Ion Channels of Excitable Membranes, Third Edition

  • Bertil Hille
Sinauer Associates, Sunderland, Massachusetts, 2001 $84.95 hardcover, pp 722 ISBN 0-878-93321-2 | ISBN: 0-878-93321-2

Every once in a while, a book comes along that not only summarizes a field but actually defines it. Bertil Hille, professor of physiology and biophysics at the University of Washington, wrote such a book with Ion Channels of Excitable Membranes, now in its third edition. The new edition of this modern classic brings the reader up to date in the important and rapidly growing field of ion channel research.

The modern era of ion channel studies began about two decades ago with two technical advances, the development of single-channel recording and the cloning of ion channels. The electrophysiological revolution dates from the publication (in 1980) by Sigworth and Neher of the first single-channel recordings made with what is now just called the 'patch clamp'. When a glass micropipette is pressed against a cell's surface, the glass seals onto the cell's membrane (forming a 'gigaseal') and permits the measurement of the tiny currents, fractions of a picoamp, that flow through the pore of a single channel. The molecular revolution, initiated with the cloning of acetylcholine receptor subunits by the Patrick and Heinemann and Numa laboratories in 1983, gave a molecular reality to the ion channel—which only a few years before had been a purely hypothetical entity—and permitted the primary structure of the channel to be determined and manipulated. The first edition of Hille's book appeared just after the start of the modern era; it summarized knowledge from the 'classical period' (1950–1980) and captured the excitement generated by the new methods that were just beginning to be applied. As the field grew and matured, the first and second editions of the book guided graduate students, postdoctoral fellows and researchers through the latest developments, both experimental and conceptual.

The third edition continues to be the authoritative source for information about ion channels. The writing is crisp and clear, the organization is logical and—importantly in a fast-moving field—the content is up to date. Although thoroughly modern, the book has consistently adopted an historical point of view, so one not only learns the latest information but also can follow the development of ideas. After an introductory chapter that provides motivation, nomenclature and essential biophysical concepts (for examples, Ohm's law, the concept of equilibrium potential and the beloved and ever-popular I–V curves), the remainder of the book is divided into two main parts. Part One covers the classical Hodgkin–Huxley theory and the basic descriptive facts about various channel types. The main emphasis is on the voltage-gated channels responsible for the electrical excitability of cells, but ligand-gated channels used in synaptic transmission, and other channel types that have special roles (in, for example, phototransduction and the release of intracellular calcium) are covered briefly, as is the important topic of neuromodulation and second-messenger signaling. In Part Two, the general principles and mechanisms that apply across channel types are explained. Here Hille reviews the relevant physical chemistry and biophysics (in a very readable form), the structure of ion channels and the mechanisms of gating and of ion permeation and selectivity.

The book concludes with two interesting chapters, the first of which places ion channels in their modern cell biological context. Because ion channels are not distributed evenly over the cell surface, their targeting to the right place (the 'trafficking problem') has provided an important model system for cell biologists studying the general question of how the right protein gets delivered to the right place at the right time. Ion channels—with their PDZ domains and other types of molecular 'Velcro'—have also provided an important system for cell biologists to study to determine how protein 'machines' are placed and maintained relative to other proteins for proper function.

The final chapter presents—as it has since the first edition, when the topic was completely new—a discussion of evolutionary relationships between channels. The attractively biomorphic phylogenetic trees, conceived and drawn by Hille himself, have always been an important feature of this final chapter, and their evolution parallels the changes that have occurred in thinking about evolutionary biology and reflects the increased knowledge provided by the many primary sequences that have recently become available.

For those who have depended on the earlier editions as a reference, this new version is a must. The third edition has expanded by over 200 pages. (The fifth edition will presumably be 1,600 pages, as the doubling time appears to be two editions.) Whereas the first edition was a combination of a long review article and an introduction to channel biophysics, as the field has expanded, the character of the book has evolved toward a more encyclopedic coverage. In the new edition, Hille has updated and expanded the treatment of channel structure, structure–function studies of permeation and gating, and the cell biology of ion channels, and he has added a new chapter on the role of channels in epithelial transport, intracellular signaling and intercellular coupling. Inside the front and back covers, Hille includes particularly useful data on the classification of ion channels and some relevant facts (such as values of constants and central equations).

This book is a model of monograph writing, and has been central in the development of ion channel studies, by both presenting the facts and providing a conceptual organization for the data. The new edition is even more important because it covers the dramatic advances of the past several years, including the first crystal structure of an ion channel and an increasingly refined picture of channel mechanisms derived by combining insights from the atomic-level structure with new information from clever structure–function studies.