In recent years, gap junction research in the cardiovascular system has considerably improved the understanding of cardiac function and the vasculature in health and disease. The present book focuses on the communication of intercellular gap junctions in the cardiovascular system but also includes aspects of physiology, medicine and cell biology. The first part of this volume highlights the principal aspects of these intercellular channels, allowing the readers unfamiliar with the field to get a deeper understanding of the physiology, pharmacology and regulation of gap junctions. The second part elucidates their role in the pathophysiology of important cardiovascular diseases, e.g. arrhythmia, heart failure, ischemia, atrial fibrillation, diabetes and arteriosclerosis. This book is of special interest to cardiologists, physiologists, pharmacologists, cardiovascular scientists, biophysicists, cell biologists as well as to industrial companies engaged in cardiovascular medicine and research.
Author(s): S. Dhein
Series: Advances in Cardiology
Edition: 1
Publisher: S. Karger AG (Switzerland)
Year: 2006
Language: English
Pages: 298
Cover......Page 1
Contents......Page 6
Preface......Page 8
Abstract......Page 10
Connexin40......Page 12
Connexin43......Page 13
Transcription of Connexins and Gene Structure and Regulation......Page 14
Are Connexins also Transcription Factors?......Page 16
Structure of Individual Connexins......Page 17
Protein Interactions of Connexins......Page 19
References......Page 22
Abstract......Page 27
Methods and Results......Page 28
Electrical Properties......Page 30
Metabolic Coupling......Page 31
A: Voltage and Chemical Gating......Page 33
B: Phosphorylation of the Connexin Protein Subunits......Page 36
B1: Phosphorylation of Cx43 Gap Junctions......Page 37
B2: Phosphorylation of Cx37,Cx40 and Cx45 Gap Junctions......Page 39
Alterations in Expression of Gap Junction Proteins......Page 40
Concluding Remarks......Page 42
Acknowledgements......Page 43
References......Page 44
Abstract......Page 50
c-Src, ZO-1, MAPK and MKP-1 at Gap Junctions during Acidosis and Hypoxia......Page 52
Drebrin: Stabilizing Cx43?......Page 58
ZO-1 at Gap Junctions:Multiple Functions?......Page 59
Adherens Junctions Meet Gap Junctions: Junction Formation and Cell Migration......Page 60
Microtubules......Page 61
Growth Inhibition Mediated by Cx43: A Role for CCN3?......Page 62
References......Page 63
Abstract......Page 66
Synthesis of Connexins......Page 67
Connexin Oligomerization and Assembly......Page 69
Connexin Degradation......Page 73
References......Page 76
Mechanisms of Action Potential Generation......Page 80
Conduction of Action Potentials......Page 82
Role of Cell Size and Gap Junction Conductance in Propagation......Page 83
Cell-to-Cell Coupling and Source-to-Sink Relationships......Page 85
Continuous versus Discontinuous Conduction......Page 87
High-Resolution Mapping of Cardiac Excitation in Mice......Page 88
Acknowledgements......Page 91
References......Page 92
Abstract......Page 95
Propagation of the Action Potential......Page 96
Impulse Propagation through the Three-Dimensional Myocardium......Page 98
Discontinuities......Page 100
Studies of Micropropagation in Patterned Cell Cultures......Page 101
Studies in Mice with Targeted Deletions in Cx43......Page 106
Cardiac-Specific Connexin43 Knockouts......Page 108
Inducible Model of Connexin43 Gene Deletion......Page 111
Conclusions......Page 112
References......Page 113
Abstract......Page 116
Protein Serine/Threonine Kinases......Page 117
Enzymes Catalyzing Dephosphorylation in Cardiac Tissues......Page 120
Influence of Protein Phosphorylation on Hemichannel Permeability......Page 121
Protein Substrate of Phosphorylation/Dephosphorylation......Page 122
Agents for Acute Closure of Gap Junctions......Page 123
Lipophilic Agents......Page 125
Receptor-Mediated Uncoupling......Page 126
Agents for Acute Opening of Gap Junctions......Page 127
Agents Affecting Expression, Synthesis, Assembly, Docking and Degradation of Gap Junctions......Page 129
References......Page 134
Abstract......Page 141
Gap Junctions in Normal and Diseased Heart......Page 142
Myocyte-Fibroblast Coupling in Cell Culture......Page 144
Myocyte-Fibroblast Coupling in the Normal Heart......Page 145
Myocyte-Fibroblast Coupling in the Diseased Heart......Page 147
Relevance of Myocyte-Fibroblast Coupling......Page 151
References......Page 154
Abstract......Page 159
Electrical Uncoupling and Arrhythmogenesis......Page 161
Mouse Models of Decreased Ventricular Coupling......Page 162
Cx43, Electrical Coupling and Conduction Reserve......Page 163
Uncoupling and Ventricular Effective Refractory Period......Page 165
Concluding Remarks......Page 166
References......Page 167
Abstract......Page 170
Initiation of Atrial Fibrillation......Page 171
Stabilization of Atrial Fibrillation......Page 172
Role of Gap Junctions in Atrial Fibrillation......Page 173
References......Page 180
Abstract......Page 184
Theoretical Requirements of the Sinoatrial Node for Electrical Coupling......Page 185
Expression of Connexins30.2,40,43 and 45 in the Center of the Sinoatrial Node......Page 189
Expression of Connexins in the Periphery of the Sinoatrial Node......Page 192
Model of the Sinoatrial Node......Page 193
Aging and Expression of Connexins in the Sinoatrial Node......Page 195
Atrioventricular Node......Page 196
Expression of Cx30.2, Cx40, Cx43 and Cx45 in the Atrioventricular Node......Page 199
Model of the Atrioventricular Node......Page 201
References......Page 203
Abstract......Page 207
Acute Ischemia......Page 210
Chronic Ischemia/Infarction......Page 217
References......Page 218
Abstract......Page 222
Regulation of Hemichannels and Gap Junctions......Page 223
Protein Kinase C......Page 224
Protein Tyrosine Kinase......Page 225
Myocardial Ischemia/Reperfusion Injury and Its Modification by Ischemic Preconditioning......Page 226
Alterations in Connexin 43 during Ischemia......Page 227
Connexin 43 and Ischemic Preconditioning......Page 229
References......Page 231
Abstract......Page 237
Gap Junctions and Connexins in Cardiomyocytes of the Normal Heart......Page 238
Structural Remodeling......Page 240
Alterations in Connexin43 Expression......Page 242
Analyzing the Significance of Altered Connexin Co-Expression......Page 244
Concluding Comment......Page 248
References......Page 249
Abstract......Page 252
Immunoblot and Immunohistochemstry of Cx43......Page 253
Expression of Cx43 at the Intercalated Disk......Page 254
Identification of the PKC Isoform That Is Activated in the Diabetic Heart......Page 255
Effects of Lysosomal and Proteasomal Inhibitors on the Expression of Cx43 in the Diabetic Heart......Page 256
Morphological Alterations of the Gap Junction in the Diabetic Heart......Page 259
Discussion......Page 260
References......Page 261
Current Concepts of Atherosclerosis and Restenosis......Page 264
Use of Mice in Atherosclerosis Research......Page 267
Gap Junctions in the Vascular Wall......Page 268
Connexins May Be Implicated in Atherogenesis and Restenosis......Page 269
Connexins Are Implicated in Atherogenesis and Restenosis......Page 272
Concluding Remarks......Page 273
References......Page 274
Necessity of Coordinated Cellular Responses for Drastic Flow Changes......Page 277
Transversal and Longitudinal Coupling in Vessels......Page 278
Conducted Vasomotor Responses Reflect Longitudinal Communication Along the Vessel......Page 279
What Initiates Conducted Vasomotor Responses?......Page 282
Pathway for the Conducted Signal......Page 284
Which Connexins Contribute to Arteriolar Coordination?......Page 286
References......Page 289
Abstract......Page 293
Patients......Page 294
Electrophysiologic Study......Page 295
Results......Page 297
Discussion......Page 298
References......Page 299
Author Index......Page 301
A......Page 302
C......Page 303
D......Page 305
P......Page 306
Z......Page 307
