Fundamentals of Intracellular Calcium

Anthony K. Campbell

• Publisher: Wiley
• Year: 2017
• ISBN:
  9781118942024
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biochemistry
• Index: Biological Sciences

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 Ca 2+ 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.

1
Calcium is Special

Ja Kalzium, das ist alles!

Otto Loewi (1959)

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Learning Objectives

1. How everyday events in animals, plants and microbes depend on calcium as a molecular switch inside cells.
2. What is special about calcium (Ca²⁺) that evolution has selected it for this task?
3. How calcium was discovered.
4. The natural history of Ca²⁺.
5. The requirement of cells for Ca²⁺.
6. How Ca²⁺ is different from the 28 other elements used in biological processes.
7. The four biological roles of Ca²⁺ – structural, electrical, cofactor and intracellular regulator.
8. The molecular biodiversity of the intracellular calcium signalling system, vital in the process of Natural Selection revealed by Charles Darwin and Alfred Russel Wallace.

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This is the amazing story of a simple cation, Ca²⁺, upon which the whole of life on our planet depends. The bricks and mortar of life depend on the proteins coded for by DNA. But without intracellular calcium, cells, tissues and organisms cannot do anything. Ca²⁺ inside cells is the trigger for life, and its evolution over 4000 million years.

1.1 Calcium and Everyday Events

Who would have thought that the serenity of a Bach chorale, the succulent taste of a coq au vin with a nice glass of Côtes du Rhône, the sensuous smell of a flower meadow in spring, the pleasure we get from seeing a puffin as it flies out of its burrow for some more sand eels, or even the intellectual excitement of a successful experiment all depend on calcium? This is not the calcium in our bones and teeth, that most people think of, but rather tiny puffs of calcium inside the cells that are responsible for all our senses, our movements and the functioning of our brain. The fertilisation of our mother’s egg by our father’s sperm started our life on a wave of intracellular calcium, and our embryo then developed on calcium signals within the cells as they differentiated into tissues. We were born on a wave of uterine intracellular calcium, as we were thrust out into the world and started to breathe. Throughout our lives we grow, develop and function through intracellular calcium signals within all of our cells. If we are lucky enough to live until 100, we will have generated over 3000 million puffs of calcium within our heart cells to keep them beating. Finally, we will die on a wave of calcium, as it floods into the cells lacking oxygen, when our heart eventually stops beating. Changes in intracellular calcium tell a nerve terminal to fire, a muscle to contract, and a cell to secrete, divide or die. Calcium is a universal switch inside animal, plant and microbial cells from all the three domains – Bacteria, Archaea and Eukaryota. There are two defining principles:

1. Calcium, always as Ca²⁺, acts as a switch to instruct a cell to cross a threshold, a Rubicon, and do something. But, it is not the energy source.
2. The diversity of molecules that determine when and how a cell fires are a living example of Darwinian variation, upon which Natural Selection depends.

These are dependent on one universal property of cells. All living cells – animal, plant, fungal and microbe – maintain a very low free Ca²⁺ in their cytosol, in the sub-micromolar range. This results in a huge gradient of Ca²⁺ across the outer membrane, 10 000-fold in the case of our own cells. It is this calcium pressure that has allowed evolution to capitalise on the unique chemistry of calcium for it to act as a cellular switch.

1.2 Discovery of Calcium

Humphry Davy (177...

Table of contents

• Cover
• Title page
• Copyright
• fprise
• dedication
• About the Author
• Preface
• List of Acronyms
• About the Companion Web Site
• 1 Calcium is Special
• 2 Intracellular Calcium – Principles
• 3 A Century plus of Intracellular Ca2+
• 4 How to Study Intracellular Ca2+ as Cell Regulator
• 5 How Ca2+ is Regulated Inside Cells
• 6 How Ca2+ Works Inside Cells
• 7 How Ca2+ Regulates Animal Cell Physiology
• 8 Intracellular Ca2+, Microbes and Viruses
• 9 Role of Intracellular Ca2+ in Plants and Fungi
• 10 Pathology of Intracellular Ca2+
• 11 Pharmacology of Intracellular Ca2+
• 12 Darwin and 4000 Million Years of Intracellular Ca2+
• 13 They Think It’s All Over
• Index
• Eula