellular Membranes 3
Copyright Page 4
Contents 6
Contributors 10
Preface 12
Chapter 1: Chloride-Transporting Proteins in Mammalian Organisms: An Overview 13
References 18
Chapter 2: Physiological Functions of the CLC Chloride Transport Proteins 21
I. Introduction 22
II. Physiological Function of CLC-0 and Mammalian CLC Proteins 27
III. CLC Proteins in Model Organisms 55
IV. Summary and Outlook 58
References 58
Chapter 3: Structure and Function of CLC Chloride Channels and Transporters 71
I. The Structure of CLC-ec1, A Bacterial CLC Transporter 72
II. Structural Conservation Among the CLCs 74
III. Ion Selectivity, Permeation and Binding 75
IV. A Multi-Ion Pore 76
V. Channels and Transporters: Where Is the Difference? 77
VI. Function of the CLC Transporters 78
VII. Speculative Modeling 80
VIII. CLC Channel Gating 81
IX. The Role of the C-Terminal Domain of CLC Channels: Recent Developments 89
X. Conclusions and Outlook 90
Acknowledgments 91
References 91
Chapter 4: Pharmacology of CLC Chloride Channels and Transporters 95
I. Introduction 95
II. The Pharmacology of the Macroscopic Skeletal Muscle Cl- Conductance gCl 96
III. New Molecules Targeting ClC-1 Identified Using Heterologous Expression 100
IV. Mechanism of Block of Muscle Type CLC Channels by Clofibric Acid Derivatives 103
V. The Binding Site for 9-AC and CPA on ClC-1 and ClC-0 and Use of CPA as a Tool to Explore the Mechanism of Gating of ClC-0 108
VI. Pharmacology of CLC-K Channels 110
VII. Other CLC Channels and Other Blockers 113
VIII. Potential of Having Blockers of ClC-2, ClC-3, ClC-5, ClC-7: Outlook 114
Acknowledgments 115
References 115
Chapter 5: The Physiology and Pharmacology of the CFTR Cl- Channel 121
I. Introduction 121
II. The Molecular Physiology of CFTR 122
III. The Cellular Physiology of CFTR 128
IV. The Role of CFTR in Epithelial Physiology 129
V. The Pathophysiology of CFTR 132
VI. The Pharmacology of CFTR 135
VII. Conclusions 149
Acknowledgments 149
References 149
Chapter 6: Gating of Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel 157
I. CFTR Overview 157
II. Regulation of CFTR by Phosphorylation/Dephosphorylation 160
III. CFTR Is an ATPase 164
IV. Structural Biology of ABC Transporters 165
V. Methods Used to Study CFTR Gating 169
VI. CFTR Gating by ATP 172
VII. Unsettled Issues and Future Directions 181
Acknowledgments 184
References 184
Chapter 7: Functional Properties of Ca2+-Dependent Cl- Channels and Bestrophins: Do They Correlate? 193
I. Summary 193
II. Introduction 194
III. Functional Properties of CaCCs 194
IV. Molecular Candidates of CaCCs 199
V. Functional Properties of Bestrophins 200
VI. Concluding Remarks 203
Acknowledgments 204
References 205
Chapter 8: Cell Volume Homeostasis: The Role of Volume-Sensitive Chloride Channels 211
I. Introduction 211
II. Cell Volume Homeostasis 212
III. Volume-Sensitive Cl- Channels 215
IV. Concluding Remarks 222
References 223
Chapter 9: GABAergic Synaptic Transmission 227
I. Postsynaptic GABA Responses 228
II. Molecular Composition and Function of GABAergic/Glycinergic Synapses 233
III. Modulation of Synaptic Functions Through Endogenous Substances and Drugs 240
IV. Perspective: Specificity of GABAergic and Glycinergic Signaling in Defined Networks 244
References 245
Chapter 10: Physiology of Cation-Chloride Cotransporters 253
I. Introduction 253
II. The Cation-Chloride Cotransporter Family 255
III. Cation-Chloride Cotransporters in the Nervous System 262
IV. Cation-Chloride Cotransporters in the Inner Ear 268
V. Cation-Chloride Cotransporters in the Kidney 271
VI. Cation-Chloride Cotransporters in RBCs 274
VII. Cation-Chloride Cotransporter and Cancer 277
VIII. Cation-Chloride Cotransport and Hypertension 278
IX. Concluding Remarks 279
References 279
Chapter 11: Plasma Membrane Cl-/HCO3- Exchange Proteins 291
I. Introduction 292
II. The Cl-/HCO3- Exchangers 292
III. Disputed Cl-/HCO3- Exchangers 312
IV. Structure 313
V. Regulation and Inhibition of Cl-/HCO3- Exchange 315
VI. Pathophysiology 321
Acknowledgments 324
References 324
Chapter 12: Orchestration of Vectorial Chloride Transport by Epithelia 341
I. Introduction 341
II. Epithelial Cell Structure and Organization 342
III. Junctional Proteins: An Overview 346
IV. Chloride Transporting Proteins in Epithelia: Channels, Transporters, and All Things in Between 348
V. PDZ Proteins: What Are They? Where Are They? What Do They Do? 359
VI. Two Diseases Involving Epithelial Chloride Transport 363
VII. Summary 368
References 369
Index 381