Fundamentals of Intracellular Calcium
, by Campbell, Anthony K.
- ISBN: 9781118941874 | 111894187X
- Cover: Paperback
- Copyright: 11/6/2017
The definitive text on the key component for cell functions—intracellular calcium
This comprehensive book reveals the evidence for intracellular calcium as a universal switch in all animal, plant, fungal and microbial cells. It shows how the components required for calcium signaling are named and classified; covers the technology that has been developed to study intracellular calcium; describes how calcium is regulated inside cells and how it works to trigger an event; explains the role of intracellular calcium in disease, cell injury, and cell death; reveals how many drugs work through the calcium signaling system; and demonstrates how intracellular calcium is involved in the action of many natural toxins. The book also illustrates how the intracellular calcium signaling system has evolved over millions of years, showing why it was crucial to the origin of life. Additionally, the book promotes the importance of the molecular variation upon which the intracellular calcium signalling system depends.
Featuring more than 100 figures (including detailed chemical structures as well as pictures of key pioneers in the field), a bibliography of some 1000 references, and a detailed subject index, this definitive work provides a unique source of scholarship for teachers and researchers in the biomedical sciences and beyond.
- Emphasizes two key scientific principles—the first to show how intracellular Ca2+ acts as a switch, to activate a wide range of cellular events, and the second demonstrating how an analogue mechanism can be superimposed on such a process
- Written by an internationally recognized expert in the field
- Filled with images and references to facilitate learning
Fundamentals of Intracellular Calcium is an all-important text for post-graduate students and researchers working in biomedicine and biochemistry. It is also essential for undergraduate lecturers and their students in physiology, medicine, pharmacy, and the biosciences.
Anthony K. Campbell, PhD, FLS, FLSW is Professor in the School of Pharmacy and Pharmaceutical Sciences, Cardiff University. He has studied intracellular calcium for over 40 years, and is a world authority on bioluminescence, developing the use of genetically engineered bioluminescence to measure chemical processes in live cells, particularly Ca2+. One of his inventions, using chemiluminescence, is now used in several hundred million clinical tests per year worldwide. He has published 9 books, and over 250 internationally peer-reviewed papers on intracellular calcium, bioluminescence, lactose and food intolerance, and Darwin.
About the Author xvii
Preface xix
List of Acronyms xxiii
About the Companion Web Site xxxv
1 Calcium is Special 1
1.1 Calcium and Everyday Events 1
1.2 Discovery of Calcium 2
1.3 A Natural History of Calcium 3
1.3.1 Calcium by the Sea 3
1.3.2 Calcium in Your Wake-Up Call 4
1.4 The Elements of Life 5
1.5 Natural Occurrence of Calcium 7
1.5.1 Isotopes of Calcium 7
1.5.2 Geology of Calcium 7
1.5.3 Calcium Outside Cells 8
1.5.4 Calcium Inside Cells 10
1.6 Requirement of Cells for Ca2+ 12
1.6.1 Calcium in External Fluids 12
1.6.2 Requirement of Cell Types for Calcium 12
1.7 The Four Biological Roles of Calcium 13
1.7.1 Structural 13
1.7.2 Electrical across Biological Membranes 13
1.7.3 Extracellular Cofactor 14
1.7.4 Intracellular Regulator 14
1.8 The Puzzle about Ca2+ Inside Cells 17
1.9 How Important Intracellular Calcium has been in Science 18
1.10 Darwin and Intracellular Ca2+ 19
1.11 The Scene Set 21
1.12 ‘Ja Kalzium, das ist alles!’ 21
1.13 Calcium – The Fundamentals 22
Recommended Reading 23
Books 23
Reviews 23
Articles 23
2 Intracellular Calcium – Principles 25
2.1 Ca2+ and the Concept of Cell Signalling 25
2.1.1 Primary Signals and Intracellular Ca2+ 25
2.1.2 The Source of Intracellular Ca2+ 27
2.2 The Problem 29
2.3 Some Key Questions 29
2.3.1 Question 1 – What is the Primary Stimulus and Secondary Regulator(s)? 29
2.3.2 Question 2 – What is the Intracellular Signal? 30
2.3.3 Question 3 – How do the Secondary Regulators Work? 30
2.4 Types of Intracellular Ca2+ Signal 31
2.4.1 Category of Cell Based on the Ca2+ Signal 31
2.4.2 Types of Ca2+ Signal 32
2.4.3 Ca2+ Sparks, Puffs and Sparklets 33
2.5 Rubicon Principle 34
2.5.1 Digital Versus Analogue Cell Events 34
2.5.2 The Ca2+ Signaling Toolkit 36
2.5.3 Amplification Mechanisms 36
2.6 Key Experiments to Answer Key Questions 38
2.6.1 Raising Cytosolic Free Ca2+ Artificially 38
2.6.2 Measurement of Free Ca2+ in Live Cells 38
2.6.3 How the Ca2+ Signal is Generated 39
2.6.4 Identifying the Ca2+ Target 39
2.6.5 How Binding of Ca2+ to its Target Causes the Cell Event 39
2.6.6 How the Cell Returns to Rest 40
2.7 Nomenclature – How Things are Named 40
2.7.1 English and Etymology 40
2.7.2 Organisms 41
2.7.3 Acronyms, Cells and Biochemistry 41
2.7.4 Genes 42
2.7.5 Proteins and Protein Sequences 43
2.7.6 Enzymes 43
2.7.7 Ion Channels 44
2.7.8 Agonists and Antagonists 47
2.7.9 Chemicals 47
2.7.10 Toxins 48
2.7.11 Drugs 48
2.7.12 Ca2+ Indicators 49
2.7.13 Units 50
2.8 Model Systems 50
2.9 Darwin, Wallace and Intracellular Ca2+ 51
2.9.1 Natural Selection in Real Time 51
2.9.2 Small Change by Small Change 52
2.10 New Knowledge 54
2.11 Conclusions 55
Recommended reading 55
Books 55
Reviews 55
Papers 56
3 A Century plus of Intracellular Ca2+ 57
3.1 Background 57
3.1.1 Pathway of Discovery and Invention for Intracellular Ca2+ 57
3.1.2 Model Systems 58
3.2 Why Study the History of Science? 59
3.3 The Tale of Three Pioneers and What Followed 59
3.3.1 Experiments of Sydney Ringer (1836–1910) 59
3.3.2 The Vision of Lewis Victor Heilbrunn (1892–1959) 61
3.3.3 Setsuro Ebashi (1922–2006): Pioneer of Intracellular Ca2+ in Muscle Contraction 63
3.4 Ca2+ as an Intracellular Regulator 64
3.4.1 Cell Theory 65
3.4.2 Origin of the Use of Ca2+ 65
3.4.3 Manipulation of Ca2+ 66
3.4.4 Measurement and Location of Free Ca2+ in Live Cells 66
3.4.5 Identification of the Components Responsible for Regulating Free Ca2+ Inside Cells 71
3.4.6 Discovery of Plasma Membrane Ca2+ Pumps and Transporters 71
3.4.7 Discovery of How Ca2+ is Released from the Sarco-/Endo-Plasmic Reticulum 72
3.4.8 Discovery of IP3 and its Receptor 73
3.4.9 Discovery of the Ryanodine Receptor 73
3.4.10 Discovery of Store-Operated Calcium Entry (SOCE) 74
3.4.11 Discovery of Ca2+ Channels in the Plasma Membrane 76
3.4.12 Discovery of TRP Channels 78
3.4.13 Discovery of G-Proteins 78
3.4.14 Ca2+ Targets Inside Cells and How They Work 78
3.4.15 Intracellular Ca2+ in Plants 80
3.4.16 Intracellular Ca2+ in Bacteria 81
3.4.17 Pathology of Intracellular Ca2+ 81
3.5 Conceptual Development of Ca2+ as an Intracellular Regulator 82
3.6 Summary 84
Recommended Reading 86
Books 86
Reviews 86
Research Papers 86
4 How to Study Intracellular Ca2+ as Cell Regulator 89
4.1 Pathway to Discover the Role of Intracellular Ca2+ in a Cell Event 89
4.2 Manipulation of Intracellular Ca2+ 90
4.3 Measurement of Intracellular Free Ca2+ 92
4.3.1 Absorbing Dyes 93
4.3.2 Fluorescent Ca2+ Indicators 94
4.3.3 Calibration of Fluors 96
4.3.4 Ca2+-Activated Photoproteins 98
4.3.5 Calibration of Ca2+-Activated Photoproteins 102
4.3.6 Ca2+ Indicators from Engineered GFP 105
4.3.7 Other Free Ca2+ Indicators for Whole Organs and Organisms 109
4.4 Detecting and Imaging Photons 109
4.5 Measurement of Total Cell Ca2+ 113
4.6 Calcium Buffers 113
4.7 Measurement of Ca2+ Fluxes 115
4.8 How to Study Ca2+ Channels 116
4.9 Discovering How the Rise in Cytosolic Free Ca2+ Occurs and then
Returns to Rest 117
4.10 Discovering the Intracellular Ca2+ Target and How it Works 118
4.11 Other Ions 118
4.12 Summary 119
Recommended Reading 120
Books 120
Reviews 120
Research Papers 121
5 How Ca2+ is Regulated Inside Cells 123
5.1 Principles 123
5.2 How Resting Cells Maintain their Ca2+ Balance 126
5.3 Electrophysiology of Intracellular Ca2+ 127
5.4 Primary Stimuli Producing a Cytosolic Ca2+ Signal 130
5.5 Plasma Membrane Ca2+ Channels 131
5.5.1 Voltage-Gated Ca2+ Channels 131
5.5.2 TRP Channels 136
5.5.3 Receptor-Activated Ca2+ Channels 137
5.5.4 Mechanosensitive Channels 138
5.5.5 Store-Operated Calcium Entry (SOCE) 138
5.5.6 Ca2+ Receptor 139
5.6 Regulation of Intracellular Ca2+ by, and within, Organelles 140
5.6.1 Endo- and Sarco-Plasmic Reticulum (ER/SR) 140
5.6.2 Mitochondrial Ca2+ 146
5.6.3 Lysosomal and Endosomal Ca2+ 148
5.6.4 Secretory Vesicle Ca2+ 149
5.6.5 Peroxisomal Ca2+ 149
5.6.6 Control of Ca2+ by the Golgi 150
5.6.7 Nucleus and Ca2+ 150
5.6.8 Plant Organelles and Ca2+ 151
5.6.9 Acidocalcisomes 152
5.7 Second Messengers and Regulation of Ca2+ Signalling in the Cytosol 152
5.8 Pore Formers and Intracellular Ca2+ 154
5.9 Gap Junctions and Connexins 154
5.10 Other Ion Channels and Ca2+ 155
5.11 Summary – How Ca2+ is Regulated Inside Cells 156
Recommended Reading 157
Books 157
Reviews 157
Research Papers 158
6 How Ca2+ Works Inside Cells 161
6.1 Biological Chemistry of Ca2+ 161
6.1.1 The Special Biological Chemistry of Ca2+ 161
6.1.2 Key Chemical Properties of Ca2+ 164
6.1.3 Ca2+ Ligands 164
6.1.4 Solvation 166
6.1.5 Activity Coefficients 167
6.1.6 Fractional Ca2+ Binding After a Ca2+ Signal 167
6.1.7 Kinetics 169
6.1.8 Diffusion 169
6.1.9 Solubility 170
6.2 Ca2+-Binding Proteins 170
6.2.1 Ca2+-Binding Proteins Inside Cells 170
6.2.2 Proteins with the EF-Hand Motif 171
6.2.3 Proteins with the C2 Motif 177
6.2.4 Proteins with a Cluster of Acidic Residues 178
6.2.5 Proteins Forming a Cluster of Oxygen Ligands 179
6.3 Ca2+ and Other Intracellular Signals 182
6.3.1 Cyclic Nucleotides and Ca2+ 182
6.3.2 Ca2+ and Protein Kinase C (PKC) 184
6.3.3 Nitric Oxide and Ca2+ 184
6.3.4 Ca2+, Inositol Phosphates and Other Intracellular Signals 185
6.4 Ca2+ and Monovalent Ions 185
6.4.1 Intracellular Ca2+ and K+ Conductance 186
6.4.2 Intracellular Ca2+ and Na+ Conductance 187
6.4.3 Ca2+ and Chloride Channels (CaCC) 188
6.5 Other Cations and Intracellular Ca2+ 188
6.6 Anions and Intracellular Ca2+ 189
6.7 Summary 189
Recommended Reading 191
Books 191
Reviews 191
Research Papers 192
7 How Ca2+ Regulates Animal Cell Physiology 193
7.1 Principles 193
7.2 Ca2+ and How Nerves Work 194
7.3 Muscle Contraction 196
7.4 Chemotaxis and Ca2+ 202
7.5 Intracellular Ca2+ and Secretion 203
7.6 Ca2+ and Endocytosis 209
7.7 Ca2+ and Phagocytosis 210
7.8 Intracellular Ca2+ and Intermediary Metabolism 210
7.9 Intracellular Ca2+ and Cell Growth 212
7.9.1 Principles 212
7.9.2 Cell Cycle and Ca2+ 212
7.9.3 Fertilisation and Intracellular Ca2+ 214
7.9.4 Differentiation and Intracellular Ca2+ 216
7.10 Intracellular Ca2+ and the Immune Response 216
7.11 Intracellular Ca2+ and Vision 217
7.11.1 Ca2+ and Vertebrate Vision 218
7.11.2 Ca2+ and Invertebrate Vision 219
7.12 Intracellular Ca2+ and Other Senses 219
7.13 Ca2+ and Bioluminescence 220
7.14 Intracellular Ca2+ and Gene Expression 222
7.15 Summary 223
Recommended Reading 224
Books 224
Reviews 225
Research Papers 225
8 Intracellular Ca2+, Microbes and Viruses 227
8.1 The Puzzle 227
8.2 What Microbes Do 228
8.3 Indirect Evidence of a Role for Intracellular Ca2+ in Bacteria 228
8.4 Direct Evidence for a Role of Intracellular Ca2+ in Bacteria 230
8.5 How Much Ca2+ is there in Bacteria? 231
8.6 How Bacteria Regulate Their Intracellular Ca2 232
8.6.1 Ca2+ Influx into Bacteria 233
8.6.2 Ca2+ Efflux out of Bacteria 236
8.7 Regulation of Bacterial Events by Intracellular Ca2+ 236
8.7.1 Ca2+ and Growth of Bacteria 236
8.7.2 Ca2+ and Bacterial Movement 236
8.7.3 Quorum Sensing and Gene Expression 240
8.7.4 Ca2+ and Bacterial Metabolism 240
8.7.5 Bacterial Defence – Dormancy, Spore Formation and Germination 241
8.7.6 Bacterial Infection – Virulence, Competence and Defence 242
8.7.7 Development of Bacterial Structures 243
8.7.8 Ca2+ and Gene Expression in Bacteria 245
8.7.9 Uptake of Nucleic Acid by Bacteria 245
8.7.10 Bacterial Metabolic Toxin Hypothesis 246
8.7.11 Intracellular Ca2+ in Bacteria – Conclusions 246
8.8 Role of Intracellular Ca2+ in Archaea 247
8.9 Intracellular Ca2+ and Viruses 249
8.9.1 Eukaryotic Viruses 249
8.9.2 Bacterial Viruses – Bacteriophages 251
8.10 Intracellular Ca2+ and Eukaryotic Microbes 251
8.10.1 Yeast 252
8.10.2 Paramecium and Related Ciliates 254
8.10.3 Slime Moulds 255
8.10.4 Luminous Radiolarians 257
8.11 Summary 257
Recommended Reading 258
Books 258
Reviews 259
Research Papers 259
9 Role of Intracellular Ca2+ in Plants and Fungi 261
9.1 Role of Ca2+ in Plants 261
9.2 What Stimulates Plants? 262
9.2.1 Plant Cell Stimuli 262
9.2.2 Plant Hormones 263
9.2.3 Intracellular Signals in Plants 265
9.3 Requirement of Plants for Ca2+ 265
9.4 Where Ca2+ is Stored in Plants 266
9.5 Measurement of Cytosolic Free Ca2+ in Plants 267
9.6 Components of Ca2+ Signalling in Plants 271
9.6.1 Ca2+ Pumps and Exchangers 271
9.6.2 Ca2+ Channels in the Plasma Membrane 271
9.6.3 Plant Organelles and Ca2+ 272
9.6.4 Ca2+-Binding Proteins in Plants 273
9.6.5 Ca2+-Sensitive Genes in Plants 274
9.7 How Intracellular Ca2+ Provokes Cellular Events in Plants 274
9.7.1 Light and Intracellular Ca2+ in Plants 275
9.7.2 Control of Opening and Closing of Stoma/Stomata 275
9.7.3 Wind and Mechanical Stimulation of Plants 276
9.7.4 Gravity Sensing and Growth 276
9.7.5 Fertilisation, Germination and Differentiation 277
9.7.6 Legumes 278
9.7.7 Intermediary Metabolism 278
9.7.8 Transport by Phloem 279
9.7.9 Defence Against Stress 279
9.8 Fungal Elicitors 280
9.9 Apoptosis 281
9.10 Intracellular Ca2+ and Plant Pathology 281
9.11 Ca2+ in Mosses, Liverworts and Ferns 281
9.12 Ca2+ in Fungi 282
9.12.1 Fungi and Intracellular Ca2+ 282
9.12.2 Intracellular Ca2+ and Yeast 283
9.12.3 Lichens 284
9.13 Ca2+ and Slime Moulds 284
9.14 Summary 284
Recommended Reading 285
Books 285
Reviews 285
Research Papers 286
10 Pathology of Intracellular Ca2+ 287
10.1 What is Pathology? 287
10.2 Types of Pathology 288
10.3 Intracellular Ca2+ – Friend or Foe? 289
10.4 Intracellular Ca2+ and Cell Death 290
10.4.1 Necrosis 291
10.4.2 Apoptosis 292
10.4.3 Autophagy 294
10.4.4 Lysis 295
10.4.5 Cell Death Conclusions 295
10.5 Genetic Abnormalities in Ca2+ Signalling Proteins 297
10.5.1 Ca2+ Channelopathies 298
10.5.2 Ca2+ Pumpopathies 298
10.5.3 Mutations in ER Ca2+ Release Proteins 299
10.5.4 Mutations in Ca2+ Target Proteins 300
10.5.5 Proteins Associated with Ca2+ Signalling 300
10.6 Oxygen and Cell Pathology 300
10.6.1 Ca2+ Paradox 300
10.6.2 Oxidative Damage and Intracellular Ca2+ 302
10.7 Inappropriate Ca2+ Signalling 302
10.7.1 Cramp 303
10.7.2 Immune System and Other Organs in Disease 303
10.7.3 Bacterial Metabolic Toxins 304
10.8 ER Stress Response 306
10.9 Summary 308
Recommended Reading 309
Books 309
Reviews 309
Research Papers 310
11 Pharmacology of Intracellular Ca2+ 313
11.1 Background 313
11.2 Pharmacological Targets for Intracellular Ca2+ 316
11.3 Drugs Used Clinically on Intracellular Ca2+ 317
11.4 Anaesthetics 317
11.5 Ca2+ Channel Effectors 319
11.5.1 Classes of Ca2+ Channel Blocker 319
11.5.2 Dihydropyridines 321
11.5.3 Phenylalkylamines 322
11.5.4 Benzothiazapines 322
11.6 Hypertension 323
11.7 Arrhythmia, Tachycardia and Bradycardia 323
11.8 Angina 324
11.9 Heart Failure 324
11.10 Agents that Affect Adrenergic Receptors 325
11.11 Cardiac Glycosides 326
11.12 Benzodiazapines 326
11.13 Anti-Psychotic Drugs 327
11.14 Stimulants and Drugs of Abuse 327
11.15 Analgesics 327
11.16 Anti-Depressants and Manic Depression 329
11.17 Diabetes 329
11.18 Muscle Relaxants 329
11.19 Anti-Allergics and Anti-Immune Compounds 330
11.20 Xanthines 331
11.21 Substances Used Experimentally to Interfere with Intracellular Ca2+ 331
11.21.1 Ca2+ Buffers and Ionophores 332
11.21.2 Ca2+ Channels 332
11.21.3 Agents which Open or Close Voltage-Gated Ca2+ Channels 332
11.21.4 IP3 Receptor Activators and Blockers 333
11.21.5 Ryanodine Receptor Agonists and Antagonists 335
11.21.6 Plasma Membrane Ca2+ Pump and Exchanger Inhibitors 335
11.21.7 SERCA Pump Inhibitors 335
11.21.8 Compounds which Affect SOCE 336
11.21.9 Mitochondrial Blockers 336
11.21.10 Ca2+ Target Inhibitors 337
11.22 Natural Toxins and Poisons 339
11.22.1 Natural Stings, Bites and Other Toxin Events 339
11.22.2 Cone Snail Toxins – Conotoxins 340
11.22.3 Spider Toxins – Agatoxins 342
11.22.4 Scorpion Toxins 342
11.22.5 Pufferfish and Octopus Toxins 343
11.22.6 Jellyfish Sting Toxins 343
11.22.7 Hymenopteran Stings and Bites 344
11.22.8 Snake Venoms 345
11.23 Plant Toxins and Intracellular Ca2+ 345
11.24 Drugs and the Ca2+ Receptor 346
11.25 Bacteria 347
11.26 Ions and Intracellular Ca2+ 347
11.27 Antibodies and Intracellular Ca2+ 348
11.28 Manipulation of mRNA 349
11.29 Summary 349
Recommended Reading 350
Books 350
Reviews 350
Research Papers 351
12 Darwin and 4000 Million Years of Intracellular Ca2+ 353
12.1 Darwin and Calcium 353
12.2 Evolution and Ca2+ 357
12.3 What is Evolution? 357
12.3.1 The Word Evolution 357
12.3.2 The Process 358
12.3.3 Sequence of Earth’s Evolution 359
12.3.4 Ca2+ and Primeval Life 360
12.3.5 Ca2+ and the Origin of the Three Fundamental Cell Types 360
12.3.6 Timescale 361
12.4 Evolution of Ca2+ Signalling 362
12.4.1 Origin of Ca2+ Signalling 362
12.4.2 Membrane Potential 362
12.4.3 Evolution of Ca2+ Signalling Based on Protein Sequences 364
12.4.4 Evolution of Ca2+-Binding Sites 368
12.4.5 Origin of the EF-Hand 369
12.5 Darwin and Knock-Outs 371
12.6 Summary 373
Recommended Reading 375
Books 375
Reviews 375
Research Papers 376
13 They Think It’s All Over 379
13.1 Calcium and the Beauty of Nature 379
13.2 What We Know About Intracellular Ca2+ 380
13.2.1 Principles 380
13.2.2 The Pathway of Discovery 383
13.3 What We Don’t Know About Intracellular Ca2+ 385
13.4 Intracellular Ca2+ at School and University 387
13.5 The Inspiration of Intracellular Ca2+ 388
13.6 Communicating the Story of Intracellular Ca2+ to Others 391
13.7 The End of the Beginning 396
Recommended Reading 398
Books 398
Reviews 398
Research Papers 398
Subject Index 399
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