Nicotinic Acetylcholine Receptors: From Molecular Biology to Cognition Jean-Pierre Changeux and Stuart J. Edelstein Odile Jacob Publishing Corporation (2005) 284 pp., $99 hardcover.

The nicotinic receptor at the nerve muscle synapse of vertebrates mediates the fast synaptic actions of the chemical transmitter acetylcholine. This receptor was the first ligand-gated receptor and ion channel to be characterized in pharmacological, biophysical, biochemical, and molecular biological terms. The nicotinic acetylcholine receptor has served as the prototype of ligand-gated ion channels. It was the most studied and the best understood, and it provided the paradigm for the study of all the other ligand-gated receptors in the brain. In Nicotinic Acetylcholine Receptors, Jean-Pierre Changeux and Stuart Edelstein give us a panoramic overview of the research on this receptor in 15 crisp chapters. The first chapter provides a historical introduction beginning with John Langley’s Croonian Lecture of 1906, in which Langley outlined his evidence for the existence of a receptor to acetylcholine in skeletal muscle based on the action of nicotine and curare. The last chapter provides a modern discussion of nicotinic receptors and brain function. The 13 intervening chapters describe the molecular universe of the nicotinic receptor. This is a universe to which the senior author, Jean-Pierre Changeux, has contributed so much. In the course of this work, Changeux made several seminal contributions to the field of receptor biology that are outlined in this book, coauthored with Stuart Edelstein, Changeux’s longstanding colleague and contributor on allosteric mechanisms. The book is informative and interesting, providing Changeux and Edelstein’s unique view of the development of the field. Nicotinic Acetylcholine Receptors is written in an accessible manner, one that covers key steps in the evolution of the field but with a personal perspective, akin to a scientific memoir. As such, Nicotinic Acetylcholine Receptors provides an important and individual introduction to the field that should be particularly valuable to students. Last but not least, Nicotinic Acetylcholine Receptors is not only a scientific monograph from major contributors to the field but also an important publishing event. It marks the entry of Odile Jacob, one of France’s most important publishers, into the American publishing scene. There is no doubt that Changeux’s scientific work on acetylcholine receptors, as well as the efforts of a world-wide cadre of Changeux-trained investigators, has influenced how we all think about the structure and function of neurotransmitter receptors and their regulation on the molecular level. While still a student at Institut Pasteur with Jacques Monod, Changeux discovered allosteric interactions. He found that he could produce a loss in the ability of the enzyme threoninedeaminase to respond to feedback inhibitory signals without interfering with its catalytic activity. These observations made it clear that proteins could assume different conformational states and thereby integrate several different signals. The discovery of allosteric properties in proteins and his interest in neurobiology next led Changeux to work on the nicotinic acetylcholine receptor of the electric organs of electric fish as a postdoctoral fellow with David Nachmansohn at Columbia University. Changeux soon realized that the nicotinic acetylcholine receptor had the properties of an allosteric protein, an idea developed independently by Arthur Karlin. Changeux and Edelstein highlight the role of allosteric interactions in signal transduction, first in nAChRs and later generalizing this idea to all ligand-gated receptors. Influenced in his physiological thinking by Bernard Katz and in his biochemical approaches by David Nachmansohn, Changeux focused on the nicotinic acetylcholine receptor as a model for studying fundamental aspects of synaptic transmission. Changeux’s earliest contributions were key to work identifying the ACh receptor and its ion channel as a protein. This important step, in conjunction with Karlin’s separation and identification of the nAChR subunits, led the way to the subsequent cloning and sequencing of the subunits by Steve Heinemann and Toni Claudio, who first cloned the gamma subunit of the nAChR from Torpedo, and then by Numa and colleagues, who quickly followed with the cloning and sequencing of the alpha, beta, gamma, and delta subunits from mouse. As the next step in this work, Changeux showed that membrane fragments purified from the organs of the electric fish formed closed vesicles that contained functional receptors capable of conducting ions in response to the binding of ligand. The demonstration that cell-free vesicles could contain functional receptors was an important contribution to the field of receptor biology, especially in developing our understanding of the process of nicotinic AChR desensitization. The combined efforts and varied technical approaches of Changeux, Heinemann,