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Ion Channels and Disease: Channelopathies
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by Frances M. Ashcroft
Sales Rank: 629858
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Discount: 13 %
$119.00
At Amazon
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Hardcover: 481 pages
Publisher: Academic Press; 1st edition January 15, 2000
Language: English
ISBN-10: 0120653109
ISBN-13: 978-0120653102
Product Dimensions:
10.2 x 7.2 x 1.1 inches
Shipping Weight: 2.6 pounds
From The New England Journal of Medicine, August 3, 2000
This book reviews a wide variety of congenital and acquired conditions caused by abnormalities in ion-transport mechanisms. It starts with a description of relatively simple channels that respond to voltage changes or certain cellular metabolites by a conformational change that opens the pore. These channels are closed by a cytosolic loop that plugs the pore. The book continues with more complex channels composed of multiple subunits of the same composition and controlled by other subunits with a different composition. The complexity increases in a last group of ion channels that regulate more than one type of ion passage and form an intrinsic part of certain receptors or combine ion-channel activity with a transport function for more complex molecules. The last few chapters describe interesting roles of ion channels in cell-cell communication by mediating electrical impulses or exchange of nutrients or regulatory signals. There are examples of autoantibodies that interfere with the function of channels, cells that transport channels from one site to another, and cells that excrete ion channels to kill their target cells by ruining their membrane resistance.
These discussions are preceded by a comprehensive and up-to-date summary of molecular biology, biochemistry, electrophysiology, and molecular genetics. This might be superfluous for some readers, whereas others might prefer more extensive textbooks, but in any case, this survey clearly defines the basis for understanding subsequent chapters.
The strength of this very readable overview is that its focus is disease. There is a uniform style throughout the book. Starting with descriptions of a few disease states related to a particular ion channel, the authors provide a model of the channel based on protein composition and structure derived from molecular biologic, biochemical, and crystallographic data. The often complex channel responses to depolarization and hyperpolarization, binding of regulatory ligands, and certain toxins are then explained on the basis of the model. Mutations that cause abnormal channel control are discussed and form the basis of the description of the clinical phenotype. The result is a fascinating voyage through the human and, in a few cases, animal body, showing the molecular defects in ion channels in diseases ranging from diabetes mellitus, deafness, and myotonia to cystic fibrosis and migraine, and all placed by the author under the common denominator "channelopathy."
A nice illustration of the foregoing is the voltage-gated sodium channel in muscle fibers. This channel is activated by positively charged residues in the channel that sense a voltage change and respond by triggering a conformational change described as a "helical screw model," which opens the channel. Binding of an intracellular inactivation "ball" connected to the channel binds to the pore, blocks further passage of ions, and closes the channel. It is clear that mutations that change the composition of the voltage-sensing domains, the structure of the inactivation ball, or the size of the acceptor domain for the inactivation ball will interfere with channel function. The results of such mutations are changes in voltage dependence or the time course of channel inactivation, resulting in enhanced muscle excitability or paralysis; both conditions sometimes occur in a single patient.
The often complex material in this book is illuminated by pleasing examples of channel malfunction in everyday life. Eating too much of the Japanese delicacy fugu (puffer fish) increases the intake of tetrodotoxin, which plugs the voltage-gated sodium channel and can be fatal. Charybdotoxin in scorpion venom blocks the voltage-gated potassium channel. Certain goats with a defect in a skeletal-muscle chloride channel fall over every time a train passes their field. The gene that causes certain mutant fruit flies to shake their legs when anesthetized with ether codes for a voltage-gated potassium channel and is called "ether-a-go-go."
The book is richly illustrated with single-channel-current recordings of the relevant ion channels; hierarchical classification schemes for the relevant genes; tables listing locations of chromosomes, the distribution of various ion channels in tissue, mutations, and related protein abnormalities; and colored models based on crystal structures. There are a few tracings and listings meant for the insider, but in general, the illustrations contribute greatly to the clarity of the chapters. An extensive index helps readers locate all this information, and the bibliography is up to date, with references as recent as 1998. This book will help readers to review basic knowledge regarding muscle and neuronal activity, the functions of the kidney and the eye, and the intracellular events that make cells excrete water, activate signaling pathways, and prevent apoptosis.
J.W.N. Akkerman, Ph.D.
Copyright © 2000 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
Blanche Schwappach, Universitate Heidelberg, in Nature Cell Biology, September 2000
"provides all the background knowledge necessary to understand the field. manages to communicate complex ideas with clarity, precision and efficiency."
Customer Reviews & Comments
This is a lucid discussion of the role of ion channels in disease. It begins with a wonderful introduction to molecular biology and physiology of ion channels suitable for neophyte as well as the seasoned investigator. Then individual ion and ligand gated channels are discussed in individual chapters. After the basic properties of each channel are introduced, diseases of the channels are discussed.
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Ion Channels and Disease: Channelopathies
Discount: 13 %
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Price: $119.00
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