Chemical and Molecular Basis of Nerve Activity by David Nachmansohn (review)

BOOK REVIEWS Chemical and Molecular Basis of Nerve Activity. By David Nachmansohn. New York: Academic Press, Inc., 1959. Pp. xi+235. $7.50. In this book we find a large amount ofimpressive information on the enzymes which are concerned with the synthesis and hydrolysis ofacetylcholine. It also gives us an interesting account ofI. B. Wilson's discovery ofpotent antidotes to Cholinesterase inhibitors. But this work has been reviewed before and is only indirectly linked to the author's main theme, which is the universal role of acetylcholine in the conduction ofnerve impulses. This is a generalization which Dr. Nachmansohn proposed some twenty years ago and has been defending with increasing vigor ever since. In die past, his thesis did not gain general acceptance, and the main purpose ofthis monograph, I take it, is to remedy that situation. The author states diat diere is a gulfbetween neurophysiologists who regard the nerve impulse as a purely physical event and himself, who believes in die participation ofchemical reactions. This seems to me to be a false line ofdivision; the real difference ofopinion concerns a much more specific point. It is known that the nerve impulse depends upon a special relation between membrane voltage and ionic permeability. Most physiologists admit diat the origin ofthis relation is as yet unknown, and also that die role, ifany, of acetylcholinewidiinthe nerveaxonis quite obscure. Dr.Nachmansohn, however, attempts to bridge these gaps in our knowledge; inshort, he proposes thatacetylcholine isreleased during the rise ofthe action potential, produces the required permeability change, and is hydrolyzed during the falling phase. I have searched the pages ofthis monograph for a piece ofdirect evidence to substantiate this view but, as on previous occasions, failed to find it. The audior's argument still rests on indirect evidence, die two principal observations being that diere is Cholinesterase near the surface ofthe cell and that large doses of anti-esterases, sufficient to inhibit intracellular acetylcholine hydrolysis, will block the impulse. This seems to me to be about as cogent as the argument diat because there is Cholinesterase indie placenta, and because the audior's dose ofeserine would undoubtedly be ledial, therefore the human race owes its power ofpropagation to die action ofacetylcholine . The audior's observations suggest that Cholinesterase activity may be connected in some way widi the maintenance ofthe cell function, but hardly more dian that. The doubt attached even to this guarded interpretation becomes apparent on pages 147-52, where the author admits thatblockage ofdie impulse may, after all, be due to some other action of die drug, such as a combination with "acetylcholine-receptors," or with some unspecified lipid, component of die membrane. The weakness of the much more farreaching conclusions which Dr. Nachmansohn bases on his findings has been pointed out inextenso before (see, e.g., del Castillo and Katz, Progress in Biophysics, 6:128, 1956), and it is surprising diat the audior continues to ignore this criticism. Much emphasis is laid on a correlation found during a comparative study ofdifferent 563 electric organs. The voltage ofdie electric discharge is shown to vary in direct proportion to the Cholinesterase content. But die pertinent common factor in this relation is die number of cells which are arranged in series. Moreover, the active surface of diese cells is known to receive a rich supply ofcholinergic nerve endings, and it is therefore hard to see anything decisive in this evidence. To overcome the old stumbling block that little or no effect ofacetylcholine and curare can be seen in nerve or muscle fibers, and yet so much at certain celljunctions, Dr. Nachmansohn proposes that the fibers are surrounded by diffusion barriers, while synapses or end-plates are not. In an earlier review, he claimed diatdiese diffusion barriers can be overcome byintracellularapplicationofthedrug, butdiishasbeendisputed, andNachmansohn now admits that his earlier evidence may have been incorrect. In fart, it is now known that even at the motor end-plate, drugs like acetylcholine and curarme are effective only if they are applied to die external surface ofthe cell and not from within the muscle fiber. Thus, the audior is driven to the assumption diat, in muscle, there are diffusion barriers everywhere except on the outside of die end-plate...