SYNAPSE 2:334-339 (1988)

Book Reviews GABAERGIC MECHANISMS IN THE MAMMALIAN PERIPH- Also, the sequence of chapters does not appear to fol-

ERY. Edited by Sandor L. Erdo and Norman G. Bow- low any order in that two chapters on the ovary are ery. Raven Press, New York, 1986. separated by one on the pancreas. This problem could

have been rectified by using subsections that would As a neuroscientist with many years of study devoted contain articles related to one specific organ. However,

to GABA neuronal function in the mammalian central the lack of such organization is partially compensated nervous system, I have overlooked in my readings many by the excellent subject index that is located at the end of the studies that have reported on GABA function in of the volume. This index facilitates finding the perti- the peripheral nervous system and in other organs of nent citations on a particular subject. the body. This volume is a welcome addition to my The overall quality of the chapters in this volume is library because it successfully provides the reader with high. They are well written and most of them are illus- a comprehensive review of GABAergic mechanisms in trated with line drawings, graphs or photomicrographs. such diverse non-brain structures as the autonomic gan- The list of references found at the back of each chapter glia, gut, urinary bladder, female genital tract, pitu- provides an excellent source for additional readings. itary, pineal gland, liver, adrenal medulla and the Many of the chapters have a summary at the conclusion vascular system. The editors are to be commended for of the text. Although i t is somewhat disappointing that compiling into this volume a number of review articles not all of the chapters have these helpful summary from experts on these subjects. To their credit, they have sections, it certainly does not detract from the useful- included 23 chapters as well as a lengthy Foreword that ness of this book. together form an impressive and useful volume. In conclusion, “GABAergic Mechanisms in the Mam-

The book is organized into two sections, Elements of malian Periphery” demonstrates that GABA is found in GABAergic Systems in Peripheral Tissues of Mammals many organs of the body and its presence in the periph- and Role of Local GABAergic Mechanisms in Peripheral ery is linked to some important functions. A usual ben- Organs. The first section covers the biochemical and efit of such books is to stimulate more research in a anatomical distribution of GABA, its associated en- field. I predict that this volume will foster further re- zymes (glutamate decarboxylase and GABA-transami- search interest in the mysteries of GABA in the nase) and receptors. The chapters in the second section periphery. explore GABAergic mechanisms in a number of organs and provide some functional significance. Unfortu- nately, the organization of the book has some flaws. For example, the illuminating Foreword by Eugene Roberts, a pioneer in GABA research in the brain and spinal cord, is not listed in the table of contents.

CHARLES E. RIBAK, h . D . Department of Anatomy and Neurobiology

Irvine, California 92717 University of California, Irvine

THE VERTEBRATE NEUROMUSCULAR JUNCTION. Edited by M. M. Salpeter. From the series Neurology and Neu- robiology 23. Alan R. Liss, Inc., New York, 1987, 439 PP . Seldom is any one textbook or review considered to be

truly essential reading for all workers in a field or dis- cipline. The Vertebrate Neuromuscular Junction, edited by M. M. Salpeter, provides such a thorough and coher- ent framework for understanding virtually all aspects of neuromuscular structure and function that it can truth- fully be described as essential reading for any serious investigator, clinician, or student of neuromuscular syn- aptic transmission.

The most basic property of neuromuscular synaptic transmission, that of vesicular quanta1 release, has a necessary consequent, which Salpeter and coworkers

0 1988 ALAN R. LISS. INC.

have designated the “saturating disk” model for post- synaptic receptor activation. In this extraordinary ref- erence book, the saturating disk model provides the conceptual framework for understanding endplate struc- ture in the normal adult vertebrate neuromuscular junc- tion, the shifting patterns of endplate organization during development, and the relevance of ultrastruc- tural alterations of pre- and post-synaptic components to the etiology of human neuromuscular disease, In the first chapter, the basic morphology and physiology of the neuromuscular synapse is described and the contribu- tions to normal synaptic transmission explained by ref- erence to the saturating disk model for ACh activation of post-synaptic membrane. This model is clearly ex- plained and beautifully illustrated using computer-sim- ulated Monte Carlo plots tracing ACh molecules from site of release through their interaction with post-syn-

335 BOOK REVIEWS

aptic ACh receptor molecules, and ultimately to their hydrolysis by acetylcholinesterase (AChE) enzymes 10- calized in the post-synaptic extracellular matrix. The molecular movements and interactions are simulated at 1 psec intervals over the time course of 15 psec to 2,000 psec following the onset of synaptic vesicle exocytosis. False-color is used advantageously to show free ACh molecules, singly- vs. doubly-ligated AChR, ACh bound to AChE, as well as alterations in the time course of AChR activation. The effects on time course and magni- tude of depolarization are also plotted with and without AChE and following inactivation of AChE, by anti-ChE agents. This innovative approach provides a significant advance to the understanding of the vesicular release hypothesis, and as such, is a tribute to the proper and skilled use of computer modeling for simulating molec- ular movements in confined compartments and for ex- amining alternative models of transmitterlreceptor interaction. Although not directly correlated with all subjects covered in this book (for example, substructure of the ACh receptor molecule), this review celebrates the major contributions that the saturating disk model has made to our current understanding of synaptic organi- zation at the NMJ.

The entire text is comprehensive, scholarly, and for the most part, extremely well written. Dr. Salpeter has exercised excellent editorial control of both content and organization. The chapters are uniformly excellent. They represent up-to-the-minute descriptions by acknowl- edged leaderslpioneers in their respective areas of syn- aptic physiology, biochemistry, and ultrastructure. Each of their respective chapters represents a broad overview as well as a detailed review of current research in the area. The chapters by Salpeter (#l, Morphology, and #2, Development), Jones (#5, Transmitter Release), Rotundo (#6, Acetylcholinesterase), and Engel (8, NMJ Diseases) are especially well written and easily comprehended, even for those not versed in the technical jargon of the respective scientific disciplines. Prof. Betz (Ch. #3, Syn- apse Elimination) often explains by analogy, which is a particularly difficult teleological device to master, since such comparisons are often meaningful only to the au- thor. Nevertheless, several of the analogies are espe- cially insightful and thought provoking. Other chapters describing detailed findings from esoteric disciplines (eg. “Ioos~” vs “tight” patch clamp; sequencing of cDNA for the ACh receptor subunits) do not represent light read- ing, but require detailed understanding of subtle differ- ences in methodologies used by diverse laboratories and frequent examination of the primary literature. Thus, the detailed bibliographies are extremely helpful in un- derstanding the significance and resolution of the con- troversies described.

Literature review and reference citations were thor- ough and representative of the much larger literature pool available (approximately 1,600 pertinent literature citations are presented in the 9 chapters, representing over 500 different literature citations). Omissions of im- portant or seminal research are minimal, especially con- sidering that the available literature for any one of the chapters numbers in the the thousands of references. Nevertheless, several important omissions should be noted. For example, in the chapter on acetylcholinester- ase (Rotundo), the original reference to the use of pro-

teases to dissolve the components of the basal lamina and to release AChE, thereby producing prolongation of the endplate currents (Albuquerque et al., 1968), has precedence to that of Hall and Kelly (1971) and Betz and Sakman (1973). The work of Albuquerque and coworkers was the first to counter the widespread belief that end- plate Ache was a protein embedded in the postsynaptic membrane (Koelle, 1951). Likewise, the reports of Rash et al. (1973) and Rash and Ellisman (1974) showing histochemical evidence that AChE sites are bound to filamentous components of the basal lamina, and that when dissected free of the endplate, retained enzymatic activity has precedence over that of McMahan et al. (1978). Unfortunately, computerized literature searches (as was used during the preparation of several of these manuscripts; Rotundo, personal communication) are not capable of finding such references, primarily because the older literature is characterized by papers with mul- tiple subject matter, some of which are not at all identi- fied in the titles. Perhaps this aspect of the computer age will force researchers either to write shorter papers addressed to single subjects, or to compose ever-longer titles containing every relevant term used by computer search programs.

The chapter by Engel (8, Human Neuromuscular Dis- eases) is both concise and beautifully written. However, I would like to have seen references included to some of the earlier literature on myasthenia gravis, especially those that provided the first clues that the disease was post-synaptic rather than presynaptic in origin. It would have been instructive to consider how the original intra- cellular electrophysiological recordings of Elmqvist and Quastel (1965) that claimed to show the absence of post- synaptic alterations were first called into question by electron microscopic images showing severe destruction of post-synaptic junctional folds (Kelly and Zacks, 1969). Those early images were easily dismissed because sev- eral were from dog rather than human endplates, while others were inappropriately dismissed a t the time as arising from “plane-of-section artifacts”. Dr. Engel rightly points out that the pioneering work of Patrick and Lindstrom (1973) and Fambrough et al. (1973) showing the development of MG-like symptoms follow- ing immunization with AChR proteins and the loss of a- BuTX binding sites in human MG were instrumental in shifting research interests back to the post-synaptic membrane. However, the work of Albuquerque, et al., (1973), showing that AChR function was severely im- paired in MG (not cited by Engel), was among the first to provide evidence contrary to that of Elmqvist and Quastel (1965), and was instrumental in overcoming the reluctance to attribute the MG lesion to post-synaptic alterations. Finally, Engel’s own work (Engel and Santa, 1971) showing breakdown of the architecture of the post- synaptic folds, provided the necessary proof of substan- tial post-synaptic destruction in human MG, and led us (Rash et al., 1976) and others (Sahashi et al., 1978) to search for components of the immune response at af- fected NMJs. Without doubt, the work of Engel and coworkers (Sahashi et al., 1978a and b) has been sem- inal in providing what is now overwhelming evidence for the humoral autoimmune etiology of human MG. His modest description of his pivotal role in the elucida- tion of the etiology of human MG can best be discerned

336 BOOK REVIEWS

by the relative effort needed to find other appropriate its way into this text, where it was substituted for its literature citations. proper cognate, “quantifying” (p.323). In two instances,

A final small reservation derives from statements in word omissions were noted that made reading the text the first chapter in which Dr. Salpeter dismissed all a matter of personal conjecture concerning exact mean- published accounts for a much lower number of AchR ing (cf. p. 289, 11.8-11). In most chapters, jargon and

in vertebrate NMJ than in Torpedo electroplax laboratory slang were kept to a minimum or were ex- (2,000-4,000/pm2 vs. 8,000-12,000/pm2) as being due to plained in context. In some cases, presumed jargon was “problems during specimen preparation.” This facile ex- not. Where they were not, confusion is to be expected. planation derived from deep-etch surface views of AChR For example, the description of measurement of “conver- in Torpedo electroplax may inappropriately discourage gence resistance through the Ringer hemisphere” (em- legitimate inquiry concerning molecular morphology/ phasis added) was confusing to this reader until it was receptor aggregation in vertebrate NMJ. Since of the recognized that electrical resistance was being mea- several laboratories describing mature or developing sured through a hemispherical volume of Ringer’s vertebrate NMJ [using both chemically-fixed as well as solution. ultrarapidly frozen endplates examined by both freeze- Despite these minor quibbles, I consider The Verte fracture and freeze-etch techniques], none have re- brute Neuromuscular Junction the most comprehensive traded their detailed estimates of IMP number (cf. Heu- and up-to-date reference work concerning neuromuscular ser et al., 1974; Rash and Ellisman, 1974; Rash et al., junction structure, function, and biochemistry. It covers 1978; Cohen and Pumplin, 1980; Peng and Nakajima, all major aspects of development, innervation, neuro- 1978; Peng and Cheng, 1981; KO, 1984), and since the trophic regulation, and disease etiology. As such, this reports of higher numbers of surface-exposed particles volume will become an essential reference work for any were from Torpedo electroplax, where a-BuTx binding investigator of neuromuscular transmission and couId sites are also 2- to %fold higher than in vertebrate easily serve as a primary reference text for any ad- NMJs, it seems more likely that the reported 4-fold vanced course in neurobiology or neurochemistry. Any difference may be real. The reported differences may laboratory contemplating or conducting research involv- reflect, for example, functional aspects of receptor aggre- ing any aspect of neuromuscular synaptic transmission gation within the hydrophobic domain of the membrane, that attempts to do so without consulting this ency- or they may indicate a splayed distribution (flower-petal clopedic reference will surely waste valuable time and display) of AChR on the exposed surface, which may resources. occur to maximize ACh binding. Regardless, the rejec- tion of all data from vertebrate NMJs based on infer- ences from deep-etch views from the functionally Colorado State University different Torpedo electroplax seems premature.

Finally, by my count, there is an average of only three typographical errors per chapter, some involving letter substitutions not identifiable by computerized “spell checker” programs (e.g. “It” substituted for “If”). The frequently encountered non-word, “quantitating,” found

JOHN RASH, h . D .

Department of Anatomy and Neuro b iology

College of Veterinary Medicine and Biochemical Sciences

Fort Collins, Colorado 80523

RESPIRATORY MUSCLES AND THEIR NEUROMOTOR CON- TROL. Edited by Gary C. Sieck, Simon C. Gandevia and William E. Cameron. Alan R. Liss, Inc., New York, 1987.

This volume summarizes the findings of over 50 pa- pers on respiratory regulation and the respiratory mus- cles presented at a n international symposium that took place in Los Angeles in 1986. The participants in the symposium are experts in this rather broad area of re- search and the volume is a timely and concise summary of recent investigations. The index is well constructed and the papers are, in general, well written.

The volume is divided into three parts. The first part on respiratory motor control includes sections on respi- ratory rhythmogenesis and suprapontine control of breathing. The second part on the respiratory motor neurons includes sections on afferent input to the respi-

ratory motor neurons, and the organization and recruit- ment of diaphragm motor units. The third part deals with respiratory muscle structure and function and is the best part of the volume. This section describes re- search on respiratory muscle metabolism, contractile and fatigue properties along with recent papers on the development of respiratory control, the effects of sleep and non-respiratory control of the diaphragm.

Many of the papers contain useful background mate- rial as well as new data. Reference lists accompanying each page allow the interested reader to pursue each topic covered in greater detail.

Some readers will be disappointed by the absence of summary chapters that help integrate the material pre- sented in the different sections of this volume. The book will be particularly useful to investigators already en- gaged in related research who want to be brought up to date. This book is crowded with data and new results