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Fundamentals of Intracellular Calcium

ISBN: 978-1-118-94187-4
464 pages
November 2017
Fundamentals of Intracellular Calcium (111894187X) cover image

Description

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.

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Table of Contents

About the author            

Preface               

Glossary of acronyms    

About the Companion Web site               

Chapter 1 Calcium is special        

1.1 Calcium and everyday events

1.2 Discovery of calcium               

1.3 A natural history of calcium 

1.3.1 Calcium by the sea               

1.3.2 Calcium in your wake-up call           

1.4 The elements of life               

1.5 The natural occurrence of calcium    

1.5.1 Isotopes of calcium             

1.5.2 Geology of calcium              

1.5.3 Calcium outside cells           

1.5.4 Calcium inside cells              

1.6 Requirement of cells for Ca2+            

1.6.1 Calcium in external fluids  

1.6.2 Requirement of cell types for calcium         

1.7 The four biological roles of calcium   

1.7.1 Structural 

1.7.2 Electrical across biological membranes        

1.7.3 Extracellular cofactor          

1.7.4 Intracellular regulator         

1.8 The puzzle about Ca2+ inside cells    

1.9 How important intracellular calcium has been in science        

1.10 Darwin and intracellular Ca2+           

1.11 The scene set          

1.12 ‘Ja Kalzium, das ist alles!’    

1.13 Calcium – the fundamentals             

1.14 Recommended reading      

Chapter 2 Intracellular calcium – principles          

2.1 Ca2+ and the concept of cell signalling            

2.1.1 Primary signals and intracellular Ca2+

2.1.2 The source of intracellular Ca2+

2.2 The problem              

2.3 Some key questions               

2.3.1 Question 1 – what is the primary stimulus and secondary regular(s)

2.3.2 Question 2 – what is the intracellular signal

2.3.3 Question 3 – how do the secondary regulators work

2.4 The types of intracellular Ca2+ signal               

2.4.1 Category of cell based on the Ca2+ signal

2.4.2 Types of Ca2+ signal

2.4.3 Ca2+ sparks, puffs and sparklets

2.5 The Rubicon principle             

2.5.1 Digital versus analogue cell events               

2.5.2 The Ca2+ signalling toolkit

2.5.3 Amplification mechansms

2.6 Key experiments to answer key questions   

2.6.1 Raising cytosolic free Ca2+ artificially

2.6.2 Measurement of free Ca2+ in live cells

2.6.3 How the Ca2+ signal is generated

2.6.4 Identifying the Ca2+ target

2.6.5 How binding of Ca2+ to its target causes the cell event

2.6.6 How the cell returns to rest

2.7 Nomenclature – how things are named         

2.7.1 English and etymology       

2.7.2 Organisms               

2.7.3 Acronyms, cells and biochemistry 

2.7.4 Genes       

2.7.5 Proteins and protein sequences    

2.7.6 Enzymes  

2.7.7 Ion channels           

2.7.8 Agonists and antagonists  

2.7.9 Chemicals

2.7.10 Toxins     

2.7.11 Drugs      

2.7.12 Ca2+ indicators   

2.7.13 Units       

2.8 Model systems         

2.9 Darwin, Wallace and intracellular Ca2+           

2.9.1 Natural Selection in real time

2.9.2 Small change by small change

2.10 New knowledge    

2.11 Conclusions              

2.12 Recommended reading      

Chapter 3 A century plus of intracellular calcium               

3.1 Background

3.1.1 The pathway of discovery and invention for intracellular Ca2+         

3.1.2 Model systems     

3.2. Why study the history of science?  

3.3 The tale of three pioneers, and what followed           

3.3.1 Experiments of Sydney Ringer (1835 – 1910)            

3.3.2 The vision of Lewis Victor Heilbrunn (1892 – 1959) 

3.3.3 Setsuro Ebashi (1922 – 2006) pioneer of intracellular Ca2+ in muscle contraction     

3.4 Ca2+ as an intracellular regulator      

3.4.1 Cell theory              

3.4.2 Origin of the use of Ca2+  

3.4.3 Manipulation of Ca2+         

3.4.4 Measurement and location of free Ca2+ in live cells             

3.4.5 Identification of the components responsible for regulating free Ca2+ inside cells 

3.4.6 The discovery of plasma membrane Ca2+ pumps and transporters               

3.4.7 The discovery of how Ca2+ is released from the sarco-/endo- plasmic reticulum    

3.4.8 Discovery of IP3 and its receptor   

3.4.9 Discovery of the ryanodine receptor           

3.4.10 Discovery of store operated Ca2+ entry (SOCE)   

3.4.11 Discovery of Ca2+ channels in the plasma membrane       

3.4.12 Discovery of TRP channels             

3.4.13 Discovery of G proteins   

3.4.14 Ca2+ targets inside cells and how they work          

3.4.15 Intracellular Ca2+ in plants             

3.4.16 Intracellular Ca2+ in bacteria         

3.4.17 Pathology of intracellular Ca2+     

3.5 Conceptual development of Ca2+ as an intracellular regulator            

3.6 Summary     

3.7 Recommended reading                        

Chapter 4 How to study intracellular Ca2+ as a cell regulator        

4.1 Pathway to discover the role of intracellular Ca2+ in a cell event        

4.2 Manipulation of intracellular Ca2+    

4.3 Measurement of intracellular free Ca2+        

4.3.1 Absorbing dyes     

4.3.2 Fluorescent Ca2+ indicators             

4.3.3 Calibration of fluors             

4.3.4 Ca2+-activated photoproteins        

4.3.5 Calibration of Ca2+-activated photoproteins            

4.3.6 Ca2+ indicators from engineered GFP         

4.3.7 Other free Ca2+ indicators for whole organs and organisms             

4.4 Detecting and imaging photons         

4.5 Measurement of total cell Ca2+        

4.6 Calcium buffers        

4.7 Measurement of Ca2+ fluxes             

4.8 How to study Ca2+ channels               

4.9 Discovering how the rise in cytosolic free Ca2+ occurs, and then returns to rest          

4.10 Discovering the intracellular Ca2+ target, and how it works

4.11 Other ions

4.12 Summary  

4.13 Recommended reading      

Chapter 5 How Ca2+ is regulated inside cells       

5.1 Principles     

5.2 How resting cells maintain their Ca2+ balance             

5.3 Electrophysiology of intracellular Ca2+           

5.4 Primary stimuli that produce a cytosolic free Ca2+ signal        

5.5 Plasma membrane Ca2+ channels    

5.5.1 Voltage-gated Ca2+ channels         

5.5.2 TRP channels          

5.5.3 Receptor-activated Ca2+ channels               

5.5.4 Mechanosensitive channels            

5.5.5 Store-operated Ca2+ entry (SOCE)               

5.5.6 Ca2+ receptor        

5.6 Regulation of intracellular Ca2+ by, and within, organelles    

5.6.1 Endo- and sarco- plasmic reticulum (ER/SR)              

5.6.1.1 Ryanodine receptor

5.6.1.2 Inositol trisphosphate (IP3) receptor

5.6.2 Mitochondrial Ca2+             

5.6.3 Lysosomal and endosomal Ca2+    

5.6.4 Secretory vesicle Ca2+       

5.6.5 Peroxisomal Ca2+

5.6.6 Control of Ca2+ by the Golgi            

5.6.7 Nucleus and Ca2+

5.6.8 Plant organelles and Ca2+

5.6.9 Acidocalcisomes   

5.7 Second messengers and regulation of Ca2+ signaling in the cytosol  

5.8 Pore formers and intracellular Ca2+ 

5.9 Gap junctions and connexins              

5.10 Other ion channels and Ca2+            

5.11 Conclusions              

5.12 Summary – how Ca2+ is regulated inside cells          

5.13 Recommended reading      

Chapter 6 How Ca2+ works inside cells  

6.1 Biological chemistry of Ca2+

6.1.1 The special biological chemistry of Ca2+     

6.1.2 Key chemical properties of Ca2+   

6.1.3 Ca2+ ligands           

6.1.4 Solvation  

6.1.5 Problem of activity coefficients      

6.1.6 Fractional Ca2+ binding after a Ca2+ signal

6.1.7 Kinetics     

6.1.8 Diffusion  

6.1.9 Solubility  

6.2 Ca2+ binding proteins            

6.2.1 Types of Ca2+ binding protein inside cells 

6.2.2 Proteins with the EF-hand motif    

6.2.2.1 Troponin C

6.2.2.2 Leiotonin

6.2.2.3 Calmodulin

6.2.24 Calmodulin-dependent kinases

6.2.2.5 Calcineurin

6.2.2.6 Calpains

6.2.27 Calsenilin and DREAM

6.2.2.8 Calbindin

6.2.2.9 S-100 proteins

6.2.2.110 STIM 1 and 2

6.2.2.11 Caldendrin/calbrain/calponin and caldesmon

6.2.3 Proteins with the C2 motif               

6.2.3.1 Synaptotagmins

6.2.3.2 Copines

6.2.3.3 Phospholipases and intracellular Ca2+

6.2.4 Proteins with a cluster of acidic residues    

6.2.4.1 Calsequestrin

6.2.4.2 Calreticulin

6.2.5 Proteins forming a cluster of oxygen ligands from the 3D structure

6.2.5.1 Annexins              

6.2.5.2 Calcimedins

6.2.5.3 Calelectrin

6.2.5.4 Gelsolin

6.2.5.5 Calcium homeostatic regulator (CALHM1)

6.2.5.6 Regucalcin

6.2.5.7 Other Ca2+-binding proteins in the SR/ER

6.2.5.8 Ca2+ pumps and exchangers

6.3 Ca2+ and other intracellular signals  

6.3.1 Cyclic nucleotides and Ca2+             

6.3.1.1 Ca2+ and adenylate cyclase         

6.3.1.2 Ca2+ and guanylate cyclase          

6.3.2 Ca2+ and protein kinase C (PKC)    

6.3.3 Nitric oxide and Ca2+          

6.3.4 Ca2+, inositol phosphates and other intracellular signals    

6.4 Ca2+ and monovalent ions  

6.4.1 Intracellular Ca2+ and K+ conductance       

6.4.1 Intracellular Ca2+ and Na+ conductance    

6.4.3 Ca2+ and chloride channels (CACC)              

6.5 Other cations and intracellular Ca2+

6.6 Anions intracellular Ca2+      

6.7 Summary     

6.8 Recommended reading                        

Chapter 7 How Ca2+ regulates animal cell physiology     

7.1 Principles     

7.2 Ca2+ and how nerves work 

7.3 Ca2+ and cell movement      

7.4 Muscle contraction 

7.5 Chemotaxis and Ca2+            

7.6 Intracellular Ca2+ and secretion        

7.6.1 Principles 

7.6.2 Neurosecretion    

7.6.3 Ca2+, the endocrine pancreas and insulin secretion             

7.6.4 Ca2+ and the salivary gland              

7.6.5 Ca2+ and the exocrine pancreas    

7.6.6 Ca2+ and the adrenal medulla        

7.6.7 Ca2+ and mast cells             

7.6 8 Ca2+, neutrophils and other phagocytes    

7.6.9 Ca2+ and platelets               

7.6.10 Ca2+ and nematocysts    

7.6.11 Ca2+ and coccolithophores            

7.6.12 Conclusions about secretion and intracellular Ca2+             

7.7 Ca2+ and endocytosis            

7.7.1 Principles 

7.7.2 Phagocytosis          

7.8 Intracellular Ca2+ and intermediary metabolism        

7.8.1 Ca2+ activation of glucose metabolism       

7.8.2 Ca2+ and mitochondrial intermediary metabolism

7.8.3 Ca2+ and lipolysis and lipogenesis 

7.9 Intracellular Ca2+ and cell growth     

7.9.1 Principles 

7.9.2 Cell cycle and Ca2+              

7.9.3 Fertilisation and intracellular Ca2+

7.9.4 Differentiation and intracellular Ca2+          

7.10 Intracellular Ca2+ and the immune response            

7.11 Intracellular Ca2+ and vision             

7.11.1 Ca2+ and vertebrate vision            

7.11.2 Ca2+ and invertebrate vision        

7.12 Intracellular Ca2+ and other senses               

7.13 Ca2+ and bioluminescence

7.14 Intracellular Ca2+ and gene expression       

7.15 Conclusions              

7.16 Recommended reading                      

Chapter 8 Intracellular Ca2+, microbes and viruses          

8.1 The puzzle  

8.2 What microbes do   

8.3 Indirect evidence of a role for intracellular calcium   

8.4 Direct evidence for a role of intracellular calcium       

8.5 How much Ca2+ is there in bacteria?               

8.6 How bacteria regulate their intracellular Ca2+             

8.6.1 Ca2+ influx into bacteria                    

8.6.2 Ca2+ efflux out of bacteria               

8.7 Regulation of bacterial events by intracellular Ca2+  

8.7.1 Ca2+ and growth of bacteria           

8.7.2 Ca2+ and bacterial movement        

8.7.2.1 Chemotaxis

8.7.2.2 Gliding

8.7.2.3 Swarming

8.7.3 Quorum sensing and gene expression        

8.7.4 Ca2+ and bacterial metabolism      

8.7.5 Bacterial defence - dormancy, spore formation and germination   

8.7.6 Bacterial infection - virulence, competence and defence   

8.7.7 Development of bacterial structures           

8.7.7.1 Heterocysts

8.7.7.2 Inclusion bodies

8.7.8 Ca2+ and gene expression in bacteria         

8.7.9 Uptake of nucleic acid by bacteria 

8.7.10 The bacterial metabolic toxin hypothesis

8.7.11 Intracellular Ca2+ in bacterial - conclusions             

8.8 Role of intracellular Ca2+ in Archaea

8.9 Intracellular Ca2+ and viruses             

8.9.1 Eukaryotic viruses

8.9.2 Bacterial viruses - bacteriophages 

8.10 Intracellular Ca2+ and eukaryotic microbes

8.10.1 Yeast       

8.10.2 Paramecium and related ciliates  

8.10.3 Slime moulds       

8.10.4 Luminous radiolarians      

8.11 Summary  

8.12 Recommended reading      

Chapter 9 Role of intracellular Ca2+ in plants and fungi  

9.1 Role of Ca2+ in plants             

9.2 What stimulates plants?       

9.2.1 Plant cell stimuli    

9.2.2 Plant hormones    

9.2.3 Intracellular signals in plants            

9.3 Requirement of plants for Ca2+        

9.4 Where Ca2+ is stored in plants           

9.5 Measurement of cytosolic free Ca2+ in plants            

9.6 Components of the Ca2+ signalling in plants

9.6.1 Ca2+ pumps and exchangers          

9.6.2 Ca2+ channels in the plasma membrane    

9.6.3 Plant organelles and Ca2+

9.6.4 Ca2+ binding proteins in plants      

9.6.5 Ca2+ sensitive genes in plants        

9.7 How intracellular Ca2+ can provoke cellular events in plants 

9.7.1 Light and intracellular Ca2+ in plants            

9.7.2 Control of opening and closing of stoma/stomata 

9.7.3 Wind and mechanical stimulation in plants

9.7.4 Gravity sensing and growth             

9.7.5 Fertilisation, germination and differentiation          

9.7.6 Legumes  

9.7.7 Intermediary metabolism 

9.7.8 Transport by phloem          

9.7.9 Defence against stress       

9.7.9.1 Wind

9.7.9.2 Water - drought or excess

9.7.9.3 High salinity

9.7.9.4 Low temperature

9.8 Fungal elicitors          

9.9 Apoptosis    

9.10 Intracellular Ca2+ and plant pathology         

9.11 Ca2+ in mosses, liverworts and ferns            

9.12 Ca2+ in fungi            

9.12.1 Fungi and intracellular Ca2+           

9.12.2 Intracellular Ca2+ and yeast          

9.12.Lichens      

9.13 Ca2+ and slime moulds       

9.14 Summary  

9.15 Recommended reading      

Chapter 10 Pathology of intracellular Ca2+           

10.1 What is pathology?               

10.2 Types of pathology               

10.3 Intracellular Ca2+ - friend or foe?   

10.4 Intracellular Ca2+ and cell death     

10.4.1 Necrosis 

10.4.2 Apoptosis              

10.4.3 Autophagy            

10.4.4 Lysis         

10.4.5 Cell death conclusions     

10.5 Genetic abnormalities in Ca2+ signalling proteins    

10.5.1 Ca2+ channelopathies     

10.5.2 Ca2+ pumpopathies         

10.5.3 Mutations in ER Ca2+ release proteins     

10.5.4 Mutations in Ca2+ target proteins              

10.5.5 Proteins associated with Ca2+ signalling  

10.6 Oxygen and cell pathology

10.6.1 The Ca2+ paradox              

10.6.2 Oxidative damage and intracellular Ca2+ 

10.7 Inappropriate Ca2+ signalling           

10.7.1 Cramp     

10.7.2 The immune system and other organs in disease

10.7.3 Bacterial metabolic toxins              

10.8 The ER stress response       

10.9 Summary  

10.10 Recommended reading    

Chapter 11 Pharmacology of intracellular Ca2+  

11.1 Background              

11.2 Pharmacological targets for intracellular Ca2+           

11.3 Drugs used clinically and intracellular Ca2+ 

11.4 Anaesthetics           

11.5 Ca2+ channel effectors       

11.5.1. Classes of Ca2+ channel blocker 

11.5.2. Dihydropyridines              

11.5.3 Phenylalkylamines            

11.5.4 Benzothiazapines              

11.6 Hypertension          

11.7 Arrhythmia, tachycardia and bradycardia    

11.8 Angina        

11.9 Heart failure            

11.10 Agents that affect adrenergic receptors   

11.11 Cardiac glycosides               

11.12 Benzodiazapines 

11.13 Antipsychotic drugs            

11.14 Stimulants and drugs of abuse      

11.15 Analgesics              

11.16 Anti-depressants and manic depression   

11.17 Diabetes 

11.18 Muscle relaxants 

11.19 Anti-allergics and immune compounds      

11.20 Xanthines               

11.21 Substances used experimentally to interfere with intracellular Ca2+           

11.21.1. Ca2+ buffers and ionophores   

11.21.2 Ca2+ channels   

11.21.3. Agents which open or close voltage-gated Ca2+ channels           

11.21.4 IP3 receptor activators and blockers       

11.21.5 Ryanodine receptor agonists and antagonists     

11.21.6 Plasma membrane Ca2+ pump and exchanger inhibitors               

11.21.7 SERCA pump inhibitors  

11.21.8 Compounds which affect SOCE 

11.21.9 Mitochondrial blockers 

11.21.10 Ca2+ target inhibitors  

11.22. Natural toxins and poisons            

11.23 Plant toxins and intracellular Ca2+               

11.24 Drugs and the Ca2+ receptor         

11.25 Bacteria   

11.26 Ions and intracellular calcium         

11.27 Antibodies and intracellular Ca2+ 

11.28 Manipulation of mRNA     

11.29 Summary

11.30 Recommended reading    

Chapter 12 Darwin and 4000 million years of intracellular Ca2+

12.1 Darwin and calcium               

12.2 Evolution and Ca2+               

12.3 What is evolution?

12.3.1 The word evolution          

12.3.2 The process          

12.3.3 Sequence of evolution    

12.3.4 Ca2+ and primaeval life   

12.3.5 Ca2+ and the origin of the three fundamental cell types  

12.3.6 Time scale             

12.4 Evolution of Ca2+ signalling               

12.4.1 Origin of Ca2+ signalling  

12.4.2 Membrane potential        

12.4.3 Evolution of Ca2+ signalling based on phylogenetic comparisons  

12.4.4 Evolution of Ca2+-binding sites    

12.4.5 The origin of the EF-hand               

12.5 Darwin and knock-outs       

12.6 Summary  

12.7 Recommended reading      

Chapter 13 They think it’s all over!          

13.1 Calcium and the beauty of Nature 

13.2 What we know about the details of intracellular Ca2+           

13.2.1 Principles

13.2.2 The pathway of discovery

13.3 What we don’t know about intracellular Ca2+          

13.4 Intracellular Ca2+ at school and University 

13.5 The inspiration of intracellular Ca2+               

13.6 Communicating the story of intracellular Ca2+ to others      

13.7 The end of the beginning   

13.8 Recommended reading      

Organism index               

Subject index   

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