Potassium channels in cardiovascular biology:
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| Format: | Book |
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| Language: | English |
| Published: |
New York [u.a.]
Kluwer
2001
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XLV, 899 S. Ill., graph. Darst. |
| ISBN: | 0306464020 |
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| 245 | 1 | 0 | |a Potassium channels in cardiovascular biology |c ed. by Stephen L. Archer ... |
| 264 | 1 | |a New York [u.a.] |b Kluwer |c 2001 | |
| 300 | |a XLV, 899 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 4 | |a Appareil cardiovasculaire - Physiologie | |
| 650 | 4 | |a Canaux ioniques | |
| 650 | 4 | |a Canaux à potassium | |
| 650 | 4 | |a Cur - Physiologie | |
| 650 | 4 | |a Cur - Physiopathologie | |
| 650 | 4 | |a Cardiovacular system |x Physiology | |
| 650 | 4 | |a Cardiovascular Diseases |x physiopathology | |
| 650 | 4 | |a Heart |x Pathophysiology | |
| 650 | 4 | |a Heart |x Physiology | |
| 650 | 4 | |a Heart |x physiology | |
| 650 | 4 | |a Muscle, Smooth, Vascular |x physiology | |
| 650 | 4 | |a Potassium Channels |x physiology | |
| 650 | 4 | |a Potassium channels | |
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| 700 | 1 | |a Archer, Stephen L. |e Sonstige |4 oth | |
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| adam_text | Contents
Part I. Molecular Biology of Potassium Channels
Chapter 1
Evolution of Potassium Channel Proteins
Warren J. Gallin and Andrew N. Spencer
1. Introduction 3
2. Origin of Major K+ Channel Families 4
3. Evolution of the Kir Family of K+Channels 7
4. Evolution of the Kv Families of K+ Channels 11
5. Evolution of EAG Related and Pacemaker K+ Channels 12
6. Future Directions for Evolutionary Studies 13
References 15
Chapter 2
Three Dimensional Structure of the K+ Channel Pore:
Basis for Ion Selectivity and Permeability
Hee Cheol Cho and Peter H. Backx
1. Introduction 17
2. Molecular Diversity of Mammalian K+Channels 18
3. The Crystal Structure of the KcsA Protein 21
4. Role of the Pore in Subunit Assembly 23
5. Role of K+ Channel Pores in Gating and Block 23
6. Molecular Basis of Permeation and Selectivity in K+ Channels 25
6.1. Selectivity in K+ Channels 25
6.2. The Inner Vestibule of the K+ Channel Pore 26
6.3. The Outer Vestibule of K+ Channels 27
7. Limitations of the KcsA Structure and Some Unanswered Questions .... 28
8. Conclusions 29
References 30
YVli
xyjii Contents
Chapter 3
Molecular Biology of Voltage Gated K+ Channels
Olaf Pongs
1. Introduction 35
2. Background 36
3. Mix and Match of Cardiac Voltage Gated K+Channel Subunits 37
4. Auxiliary Voltage Gated K+ Channel Subunits 41
5. Implications from Crystal Structures 45
References 46
Chapter 4
Molecular Biology of High Conductance, Ca2+ Activated Potassium Channels
Pratap Meera, Martin Wallner, and Ligia Tow
1. Molecular Properties of the BKCa Channel Pore Forming
a Subunit (Slol) and Structurally Related Genes (Slo2 and Slo3) 49
1.1. Slol, the BKCa Channel a Subunit 49
1.2. Slo2 and Slack, Novel BKCa Channel Homologs 51
1.3. Slo3, a Voltage and pH Sensitive BKCa Channel Homolog 53
2. Diversity of Slol Generated by Alternative Splicing 55
2.1. Drosophila Splice Variants 55
2.2. Vertebrate Splice Variants 55
2.3. Physiological Impact 58
3. Modulatory Subunits of Slol 59
3.1. Molecular Properties of Transmembrane j51 and /?2 Subunits .... 59
3.2. Molecular Determinants of j82 Induced Fast Inactivation
of Slol Channels 59
3.3. Facilitation of Channel Opening and Pharmacological Changes
Caused by /? Subunits 63
3.4. Molecular Determinants for /?1 Subunit Modulation in Slol
Channels 64
3.5. Other Slo Interacting Subunits 65
3.6 Physiological Impact 66
4. Physiological Function of Slol Channels 66
Summary 68
References 68
Chapter 5
Molecular Biology of Inward Rectifier and ATP Sensitive Potassium Channels
5. L. Shyng, A. N. Lopatin, and C. G. Nichols
1. Functional Diversity of Cardiac K+ Channels: The Role of Inward
Rectification 71
2. The Kir Channel Family: Two Transmembrane Domain K+ Channels ... 73
2.1. Kirl Subfamily 74
Contents xix
2.2. Kir2 Subfamily 74
2.3. Kir3 Subfamily 74
2.4. Kir4 and Kir5 Subfamilies 75
2.5. Kir6 Subfamily 75
2.6. Kir7 Subfamily 75
2.7. Inward Rectification in Other K+ Channels 75
3. The Nature of Inward Rectification: New Insights from Cloned Channels . 76
3.1. Polyamines as the Cause of Strong Inward Rectification 76
3.2. The Structure of the Kir Channel Pore: Binding Sites for Polyamines . 77
4. Nucleotide Regulation of KATP Channels: New Insights from Cloned
Channels 78
4.1. The Classical View of Nucleotide Regulation 78
4.2. Separable Roles of the Sulfonylurea Receptor (SUR) and Kir6
Subunits: SUR Controls Nucleotide Activation 79
4.3. Kir6.2 Controls Nucleotide Inhibition 81
4.4. ATP Stabilizes the Closed Channel 82
4.5. Membrane Phospholipid Control of ATP Sensitivity: Getting to
the Underlying Mechanism 82
5. Conclusions 83
References 83
Part II. Potassium Channel Expression and Function
Chapter 6
Design and Use of Antibodies for Mapping K+ Channel Expression in the
Cardiovascular System
Robert O. Koch, Maria Trieb, Alexandra Koschak, Siegmund G. Wanner,
Kathryn M. Gauthier, Nancy J. Rusch, and Hans Guenther Knaus
1. Introduction 91
2. Antipeptide Antibodies Selective for K+ Channels 92
3. Selection of the Peptide Sequence 92
4. Peptide Synthesis 93
5. Production of Antipeptide Antibodies 95
6. Selection of Suitable Antibodies 96
7. Use of Antibodies to Detect K+Channels of Interest 97
8. Summary 100
References 101
Chapter 7
Molecular Methods for Evaluation of K+ Channel Expression and
Distribution in the Heart
Michael J. Morales, Mulugu V. Brahmajothi, Donald L. Campbell,
and Harold C. Strauss
1. Introduction 103
2. Heart Extract Methods 104
xx Contents
2.1. Northern Hybridization 104
2.2. Ribonuclease Protection Assay 105
2.3. Quantitative Polymerase Chain Reaction of Reverse
Transcribed mRNA 106
2.4. Immunoblotting 108
3. Methods Which Preserve Underlying Structure 108
3.1. In Situ Hybridization and Immunofluorescence of
Individual Myocytes 108
3.2. In Situ Hybridization and Immunofluorescence of Whole Tissue ... Ill
4. In Vivo Methodologies 112
4.1. Antisense Oligonucleotide Inhibition of Channel Biosynthesis 112
4.2. Approaches to Manipulation of Mammalian Hearts In Vivo 113
5. Conclusion 114
References 114
Chapter 8
Concepts for Patch Clamp Recording of Whole Cell and
Single Channel K+ Currents in Cardiac and Vascular Myocytes
Antonio Guia, Carmelle V. Remillard, and Normand Leblanc
1. Introduction 119
2. Historical Perspective 120
3. Single Cell Isolation Procedures 120
3.1. Isolation of Cardiac Myocytes 121
3.2. Isolation of Vascular Smooth Muscle Cells 124
4. Description of the Patch Clamp Technique 125
4.1. Formation of a Gigaseal 125
4.2. Patch Clamp Configurations 126
5. General Properties of Ion Channels 129
5.1. Protocols to Analyze the Permeation and Selectivity of K+ Channels . 130
5.2. Protocols to Investigate Gating Mechanisms 133
5.2.1. Current Voltage Relationships 134
5.2.2. Protocols Designed to Study Activation 135
5.2.3. Protocols Designed to Study Inactivation 137
6. Conclusion 141
References 141
Chapter 9
The Patch Clamp Technique for Measurement of K+ Channels in
Xenopus Oocytes and Mammalian Expression Systems
Laura Conforti and Nicholas Sperelakis
1. Introduction 143
2. Applications of Heterologous Expression Systems 144
2.1. Xenopus Oocyte Expression System 144
2.1.1. Preparation of Oocytes for Electrophysiological Experiments . 144
Contents xxi
2.1.2. Electrophysiological Recording from Xenopus Oocytes .... 147
2.1.3. Advantages of the Oocyte Expression System 150
2.1.4. Limitations of the Oocyte Expression System 150
2.2. Mammalian Cell Lines 151
2.2.1. Transfection of Mammalian Cell Lines 152
2.2.2. Electrophysiological Recordings of Transfected Cells 154
2.2.3. Advantages of Mammalian Cell Lines 157
2.2.4. Limitations of Mammalian Cell Lines 157
3. Summary 157
Appendix 158
References 158
Chapter 10
Heteromultimer Formation in Native K+ Channels
James S. Trimmer and Kenneth J. Rhodes
1. Introduction 163
2. Biochemical Characterization of Voltage Gated K+ Channel Complexes . . 164
2.1. Biochemical Characterization of a Subunit Heteromultimerization . . 165
2.2. Biochemical Characterization of /? Subunit Involvement in
Kv Channel Complexes 168
3. Immunohistochemical Localization of Kv a and /? Subunit Polypeptides
in Mammalian Brain 169
4. Summary 172
References 173
Chapter 11
Use of Transgenic and Gene Targeted Mice to Study K + Channel Function in the
Cardiovascular System
Barry London
1. Introduction 177
2. Dominant Negative Transgenic Mice 178
2.1. Methods 178
2.2. Advantages and Disadvantages 180
3. Targeted Disruption of K+Channel Genes in Mice 182
3.1. Methods 182
3.2. Advantages and Disadvantages 183
4. Analysis of the Phenotype of Genetically Modified Mice 183
5. Examples 184
5.1. Dominant Negative Disruption of Kv 1.x Channels 184
5.2. Targeted Disruption of Kvl.5 and Kvl.4 186
5.3. Kv4.x Dominant Negative Mice 187
5.4. HERG Dominant Negative Mice 188
6. Future Directions 188
References 189
xxii Contents
Part III. Pharmacology of Potassium Channels
Chapter 12
Pharmacology of Voltage Gated K+ Channels
Brian Robertson
1. Introduction 195
2. Kvl Channels 196
2.1. Kvl Modulation by ^ Subunits 198
2.2. Kvl.5 Channels and Channel Antagonists 198
2.3. Effects of Antihistamines on Kvl.5 Channels 199
2.4. Miscellaneous Inhibitors of Kvl.5 Channels 200
2.5. Kvl.7 Channels 200
3. Kv2 channels 201
3.1. Physiologically Silent a Subunits Modulate Kv2 Channels 201
4. Kv3 Channels 202
5. Kv4 Channels 202
6. HERG Channels 205
7. KvLQTl/IsK Oligomeric Channels 209
8. The Pacemaker Current—Hyperpolarization Activated Cation Channels . . 209
9. Concluding Comments 212
References 212
Chapter 13
Pharmacology of High Conductance, Ca2 + Activated Potassium Channels
Maria L. Garcia and Gregory J. Kaczorowski
1. Introduction 219
2. Pharmacology of BKCa Channels 223
2.1. Peptidyl Inhibitors 223
2.2. Small Molecule Modulators of BKCa Channels 225
3. Conclusions 230
References 231
Chapter 14
Pharmacology of Small Conductance, Calcium Activated K+ Channels
Eric Blanc and Herve Darbon
1. Introduction 235
1.1. Potassium (K+) Channels 235
1.2. Overall Topology of K+ Channels 236
1.3. Interaction of K+Channels with Peptidic Toxins 236
Contents xxiii
2. SKCa Channels 239
2.1. Homologies with the K+ Channel Superfamily 239
2.2. Subunits 240
2.3. SKCa Channel Blockers 241
2.3.1. Apamin 241
2.3.2. Scorpion Toxins 242
2.3.3. The Dipole Moment: A Key to Locating Interacting Surfaces . 244
2.3.4. Prediction of Toxic Surfaces 245
2.4. Receptor Counterparts of Apamin Critical Residues 247
2.4.1. A Lack of Experimental Data 248
2.4.2. A K+ Channel Structure Available 248
2.4.3. Docking Model 249
2.5. Organic Compounds 250
2.6. An Auxiliary /? Subunit 252
3. Conclusion 252
References 253
Chapter 15
Molecular Pharmacology of ATP Sensitive K+ Channels: How and Why?
Andre Terzic and Michel Vivaudou
1. KATP Channels: From Discovery to Structure 257
2. Targets for KATP Channels: From Endogenous Ligands to Synthetic
Agents 259
2.1. Endogenous Ligands 259
2.1.1. Adenine Mononucleotides 259
2.1.2. Dinucleotide Polyphosphates 260
2.1.3. Endosulfine 261
2.1.4. Neurohormones 261
2.2. Synthetic agents 261
2.2.1. Sulfonylureas and Other Blockers 261
2.2.2. Potassium Channel Openers 261
3. Molecular Pharmacology of KATP Channels: From Binding to Gating . . . 263
3.1. Characterization of Sulfonylurea Binding Sites 263
3.2. Closing in on Binding Sites for Potassium Channel Openers 264
3.3. From Binding Sites to Channel Gating 267
4. Cellular Pharmacology of Cardiac KATP Channels:
From the Sarcolemma to Mitochondria 268
4.1. Action on the Sarcolemma 268
4.2. Action on Mitochondria 269
5. Perspectives: From Translational Pharmacology to Therapeutics 269
5.1. Priorities 269
5.2. Challenges and Strategies 271
References 271
xxjv Contents
Part IV. Potassium Channels in the Heart
Chapter 16
Overview: Molecular Physiology of Cardiac Potassium Channels
B. M. Heath, X. Wehrens, and R. S. Kass
1. Introduction 281
2. Voltage Dependent K+ Channels 283
2.1. Transient Outward K+ Current 284
2.2. Delayed Rectifier K+ Currents 285
2.3. Ultrarapid K+ Current 288
2.4. Potassium Channels and Long QT Syndrome 288
3. Inward Rectifier K+ Channels 288
3.1. Cardiac Inward Rectifier K+ Current 289
3.2. Acetylcholine Activated K+ Current 289
3.3. ATP Sensitive K+ Current 289
4. Background K+ Current 290
5. Summary 291
References 292
Chapter 17
Molecular Mechanisms Controlling Functional Voltage Gated K+ Channel
Diversity and Expression in the Mammalian Heart
Jeanne M. Nerbonne
1. Introduction 297
2. Electrophysiological Diversity of Voltage Gated K+ Currents 298
2.1. Transient Outward K+ Currents/Channels, /t0, in Cardiac Cells . . . 299
2.1.1. /to,fas,(/,o,f) 299
2.1.2. Jto,slow(/to,s) 301
2.2. Delayed Rectifier K+ Currents/Channels, /K, in Cardiac Cells .... 303
2.2.1. /K,raPid(/Kr) and/K,slow(/Ks) 304
2.2.2. /KiUltrar.pid(/Kur) 304
2.2.3. Other Delayed Rectifiers 305
2.3. Regional Differences in Voltage Gated K+ Channel Expression .... 305
3. Molecular Diversity of Kv Channels in Cardiac Cells 306
3.1. Voltage Gated K+ Channel Pore Forming a Subunits 306
3.1.1. Homologous Voltage Gated (Kv) Subfamilies of a Subunits . . 306
3.1.2. Ether a go go Related Gene Subfamily, ERG 309
3.1.3. KvLQTl Subfamily 309
3.2. Accessory Subunits of Voltage Gated K+ Channels 311
3.2.1. Minimal K+ Channel Subunit, IsK or minK 311
3.2.2. Accessory /J Subunits 311
3.2.3. K+ Channel Regulatory Proteins 312
4. Molecular Correlates of Functional Kv Channels 312
Contents xxv
4.1. Molecular Correlates of Cardiac Transient Outward K+ Currents . . 313
4.1.1. Kv4.2/Kv4.3 a Subunits Underlie /t0,f 313
4.1.2. Kvl.4 Underlies /t0,s . 314
4.2. Molecular Correlates of Cardiac Delayed Rectifiers 314
4.2.1. ERG Underlies /Kr 315
4.2.2. KvLQTl Underlies 7Ks 315
4.2.3. Kvl.5 Underlies /Kur 315
4.2.4. Molecular Correlates of Other Cardiac Delayed Rectifiers . . . 316
5. Regulation of Functional Cardiac Kv Channels 316
5.1. Developmental Regulation of Cardiac K+ Channel Expression
and Properties 317
5.1.1. Development of Cardiac Transient Outward K +
Currents/Channels 317
5.1.2. Development of Cardiac Delayed Rectifier K +
Currents/Channels 318
5.2. Changes in Kv Current Expression in Myocardial Disease 319
5.3. Transcriptional Regulation of Functional Kv Channels 321
5.4. Posttranscriptional Regulation of Functional Kv Channels 322
References 324
Chapter 18
Voltage Gated Potassium Channels in the Myocardium
Joanne T. Hulme, Jeffrey R Martens, Ricardo A. Navarro Polanco,
Atsushi Nishiyama, and Michael M. Tamkun
1. Introduction 337
1.1. Cardiac Action Potential 337
1.2. Diversity of Voltage Gated K+Channels in Myocardial Cells .... 338
1.2.1. Transient Outward K+ Current (Jt0) 338
1.2.2. Delayed Rectifier K+Current (/K) 339
1.2.3. Limitations of Traditional Electrophysiological
and Biochemical Approaches 339
2. Overview of Molecular Approaches to the Study of Voltage Gated
K+ Channels 340
2.1. Cloning Strategies 340
2.1.1. The Drosophila Genetic Approach: Cloning Based
Chromosomal Location 340
2.1.2. Homology Screening 341
2.1.3. Expression Cloning 342
2.1.4. Cloning Based on K+ Channel Protein Purification 342
2.2. Heterologous Expression Systems 342
2.3. Relation of Cloned Channels with Native Currents 343
2.3.1. Antisense Studies 343
2.3.2. Transgenic Studies 344
xxvj Contents
3. Functional Expression of Cloned Kv Channels 344
3.1. Shaker Like Kv Channels with Delayed Rectifier Like Properties ... 345
3.1.1. Kvl.2 345
3.1.2. Kvl.5 346
3.1.3. Kv2.1 347
3.2. S/iafcer Like Kv Channels with Rapid Inactivation
(/t0 Like Channels) 349
3.2.1. Kvl.4 349
3.2.2. Kv4.2 and Kv4.3 350
3.2.3. Are Other Shaker Like Channels Expressed in the Heart? ... 350
3.3. Accessory jS Subunits 351
3.4. Erg (H erg and M erg) Kv Channels 352
3.5. KvLQTl and minK (ISK) 353
3.5.1. KvLQTl 353
3.5.2. minK(ISK) 354
4. Summary and Conclusions 355
References 356
Chapter 19
Inward Rectifying and ATP Sensitive K+ Channels in the Ventricular Myocardium
Akikazu Fujita and Yoshichisa Karachi
1. Introduction 363
2. Classical Inward Rectifying K+ Channels in Heart: /K1 365
2.1. Physiological Roles of /Ki Channels 365
2.2. Molecular Aspect of JK1 Channels 367
2.3. Modulation of Kir2.0 Channels 368
3. ATP Sensitive K+ Channels 368
3.1. Physiological Roles of KATP Channels 368
3.2. Electrophysiological Properties of KATP Channels 369
3.3. Regulation of KATP Channels by Intracellular Nucleotides 369
3.4. Pharmacological Regulation of KATP channels 371
3.5. Molecular Aspect of KATP Channels 371
3.6 Molecular Heterogeneity of Sulfonylurea Receptors 372
3.7. Molecular Mechanism of KATP Channel Inhibition by
Intracellular ATP 374
3.8. Molecular Mechanism of Response to Intracellular Nucleoside
Diphosphates 376
3.9. Molecular Mechanism of Rundown 378
4. Na+ Activated K+ Channels 379
4.1. Physiological Roles and Electrophysiological Properties of
KNa Channels 379
4.2. Pharmacological Regulation of KNa Channels 379
5. Conclusions 380
References 380
Contents xxvii
Chapter 20
Cholinergic and Adrenergic Modulation of Cardiac K+ Channels
Christopher Parker and David Fedida
1. Introduction 387
2. Cholinergic Responses 388
2.1. Effects of Cholinergic Stimulation on Cardiac K+Currents 388
2.1.1. Effects on /K(ACh) 388
2.1.2. Effects on Other Cardiac K+ Currents 390
2.2. Signal Transduction Mechanisms 390
2.2.1. Direct Pathways 391
2.2.2. Indirect Pathways 392
2.3. Correlation with Cloned Channel Currents 394
3. j9 Adrenergic Responses 395
3.1. Effects of /S AR Stimulation on Cardiac K+ Currents 395
3.1.1. Effects on Components of the Delayed Rectifier,/K 396
3.1.2. Effects on Other Cardiac K+ Currents 397
3.2. jS AR Receptor Subtypes Present in the Heart 397
3.3. Signal Transduction Mechanisms 398
3.3.1. G Proteins and Adenylate Cyclose 398
3.3.2. Role of cAMP Dependent Protein Kinase 400
3.4. Correlation with Cloned Channel Currents 401
4. a! Adrenergic Responses 402
4.1. Effects of oq AR Stimulation on Cardiac Function and K+ Currents . 403
4.1.1. Effects on 7t0 405
4.1.2. Effects on Components of /K 407
4.1.3. Effects on the Inwardly Rectifying /K1 407
4.1.4. Effects on /K(ACh) 407
4.2. ax AR Subtypes Present in the Heart 408
4.3. Signal Transduction Mechanisms 408
4.3.1. G Proteins 408
4.3.2. Role of Phospholipases (PLC/PLA2) 409
4.3.3. Role of Increased [Ca2+], 410
4.3.4. RoleofPKC 411
4.4. Correlation with Cloned K+Channel Currents 411
References 415
Chapter 21
Cardiac K + Channel Expression and Function at Birth and in the Neonate
Fuhua Chen and Thomas S. Klitzner
1. Introduction 427
2. Inward Rectifier K+ Current 429
3. Delayed Rectifier K+ Current 430
4. ATP Sensitive K+ Current 432
5. Transient Outward K+ Current 435
xxviii Contents
6. Muscarinic K+ Current 437
7. Summary 437
References 438
Part V. Potassium Channels in Vascular Smooth Muscle
Chapter 22
Overview: Physiological Role of K+ Channels in the Regulation of Vascular Tone
Joseph E. Bray den
1. Introduction 443
2. BKCa Channels: Role in Regulation of Myogenic Tone 443
3. SKCa Channels: Possible Role in Actions of EDHF 445
4. Kv Channels: Regulation of Membrane Potential and Inhibition
by Agonists 446
5. KATP Channels: Activation by Pharmacological and Endogenous
Vasodilators 447
6. Kir Channels: Regulation of Resting Membrane Potential and Role
in K+ Induced Dilations 450
7. Summary 451
References 452
Chapter 23
Modulation of Vascular K+ Channels by Extracellular Messengers
D. J. Beech, A. Cheong, R. Flemming, C. Guibert, and S. Z. Xu
1. Introduction 457
2. Role of K+ Channels in the Actions of Extracellular Messengers
on Blood Vessels 460
2.1. Nitric Oxide 460
2.2. Oxygen and Reactive Oxygen Species 462
2.3. Protons 464
2.4. Potassium 465
2.5. Arachidonic Acid, Prostaglandins, HETEs, and EETs 467
2.6. Acetylcholine, Bradykinin, and Substance P 468
2.7. Adenosine 468
2.8. Calcitonin Gene related Peptide 470
2.9. 17j3 Estradiol 470
2.10. Histamine 471
2.11. Adrenoceptor Agonists and 5 Hydroxytryptamine 473
2.12. Endothelins 473
2.13. Other Extracellular Messengers Linked with K+ Channels . . . 474
Contents xxix
3. Conclusions 474
References 476
Chapter 24
Delayed Rectifier K+ Channels of Vascular Smooth Muscle: Characterization,
Function, and Regulation by Phosphorylation
W. C. Cole and M. P. Walsh
1. Introduction 485
2. Properties of Vascular KDR Channels 486
3. Molecular Identity of Vascular KDR Channels 489
4. Regulation of Vascular KDR Channels by Phosphotransferase Reactions . . 490
5. Role of KDR Channels in Control of Vascular Tone 495
6. Summary 498
References 499
Chapter 25
Potassium Channels in the Circulation of Skeletal Muscle
William F. Jackson
1. Introduction 505
2. ATP Sensitive K+ Channels in the Skeletal Muscle Circulation 505
2.1. Evidence for KATP Channels in Skeletal Muscle Arteries and
Arterioles 505
2.2. Resting Membrane Potential, Tone, and KATP Channels 507
2.3. Vasodilators and KATP Channels 507
2.4. Vasoconstrictors and KATP Channels 508
3. BKCa Channels in the Skeletal Muscle Circulation 510
3.1. Evidence for BKCa Channels in Skeletal Muscle Arteries
and Arterioles 510
3.2. Resting Membrane Potential, Tone, and BKCa Channels 510
3.3. Vasodilators and BKCa Channels 511
3.4. Vasoconstrictors and BKCa Channels 513
4. Kv Channels in Skeletal Muscle Circulation 513
4.1. Evidence for Kv Channels in Skeletal Muscle Arteries and Arterioles . 513
4.2. Resting Membrane Potential, Tone, and Kv Channels 514
4.3. Vasodilators and Kv Channels 514
4.4. Vasoconstrictors and Kv Channels 516
5. KIR Channels in the Skeletal Muscle Circulation 516
5.1. Evidence for Kir Channels in Skeletal Muscle Arterioles 516
5.2. Resting Membrane Potential, Tone, and Kir Channels 516
5.3. Vasodilators and Kir Channels 517
6. Conclusion and Questions for the Future 517
References 517
xxx Contents
Chapter 26
Regulation of Cerebral Artery Diameter by Potassium Channels
George C. Wellman and Mark T. Nelson
1. Introduction 523
2. Strong Inwardly Rectifying Potassium (Kir) Channels 524
2.1. Molecular Structure of Kir Channels in Cerebral Artery Myocytes . . 524
2.2. Selective Inhibition of Channels by Micromolar Ba2 + :
A Functional Fingerprint for the Role of Kir Channels in
the Regulation of Cerebral Blood Flow 526
2.3. Voltage Dependence of Kir Activity: Contribution of Kir Channels
to Resting Membrane Potential and Indirect Augmentation of
the Action of Vasoactive Compounds 527
2.4. Modulation of Kir Gating by Extracellular K + : Coupling of
Neuronal Metabolic Activity to Cerebral Blood Flow 527
3. ATP Sensitive Potassium (KATP) Channels 528
3.1. Molecular Distinction of Vascular KATP Channels 529
3.2. Pharmacology of KATP Channels in Cerebral Vascular
Smooth Muscle 529
3.3. Modulation by Endogenous Compounds: Role of Second Messengers
and Protein Phosphorylation 530
3.4. KATP Channel Activity and Changes in Cellular Metabolic State . . . 532
4. Kv Channels 533
4.1. Kv Subtypes in Cerebral Arterial Smooth Muscle 533
4.2. Identification of Kv Currents in Cerebral Vascular Smooth Muscle . . 533
4.3. Pharmacology of Kv Currents in Cells Isolated from Vascular
Smooth Muscle 535
4.4. Physiological Contribution of Kv Channels to the Regulation
of Cerebral Artery Diameter 535
5. BKCa Channels 536
5.1. Molecular Structure of BKCa Channels 536
5.2. Modulation of BKCa Channels in Cerebral Vascular Smooth
Muscle by Ca2+ Sparks 537
5.3. Modulation of Ca2+ Spark/STOC Activity in Cerebral Arteries ... 537
6. Summary 540
References 540
Chapter 27
The Role of Potassium Channels in the Control of the Pulmonary Circulation
Stephen Archer
1. Introduction 543
2. Synopsis of Pulmonary Vascular Physiology—Adult and Neonatal . ... 544
3. Hypoxic Pulmonary Vasoconstriction 546
4. Vasodilator and Vasoconstrictor Agonists 546
Contents xxxi
5. Pulmonary Vasocilation and Vasoconstriction—the Opening
and Closing of K+ Channels 547
6. Pharmacological Evidence for a Role for K+ Channels in Determining
Pulmonary Vascular Resistance 548
7. Pulmonary Arterial Smooth Muscle Cells Express Several K+
Channel Types 549
8. Electrical Remodeling of the Pulmonary Circulation 552
9. K+ Channel Inhibition Contributes to Endothelin Induced
Vasoconstriction 552
10. NO and cGMP Are BKCa Channel Openers in Pulmonary Arterial
Smooth Muscle Cells 553
11. Hypoxic Pulmonary Vasoconstriction: A Tale of Two Channels 555
12. Redox Regulation of Pulmonary Vascular K+ Channels 556
13. Molecular Identification of Kv Channels That Set Em and Respond
to Hypoxia in Pulmonary Arterial Smooth Muscle Cells 556
14. Immunoelectropharmacology 559
15. New Concepts in the Molecular Regulation of Kv Channels 561
15.1. Heterotetramers 561
15.2. ,3 Subunits 562
15.3. Electrically Silent Kv Channels 562
15.4. Regional Diversity of K+ Channel Expression 562
16. Chronic Hypoxic Pulmonary Hypertension 563
References 564
Chapter 28
Potassium Channels in the Renal Circulation
James D. Stockand and Steven C. Sansom
1. Introduction 571
1.1. Structure/Function of the Renal Corpuscle 571
1.2. Roles of K+ Channels 572
2. K+ Channels in Renal Arteries 573
2.1. BKCa Channels 574
2.2. Kv Channels 575
2.3. KATP Channels 575
2.4. Other K+ Channels in Renal Arteries 576
2.5. Regulation of K+ Channels by NO and Metabolites of
Arachidonic Acid 576
3. K+ Channels of Renal Arterioles 577
3.1. BKCa Channels 578
3.2. KATP Channels 578
3.3. Other K + Selective Channels 579
3.4. K+ Channels of Efferent Arterioles 580
3.5. Regulation of Renal Arteriolar K+ Channels 580
4. K+ Channels in Mesangial Cells 581
4.1. Mesangial Cell BKCa Channels 582
xxxii Contents
4.2. Mesangial Cell KATP Channels 582
4.3. Other K+ Channels 582
4.4. Regulation by Vasorelaxants 583
5. Pathophysiological Regulation of K+ Channels in the Renal Vasculature . . 584
6. Summary and Conclusions 585
References 587
Chapter 29
Potassium Channels in the Coronary Circulation
Maik Gollasch
1. Introduction 591
2. Voltage Dependent Ca2 + Channels, Membrane Potential, and
Regulation of Coronary Myogenic Tone 593
3. Effect of Membrane Potential on Ca2+ Influx through
Voltage Dependent Ca2+ Channels 595
4. Outwardly Rectifying K+ Channels 596
4.1. Ca2 + Activated K+ Channels 597
4.2. Kv Channels 598
4.3. Transient Outward K+ Channels 601
5. Voltage Independent KAtp Channels 601
6. Inward Rectifier K+ Channels 603
7. STOCs 605
8. Ion Channels and Differentiation of Vascular Smooth Muscle Cells .... 607
References 609
Chapter 30
Vascular K+ Channel Expression and Function at Birth and in the Neonate
Helen L. Reeve and David N. Cornfield
1. Introduction 617
2. Dilation of the Fetal Pulmonary Vasculature 618
3. K+ Channels in the Fetal and Neonatal Pulmonary Artery 618
3.1. ATP Dependent K+ Channels 619
3.2. Large Conductance, Ca2 + Dependent K+Channels 619
4. Constriction of the Ductus Arteriosus 622
5. K+ Channels in the Ductus Arteriosus 622
6. Modulation of K+ Channels in the Transition From Fetus to Neonate . . . 625
6.1. The Fetal Pulmonary Artery, K+ Channels, and Ventilation 625
6.2. The Fetal Pulmonary Artery, K+ Channels, and Shear Stress 625
6.3. The Fetal Pulmonary Artery, K+ Channels, and Oxygen 626
6.4. The Fetal Pulmonary Artery, K+ Channels, and NO 627
6.5. The Ductus Arteriosus, K+ Channels, and Oxygen 628
7. Clinical Implications 631
7.1. K+ Channel Agonists 631
7.2. Phosphodiesterase Inhibitors 632
References 633
Contents xxxiii
Part VI. Potassium Channels in the Endothelium
Chapter 31
Overview: Potassium Channels in Vascular Endothelial Cells
Guy Droogmans and Bernd Nilius
1. Introduction 639
2. K+ Channels of Endothelium 639
2.1. Inward Rectifier K+ Channels 639
2.1.1. Biophysical Properties 641
2.1.2. Modulation 641
2.1.3. Molecular Identity 642
2.2. Ca2+ Activated K+ Channels 642
2.2.1. BKCa Channels 643
2.2.2. IKCa Channels 643
2.2.3. SKCa Channels 645
2.3. ATP Sensitive K+ Channels 645
2.4. Other K+ Channels 646
3. Functional Aspects of K+ Channels 646
References 647
Chapter 32
Single Channel Properties of Ca2+ Activated K+ Channels
in the Vascular Endothelium
Stewart O. Sage and Sergey M. Marchenko
1. Introduction 651
1.1. Cytosolic Ca2 + in Endothelial Function 651
1.2. Generation of Endothelial Ca2+ Signals 651
1.3. Importance of Membrane Potential in Endothelial Ca2 + Signaling . . 652
1.4. Vasodilator Evoked Changes in Endothelial Membrane Potential . . . 652
2. Vasodilator Evoked Endothelial Hyperpolarization 653
2.1. The Role of a K+ Conductance 653
2.2. Evidence for a Ca2+ Activated K+ Conductance 653
3. Classification of Ca2+ Activated K+ Channels 655
4. Ca2 + Activated K+ Channels in Cultured Endothelial Cells 655
5. Ca2+ Activated K+ Channels in Freshly Isolated Endothelial Cells .... 656
6. Ca2+ Activated K+ Channels in the Endothelium of Intact Rat Aorta . . . 657
6.1. Single Channel Properties 657
6.2. Physiological Role of KAp and KCh Channels 661
6.3. Other Studies in Intact Preparations 661
7. Conclusions 662
References 663
xxxiv Contents
Chapter 33
Endothelial Cell K+ Channels, Membrane Potential, and the Release of Vasoactive
Factors from the Vascular Endothelium
Christopher R. Triggle
1. Introduction 667
2. Endothelial Cell Membrane Potential 668
2.1. Ca2+ ActivatedK+ Channels 669
2.2. Inward Rectifying K+ Channels 670
2.3. ATP Sensitive K+ Channel 670
2.4. Voltage Sensitive K+ Channels 670
2.5. ACh Gated K+ Channels 671
3. Nature of Endothelium Derived Relaxing Factors 671
3.1. Epoxyeicosatrienoic Acids 672
3.2. Cannabinoids 672
3.3. Gap Junctions 673
3.4. K+ as an EDHF 674
4. Ca2+ Dependency of the Synthesis and Action of
Endothelium Derived Vasoactive Factors 676
5. Nature of Endothelial K+ Channels Involved in the Synthesis
and Release of EDRF and EDHF 679
6. Conclusions 682
7. Directions for Future Investigation 683
References 683
Chapter 34
Activation of Vascular Smooth Muscle K+ Channels by
Endothelium Derived Factors
Michel Feletou and Paul M. Vanhoutte
1. Endothelium Derived Vasodilators 691
1.1. Existence of a Third Pathway 691
1.2. Other Vasoactive Substances Released by Endothelial Cells 694
2. Endothelium Derived Mediators and Vascular Smooth Muscle K +
Channels 694
2.1. Prostacyclin 694
2.2. Nitric Oxide 696
2.3. EDHF 701
2.4. Other Identified Endothelium Derived Hyperpolarizing Factors ... 705
2.4.1. Epoxyeicosatrienoic Acids 705
2.4.2. Anandamide 707
2.4.3. Adenosine 707
2.4.4. Carbon Monoxide 709
2.4.5. Hydrogen Peroxide 709
Contents xxxv
2.4.6. K+ Ions 710
2.4.7. Others 710
3. Conclusion 712
References 712
Part VII. Potassium Channels in Cardiac Disease
Chapter 35
Overview: Role of Potassium Channels in Cardiac Arrthythmias
Albert J. D Alonzo, Paul C. Levesque, and Michael A. Blanar
1. Introduction 727
2. Genetic Models of Arrhythmia 730
2.1. Inheritable Arrhythmias of Humans: The Long QT Syndrome .... 730
2.2. Potassium Channels in Engineered Cellular and Mouse Models . . . 732
3. Animal Models of Arrhythmia 733
3.1. Acute Ischemia 733
3.2. Heart Failure and Hypertrophy 734
3.3. Atrial Fibrillation 735
3.4. Drug Induced QT Prolongation 739
4. Conclusion 739
References 740
Chapter 36
The Molecular Basis of the Long QT Syndrome
Martin Tristani Firouzi and Michael C. Sanguinetti
1. Introduction 753
2. Cardiac Action Potentials and the QT Interval 754
3. Molecular Genetic Approaches to the Identification of LQTS Genes . . . 755
4. Molecular Mechanisms of LQTS Mutations 757
5. Mutations in KVLQT1, the Gene Encoding the a Subunit of
JKs Channels 759
6. Mutations in KvLQTl Like Channels Also Cause Disease 760
7. Mutations in minK, the Gene Encoding the /? Subunit of IKs Channels . . 760
8. Recessive Mutations in KVLQT1 or minK Cause LQTS and
Congenital Sensorineural Hearing Loss 761
9. Mutations in HERG, the Gene Encoding the a Subunit of 7Kr Channels . . 762
10. Mutations in SCN5A, the Gene Encoding the a Subunit
of Cardiac Na+ Channels 764
11. Cellular Mechanisms of Torsade de Pointes Arrhythmia 764
12. Genotype Prediction of Clinical Phenotype 765
13. Genotype Specific Therapy 767
References 768
xxxvi Contents
Chapter 37
Altered K+ Channel Expression in the Hypertrophied and Failing Heart
Koichi Takimoto and Edwin S. Levitan
1. Introduction 773
2. Electrophysiological Alterations in Myocytes from Hypertrophied
and Failing Hearts 773
3. Decreased Expression of Kv4 Subfamily Channel Subunit mRNAs in
Hypertrophied and Failing Hearts—a Molecular Mechanism
Underlying the Reduction in /t0 775
4. Mechanisms for the Decreased Expression of Kv4 Subfamily Channel
mRNAs and 7t0 Channels in Hypertrophied and Failing Hearts 777
5. Region Specific Expression of /to and Its Alterations by Hypertrophy
and Heart Failure 778
6. Conclusions and Future Directions 781
References 781
Chapter 38
Role of ATP Sensitive K+ Channels in Cardiac Preconditioning
Garrett J. Gross
1. Introduction 785
1.1. KATP Channels 786
1.2. Ischemic Preconditioning 786
2. KATP Channels and Classical Preconditioning 788
2.1. Animal Studies 788
2.2. Human Studies 790
3. Subtype of KATP Channel That Mediates Ischemic Preconditioning 791
3.1. Sarcolemmal KATP Channels 791
3.2. Mitochondrial KATP Channels 794
4. KATP Channels in Delayed Preconditioning 796
5. Summary and Future Directions 797
References 797
Chapter 39
Therapeutic Potential of ATP Sensitive K+ Channel Openers in Cardiac Ischemia
Gary J. Grover
1. Introduction 801
2. Cardioprotective Profile for KATP Channel Openers: Early Studies 803
3. Drug Development of KATP Channel Openers for Treatment of Acute
Myocardial Ischemia: Development of Nonvasodilating
KATP Channel Openers 805
4. Recent Insights: Cardioprotective Mechanism of Action 808
Contents xxxvii
5. Potential Clinical Applications for Cardioprotective KATP
Channel Openers 813
6. Summary and Conclusions 815
References 815
Part VIII. Potassium Channels in Vascular Disease
Chapter 40
Altered Expression and Function of Kv Channels in Primary
Pulmonary Hypertension
Jason Xiao Jian Yuan and Lewis J. Rubin
1. Introduction 821
1.1. Pathophysiology and Pathogenesis of Primary
Pulmonary Hypertension 821
1.2. K+ Channel Regulation of Vasoconstriction and
Vascular Remodeling 822
1.3. A Proposed Pathogenic Hypothesis of PPH 822
2. Molecular Identity and Electrophysiological Characterization
of Kv Channels in Human Pulmonary Arterial Smooth Muscle Cells .... 823
2.1. Molecular Identity 823
2.2. Electrophysiological and Pharmacological Properties 824
2.3. Kv Channel Regulation of £m and [Ca2+]; 826
2.4. Single Channel 7K(V) and /K(Ca) 826
3. Comparison of Kv Channels in Pulmonary Arterial Smooth Muscle
Cells from Patients with Primary and Secondary Pulmonary Hypertension . 827
3.1. Reduced Level of a Subunit mRNA in PASMC from PPH Patients . 827
3.2. Reduced /KV in PASMC from PPH Patients 829
3.3. Depolarized Em and Increased [Ca2+], in PASMC
from PPH Patients 832
4. Conclusion: Possible Etiological Mechanisms of PPH 834
References 834
Chapter 41
Anorectic Drugs and the Vasculature
Evangelos D. Michelakis and E. Kenneth Weir
1. Introduction 837
2. Anorectic Drugs and the Pulmonary Vasculature 838
3. Anorectic Drugs and the Systemic Vasculature 839
4. Anorectic Drugs and the Heart Valves 839
5. Role of K+ Channels in Vascular Tone 840
6. Anorectic Drugs Inhibit K+Current in Vascular Smooth Muscle 840
7. Anorectic Drugs and the Endothelium 844
8. Anorectic Drugs and Platelets 845
xxxviii Contents
9. Anorectic Drugs and Myocardial Cells 848
10. Questions for the future 848
References 849
Chapter 42
Induction of Ca2+ Activated K+ Channel Expression during Systemic
Hypertension: Protection against Pathological Vasoconstriction
Marcie G. Berger and Nancy J. Rusch
1. Introduction 853
2. Expression and Function of BKCa Channels in the Vasculature 854
3. Early Evidence for Augmented BKCa Channel Current in Hypertension . . 855
4. Molecular Mechanisms of BKCa Channel Upregulation in Aortic
Smooth Muscle Cells 858
5. Functional Implications of BKCa Channel Upregulation in the
Microcirculation 861
6. Therapeutic Targeting of Vascular BKCa Channels in Hypertension .... 863
7. Summary 863
References 864
Chapter 43
Antisense Approaches and the Modulation of Potassium Channel
Function in the Cardiovascular System
Craig H. Gelband
1. Introduction 869
2. The Antisense Approach 870
3. Use of Antisense Oligonucleotides to Modify K+ Channel Expression
In Vitro 872
4. K+ Channel Alterations in Cardiovascular Pathologies: Potential Targets
of Antisense Therapies 873
5. Voltage Gated K+ (Kv) Channels in Vascular Smooth Muscle Membranes . 874
6. Vascular Kv and Ca2+ Channel Alterations Are Coexpressed in
Hypertension 876
7. Prevention of Hypertension and Ion Channel Alterations by
Retroviral Mediated Delivery of ATX Receptor Antisense 878
8. Can Antisense Gene Therapy Reverse Hypertension? 882
9. Summary 883
References 883
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| id | DE-604.BV013745278 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:51:16Z |
| institution | BVB |
| isbn | 0306464020 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009396262 |
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| physical | XLV, 899 S. Ill., graph. Darst. |
| publishDate | 2001 |
| publishDateSearch | 2001 |
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| publisher | Kluwer |
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| spelling | Potassium channels in cardiovascular biology ed. by Stephen L. Archer ... New York [u.a.] Kluwer 2001 XLV, 899 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Appareil cardiovasculaire - Physiologie Canaux ioniques Canaux à potassium Cur - Physiologie Cur - Physiopathologie Cardiovacular system Physiology Cardiovascular Diseases physiopathology Heart Pathophysiology Heart Physiology Heart physiology Muscle, Smooth, Vascular physiology Potassium Channels physiology Potassium channels Kaliumkanal (DE-588)4258505-3 gnd rswk-swf Kardiovaskuläres System (DE-588)4024665-6 gnd rswk-swf Kardiovaskuläres System (DE-588)4024665-6 s Kaliumkanal (DE-588)4258505-3 s DE-604 Archer, Stephen L. Sonstige oth HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009396262&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Potassium channels in cardiovascular biology Appareil cardiovasculaire - Physiologie Canaux ioniques Canaux à potassium Cur - Physiologie Cur - Physiopathologie Cardiovacular system Physiology Cardiovascular Diseases physiopathology Heart Pathophysiology Heart Physiology Heart physiology Muscle, Smooth, Vascular physiology Potassium Channels physiology Potassium channels Kaliumkanal (DE-588)4258505-3 gnd Kardiovaskuläres System (DE-588)4024665-6 gnd |
| subject_GND | (DE-588)4258505-3 (DE-588)4024665-6 |
| title | Potassium channels in cardiovascular biology |
| title_auth | Potassium channels in cardiovascular biology |
| title_exact_search | Potassium channels in cardiovascular biology |
| title_full | Potassium channels in cardiovascular biology ed. by Stephen L. Archer ... |
| title_fullStr | Potassium channels in cardiovascular biology ed. by Stephen L. Archer ... |
| title_full_unstemmed | Potassium channels in cardiovascular biology ed. by Stephen L. Archer ... |
| title_short | Potassium channels in cardiovascular biology |
| title_sort | potassium channels in cardiovascular biology |
| topic | Appareil cardiovasculaire - Physiologie Canaux ioniques Canaux à potassium Cur - Physiologie Cur - Physiopathologie Cardiovacular system Physiology Cardiovascular Diseases physiopathology Heart Pathophysiology Heart Physiology Heart physiology Muscle, Smooth, Vascular physiology Potassium Channels physiology Potassium channels Kaliumkanal (DE-588)4258505-3 gnd Kardiovaskuläres System (DE-588)4024665-6 gnd |
| topic_facet | Appareil cardiovasculaire - Physiologie Canaux ioniques Canaux à potassium Cur - Physiologie Cur - Physiopathologie Cardiovacular system Physiology Cardiovascular Diseases physiopathology Heart Pathophysiology Heart Physiology Heart physiology Muscle, Smooth, Vascular physiology Potassium Channels physiology Potassium channels Kaliumkanal Kardiovaskuläres System |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009396262&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT archerstephenl potassiumchannelsincardiovascularbiology |