Molecular biology of membrane transport disorders:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
New York [u.a.]
Plenum Press
1996
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XXIII, 681 S. graph. Darst. |
| ISBN: | 0306451646 |
Internformat
MARC
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| 245 | 1 | 0 | |a Molecular biology of membrane transport disorders |c ed. by Stanley G. Schultz ... |
| 264 | 1 | |a New York [u.a.] |b Plenum Press |c 1996 | |
| 300 | |a XXIII, 681 S. |b graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 7 | |a Biofisica da membrana celular |2 larpcal | |
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| 650 | 7 | |a Pathologie |2 gtt | |
| 650 | 7 | |a Stoftransport |2 gtt | |
| 650 | 4 | |a Biological Transport | |
| 650 | 4 | |a Ion Channels | |
| 650 | 4 | |a Membrane disorders | |
| 650 | 4 | |a Membranes |x physiology | |
| 650 | 4 | |a Membranes |x physiopathology | |
| 650 | 4 | |a Metabolic Diseases | |
| 650 | 4 | |a Pathology, Molecular | |
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Datensatz im Suchindex
| _version_ | 1810687765712470016 |
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| adam_text |
Molecular Biology of
Membrane Transport
Disorders
Edited by
Stanley G Schultz
University of Texas Medical School at Houston
Houston, Texas
Thomas E Andreoli
University of Arkansas College of Medicine
Little Rock, Arkansas
Arthur M Brown
Case Western Reserve University
Cleveland, Ohio
Douglas M Fambrough
The Johns Hopkins University
Baltimore, Maryland
Joseph F Hoffman
Yale University School of Medicine
New Haven, Connecticut
and
Michael J Welsh
University of Iowa College of Medicine
Iowa City, Iowa
Plenum Press • New York and London %
Contents
1 Membrane TVaffic and Compartmentalization within the Secretory Pathway
Jennifer Lippincott-Schwartz
1 1 Introduction 1
1 2 Compartmental Organization 1
121 The Endoplasmic Reticulum 1
122 The Intermediate Compartment 2
123 The Golgi Complex 2
1 3 Characteristics of Transport Intermediates 3
131 Cargo Specificity: Bulk Flow versus Concentration 3
132 Morphological and Functional Characteristics of Transport Intermediates: Roles of Vesicles,
Organelles, and Tubules 3
1 4 Molecular Mechanisms for Transport 5
141 Vesicle Formation 5
142 Membrane Targeting and Fusion 7
1 5 Conclusions 8
References 8
2 Cell Adhesion
Jonathan Covault
2 1 Introduction 11
2 2 Early Studies-of Cell Adhesion 11
2 3 Cell Adhesion Molecular Families 12
231 Cadherins 13
232 Immunoglobulin (Ig)-Related CAMs 20
233 Integrins 21
234 Selectins 22
2 4 Cell Adhesion Molecules Do More than Bind Cells Together 22
2 5 Cell Adhesion Processes Typically Involve Multiple CAMs 22
251 Cell Junctional Complexes 22
252 Leukocyte Adhesion 23
253 Adhesion and Neural Development 25
2 6 Disorders of Cell Adhesion in Disease Processes 30
261 CAM Involvement in the Intracellular Uptake of Viruses and Parasites 30
262 Altered Cell Adhesion and Cancer 31
263 Disorders of Leukocyte Adhesion 32
264 Disorders of Neural Development 32
2 7 Potential Therapeutic Modulation of CAM Activities 33
2 8 Summary 34
References 35
xi
xii Contents
3 The Membrane-Associated Cytoskeleton and Exoskeleton
Robert J Bloch
3 1 Introduction 47
3 2 Cytoskeletal-Membrane Interactions 47
321 Membrane Skeleton 47
322 Focal Adhesions 55
3 3 Interactions of the Exoskeleton with the Plasma Membrane 57
331 The Basal Lamina 57
332 Fibronectin 59
333 Integrins as Receptors for Extracellular Proteins 59
334 Other Extracellular Matrix Receptors 61
335 Membrane Domains and the Exoskeleton 62
3 4 Concluding Remarks 62
References 63
4 Methods of Reconstitution of Ion Channels
William P Dubinsky and Otilia Mayorga-Wark
4 1 Introduction 73
411 Resolution-Reconstitution Approaches to Study Ion Channels 73
412 General Strategies for the Reconstitution of Ion Channels 74
413 Vesicles versus Bilayers 75
4 2 Characterization and Isolation of an Epithelial K Channel 75
421 Identifying the Ion Conductant in the Intact Tissue or Cell 75
422 Reconstitution of the Necturus Basolateral K Channel 75
423 Characterization of the Reconstituted Basolateral K Channel 76
424 Purification of the Channel 80
4 3 Characterization of Ion Channels in Subcellular Membranes 81
431 Tracheal Apical Membrane Permeabilities 81
432A Tracheal Subcellular Membrane Anion Channel 82
4 4 Confirmation of Ion Channel Activity 82
441 Cystic Fibrosis Transmembrane Conductance Regulator 82
442 Protein-Replacement Therapy 83
References T T 83
5 Permeability and Conductance in Ion Channels: A Primer
David C Dawson
5 1 Introduction 87
5 2 Measurable Properties of Ion Channels: Conductance and Permeability 87
521 Conductance: Ohm's Law 87
522 Permeability: Tracer Flows 89
523 The Flux-Ratio Equation 90
524 Conductance/Permeability Relation 91
525 Ion Gradients, Electromotive Forces, and Reversal Potential 91
5 3 The Nernst-Planck Constant Field Channel 94
531 Conductance and Permeability 94
532 Equilibrium Selectivity 95
533 Nonequilibrium Selectivity 96
534 i-V Relations for the Nemst-Planck Channel 97
535 The Definition of Conductance: Slope vs Chord 99
5 4 Channels that Bind Ions: Rate Theory Interpretations of Conductance and Permeability 101
541 Beyond Nernst-Planck: Ion-Channel and Ion-Ion Interactions 101
542 Rate Theory and Flows 101
543 Single-Site, One-Ion Channel 102
Contents xi
544 Selectivity: Conductance Ratios and Permeability Ratios 105
545 Multiion Channels and the Interactions of Permeating Ions 107
References 109
6 The Lactose Permease of Escherichia coli: An Update
H Ronald Kaback
6 1 Lac Permease Contains 12 Transmembrane Domains in a-Helical Conformation Ill
6 2 Lac Permease Is Functional as a Monomer 113
6 3 Site-Directed Mutagenesis 115
631 Few Amino Acid Residues Are Essential for Activity 115
632 Cys Residues and Construction of a Functional Permease Devoid of Cys Residues 115
633 Cys-Scanning Mutagenesis 116
6 4 Helix Packing in the C-Terminal Half of the Permease 116
641 Functional Interactions between Putative Intramembrane Charged Residues 116
642 Site-Directed Excimer Fluorescence 118
6 5 Ligand Binding Induces Widespread Conformational Changes 120
6 6 Lactose-Coupled H+Translocation 120
67A Novel Approach to Crystallization of Hydrophobic Membrane Proteins 122
6 8 Insertion of Permease into the Membrane 122
681 Membrane Insertion and Stability 122
682 Expression of Lac Permease in Fragments as a Probe for Membrane-Spanning Domains 123
683 Membrane Insertion May Involve Multiple Mechanisms 124
6 9 Summary and Concluding Remarks 124
References 125
7 Structure and Function of Voltage-Gated Ion Channels
William A Catterall
7 1 Introduction 129
7 2 Ion Channel Subunits 129
721 Structures of Sodium Channel Subunits 129
722 Functional Expression of Sodium Channel Subunits 130
723 Structures of Calcium Channel Subunits 130
724 Functional Expression of Calcium Channels 131
725 Structures of Potassium Channel Subunits 132
726 Functional Expression of Potassium Channel Subunits 133
7 3 Structure and Function of the Voltage-Gated Ion Channels 133
731 Voltage-Dependent Activation 133
732 Ion Conductance 135
733 Inactivation 138
7 4 Naturally Occurring Mutations in Human Sodium Channel Genes 141
741 Hyperkalemic Periodic Paralysis 141
742 Paramyotonia Congenita 141
743 Molecular Mechanisms of the Periodic Paralyses 141
7 5 Conclusion 142
References 142
8 Nicotinic Receptors in the Central Nervous System
C K lfune and Joe Henry Steinbach
8 1 Introduction 147
8 2 Structure: How Many Kinds of Nicotinic Receptors? 147
821 Primary Amino Acid Sequence and Membrane Disposition 147
822 The Ion Channel 148
823 The Quaternary Structure Is Pentameric 149
xiv Contents
824 Neuronal Nicotinic Receptor Subunits: Primary Sequences 149
825 Neuronal Nicotinic Receptor Subunits: Assembly by Expression 149
826 Neuronal Nicotinic Receptor Subunits: Assembly in Vivo 150
827 Receptor Structure: A Summary 151
8 3 Pharmacology of Neuronal Nicotinic Receptors 151
831 Sites of Drug Action 151
832 Nicotinic Agonists and Antagonists 152
833 Receptor Structure and Pharmacological Properties 153
834 Correspondence between Nicotinic Receptors on Cells and Expressed Subunits 154
835 Summary of Pharmacology 154
8 4 Desensitization, Modulation, and Endogenous Ligands 154
841 Desensitization 154
842 Modulation of Neuronal Receptor Functions 155
843 Endogenous Ligands: Peptides, Steroids, and Ca2+ 155
844 Summary of Desensitization and Modulation 156
8 5 Physiology: What Do Nicotinic Receptors in the CNS Do? 156
851 Neuronal Nicotinic Receptor Function 156
852 Postsynaptic Nicotinic Responses in the CNS 156
853 Nicotinic Agents and Release: Presynaptic Receptors 157
854 Physiology: What Might Nicotinic Receptors Do? 158
855 Summary of Physiology 159
8 6 Disorders of Neuronal Nicotinic Receptor Function 159
861 Nicotine Dependence 160
862 Alzheimer's Disease 161
863 Parkinson's Disease 161
864 Schizophrenia 161
865 Summary of Disorders of Neuronal Nicotinic Receptors 161
8 7 Overall Summary 161
References 162
9 GABA-, Glycine-, and Glutamate-Gated Channels in Neurological and Psychiatric Illness
Mark G Darlison and Robert J Harvey
9 1 General Introduction and Scope of the Chapter 169
9 2 GABA-, Glycine, and Glutamate-Gated Ion Channels 170
921 GABAa Receptors and Their Polypeptides 170
922 Glycine Receptors and Their Polypeptides 170
923 Glutamate Receptors and Their Polypeptides 171
9 3 The Genes of GABA-, Glycine, and Glutamate-Gated Ion Channels 172
931 GABAa and Glycine Receptor Genes 172
932 Glutamate Receptor Genes 173
9 4 Chromosomal Locations of the Genes that Encode GABA-, Glycine-, and Glutamate-Gated Ion-Channel
Polypeptides 173
941 The Mapping of Human GAB Aa Receptor Genes 173
942 GABAa Receptor Genes and Neurological/Psychiatric Illness 174
943 The Mapping of Human Glycine Receptor Genes 175
944 Glycine Receptor Genes and Neurological/Psychiatric Illness 175
945 The Mapping of Human Glutamate Receptor Genes 175
946 Glutamate Receptor Genes and Neurological/Psychiatric Illness 176
9 5 Concluding Remarks 176
References 177
10 The Genetic and Physiological Basis of Malignant Hyperthermia
David H MacLennan, Michael S Phillips, and Yilin Zhang
10 1 Introduction 181
10 2 Malignant Hyperthermia 181
10 2 1 Human Malignant Hyperthermia 181
Contents *v
10 2 2 Diagnostic Tests for Malignant Hyperthermia 182
10 2 3 Porcine Malignant Hyperthermia 184
10 3 The Physiological and Genetic Basis for Malignant Hyperthermia 185
10 3 1 The Ca2+ Release Channel 185
10 3 2 Excitation-Contraction Coupling 186
10 3 3 The Role of the Ca2+Release Channel in Malignant Hyperthermia 188
10 3 4 Dantrolene and Ryanodine 189
10 3 5 Linkage of the RYR1 Gene to Malignant Hyperthermia in Humans and Swine 189
10 3 6 Malignant Hyperthermia Mutations in Swine 190
10 3 7 Malignant Hyperthermia Mutations in Humans 190
10 3 8 Searching for a Second MHS Locus 191
10 4 Central Core Disease 192
10 5 King-Denborough Syndrome 193
10 6 Future Directions 193
References 194
11 Stretch-Activated Ion Channels
Henry Sackin
11 1 Introduction 201
11 2 Functional Classification of S A Channels 201
11 2 1 SA Cation Channels 201
11 2 2 SA Potassium Channels 206
11 2 3 SA Anion Channels 208
11 2 4 SA Nonselective Channels and Stretch-Inactivated Channels 208
11 3 The Mechanics of Stretch-Activation 209
11 3 1 Properties Common to S A Channels 209
11 3 2 Theories of Mechanosensitive Channel Activation 212
11 4 Do Mechanosensitive Channels Mediate Cellular Currents? 217
11 4 1 SA-cat, SA-non Channels and Macroscopic Currents 217
11 4 2 SAK Channels and Macroscopic Currents 218
11 4 3 Concluding Remarks 219
References 220
12 Cation Transport ATEases
Douglas M Fambrough and Giuseppe Inesi
12 1 Introduction 223
12 2 Evolution of the Major Families of P-Type ATPases 223
12 3 Subcellular Distributions of P-Type ATPases 225
12 4 Ca2+Transport ATPases 226
12 4 1 Intracellular Ca2+ Transport ATPases 226
12 4 2 Protein Structure 226
12 4 3 Catalytic and Transport Cycle 227
12 4 4 The Energetics of the Catalytic and Transport Cycle 229
12 4 5 Topology of Functional Domains within the ATPase Structure 229
12 4 6 Long-Range Linkage between Phosphorylation and Cation Binding Sites 230
12 4 7 Regulation of Intracellular Ca2+ Transport 231
12 4 8 Thapsigargin, a Specific Inhibitor of Intracellular Ca2+-ATPases 231
12 4 9 Disorders Involving Intracellular Ca2+-ATPases 231
12 4 10 The Plasmalemmal Ca2+ Transport ATPases 231
12 5 Na+,K+-ATPases, the Sodium Pumps 232
12 5 1 Structure 233
12 5 2 Mechanism of Cation Transport 233
12 5 3 Na+,K+-ATPase Regulation 233
12 5 4 Involvement of the Na+,K+-ATPase in Disease 234
12 6 H+,K+-ATPases 235
12 7 Cu2+-Transporting ATPases in Menkes Disease and Wilson Disease 235
xvi Contents
12 8 Summary 236
References 236
13 Multidrug Resistance Transporter
Michael M Gottesman, Suresh V Ambudkar, Marilyn M Cornwell, Ira Pastan, and Ursula A Germann
13 1 Introduction 243
13 1 1 Physiology of Multidrug Resistance 243
13 1 2 Cloning of the MDR Genes 243
13 2 The ABC Superfamily of Transporters 244
13 3 General Mechanisms of Action 245
13 4 Substrate-Transporter Interactions 246
13 4 1 Photoaffinity Labeling 246
13 4 2 Mutants 247
13 5 ATP Binding/Utilization 248
13 5 1 Mutational Analysis 248
13 5 2 Biochemistry 249
13 6 Regulation of MDR Gene Expression 250
13 6 1 Expression in Normal Tissues and Cultured Cells 250
13 6 2 Functional Studies of MDR Regulatory Sequences 251
13 7 Posttranslational Modifications 252
13 7 1 Glycosylation 252
13 7 2 Phosphorylation 252
13 8 Relevance of Molecular Biology to Human Disease 253
References 253
14 Molecular Studies of Members of the Mammalian Na+/H+ Exchanger Gene Family
Mark Donowitz, Susan A Levine, C H Chris Yun, Steven R Brant, Samir Nath, Jeannie Yip, Freddie Kokkie,
Sandra Hoogerwerf, Jami Montgomery, Laurence Bianchini, Jacques Pouyssegur, and Chung-Ming Tse
14 1 Introduction 259
14 2 Molecular Identification of Na+/H+ Exchanger Gene Family 260
14 3 Tissue and Cellular Distribution of Na+/H+ Exchanger Message and Protein 260
14 4 Topology ofthe Mammalian NHE Gene Family: Two Functional Domains 261
14 5 Glycosylation 262
14 6 Oligomerization 263
14 7 Amiloride Binding Domain 263
14 8 Kinetics 264
14 8 1 Na+Kinetics 264
14 8 2 H+ Kinetics 265
14 8 3 Steady-State pHj and Initial Rate of Na+/H+-Exchange 265
14 9 Regulation 265
14 9 1 Short-Term Regulation 266
14 9 2 Effect of Cell Type on the NHE Plasma Membrane Location and Protein Kinase Regulation 269
14 9 3 Long-Term Regulation 269
14 10 NHE1 Is the Housekeeping Isoform Na+/H+ Exchanger and NHE3 Is the Brush Border Na+/H+
Exchanger of Intestinal and Renal Epithelial Cells 272
14 11 Concluding Remarks and Future Studies 272
References 272
15 Mitochondrial Transport Processes
Ronald S Kaplan
15 1 Introduction 277
15 2 Identification, Metabolic Significance, and Organ Distribution of the Major Mitochondrial Transporters 277
15 3 Molecular Properties of Mitochondrial Transport Proteins 278
15 3 1 Purification and Functional Reconstitution ~: 278
15 3 2 Primary Structure 280
Contents xvi'
15 3 3 Membrane Topology 281
15 3 4 Dimeric Nature 283
15 3 5 Kinetic Mechanism 284
15 3 6 The Molecular/Chemical Bases for Transporter Function 284
15 4 Mitochondrial Transporter Genes 287
15 4 1 The Number of Genes Encoding a Given Transporter 287
15 4 2 Gene Structure 287
15 4 3 Differential Expression of Transporter Genes 288
15 5 Hormonal Regulation of Transporter Function 289
15 6 Alteration of Mitochondrial Transporter Function in Disease, Development, and Aging 290
15 6 1 Heart Disease, Primary Biliary Cirrhosis, and Other Mitochondrial Myopathies 290
15 6 2 Cancer 291
15 6 3 Diabetes Mellitus 291
15 6 4 Other Diseases 293
15 6 5 Development and Aging 293
15 7 Summary 293
References 294
16 Receptor-Mediated Endocytosis
Victoria P Knutson, Patricia V Donnelly, Maria M Lopez-Reyes, and Yvonne L O Balba
16 1 Introduction 303
16 2 Receptor-Mediated Endocytosis: General Processes 303
16 2 1 Plasma Membrane Processes 303
16 2 2 Endosomes 304
16 3 Endocytosis and Nutrient Uptake 306
16 3 1 The Low-Density Lipoprotein Receptor 306
16 3 2 The Transferrin Receptor 307
16 4 Scavenger Receptor Systems 308
16 4 1 The Carbohydrate-Binding Receptors 308
16 4 2 The a2-Macroglobulin/Lipoprotein Receptor-Related Protein Receptor 309
16 5 Endocytosis in Immune Function: Antigen Presentation through the MHC Class II Molecule 310
16 6 Endocytosis in Neurotransmission 311
16 7 Endocytosis in Signal Transduction: The Receptor-Linked Tyrosine Kinases 312
16 7 1 Ligand Sequestration and Degradation 313
16 7 2 Dephosphorylation of the Receptor 313
16 7 3 Endosomal RTKs as Signal Transducers 313
16 8 Summary 314
References 314
17 Signal TVansduction by G Protein-Coupled Receptors
Mariel Birnbaumer and Lutz Birnbaumer
17 1 Introduction 321
17 2 G Protein-Coupled Receptors 321
17 2 1 Subfamilies 323
17 2 2 Naturally Occurring Receptor Mutations 334
17 23G Protein Activation by Non-Heptahelical Receptors 340
17 3 The G Proteins 340
17 3 1 The Regulatory Cycle—Mechanism of Action of a Receptor 341
17 3 2 |J-y Dimers as Potential Activators of a Subunits by Transphosphorylation 343
17 33G Protein Structure 343
17 3 4 Patterns of G Protein Subunit Expression 347
17 3 5 The a Subunit: Structure and Function 347
17 4 Functional Correlates to Molecular Diversity in G Proteins and Effectors 352
17 4 1 Multiple Effectors for a Single G Protein 352
17 4 2 Signaling through ($-y Dimers 353
xviii Contents
17 4 3 Molecular and Functional Diversity of Adenylyl Cyclases 353
17 4 4 Phospholipase C 355
17 5 Subunit Concentrations that Cause Half-Maximal Effects—Role of GAP Activity of the Effector 356
17 6 Specificity of Receptors for G Proteins—Dual Coupling Phenomena 356
17 7 Conclusion 357
References 359
18 Egg Membranes during Fertilization
Laurinda A Jaffe
18 1 Introduction 367
18 2 Membrane Fusion Events at the Egg Plasma Membrane 367
18 3 Electrical Regulation of Sperm-Egg Fusion and Entry of the Sperm Nucleus into the Egg Cytoplasm 367
18 4 Ionic Mechanisms of the Fertilization Potential 369
18 5 Intracellular Free Calcium Increase at Fertilization 369
18 6 Other Changes in Egg Membrane Transport at Fertilization 370
18 7 Signal Transduction during Sperm Interaction with the Egg Plasma Membrane 371
18 8 Structural Changes in the Egg's Endoplasmic Reticulum at Fertilization 372
18 9 Development of Egg Membranes during Oocyte Maturation 372
18 10 Summary 373
References 373
19 Cell Volume Regulation
John R Sachs
19 1 Introduction 379
19 2 Properties of Cell Water and Osmotic Phenomena 381
19 2 1 Osmotic Equilibrium 381
19 2 2 Osmotic Equilibrium in More Complicated Cells 382
19 2 3 Water Transport 383
19 3 Volume-Regulated Inorganic Ion Transport Pathways 385
19 3 1 Swelling-Activated K and CI Channels 386
19 3 2 K-Cl Cotransport 388
19 3 3 K-H Exchange Coupled with C1-HC03 Exchange 390
19 3 4 Na-Ca Exehange 390
19 3 5 Na, K, 2C1 Cotransporr 391
19 3 6 Na-H Exchange 392
19 4 Role of Organic Osmolytes in Cell Volume Regulation 392
19 5 Isovolumetric Volume Regulation and Volume Regulation in Isotonic Solutions 394
19 6 Sensors and Signal Transduction 395
19 6 1 The Set Point 395
19 6 2 Macromolecular Crowding 396
19 6 3 Phosphorylation-Dephosphorylation Events 397
19 6 4 Signal Transduction 399
19 6 5 Cytoskeleton 400
19 7 Summary 401
References 402
20 Regulation of Cell pH
Orson W Moe and Robert J Alpern
20 1 Introduction 407
20 2 Acid-Base Chemistry 407
20 3 Measurement of Intracellular pH 407
20 3 1 Distribution of Weak Acids and Bases 407
20 3 2 Magnetic Resonance Spectroscopy 408
20 3 3 pH-Sensitive Microelectrodes 408
20 3 4 pH-Sensitive Dyes 408
Contents xlx
20 4 Cell pH Regulation 409
20 4 1 Physicochemical Buffering 409
20 4 2 Plasma Membrane Transporters 410
20 4 3 Regulation of H Transporter Activity 415
20 4 4 Integrated Cell pH Regulation 417
20 5 Regulation of Cell Function by pH 418
20 5 1 Role of Cell pH in Growth Regulation 418
20 5 2 Interaction of Cell pH and Cell Ca 418
20 5 3 Role of pH in Receptor-Mediated Endocytosis 419
References 420
21 Regulation of Intracellular Free Calcium
William B Busa
21 1 Overview and Historical Perspective 427
21 2 Physical Constraints on [Ca2+]j 428
21 2 1 The Electrochemical Gradient for Ca2+ across the Plasma Membrane 428
21 2 2 Physicochemical Buffering 428
21 3 Calcium Fluxes across Membranes 430
21 3 1 Plasma Membrane Ca2+ Channels 430
21 3 2 Plasma Membrane Ca2+Exchangers and Pumps 433
21 3 3 Intracellular Ca2+Pumps and Channels 434
21 4 Ca2+Dynamics in Nonexcitable Cells 438
21 4 1 [Ca2+]j Waves 438
21 4 2 [Ca2+]j Oscillations 439
21 5 Conclusion 441
References 441
22 Sodium Transport by Epithelial Cells
Lawrence G Palmer
22 1 Introduction 447
22 1 1 The Koefoed-Johnsen and Ussing Model 447
22 1 2 Applicability of the Model 447
22 2 The Components of the System 448
22 2 1 The Na/K Pump 448
22 2 2 Na Channels 449
22 23K Channels 452
22 2 4 Rate-Determining Steps 455
22 2 5 Conclusions 455
22 3 Regulation of Na Transport 455
22 3 1 Hormonal Regulation 455
22 3 2 Cellular Homeostasis 459
22 3 3 Conclusions 461
22 4 Counterion Movements in Na-Transporting Epithelia 461
22 4 1 Reabsorption of CI- 461
22 4 2 Proton Secretion 463
22 43K Secretion 463
22 4 4 Conclusions 464
22 5 Summary 464
References 464
23 Gastric Acid Secretion: The H,K-ATPase and Ulcer Disease
George Sachs, Jai Moo Shin, Krister Bamberg, and Christian Pr'tnz
23 1 Introduction 469
23 2 The Acid Barrier 470
xx Contents
23 3 The Acid Pump 472
23 3 1 Stimulation of Acid Secretion 472
23 3 2 The Acid Pump and Stimulation 473
23 3 3 Coupling of Hydrolysis and Transport 473
23 3 4 The Membrane Domain of the H,K-ATPase 474
23 3 5 The Ion Transport Pathway of the Gastric H,K-ATPase 476
23 3 6 Ion Transport Inhibitors 476
23 3 7 Turnover of the Acid Pump 479
23 3 8 Membrane Targeting of the Acid Pump 479
23 4 Clinical Use of Pump Inhibitors 479
23 5 H pylori and the Future of Peptic Ulcer Treatment 480
References 481
24 Cell Death
Thomas J Burke and Robert W Schrier
24 1 Introduction 485
24 2 Adenine Nucleotide Metabolism 485
24 2 1 Cellular Consequences of ATP Depletion 486
24 2 2 MgATP and Cell Protection 489
24 3 Phospholipase Activation 489
24 3 1 Calcium Dependent 490
24 3 2 Calcium Independent 490
24 3 3 Inhibition of PLA2 490
24 3 4 pH Modulation 490
24 4 Proteases 491
24 4 1 Classification of Proteases 491
24 4 2 Calpain 491
24 4 3 Protease Inhibitors 492
24 5 Cell Polarity/Cytoskeleton 492
24 5 1 Cell Polarity 492
24 5 2 Actin Cytoskeleton 492
24 5 3 Cell Swelling/Vacuoles 493
24 6 Adhesion Molecules 493
24 7 Oxygen Radicalsrr- 494
24 7 1 Intracellular Generation 494
24 7 2 Cyclooxygenases 495
24 7 3 Xanthine/Xanthine Oxidase Production of Oxygen Radicals 495
24 7 4 Extracellular Sources 495
24 7 5 Lipid Peroxidation 496
24 7 6 Oxygen Radical Scavengers 497
24 8 Membrane Damage 498
24 8 1 The Permeability Barrier 498
24 8 2 Fatty Acid Release 498
24 9 Apoptosis 499
24 9 1 DNA Laddering 499
24 9 2 Gene Expression 499
24 10 Tubular Epithelial Regeneration 500
24 10 1 Growth Factors 500
24 10 2 Heat-Shock Proteins 501
24 11 Summary 501
References 501
25 Genetic Variants of Erythrocytes
John C Parker
25 1 Introduction 507
25 2 Band 7 2b Deficiency (Congenital Hydrocytosis) 507
Contents xxi
25 3 Congenita] Increase in Red Cell Pump Sites 508
25 4 Hemoglobinopathies 509
25 5 Congenital Alteration of Urea Transport 513
25 6 Mutants of Band 3 that Affect Anion Exchange 513
References 514
26 Disorders of Biliary Secretion
Piotr Zimniak and Roger Lester
26 1 Introduction 519
26 2 Biliary Secretion 519
26 3 Active Transport 521
26 4 F-, V-, and P-ATPases 522
26 4 1 F-ATPases 523
26 4 2 V-ATPases 523
26 4 3 P-ATPases 524
26 5 Primary Transport of Organic Compounds 525
26 5 1 P-Glycoproteins 525
26 5 2 Bile Acid Transporters 527
26 5 3 Transporters of Non-Bile Acid Organic Anions 529
26 6 Transport Defects 530
26 7 Dubin-Johnson Syndrome 531
26 8 Animal Models 532
26 9 Possible Molecular Basis of Dubin-Johnson Syndrome and Similar Conjugated Hyperbilirubinemias 534
26 9 1 Extrahepatic MOAT 534
26 9 2 Hepatic MOAT 534
26 9 3 Possible Primary Defects in the Dubin-Johnson Syndrome 535
26 10 Conclusion 000
References 535
27 The Pathophysiology of Diarrhea
Joseph H Sellin
27 1 Introduction 541
27 2 Classifications of Diarrhea 541
27 3 Basic Considerations in Ion Transport 541
27 3 1 Segmental Heterogeneity 541
27 3 2 Basics of Electrogenic Chloride Secretion 543
27 3 3 NHEs: Sodium-Hydrogen Exchangers 545
27 3 4 Bicarbonate 545
27 4 Regulation of Ion Transport 547
27 4 1 Extracellular Regulation 547
27 4 2 Intracellular Mediators 551
27 4 3 Homocellular Regulation 552
27 5 Case Studies of Diarrhea 552
27 5 1 Cholera, the Paradigm of Secretory Diarrhea 552
27 5 2 Inflammatory Bowel Disease 555
27 5 3 AIDS 557
References 559
28 The Myasthenic Syndromes
Henry J Kaminski and Robert L Ruff
28 1 Introduction 565
28 2 Overview of Neuromuscular Physiology 565
28 2 1 The Neuromuscular Junction Is a Chemical Synapse with Acetylcholine as the Transmitter 565
28 2 2 Transmitter Release Requires Calcium Influx 565
28 2 3 Calcium Entry Triggers Synaptic Vesicle Fusion 566
xxii Contents
28 2 4 ACh Diffuses across the Synaptic Cleft to Activate AChRs 566
28 2 5 Postsynaptic Membrane Specialization 566
28 2 6 The Safety Factor for Neuromuscular Transmission 567
28 3 Structure and Function of the AChR 568
28 3 1 The AChR Is an Allosteric Pentameric Glycoprotein 568
28 3 2 Differences between AChR Isoforms 569
28 3 3 Ion Passage through the AChR 569
28 3 4 Molecular Structure of the AChR Subunits 570
28 3 5 ACh Binding Site 570
28 3 6 Lining of the Ion Pore 570
28 3 7 Effect of Site-Directed Mutagenesis on Ion Passage 570
28 3 8 Effect of Site-Directed Mutagenesis on Open Time 570
28 4 Congenital Disorders of Neuromuscular Transmission 571
28 4 1 Introduction 571
28 4 2 Presynaptic Disorders 571
28 4 3 Acetylcholinesterase Deficiency 573
28 4 4 Abnormal Development of the Postsynaptic Membrane 573
28 4 5 Defects of AChR Function 574
28 4 6 Identification of the Patients with CDNT 576
28 5 Myasthenia Gravis 577
28 5 1 Autoimmune Pathogenesis 577
28 5 2 Possible Explanations for Differential Involvement of Muscles by MG 579
28 5 3 Diagnosis 581
28 5 4 Treatment 583
28 6 Lambert-Eaton Myasthenic Syndrome 584
28 6 1 Introduction 584
28 6 2 Electrophysiologic Findings 584
28 6 3 Autoimmune Pathogenesis 585
28 6 4 Diagnosis 585
28 6 5 Treatment 585
28 7 Summary 586
References 586
29 Genesis of Cardiac Arrhythmias: Roles of Calcium and Delayed Potassium Channels in the Heart
Robert S Kass
29 1 Introduction 595
29 2 Repolarization of the Cardiac Action Potential: Crucial Roles of Calcium and Potassium Channels 595
29 3 The Importance of Potassium Channel Currents in Regulation of the Action Potential Duration 596
29 4 Delayed Potassium Channel Currents in the Heart: Multiple Channel Types? 596
29 5 Neuromodulation of Cardiac IK 597
29 6 (J-Adrenergic Stimulation 597
29 7 Multiple Roles of Calcium Movement during the Action Potential Plateau 597
29 8 Defining the Problem: Two Classes of Calcium-Dependent Arrhythmias 599
29 9 Acquired LQTS: Is There Drug Induction or Genetic Susceptibility? 600
29 10 Congenital LQTS: A Molecular Hypothesis 601
References 603
30 Cystic Fibrosis
Michael J Welsh
30 1 Introduction 605
30 2 Clinical Manifestations of Cystic Fibrosis 605
30 3 Abnormalities of EpitheliaLElectrolyte Transport 606
30 3 1 Electrolyte Transport by Airway Epithelia 606
30 3 2 Sweat Gland 607
30 3 3 Abnormal Intestinal Electrolyte Transport 608
30 3 4 Apparent Anomalies in CI-Transport 608
Contents xxiii
30 4 The CFTR Gene 608
30 5 CFTR 609
30 5 1 Predicted Structure of CFTR 609
30 5 2 Localization of CFTR 609
30 5 3 Topology of CFTR 609
30 6 Chloride Channel Function of CFTR 610
30 6 1 Evidence that CFTR Is a CI-Channel 610
30 6 2 The MSDs Contribute to the Formation of the CI- Channel Pore 611
30 7 Regulation of CFTR by the R Domain 611
30 7 1 Identification of Phosphorylated Sites in CFTR 613
30 7 2 Functional Consequences of Mutating Phosphorylation Sites in CFTR 614
30 8 Regulation of CFTR by the NBDs 615
30 9 Mechanisms by Which CF-Associated Mutations Cause Channel Dysfunction 617
30 9 1 Class I Mutations: Defective Protein Production 617
30 9 2 Class II Mutations: Defective Protein Processing 617
30 9 3 Class III Mutations: Defective Regulation 618
30 9 4 Class IV Mutations: Defective Conduction 618
30 9 5 Relationship between Genotype and Clinical Phenotype 618
30 10 Summary 619
References 619
31 Familial Periodic Paralysis
Louis Ptacek and Robert C Griggs
31 1 Introduction 625
31 2 Disease Classification 625
31 2 1 Sodium Channel Disorders of Muscle 625
31 2 2 Calcium Channel Disorder of Muscle 633
31 2 3 Chloride Channel Periodic Paralysis 635
31 2 4 Disorders of Unknown Pathogenesis 637
31 2 5 Episodic Ataxias 638
31 3 Implications for Future Work 638
31 3 1 Diagnosis 638
31 3 2 Treatment 638
31 4 Summary rr 639
References 639
32 Disorders of Renal Tabular Transport Processes
W Brian Reeves and Thomas E Andreoli
32 1 Introduction 643
32 2 Aminoaciduria 643
32 2 1 Cystinuria 644
32 2 2 Hartnup Disorder 644
32 2 3 Iminoglycinuria 645
32 3 Renal Glycosuria 645
32 4 Nephrogenic Diabetes Insipidus 646
32 4 1 Pathogenesis of NDI 647
32 4 2 Treatment of NDI 649
32 5 Renal Tubular Acidosis 649
32 5 1 Proximal Tubule Bicarbonate Transport 649
32 5 2 Distal Tubule Proton Transport 651
32 5 3 Role of Urinary Buffers in Renal Acidification 651
32 5 4 Proximal RTA 652
32 5 5 Distal RTA 653
References 655
Index 659 |
| any_adam_object | 1 |
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| id | DE-604.BV011033327 |
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| indexdate | 2024-09-20T04:26:57Z |
| institution | BVB |
| isbn | 0306451646 |
| language | English |
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| physical | XXIII, 681 S. graph. Darst. |
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| spelling | Molecular biology of membrane transport disorders ed. by Stanley G. Schultz ... New York [u.a.] Plenum Press 1996 XXIII, 681 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Biofisica da membrana celular larpcal Biofisica larpcal Membranen gtt Pathologie gtt Stoftransport gtt Biological Transport Ion Channels Membrane disorders Membranes physiology Membranes physiopathology Metabolic Diseases Pathology, Molecular Membrantransport (DE-588)4038575-9 gnd rswk-swf Molekularpathologie (DE-588)4170396-0 gnd rswk-swf Funktionelle Störung (DE-588)4237448-0 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Membrantransport (DE-588)4038575-9 s Funktionelle Störung (DE-588)4237448-0 s DE-604 Molekularpathologie (DE-588)4170396-0 s Schultz, Stanley G. Sonstige oth HEBIS Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007388248&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Molecular biology of membrane transport disorders Biofisica da membrana celular larpcal Biofisica larpcal Membranen gtt Pathologie gtt Stoftransport gtt Biological Transport Ion Channels Membrane disorders Membranes physiology Membranes physiopathology Metabolic Diseases Pathology, Molecular Membrantransport (DE-588)4038575-9 gnd Molekularpathologie (DE-588)4170396-0 gnd Funktionelle Störung (DE-588)4237448-0 gnd |
| subject_GND | (DE-588)4038575-9 (DE-588)4170396-0 (DE-588)4237448-0 (DE-588)4143413-4 |
| title | Molecular biology of membrane transport disorders |
| title_auth | Molecular biology of membrane transport disorders |
| title_exact_search | Molecular biology of membrane transport disorders |
| title_full | Molecular biology of membrane transport disorders ed. by Stanley G. Schultz ... |
| title_fullStr | Molecular biology of membrane transport disorders ed. by Stanley G. Schultz ... |
| title_full_unstemmed | Molecular biology of membrane transport disorders ed. by Stanley G. Schultz ... |
| title_short | Molecular biology of membrane transport disorders |
| title_sort | molecular biology of membrane transport disorders |
| topic | Biofisica da membrana celular larpcal Biofisica larpcal Membranen gtt Pathologie gtt Stoftransport gtt Biological Transport Ion Channels Membrane disorders Membranes physiology Membranes physiopathology Metabolic Diseases Pathology, Molecular Membrantransport (DE-588)4038575-9 gnd Molekularpathologie (DE-588)4170396-0 gnd Funktionelle Störung (DE-588)4237448-0 gnd |
| topic_facet | Biofisica da membrana celular Biofisica Membranen Pathologie Stoftransport Biological Transport Ion Channels Membrane disorders Membranes physiology Membranes physiopathology Metabolic Diseases Pathology, Molecular Membrantransport Molekularpathologie Funktionelle Störung Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=007388248&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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