Pharmacology of ionic channel function: activators and inhibitors ; [with 25 tables]
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Berlin [u.a.]
Springer
2000
|
| Schriftenreihe: | Handbook of experimental pharmacology
147 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XXXI, 662 S. Ill., graph. Darst. |
| ISBN: | 3540661271 |
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| 245 | 1 | 0 | |a Pharmacology of ionic channel function |b activators and inhibitors ; [with 25 tables] |c contributors S. Adachi-Akahane ... Ed.: M. Endo ... |
| 264 | 1 | |a Berlin [u.a.] |b Springer |c 2000 | |
| 300 | |a XXXI, 662 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 1 | |a Handbook of experimental pharmacology |v 147 | |
| 650 | 7 | |a Ion Channels |2 cabt | |
| 650 | 7 | |a Pharmacology |2 cabt | |
| 650 | 7 | |a Agonisten |2 gtt | |
| 650 | 7 | |a Inhibitie |2 gtt | |
| 650 | 7 | |a Ionenkanalen |2 gtt | |
| 650 | 4 | |a Calcium Channel Blockers |x pharmacology | |
| 650 | 4 | |a Cell Membrane |x physiology | |
| 650 | 4 | |a Ion Channels |x antagonists & inhibitors | |
| 650 | 4 | |a Ion Channels |x physiology | |
| 650 | 4 | |a Ion channels | |
| 650 | 4 | |a Ion channels |x Effect of drugs on | |
| 650 | 4 | |a Membrane Potentials |x physiology | |
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Datensatz im Suchindex
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| adam_text | Contents
Section I: Voltage Dependent Ion Channels
A. Voltage Dependent Na Channels 1
CHAPTER 1
Structure and Functions of Voltage Dependent Na+ Channels
K. Imoto. With 3 Figures 3
A. Introduction 3
B. General Architecture 4
C. a Subunit 4
I. Brain Types I, II, and III 7
1. Brain Type II/IIA 7
2. Brain Type I 8
3. Brain Type III 9
II. Skeletal Muscle iuI/SkMl/SCN4A 9
III. Heart I/SkM2/hHl/SCN5A 9
IV. NaCh6 (Rat)/Scn8a (Mouse)/PN4 10
V. PNl/Nas/hNE Na/Scn9a 12
1. hNE Na 12
2. Nas 12
3. PN1 12
VI. SNS/PN3/NaNG/Scnl0a 13
1. SNS/PN3/Scnl0a 13
2. NaNG 13
VII. NaN/SNS2 13
VIII. Atypical Sodium Channels 14
1. hNav2.1 14
2. mNav2.3 14
3. SCL 11 14
D. Accessory Subunits 15
I. J81 Subunit 15
II. J32 Subunit 15
III. Other Associated Proteins 16
1. TipE 16
2. AnkyrinG 16
XIV Contents
3. AKAP15 17
4. Syntrophins 17
5. Extracellular Matrix Molecules 17
E. Genomic Structure 17
F. Concluding Remarks 17
References 19
CHAPTER 2
Sodium Channel Blockers and Activators
A.O. Grant. With 3 Figures 27
A. Introduction 27
B. Classification and Structure of Na+ Channels 27
C. Mechanisms of Na+ Channel Blockade by
Antiarrhythmic drugs 30
D. Models of Antiarrhythmic Drug Interaction with
the Sodium Channel 32
E. The Highly Specific Na+ Channel Blockers TTX and STX 38
F. Peptide Na Channel Blockers: /I Conotoxins 41
G. Na Channel Activators 42
H. Conclusions 45
References 45
B. Voltage Dependent Ca Channels
CHAPTER 3
Classification and Function of Voltage Gated Calcium Channels
IB. Bergsman, D.B. Wheeler, R.W. Tsien. With 2 Figures 55
A. Generic Properties of Voltage Gated Ca2+ Channels 55
I. Basic Functional Properties 55
II. Subunit Composition 56
1. a, 57
2. p 57
3. a2/8 58
4. 7 58
B. Classification of Native Ca2+ Channels According to Biophysical,
Pharmacological, and Molecular Biological Properties 58
I. Molecular Biological Nomenclature 59
II. Cavl/L Type Ca2+ Channels 59
III. Cav2 61
1. Cav2.2/N Type Ca2+ Channels 61
2. Cav2.1/P and Q Type Ca2+ Channels 62
3. Cav2.3/R Type Ca2+ Channels 63
Contents XV
IV. Cav3/T Type Ca2+ Channels 64
V. Note on Pharmacology 65
VI. Evolutionary Conservation of Ca2+ Channel Families 65
C. Functional Roles of Ca2+ Channels 66
I. Introduction/Subcellular Localization 66
II. Excitation Contraction Coupling 66
III. Rhythmic Activity 67
1. Pacemaker 67
2. Other 67
IV. Excitation Secretion Coupling 68
1. Generic Properties 68
2. Peripheral 69
3. Central 70
V. Postsynaptic Ca2+ Influx 71
1. Dendritic Information Processing 71
2. Excitation Expression Coupling and Changes in Gene
Expression 72
D. Concluding Remarks 73
References 73
CHAPTER 4
Structure of the Voltage Dependent L Type Calcium Channel
F. Hofmann, N. Klugbauer. With 3 Figures 87
A. Introduction 87
B. Subunit Composition and Genes of the Calcium Channel
Complex 87
I. Subunit Composition of L Type Calcium Channels 87
II. Genes 87
1. The a, Subunit 87
a) The L Type a, Channels 89
a) The Class S a. Gene 89
j8) The Class C a. Gene 89
y) The Class D a, Gene 89
S) The Class F a. Gene 90
b) The None L Type a. Channels 90
a) The Class A a. Gene 90
P) The Class B a. Gene 90
7) The Class E a, Gene 90
c) The Low Voltage Activated a, Channels 90
a) The Class G and H Gene 90
2. Auxiliary Subunits of the Calcium Channel 91
a) The a25 Subunit 91
b) The j3 Subunit 92
c) The /Subunit 93
XVI Contents
III. Functional Domains of the a, Subunit 94
1. The Pore and Ion Selectivity Filter 94
2. Channel Activation 95
3. Channel Inactivation 96
IV. Sites for Interaction with Other Proteins 98
1. Interaction of the a, Subunit with the Ryanodine
Receptor 98
2. Interaction of the a, Subunit with the fi Subunit 99
V. Binding Sites for L Type Calcium Channel Agonists and
Antagonists 100
1. The Dihydropyridine Binding Site 100
2. The Phenylalkylamine and Benzothiazepine
Binding Site 103
3. Modulation of Expressed L Type Calcium Channel by
cAMP Dependent Phosphorylation 104
4. Modulation of Expressed L Type Calcium Channel by
Protein Kinase C Dependent Phosphorylation 106
References 107
CHAPTER 5
Ca2+ Channel Antagonists and Agonists
S. Adachi Akahane,T, Nagao. With 9 Figures 119
A. Ca2+ Channel Antagonists 119
I. Historical Background 119
II. Allosteric Interaction Between Ca2+ Channel Antagonist
Binding Sites 121
III. Biophysical and Pharmacological Properties of Ca2+
Channel Antagonists 127
1. Dihydropyridines 128
2. Phenylalkylamines 130
3. Benzothiazepines 131
4. Other Ca2+ Channel Antagonists 132
IV. Binding Sites 133
1. Electrophysiological Identification of Binding Sites for
Ca2+ Channel Blockers 133
2. Biochemical Characterization of Drug Ca2+ Channel
Interaction: Photoaffinity Labeling of Ca2+ Channels .... 135
3. Molecular Biological Characterization of Drug Ca2+
Channel Interaction: Studies with Experimental Ca2+
Channel Mutants 135
B. Inorganic Blockers 138
C. Natural Toxins and Alkaloids 139
D. Ca2+ Channel Agonists 142
I. DHPs 142
II. Non DHPs 144
Contents XVII
E. Concluding Remarks 144
References 145
C. Voltage Dependent K Channels
CHAPTER 6
Overview of Potassium Channel Families: Molecular Bases of
the Functional Diversity
Y. Kubo. With 7 Figures 157
A. Introduction 157
B. Primary Structure of the Main Subunit 157
I. 6 Transmembrane (TM) Type 157
II. 2 TM Type 158
III. 1 TM Type 158
IV. 2 Repeat Type 159
C. Heteromultimeric Assembly: Bases of Further Diversity 159
I. Heteromultimer Formation with Other Members of
the Same Subfamily 159
1. Kv Channels 159
2. GIRK1,2,4 159
II. Suppression of Functional Expression by
Heteromultimeric Assembly 160
III. Heteromultimeric Assembly of Main Subunits of
Different Families 160
IV. Assembly with fi Subunit 160
V. Assembly with Regulatory Subunits 161
VI. Assembly with Anchoring Protein 162
D. Structural Bases of the Gating Mechanism 162
I. Activation of Kv Channels 162
II. N Type Inactivation of Kv Channels 163
III. C Type Inactivation of Kv Channels 164
IV. Activation of IsK 165
E. Structural Bases of the Ion Permeation and Block 165
I. H5 Pore Region 165
II. Re evaluation 165
III. Inward Rectification Mechanism 166
IV. Direct Structure Analysis 168
F. Structural Bases of Various Regulation Mechanisms 168
I. G/3y 168
II. Block by Cytoplasmic ATP 169
III. Regulation by Phosphorylation 169
IV. Mg2+ as a Cytoplasmic Second Messenger 170
V. Regulation by Extracellular K+ 170
VI. Other Mechanisms 170
XVIII Contents
G. Perspectives 170
References 171
CHAPTER 7
Pharmacology of Voltage Gated Potassium Channels
0. Pongs, C. Legros. With 8 Figures 177
A. Introduction 177
B. Molecular and Functional Organization of the Voltage Gated
Potassium Channels 178
I. Structural Domains in Kva Subunits 178
II. Modulatory Kv/3 Subunits 181
C. Peptide Toxin Binding Sites 182
I. Scorpion Toxins 182
II. Snake Toxins 186
III. Sea Anemone Toxins 188
IV. Snail Toxins 189
V. Spider Toxins 190
D. Conclusions 191
References 191
CHAPTER 8
Voltage Gated Calcium Modulated Potassium Channels of
Large Unitary Conductance: Structure, Diversity, and Pharmacology
R. Latorre, C. Vergara, E. Stefani, L.Toro. With 2 Figures 197
A. Introduction 197
B. Channel Structure 198
C. Auxiliary Subunits 204
D. Calcium Sensitivity and Diversity of BKCa Channels in
Different Cells and Tissues 205
E. Ca2+ Sensing Domain(s): The Calcium Bowl 207
F. Origin of Voltage Dependence in BKCa Channels 208
G. Channel Inactivation 209
H. Metabolic Modulation 210
1. Pharmacology 211
I. BK ¦„ Channels Blockers 211
1. Toxins 211
2. Organic Blockers 212
a. Tetraethylammonium 212
b. Indole Diterpenes 213
c. General Anesthetics 213
II. BKCa Channel Activators 213
1. Activators Isolated from Desmodium adscendens: A
Medicinal Herb 213
Contents XIX
2. Anti Inflamatory Aromatic Compounds (Fenamates) ... 214
3. Benzimidazolones 214
4. Phloretin 214
5. Ethanol 214
J. Summary and Conclusions 215
References 215
CHAPTER 9
Classical Inward Rectifying Potassium Channels: Mechanisms of
Inward Rectification
C.G. Nichols. With 3 Figures 225
A. The Nature of Inward Rectification: Classical Considerations .... 225
B. The Inward Rectifier Ion Channel Family:
Two Transmembrane Domain Potassium Channels 227
I. Kir 1 Subfamily 227
II. Kir 2 Subfamily 228
III. Kir 3 Subfamily 228
IV. Kir 4 and 5 Subfamilies 228
V. Kir 6 Subfamily 229
VI. KirD a New Family of Double Pored Inward
Rectifier Channels? 229
VII. Inward Rectification in Other K+ Channels 229
C. The Mechanism of Inward Rectification:
Pore Block and Intrinsic 230
D. The Structure of the Kir Channel Pore:
Binding Sites for Polyamines 231
E. The Structural Requirements for Inward Rectification:
The Blocking Particles 233
F. The Physiological Significance of Polyamine Induced
Rectification 236
References 236
CHAPTER 10
ATP Dependent Potassium Channels in the Kidney
G. Giebisch, W. Wang, S.C. Hebert. With 13 Figures 243
A. Introduction 243
B. The Function of ATP Sensitive K Channels in the Proximal
Tubule 243
C. The Function of ATP Sensitive K Channels in the Thick
Ascending Limb (TAL) of Henle s Loop 245
D. The Function of ATP Sensitive K Channels in the Cortical
Collecting Duct (CCD) 247
E. The Regulation of ATP Sensitive K Channels 248
XX Contents
I. Proximal Tubule 248
II. Thick Ascending Limb of Henle s Loop 249
III. Cortical Collecting Tubules Apical Membrane of
Principal Cells 250
F. Properties of Cloned ATP Sensitive K Channels (ROMK) 252
I. Channel Structure 252
II. Channel Isoforms and Localization 254
III. Comparison of ROMK with the Native Secretory
ATP Sensitive K Channel 256
IV. The Channel Pore Rectification 256
V. Regulation by Phosporylation: Protein Kinase A (PKA) ... 257
VI. Regulation by Phosphorylation: Protein Kinase C
(PKC) 259
VII. Regulation by Nucleotides 259
VIII. Regulation by Interaction with Cystic Fibrosis
Transmembrane Conductance Regulator (CFTR) 260
IX. Regulation by pH 260
X. Regulation by Phosphoinositides 262
XI. Regulation of ROMK Density in CCD 262
G. ROMK and Bartter s Syndrome 263
References 264
CHAPTER 11
Structure and Function of ATP Sensitive K+ Channels
T. Gonoi, S. Setno. With 5 Figures 271
A. Introduction 271
B. Properties of KATP Channels in Native Tissues 272
I. Heart 272
II. Skeletal Muscles 273
III. Pancreatic 0 Cells 273
IV. Brain 274
V. Smooth Muscles 275
VI. Kidney 275
VII. Mitochondria 276
C. Structure and Functional Properties of Reconstituted
KAIP Channels 276
I. The Pancreatic /3 Cell Type KATP Channel 276
1. The Inwardly Rectifying K+ Channel
Subfamily Kir6.0 276
2. The Sulfonylurea Receptor SUR1 277
3. Reconstitution of the Pancreatic J3 Cell Type
KATP Channel 281
II. The Cardiac and Skeletal Muscle Type KATP Channel 283
1. The Sulfonylurea Receptor SUR2A 283
Contents XXI
2. Reconstitution of the Cardiac and Skeletal Muscle
Type KATP Channel 283
III. The Smooth Muscle Type KATP Channel 283
1. The Sulfonylurea Receptor SUR2B 283
2. Reconstitution of the Smooth Muscle Type
KATP Channel 283
IV. The Vascular Smooth Muscle Type KATP Channel 284
1. Reconstitution of the Vascular Smooth Muscle
Type KATP Channel 284
D. Physical Interaction and Stoichiometry of the Pancreatic /3 Cell
Type KATP Channel Subunits 284
I. Physical Interaction Between the SUR1 Subunit and the
Kir6.2 Subunit 284
II. Subunit Stoichiometry of the SUR1/Kir6.2 Channel 285
E. Domains Conferring Sensitivities to the Nucleotides and
Pharmacological Agents 285
I. ATP Sensitivity 285
II. Nucleotide Diphosphate (NDP) Sensitivity 286
III. Diazoxide Sensitivity 286
IV. Sulfonylurea Sensitivity 287
V Mg2+ and Spermin Sensitivity 287
VI. Phentolamine Sensitivity 287
VII. G Protein Sensitivity 287
F. Pathophysiology of the Pancreatic /J Cell KATP Channel 288
I. Persistent Hyperinsulinemic Hypoglycemia of Infancy 288
II. Transgenic Mice 288
G. Conclusions 288
References 289
CHAPTER 12
G Protein Gated K+ Channels
A. Inanobe, Y. Kurachi*. With 11 Figures 297
A. Introduction 297
B. Acetylcholine Activation of Muscarinic K+ Channels 298
I. G Protein s Cyclic Reaction 299
II. Positive Cooperative Effect of GTP on the Muscarinic
K+ Channel Activity 302
III. Incorporation of Receptor G Protein Reaction to the
Model of KACh Channel 304
C Molecular Analyses of G Protein Gated K+ Channels 305
I. Cloning of Inwardly Rectifying K+ Channels and Kir
Subunits for G Protein Gated K+ Channels 305
II. GIRK Subfamily 307
XXII Contents
III. Expression of GIRK Channels 309
IV. Tetrameric Structure of Kir Channels 312
V. Molecular Mechanism Underlying Activation of the G
Protein Gated K+ Channels by j3y Subunits of G Protein ... 313
1. The G Protein /Jy Subunit Binding Domains in GIRK
Subunits 313
2. Putative Mechanism Underlying the G Protein jiy
Subunit Induced Activation of the G Protein Gated
K+ Channels 316
3. PIP2 Mediation of G^ Activation of KG Channels 316
VI. The Possible Role of G Protein a Subunits in the G
Protein Gated K+ Channel Regulation 317
1. Possibility of Microdomain Composed of Receptor,
G Protein and the G Protein Gated K+ Channel 317
2. Specificity of Signal Transduction
Based on the Receptor/G Protein/
G Protein Gated K+ Channel Interaction 317
D. Localization of the G Protein Gated K+ Channel Systems in
Various Organs 318
I. Cardiac Atrial Myocytes 319
II. Neurons 321
III. Endocrine Cells 322
E. Weaver Mutant Mice and GIRK2 Gene 323
F. Conclusions 323
References 324
CHAPTER 13
Potassium Channels with Two Pore Domains
F. Lesage, M. Lazdunski. With 3 Figures 333
A. K+ Channels with One Pore Domain 333
B. K+ Channels with Two Pore Domains 334
I. TWIK, the Archetype of a Novel Structural Class of K+
Channel 334
1. Cloning and Gene Organization 334
2. Functional Expression 335
3. Structure of the Channel 337
II. Related K+ Channels in Mammals 337
1. TREK is an Unusual Outward Rectifier K+ Channel .... 338
2. TASK is an Open Rectifier Channel Highly Sensitive
to External pH 339
3. TRAAK Forms K+ Channels Activated by
Unsaturated Fatty Acids 340
III. Related Channels in Worm, Fly, Yeast, and Plant 340
Contents XXIII
C. Concluding Remarks 341
References 343
CHAPTER 14
Cardiac K+ Channels and Inherited Long QT Syndrome
M. D. Drici, J. Barhanin. With 3 Figures 347
A. Long QT Syndromes 347
B. HERG and LQT2 348
I. The HERG Gene 348
II. IKr Current and LQT2 348
C. KvLQTl/IsK, LQT1, and LQT5 352
I KVLQT1 and ISK Genes 352
II. Ik, Current, LQT1, and LQT5 352
III. Physiological Role of IKs in Cardiac Repolarization 355
D. Pharmacological Considerations in the Acquired LQTS 356
I. Determinants of Cardiac Repolarization 356
II. Pharmacological Modulation of Cardiac Repolarization
and Acquired Long QT Syndromes 357
E. Conclusion ^
References Section II: Ligand Operated Ion Channels
CHAPTER 15
Gating of Ion Channels by Transmitters: The Range of Structures of
the Transmitter Gated Channels
E.A. Barnard. With 4 Figures 365
A. Introduction: The Scope of the Transmitter Gated
Channel Class 365
B. Structural Elements of the Membrane Domains of the
Transmitter Gated Channels 366
I. Transmembrane Domains 366
II The a Helix in Channel Transmembrane Domains 367
III Supporting Transmembrane Structures 371
IV. Pore Loops (P Domains) 371
C. The Subclasses of the Transmitter gated Channels 373
I The TGCs are in Completely Diverse Superfamilies 373
II*. The Cys Loop Receptors 374
III Glutamate Gated Cation Channels 378
IV. Channels Structurally Related to Voltage Gated
Channels 379
1. Cyclic Nucleotide Gated Channels 379
XXIV Contents
2. Inositol Trisphosphate (IP3) Receptors 380
3. Ryanodine Receptors 380
4. Vanilloid Receptors and Store Operated Channels 380
V. Channels Topologically Related to Epithelial Na+
Channels 381
1. P2X Channels 381
2. Proton Gated Channels 381
3. Peptide Gated Channels 383
VI. Channels Related to Inward Rectifier K+ Channels 383
1. Nucleotide Sensitive K+ Channels 383
2. Nucleotide Dependent K+ Channels 384
3. Channels Containing Bi Functional Kir Subunits 384
VII. Channels Related to ATP Binding Transporters 385
VIII. Channels Related to Neurotransmitter Transporters 385
D. Conclusion 386
References 386
CHAPTER 16
Molecular Diversity, Structure, and Function of Glutamate
Receptor Channels
M. Mishina. With 2 Figures 393
A. Introduction 393
B. Structure and Molecular Diversity of the GluR Channel 393
I. Subunit Families and Subtypes 393
II. Primary Structure and Transmembrane Topology Model ... 394
C. AMPA Subtype 395
I. AMPA Type Subunits 395
II. GluR2 Subunit and Ca2+ Permeability 396
III. Q/R Site as a Determinant of Channel Properties 396
IV. Phosphorylation 397
V. Autoimmune Disease 397
VI. GRIP, an Associated Protein 397
D. Kainate Subtype 397
E. NMDA Subtype 398
I. Heteromeric Nature of NMDA Receptor Channels 398
II. Dynamic Variations of the Distribution of the Subunits .... 399
III. Splice Variants 400
IV. Channel Pore and Gating 401
V. Agonist Binding 402
VI. Phosphorylation 403
VII. Modulation 403
VIII. Synaptic Plasticity, Learning, and Neural Development .... 404
IX. Associated Post Synaptic Proteins 404
Contents XXV
F. Additional Members of the GluR Channel Family 405
I. GluR 5 Subfamily 405
II. GluR;t Subfamily 406
References 406
CHAPTER 17
Glutamate Receptor Ion Channels: Activators and Inhibitors
D.E. Jane, H. W. Tse, D.A. Skifter, J.M. Christie,
D.T. Monaghan. With 15 Figures 415
A. Introduction 415
I. Receptor Classification 415
II. Molecular Biology of AMPA, Kainate, and
NMDA Receptors 416
B. Pharmacology of AMPA Receptors 417
I. AMPA Receptor Agonists 417
II. Competitive AMPA Receptor Antagonists 419
1. Quinoxalinediones and Related Compounds 419
2. Decahydroisoquinolines 423
3. Isoxazoles 425
4. Phenylglycine and Phenylalanine Analogues 426
III. Benzodiazepine Analogues as Non Competitive AMPA
Receptor Antagonists 427
IV. Positive Allosteric Modulators 428
V. Channel Blockers 429
C. Kainate Receptor Pharmacology 431
I. Kainate Receptor Agonists 431
II. Competitive Kainate Receptor Antagonists 433
1. Quinoxalinediones and Related Compounds 433
2. Decahydroisoquinolines 433
3. Positive Allosteric Modulators Acting on Kainate
Receptors 434
D. Therapeutic Potential of AMPA and Kainate
Receptor Ligands 434
E. Pharmacology of NMDA Receptors 436
I. Therapeutic Considerations 436
II. The NMDA Receptor Glutamate Recognition Site 438
1. Glutamate Recognition Site Radioligands 438
2. Glutamate Binding Site Agonists 439
3. Glutamate Recognition Site Competitive Antagonists ... 440
4. Antagonist Specificity for Subtypes of Glutamate
Recognition Sites 443
III. NMDA Receptor Channel Blockers 444
1. Channel Blocker Pharmacology 444
XXVI Contents
2. Channel Blocker Receptor Subtype Selectivity 446
IV. The NMDA Receptor Glycine Recognition Site 447
1. Radioligand Binding and Functional Characteristics of
the Glycine Receptor 447
2. NMDA Receptor Glycine Site Agonists 449
3. NMDA Receptor Glycine Site Antagonists 450
V. Allosteric Modulatory Sites on the NMDA Receptor 452
1. Polyamines 452
2. Spider and Wasp Toxins 453
3. Ifenprodil and Other NR2B Selective Compounds 453
4. Proton Inhibition 455
5. Zinc 455
F. Conclusions 456
References 459
CHAPTER 18
Structure, Diversity, Pharmacology, and Pathology of Glycine
Receptor Chloride Channels
R.J. Harvey, H. Betz. With 2 Figures 479
A. Introduction 479
I. The Neurotransmitter Glycine 479
B. Structure and Diversity of Glycine Receptor Channels 479
I. GlyRs are Ligand Gated Ion Channels of the nAChR
Superfamily 479
II. Glycine Receptor Heterogeneity 480
HI. The GlyR Ligand Binding Domain 482
IV. Determinants of Ion Channel Function 483
V. Clustering of GlyRs by the Anchoring
Protein Gephyrin 484
C. Pharmacology of Glycine Receptors 484
I. Strychnine is a Selective GlyR Antagonist 484
II. Amino Acids and Piperidine Carboxylic
Acid Compounds 486
III. Antagonism by Picrotoxinin, Cyanotriphenylborate, and
Quinolinic Acid Compounds 487
IV. Potentiation of GlyR Function by Anesthetics,
Alcohol and Zn2+ 488
D. Pathology of Glycine Receptors 489
I. Mouse Glycine Receptor Mutants:
Spastic, Spasmodic, and Oscillator 489
II. Mutations in GLRA1 Underlie the Human Hereditary
Disorder Hyperekplexia 490
E. Conclusions 491
References 492
Contents XXVII
CHAPTER 19
GABAA Receptor Chloride Ion Channels
R.W. Olsen, M. Gordey. With 4 Figures 499
A. GABAA Receptors: Physiological Function, Molecular Structure,
Pharmacological Subtypes 499
B. Activators and Inhibitors of GABAA Receptors 502
I. GABA Site 502
1. Agonists 502
2. Antagonists 504
II. The Picrotoxin Site 505
III. Benzodiazepine Site Ligands 506
IV. Barbiturates and Related Drugs 509
V. Neuroactive Steroids 511
VI. General Anesthetics: Propofol, Volatile Agents,
and Alcohols 511
VII. Miscellaneous Agents 512
C. Discussion 512
References 512
CHAPTER 20
P2X Receptors for ATP: Classification, Distribution, and Function
R.J. Evans. With 1 Figure 519
A. Introduction 519
B. Molecular Biology of P2X Receptors 519
I. A New Structural Family of Ligand Gated Ion Channels ... 520
II. The Extracellular Loop/Ligand Binding Site 520
III. Transmembrane Domains; Location of the Ionic Pore 522
1. Intracellular N and C Termini 523
2. Genomic Organisation, Human P2X Receptors and
Chromosomal Location 523
C. Distribution of P2X Receptors 523
I. P2X, Receptors 524
II. P2X2 Receptors 524
III. P2X, Receptors 525
IV. P2X4 Receptors 525
V. P2X5 Receptors 526
VI. P2X6 Receptors 526
VII. P2X7 Receptors 526
D. Functional Properties of P2X Receptors 527
I. General Features of P2X Receptors 527
1. P2X, Receptors 528
2. P2X2 Receptors 528
3. P2X3 Receptors 529
XXVIII Contents
4. P2X2/P2X3 Heteromeric Receptors 529
5. P2X4 Receptors 529
6. P2X5 Receptors 530
7. P2X6 Receptors 530
8. P2X7 Receptors 530
II. Modulation of P2X Receptors 531
III. Native P2X Receptor Phenotypes; Molecular
Correlates 532
1. Smooth Muscle 532
2. Sensory Neurons 533
3. Peripheral Neurons 534
4. Brain 534
5. Immune/Blood Cells 534
6. Salivary Gland 535
E. Future Directions 535
References 535
CHAPTER 21
The 5 HT3 Receptor Channel: Function, Activation and Regulation
J.L. Yakel. With 1 Figure 541
A. Introduction 541
B. Receptor Distribution 542
C. Molecular Structure 542
I. Sequence, Assembly, and Splice Variants 542
II. Gene Structure 544
III. Developmental Regulation 544
IV. Homo Oligomeric Vs Hetero Oligomeric Assembly 544
D. Function in the Nervous System 545
I. Presynaptic Role and Neurotransmitter Release 545
II. Postsynaptic Role 546
III. Physiological Properties 547
1. Receptor Activation 547
2. Single Channel Properties 547
3. Desensitization 548
4. Ion Permeation and Pore Structure 549
5. Rectification and Voltage Dependence 550
IV. Modulation, Synaptic Plasticity, and Learning and
Memory 551
E. Pharmacological Properties 552
I. 5 HTjR Ligands: Agonists and Antagonists 552
II. 5 HT3R Ligand Binding Site 553
F. Allosteric Regulation 554
I. Alcohols 554
II. Anesthetics 554
Contents XXIX
III. 5 Hydroxyindole 555
G. Conclusion 555
References 556
CHAPTER 22
Cyclic Nucleotide Gated Channels:
Classification, Structure and Function, Activators and Inhibitors
M.E. Grunwald, H. Zhong, K. W. Yau. With 2 Figures 561
A. Introduction 561
B. Structure 562
C. Ion Permeation Properties 563
D. Cyclic Nucleotide Binding and Channel Gating 565
E. Modulations 568
I. Ca2± Calmodulin 568
II. Ca2± 569
III. Phosphorylation 569
IV. Transition Metals 570
V. Sulfhydryl Reagents 570
VI. Protons 571
VII. Other Modulators 571
F. Blockers 571
G Conclusions 572
References 573
Section III: Miscellaneous Ion Channels Intracellular Ca
Release Channels
CHAPTER 23
Regulation of Ryanodine Receptor Calcium Release Channels
M. Endo, T. Ikemoto 583
A. Introduction 583
B. Molecular Structure and Function of RyR 584
C. Different Modes of Opening of RyRl Calcium
Release Channel 585
D. Activators of RyRs 588
I. Calcium, Strontium, and Barium Ions 589
II. Adenine Compounds 590
III. Caffeine and Related Compounds 590
IV. Ryanodine and Ryanoid 591
V. Halothane and Other Inhalation Anesthetics 592
VI. Oxidizing Agents and Doxorubicin 593
XXX Contents
VII. Cyclic ADP Ribose 593
VIII. Calmodulin and Other Endogenous Modulatory
Proteins 593
IX. Imperatoxin Activator 594
X. Clofibric Acid 594
XI. Miscellaneous Activators 595
E. Inhibitors of RyRs 595
I. Magnesium Ion 595
II. Procaine and Other Local Anesthetics 596
III. Ruthenium Red 596
IV. Dantrolene 596
F. Closing Remarks 596
References 597
CHAPTER 24
Regulation of IP., Receptor Ca2+ Release Channels
M. Iino. With 1 Figure 605
A. Introduction 605
B. Molecular Structure and Function of IP3R 605
C. Physiological Agonists and Modulators of IP3R 607
I. IP3 607
II. Ca2+ 609
III. ATP 610
IV. Phosphorylation 610
D. Activators of IP3R 611
I. IP3 Analogues 611
II. Caged IP3 612
III. Thimerosal 612
IV. Immunophilin Ligands 613
V. Mn2+ 613
E. Inhibitors of IP3R 613
I. Heparin 613
II. Xestospongin 614
III. Caffeine 614
IV. Cyclic ADP Ribose 614
F. Comparison of Pharmacology Between IP3R and RyR 615
G. Spatio Temporal Patterns of IP3R Mediated Ca2+ Signals 615
H. Perspectives 617
References 617
CHAPTER 25
Ca2+ Activated Non Selective Cation Channels
J. Teulon 625
Contents XXXI
A. Introduction 625
B. Tissue Distribution 625
C. Conductive Properties 628
I. Unit Conductance and Voltage Dependence 628
II. Ion Selectivity 629
III. Ca Permeable, Ca Dependent Cation Channels:
A Subtype of theNSCCa Channel? 630
D. Blockers and Pharmacological Stimulators 630
I. Blockers 630
II. Pharmacological Stimulators 632
E. Intracellular Regulatory Elements 633
I. Calcium Sensitivity 633
II. Inhibition by Intracellular Nucleotides 633
III. Tonic Influence of Intracellular ATP 635
IV. Stimulatory Effects of Intracellular Cyclic Nucleotides .... 635
V. Other Regulators: Internal pH and Oxidation 635
F. Phosphorylation Dependent Regulation 636
I. Regulation via Protein Kinase A 636
II. Effects of Other Protein Kinases 637
G. Dependence on Hypertonicity 637
H. Agonist Mediated Control of NSCCa Channels 638
I. Physiological Role 639
I. Excitable Cells: Voltage Signal 640
II. Exocrine Glands: Participation in Cl Transport 641
III. Other Epithelia: Speculative Functions 642
References 643
Subject Index 651
|
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| id | DE-604.BV013109366 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:39:14Z |
| institution | BVB |
| isbn | 3540661271 |
| language | English |
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| physical | XXXI, 662 S. Ill., graph. Darst. |
| publishDate | 2000 |
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| publisher | Springer |
| record_format | marc |
| series | Handbook of experimental pharmacology |
| series2 | Handbook of experimental pharmacology |
| spelling | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] contributors S. Adachi-Akahane ... Ed.: M. Endo ... Berlin [u.a.] Springer 2000 XXXI, 662 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Handbook of experimental pharmacology 147 Ion Channels cabt Pharmacology cabt Agonisten gtt Inhibitie gtt Ionenkanalen gtt Calcium Channel Blockers pharmacology Cell Membrane physiology Ion Channels antagonists & inhibitors Ion Channels physiology Ion channels Ion channels Effect of drugs on Membrane Potentials physiology Rezeptor (DE-588)4049722-7 gnd rswk-swf Ionenkanal (DE-588)4138699-1 gnd rswk-swf Pharmakologie (DE-588)4045687-0 gnd rswk-swf Pharmakologischer Antagonist (DE-588)4198682-9 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Ionenkanal (DE-588)4138699-1 s Pharmakologie (DE-588)4045687-0 s DE-604 Rezeptor (DE-588)4049722-7 s Pharmakologischer Antagonist (DE-588)4198682-9 s Endo, Makato 1933- Sonstige (DE-588)121762998 oth Adachi-Akahane, S. Sonstige oth Handbook of experimental pharmacology 147 (DE-604)BV002390716 147 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=008931463&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] Handbook of experimental pharmacology Ion Channels cabt Pharmacology cabt Agonisten gtt Inhibitie gtt Ionenkanalen gtt Calcium Channel Blockers pharmacology Cell Membrane physiology Ion Channels antagonists & inhibitors Ion Channels physiology Ion channels Ion channels Effect of drugs on Membrane Potentials physiology Rezeptor (DE-588)4049722-7 gnd Ionenkanal (DE-588)4138699-1 gnd Pharmakologie (DE-588)4045687-0 gnd Pharmakologischer Antagonist (DE-588)4198682-9 gnd |
| subject_GND | (DE-588)4049722-7 (DE-588)4138699-1 (DE-588)4045687-0 (DE-588)4198682-9 (DE-588)4143413-4 |
| title | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] |
| title_auth | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] |
| title_exact_search | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] |
| title_full | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] contributors S. Adachi-Akahane ... Ed.: M. Endo ... |
| title_fullStr | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] contributors S. Adachi-Akahane ... Ed.: M. Endo ... |
| title_full_unstemmed | Pharmacology of ionic channel function activators and inhibitors ; [with 25 tables] contributors S. Adachi-Akahane ... Ed.: M. Endo ... |
| title_short | Pharmacology of ionic channel function |
| title_sort | pharmacology of ionic channel function activators and inhibitors with 25 tables |
| title_sub | activators and inhibitors ; [with 25 tables] |
| topic | Ion Channels cabt Pharmacology cabt Agonisten gtt Inhibitie gtt Ionenkanalen gtt Calcium Channel Blockers pharmacology Cell Membrane physiology Ion Channels antagonists & inhibitors Ion Channels physiology Ion channels Ion channels Effect of drugs on Membrane Potentials physiology Rezeptor (DE-588)4049722-7 gnd Ionenkanal (DE-588)4138699-1 gnd Pharmakologie (DE-588)4045687-0 gnd Pharmakologischer Antagonist (DE-588)4198682-9 gnd |
| topic_facet | Ion Channels Pharmacology Agonisten Inhibitie Ionenkanalen Calcium Channel Blockers pharmacology Cell Membrane physiology Ion Channels antagonists & inhibitors Ion Channels physiology Ion channels Ion channels Effect of drugs on Membrane Potentials physiology Rezeptor Ionenkanal Pharmakologie Pharmakologischer Antagonist Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=008931463&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV002390716 |
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