Ion channels are membrane proteins that act as gated pathways for the movement of ions across cell membranes. They play essential roles in the physiology of all cells. In recent years, an ever-increasing number of human and animal diseases have been found to result from defects in ion channel function. Most of these diseases arise from mutations in the genes encoding ion channel proteins, and they are now referred to as the channelopathies. Ion Channels and Disease provides an informative and up-to-date account of our present understanding of ion channels and the molecular basis of ion channel diseases. It includes a basic introduction to the relevant aspects of molecular biology and biophysics and a brief description of the principal methods used to study channelopathies. For each channel, the relationship between its molecular structure and its functional properties is discussed and ways in which genetic mutations produce the disease phenotype are considered. This book is intended for research workers and clinicians, as well as graduates and advanced undergraduates. The text is clear and lively and assumes little knowledge, yet it takes the reader to frontiers of what is currently known about this most exciting and medically important area of physiology. Introduces the relevant aspects of molecular biology and biophysics - Describes the principal methods used to study channelopathies - Considers single classes of ion channels with summaries of the physiological role, subunit composition, molecular structure and chromosomal location, plus the relationship between channel structure and function - Looks at those diseases associated with defective channel structures and regulation, including mutations affecting channel function and to what extent this change in channel function can account for the clinical phenotype 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 interfer