Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 356
OCR for page 357
DAVID NACHMANSOHN
March 17, 1899-November2, 1983
BY SEVERO OCHOA
DA V ~ D N A C H M A N S O H N S scientific lifepath was strongly
influenced by his early studies on the biochemistry of
muscle in Otto Meyerhof's laboratory. This experience led to
an interest in the biochemistry of nerve activity, a field of
study to which he wouIcl devote most of his scientific life. In
so doing, he contributed perhaps more than any other in-
vestigator to our understanding of the molecular basis of
bioelectricity.
David Nachmansohn was born in Jekaterinoslav, Russia
(now Dnjetropetrowsk, USSR). His parents came from
mid(lle-cIass families among whom were many lawyers, phy-
sicians, anc! other professionals. Before David and his two
sisters reacher! school age, the family moved to Berlin where
they had many relatives. Thus, Davicl's background and eclu-
cation were essentially, if not exclusively, German. His college
education was strongly humanistic, with Latin, Greek, liter-
ature, and history as mainstays, some mathematics, and the
rudiments of physics. Through his readings, perhaps pri-
marily through his reacting of the second part of Goethe's
Faust when he was only seventeen years of age, he became
interested in philosophy—so much so that he continued to
attend courses anc! seminars in philosophy even while a med-
ical student at Heidelberg in 1920.
357
OCR for page 358
358
BIOGRAPHICAL MEMOIRS
When he entered the University of Berlin in the spring
of HIS, Davict was strongly oriented toward the humanities.
After Germany's defeat in World War I, however, the newly
establishe(1 republic face(1 grave social, political, and eco-
nomic problems, ant] David was advisect to study medicine, a
profession that could provide economic indepenclence. He
accepted this advice and became a medical student; but as
time went on, he became more and more interested in biol-
ogy through his avid readings about the lives and scientific
accomplishments of Bernard, Pasteur, Helmholtz, Ehrlich,
and others. Eventually, he deciclect to devote his life to bio-
mectical research and after his graduation in 1924 joined the
laboratory of Peter Rona at the Charite for training in bio-
chemistry.
The Charite was the university hospital of Berlin Univer-
sity Medical School in whose Department of Pathology Rona
directed a division of biochemistry. There, Nachmansohn
joine(1 an exceptional company of bright young people:
among them, Fritz Lipmann, Hans Adolph Krebs, Ruclolph
Schoenheimer, Ernst Chain, Karl Meyer, and Hans H. Weber.
Nachmansohn's first paper, "Vital Staining and Adsorption,"
was publisher! in collaboration with Krebs, an endeavor that
began a lifelong friendship between the two. Nachmansohn
also (lic1 some collaborative work with Weber that lecl to the
publication of a paper entitIec3, "The Independence of Pro-
tein Hydration anti lonisation."
At Rona's, he became familiar with the work of the great
Dahiem biochemists Meyerhof, Warburg, and Neuberg,
which he found fascinating. Weber adviser! Nachmansohn to
go to Otto Meyerhof at the Kaiser-Wilhelm Institut fur Biol-
ogie in Berlin-DahIem for further training. But when Nach-
mansohn approached Meyerhof, the eminent researcher in-
formec! him abruptly that he die] not accept beginners a
position he reversed after speaking with the young Nach-
OCR for page 359
DAVID NACHMANSOHN
359
mansohn awhile. In Meyerhof's laboratory, Nachmansohn's
postcloctoral contemporaries included Fritz Lipmann, Her-
mann Blaschko, Francis O. Schmitt, and this author. Karl
Lohmann, who later discovered ATP, was Meyerhof's assist-
ant, and Dean Burk was a visiting scientist. Hans Krebs was
also in the same building, in Otto Warburg's laboratory.
Nachmansohn often mentioned that it was Meyerhof who
had had the most profound! impact on his later work anct
scientific outlook.
Nachmansohn joined the Meyerhof laboratory in ~ 926.
At that time, Grace and Philip Eggleton at the Cambridge
biochemical laboratory had recently discovered a new phos-
phorylated compound in muscle they called "phosphagen"
because it liberated inorganic phosphate cluring contraction.
Soon thereafter, Fiske anc! Subbarow at Harvard Medical
School showed the new compound to be phosphocreatine in
which phosphate is linked to creatine through a phosphoam-
icle boncI.
During this period, Meyerhof was interested in the ener-
getics of muscular contraction. He worked to determine, as
he had previously with various hexose phosphates, the heat
of hy(lrolysis of phosphocreatine. It proved to be very high-
of the order of 10,000 to 12,000 calories per mole- which
contrasted with the low heat of hyclrolysis of hexose phos-
phates (1,500 to 3,000 calories per mole). This finding en-
ablec! researchers to ctistinguish between high- and low-
energy compounds in metabolism. (Some years later, it was
shown that the breakdown of ATP to ADP and inorganic
phosphate was the energy-yielding process more immedi-
ately related to muscular contraction, whereas the break-
down of phosphocreatine served to resynthesize the AT P.
Lactic acid formation, most of which took place after con-
traction, was like phosphocreatine breakdown—a recovery
process aimed at restoring rapidly the relatively small ATP
OCR for page 360
360
BIOGRAPHICAL MEMOIRS
stores of resting muscle. Finally, the glycogen that gave rise
to the lactic acid was resynthesized from lactic acid using the
energy released by officiation of a fraction of the lactic acic!
produced).
These clevelopments fascinated the young David Nach-
mansohn and greatly influenced his later work. During his
early years in Meyerhof's laboratory, the function of phos-
phocreatine was unknown, and interest in this compound
was very strong. It is therefore not surprising that Nachman-
sohn was given the assignment of looking for the relations
among phosphocreatine breakdown, lactic acict formation,
and the tension cleveloped by muscle during isometric con-
traction in anaerobiosis. He also compared the phosphocrea-
tine content of cli~erent kinds of muscle, especially muscles
slivering in the rapidity of their contraction. He found that
rapidly contracting muscles contained much more phospho-
creatine than slowly contracting ones, a fact that was consis-
tent with, and in a way foretold, the function of phospho-
. . .
creating In muscular contraction.
Nachmansohn viviclly clescribed the atmosphere at Dah-
lem in the 1920S2 when several Kaiser-Wilhelm research in-
stitutes were concentrated in a relatively small area: the In-
stitute of Physical Chemistry, with Haber, l~adenburg,
Polanyi, Freun~llich, and Bonhoeffer; the Institute of Chem-
istry, with Beckmann, WilIstatter, Otto Hahn, and Lise
, . 1 ~ ~ ~ ~ . ~ ~ .
... . ~ ~ . ~
Meatier; the Neuberg Institute of Biochemistry; and the In-
st~tute ot Biology, with Meyerhof, Warburg, Gol(lschmidt,
Correns, and Hartmann. The young Nachmansohn was par-
ticularly stimulates! by the "Haber Colloquia" in which Fritz
Haber, the discoverer of the process for conversion of nitro-
gen and hydrogen into ammonia, attempted to bridge the
' Nachmansohn Ascribed these influences in an unpublished manuscript entitled
"Molecular Aspects of Bioelectricity: An Autobiography."
2 David Nachmansohn, "Molecular Aspects of Bioelectricity"; "Biochemistry As
Part of My Life," Annual Review of Biochemistry 41(1972):1-27.
OCR for page 361
DAVID NACHMANSOHN
361
gap between physicists, chemists, and biologists so as to pro-
mote better unclerstancling and cooperation among them.
Nachmansohn credited these monthly colloquia, which were
regularly attencled by many members of the various insti-
tutes, with having greatly expanclect his scientific and spiri-
tual horizons.
Like so many others of Jewish origin, Nachmansohn left
Germany when Hitler came to power. He was offerer! the
opportunity of working at the Sorbonne, and in 1933 estab-
lishecl himself in Paris with his wife, Edith, ant! their baby
daughter, Ruth. From Paris, Nachmansohn made several vis-
its to London, only a few hours away, to attend meetings of
the British Physiological Society. As he explainect in the 1972
autobiographical article in the Annual Review of Biochemistry,
he could never have anticipated that, by attending those
meetings, his scientific interests wouIc] take a new, unex-
pectec! turn. He conic! also not have preclictect that this new
turn wouIc! determine the direction of his scientific work for
the rest of his life.
At that time, one of the main topics of discussion in the
London meetings was the role of acety~choline in nerve ac-
tivity. Following the pioneering work of Otto Loewi and of
Dale and his colleagues, Dale proposed that acety~choline acts
as a transmitter of nerve impulses across junctions (synapses)
between neurons or between nerve and muscle, in contrast
to the electric currents that propagate impulses along nerve
ant! muscle fibers. This idea was supported by two main lines
of observations: (~) the release of acety~choline at synaptic
junctions, as judges! by its appearance in the perfusion fluid
of certain ganglia, or striated muscle motor enclplates, upon
electrical stimulation of the adherent nerves; and (2) the pow-
erful stimulating action of acety~choline when applied locally
to synaptic junctions, which was in striking contrast to its
failure to elicit a response when applied to nerve fibers.
Acety~choline was known to be rapidly hy(lrolyzecl by an
OCR for page 362
362
BIOGRAPHICAL MEMOIRS
enzyme, acetylcholine esterase, which is strongly inhibited by
the alkaloid, eserine. In fact, no acetylcholine was found in
the perfusion fluid of stimulated ganglia unless the fluid con-
tained eserine, an indication that the acetylcholine released
by electrical stimulation was rapidly hydrolyzed.
It seemed to Nachmansohn that much more knowledge
was needler} on the nature, distribution, and concentration of
acety~choline esterase in various tissues and that such infor-
mation might provide clues to the role of this enzyme in
nerve activity. He began work on this problem in Paris in
1936 and soon fount! that acetylcholine esterase was present
at high concentrations in many different types of excitable
fibers of nerve and muscle ant! in brain tissue, in both ver-
tebrates and invertebrates; it was hardly detectable, however,
in such organs as the liver or kidney. In aciclition, the con-
centration appeared! to be several-fold higher at the neuro-
muscular junctions than in the nerve fibers.
In his study of the literature on the neuromuscular junc-
tion, Nachmansohn came across an article by I. Linhard in
which the electric organs of fish were clescribect as moclified
muscle fibers, comparable to motor en(lplates, in which the
muscular elements were either missing or present only in
rudimentary form. He thought it would be of interest to cle-
termine the acety~choline esterase content of electric tissue.
Nachmansohn had happened to see live Torpedo at the 1937
Paris Worlds Fair; he manager! to procure some for study
and found the concentration of acety~choline esterase in the
electric organ to be exceedingly high. In his own words, "The
result was simply stunning: ~ g of electric tissue (fresh weight)
hyclrolyzecl 3-4 g of acetylcholine per hour, although the
tissue is 92% water ant! only 3% protein."3
3 David Nachmansohn, "Biochemistry As Part of My Life," Annual Review of Bio-
chemistry 45(1972):1-27.
OCR for page 363
DAVID NACHMANSOHN
363
The importance of this discovery, which opened the way
for the elucidation of the molecular mechanisms involved in
the generation of bioelectricity, can hardily be overestimated.
In collaboration with Egar Lederer, Nachmansohn soon used
the electric organ of the Torpedo fish to purify acety~choline
esterase. (This work was reported in a 1939 paper publishect
in the Bulletin de la Societe de Chimie Biologique EParis].) In ad-
clition, Nachmansohn carries] out experiments on the same
organ in June 1939 at the Marine Biological Station at Ar-
cachon, near Bordeaux. Together with W. Feldberg (a phar-
macologist from Dale's group) ant! A. Fessarc! (an electro-
physiologist at the Sorbonne), Nachmansohn provider} the
first unequivocal evidence for the electrogenic action of ace-
ty~choline; the results were published in 1940 in the Journal
of Physiology.
His next paper on electric tissue, prepared in colIabora-
tion with C. W. Coates and R. T. Cox, was publishecT from
Yale in 1941 in the journal of General Physiology. This paper
dealt with the correlation between the electrical potential and
the acety~choline esterase content of different sections of the
electric organ of the electric eel. The use of electric tissue
later made possible the crystallization and biochemical char-
acterization of acety~choline esterase in Nachmansohn's lab-
oratory as well as the isolation of choline acetylase anct the
acety~choline receptor.
In 1939, John Fulton invitec! Nachmansohn to join his
department at Bale University. He stayed in New Haven until
1942, when he mover! to Columbia University and became
associated with the Departments of Neurology and Biochem-
istry at the College of Physicians and Surgeons. In New Ha-
ven, he hac] aIreacly begun to work with the electric organ of
the electric eel (which he obtainer! from the New York Aquar-
ium) and found not only that the acety~choline esterase con-
centration was as high as in Torpedo but that the electric tissue
OCR for page 364
364
BIOGRAPHICAL MEMOIRS
contained phosphocreatine and ATP in concentrations com-
parable to those in striated muscle. Furthermore, the electri-
cal discharge was accompanied by phosphocreatine break-
down. These observations suggested to him that the energy
required for resynthesis of the acety~choline hydrolyzect clur-
ing the electrical discharge was supplied by the same pro-
cesses that provide the energy required for muscular con-
traction, namely ATP ant! phosphocreatine breakdown, lactic
acid formation, anti, in the last instance, carbohydrate oxi-
clation.
Soon after Nachmansohn moved to Columbia, he tested
the Plea that electric tissue contains enzymes capable of uti-
lizing the energy of ATP for the acetylation of choline, an
idea that indeed prover! to be the case. This was, in many
respects, key because it was the first time that ATP was found
to drive a synthetic reaction other than through phosphory-
lation. Nachmansohn soon found that choline acetylase, the
enzymeks) responsible for the acetylation reaction, requires!
a coenzyme because the activity of the acetylase-containing
extracts was lost after dialysis ant! was restorer! by the addi-
tion of boiled enzyme. The identity of this coenzyme re-
mainec! obscure, however, until Lipmann and coworkers
found that an enzyme catalyzing the formation of acetyIsul-
fonamicle from ATP, acetate; and sulfonamicle also required
a coenzyme (coenzyme A, or CoA for short) for activity. They
elucidates! the structure of this coenzyme in 1947.
The discovery of choline acetylase was published by Nach-
mansohn ant! Machaclo in the journal of Neurophysiology in
~ 943. Ironically, three journals (Science, Journal of Biological
Chemistry, and Proceedings of the Society for Experimental Biology
and Medicine) refused to publish this eminent and trail-
blazing biochemical paper. The reviewers apparently could
not believe that ATP would participate in reactions other
than phosphorylations. In retrospect, they cannot be blamed
OCR for page 365
DAVID NACHMANSOHN
365
for their skepticism because Nachmansohn's finding was to-
tally unexpected. Acetylation was eventually found to result
from the coupling of two reactions: (~) ATP + acetate +
CoA ~ AMP + inorganic pyrophosphate + acetyI-CoA; and
(2) acety! CoA + choline (or sulfonamicle) ~ CoA + acetyI-
choline (or acetyI-sulfonamide).
Work proceeded in a number of laboratories on the To-
calization of acety~choline esterase using biochemical assays
(e.g., of the extrucled axoplasm and the sheath of the giant
axon of the squid) and electron microscopic observations.
The results of these studies macle it appear highly probable
that the enzyme was a component of excitable membranes
everywhere not only of synaptic membranes but also of the
membranes of axons anct conducting fibers in general. In his
Harvey Lecture entities! "Metabolism and Function of the
Nerve Cell" (cleliverec} in 1953 and publishecl in 1955), Nach-
mansohn acivanced the view that acety~choline acts as a signal
recognizes! within the membrane by an acety~choline recep-
tor protein; this results in a conformational change that leacis
to increased local permeability to ions and membrane depo-
larization, thus generating an action potential an idea that
prover! to be correct. Ernest Schoffeniels, in Nachmansohn's
laboratory, was able to isolate the electroplax, the single-
celled elementary unit of electric tissue, which was found to
be extremely rich in acety~choline esterase ant] receptor
protein.
If one considers that receptors are now recognized as the
initial elements in the response of all cells to specific stimuli
and that the concept originated with the acety~choline recep-
tor, it becomes evident that Nachmansohn set a biological
lancimark. This was also the first neurotransmitter receptor
to be characterizes! biochemically, thanks to its accessibility in
the vertebrate muscle endplate and its abundance in the spe-
cialize{l electric organ of electric fish.
OCR for page 366
366
BIOGRAPHICAL MEMOIRS
The finding that acety~choline esterase activity is very
high in excitable membranes including nerve fiber mem-
branes ant! that the localization of the acety~choline recep-
tor is the same as that of the esterase led Nachmansohn to
postulate that the nerve impulse is generated through a de-
polarization of the membrane by acety~choline releaser! by
the stimulus from an inactive complex with protein. The ac-
tion potential thus generated wouIc! give rise to the release
of acety~choline in adjacent sites leading to propagation of
the current along the fiber by successive acety~choline bursts.
Rapid hycirolysis of acety~choline by the esterase anct the ion
pump mechanism coupled to the breakdown of ATE wouIc!
restore membrane polarization at each point as the impulse
travelled down the fiber.
Nachmansohn's theory, aIreacly suggested in earlier pub-
lications, was presenter! in cletai! in his book, Chemical and
Molecular Basis of Nerve Activity, first publisher} in 1959. A
revised edition appeared! in 1975 with considerably more ex-
perimental support for his Fleas. The revised edition also
container! two supplements, one by Nachmansohn on the
properties and functions of proteins of the acety~choline
cycle in excitable membranes anct one by E. Neumann that
presented a molecular mode} for bioelectricity.
Nachmansohn's ideas, however, were not accepted by neu-
rophysiologists. His molecular theory of nerve conduction is
still highly controversial, despite the fact that a variety of
experiments by Nachmansohn and others (detailec! in the
1975 edition of his book) would appear to nullify objections
to his theory. The fact, for instance, that acety~choline when
appliecl locally stimulates at synaptic junctions or motor end-
plates but has no effect on axons, may be explainec! by im-
permeability of the intact axonal membrane to quaternary
ammonium ions. Acety~choline, therefore, stimulates axons
when applied at the Ranvier node sites where the myelin
OCR for page 395
DAVID NACHMANSOHN
395
of axonal conduction by curare. Biochim. Biophys. Acta,
75:116-28.
With W. H. Harrison. Ascorbic acid-induced fluorescence of a
noradrenaline oxidation product. Biochim. Biophys. Acta, 78:
705-10.
With H. B. Higman, T. R. Podleski, and E. Bartels. Apparent dis-
sociation constants between carbamylcholine, d-tubocurarine
and the receptor. Biochim. Biophys. Acta, 75:187-93.
With T. R. Podleski and E. Bartels. Difference between tetracaine
and d-tubocurarine in the competition with carbamylcholine.
Biochim. Biophys. Acta, 75:387.
With W.-D. Dettbarn. Hydrolysis of choline esters by invertebrate
nerve fibers. Biochim. Biophys. Acta, 77:430-35.
With F. C. G. Hoskin. Stereospecificity in the reactions of acetyl-
cholinesterase. Proc. Soc. Exp. Biol. Med., 113:320-21.
The chemical basis of Claude Bernard's observations on curare.
Biochem. Z., 338:454-73.
With F. C. G. Hoskin and C. von Eschen. Stimulation by quinones
of initial pentose phosphate pathway steps in soluble brain
preparations. Arch. Biochem. Biophys., 103: 111-16.
1964
With P. Rosenberg, E. A. Machey, H. B. Higman, and W.-D. Dett-
barn. Choline acetylase and cholinesterase activity in dener-
vated electroplax. Biochim. Biophys. Acta, 82:266-75.
With H. B. Higman, R. R. Podlewski, and E. Bartels. Correlation
of membrane potential and K flux in the electroplax of Electro-
phorus. Biochim. Biophys. Acta, 79:138-50.
With H. C. Lawler. The preparation of a soluble acetylcholinester-
ase from brain. Biochim. Biophys. Acta, 81:280-88.
Chemical control of ion movements across conducting membranes.
In: Symposium on New Perspectives in Biology, BBA Library vol. 4,
ed. M. Sela, pp. 176-204. Amsterdam: Elsevier.
With F. C. G. Hoskin and P. Rosenberg. Alteration of acetylcholine
penetration into, and effects on, venom-treated squid axons by
physostigmine and related compounds. ~. Gen. Physiol., 47:
1117-27.
With W.-D. Dettbarn. Action of acetylcholine and curare on lobster
axons. Life Sci., 12 :910 -16.
With E. Bartels and T. R. Podleski. Action of nicotine on the elec-
OCR for page 396
396
BIOGRAPHICAL MEMOIRS
troplax and difference of potency between ionized and union-
ized forms. Biochim. Biophys. Acta, 79:511-20.
With W.-D. Dettbarn and P. Rosenberg. Restoration by a specific
chemical reaction of "irreversibly" blocked axonal electrical ac-
tivity. Life Sci., 3:55-60.
With W.-D. Dettbarn. Distinction between action on acetylcholin-
esterase and on acetylcholine receptor in axons. Biochim. Bio-
phys. Acta, 79:629-30.
With F. A. Davis. Acetylcholine formation in lobster sensory axons.
Biochim. Biophys. Acta, 88:384-89.
With H. D. Markman, P. Rosenberg, and W.-D. Dettbarn. Eye
drops and diarrhea: Diarrhea as a first symptom of phospholine
iodide toxicity. New Engl. I. Med., 271:197-99.
With P. Rosenberg and W.-D Dettbarn. Increased acetylcholines-
terase activity of intact cells produced by venoms. Biochem.
Pharmacol., 13: 1157-65.
Perspectives in research on the molecular basis of nerve activity.
In: Tribute to ~ A. Engelhardt. Molecular Biology: Problems and Per-
spectives, pp. 282-303. Moscow: Academy of Sciences of the
USSR.
Chemical control of bioelectric currents in membranes of conduct-
ing cells. I. M. Sinai Hosp. N.Y., 31 :549-83.
With A. Karlin. The association of acetylcholinesterase and of
membrane in subcellular fractionations of the electric tissue of
Electrophorus. ]. Cell Biol., 25: 159-69.
With F. C. G. Hoskin. Stimulation of respiration and inhibition of
glycolysis in lobster axons by quinones. Arch. Biochem. Bio-
phys., 108:506-9.
With A. M. Gold and D. Fahrney. Sulfonyl fluorides as inhibitors
of esterase. II. Formation and reactions of phenylmethanesul-
fonyl cx-chymotrypsin. Biochemistry, 3:783 -91.
With I. Steinhardt and S. Beychok. Interaction of proteins with
hydrogen ions and other small ions and molecules. In: Proteins,
vol. 2, ed. H. Neurath, pp. 139-304. New York: Academic
Press.
With S. Beychok. Effect of ligands on the optical rotatory disper-
sion of hemoglobin. Biopolymers, 3 :575-84.
With S. Beychok and G. D. Fasman. Circular dichroism of poly-L-
tyrisine. Biochemistry, 3: 1675 -78.
. , . .. ~ . .
OCR for page 397
DAVID NACHMANSOHN
1965
397
With W.-D. Dettbarn, H. B. Higman, E. Bartels, and T. R. Podleski.
Effects of marine toxins on electrical activity and K ion efflux
of excitable membranes. Biochim. Biophys. Acta, 94:472-78.
With S. Beychok. On the problem of isolation of the specific ace-
tylcholine receptor. Biochem. Pharmacol., 14:1249-55.
With G. D. Webb. Affinity of benzoguinonium and ambenonium
derivatives for the acetylcholine receptor, tested on the electro-
plax, and for acetylcholinesterase in solution. Biochim. Bio-
phys. Acta, 102: 172-84.
With E. Breslow, S. Beychok, K. Hardman, and F. R. N. Gurd. Rel-
ative conformations of sperm whale metmyoglobin and apo-
myoglobin in solution. }. Biol. Chem., 240:340-49.
With H. Greenberg. Studies of acid phosphomonoesterase and
their inhibition by diisopropylphosphorofluoridate. J. Biol.
Chem., 240:1639-46.
With M. Brzin, W.-D. Dettbarn, and P. Rosenberg. Acetylcholines-
terase activity per unit surface of conducting membranes. I. Cell
Biol., 26:353-64.
With A. de Roetth, Jr., W.-D. Dettbarn, P. Rosenberg, i. G. Wilen-
sky, and A. Wong. Effect of phospholine iodide on blood
cholinesterase levels of normal and glaucoma subjects. Am. I.
Ophthalmol., 59:586 -91.
With M. Brzin, W.-D. Dettbarn, and P. Rosenberg. Penetration of
enostigmine, physostigmine and paraxon into the squid giant
axon. Biochem. Pharmacol., 14:919-24.
With P. Rosenberg and W.-D. Dettbarn. Cholinesterase activity of
rabbit aorta. Life Sci., 4:567-72.
With A. Karlin and N. I. A. Overweg. An inhibitor of oxytocin
from the urinary bladder of the toad, Bufo marinus. Nature
(London), 207: 1401-2.
With E. Bartels. Relationship between acetylcholine and local anes-
thetics. Biochim. Biophys. Acta, 109:194-203.
With F. C. G. Hoskin and P. Rosenberg. Penetration of sugars, ste-
roids, amino acids and other organic compounds into the in-
terior of the squid giant axon. }. Gen. Physiol., 49:47-56.
Chemische Kontrolle des Permeabilitaetszyklus. Erregbarer Mem-
branen Wahrend Elektrischer Aktivitat. Nova Acta Leopold.,
30:207-33.
OCR for page 398
398
BIOGRAPHICAL MEMOIRS
With P. Rosenberg and W.-D. Dettbarn. Use of venoms in testing
for essentiality of cholinesterase in conduction. In: Animal Toxin.
Oxford: Pergamon Press.
With E. Bartels. Molecular structure determining the action of lo-
cal anesthetics on the acetylcholine receptor. (Ochoa Anniver-
sary Volume.) Biochem. Z., 342:359-74.
With P. Rosenberg and F. C. G. Hoskin. Penetration of acetylcho-
line into squid giant axons. Biochem. Pharmacol., 14: 1765-72.
With P. Rosenberg. Effects of venoms on the squid giant axon.
Toxicon,3:125-31.
Chemical control of the permeability cycle in excitable membranes
during activity. Isr. J. Med. Sci., 1: 1201-19.
1966
Sechs deutschjuedische Wissenschaftler: Haber, Willstatter, Neu-
berg, Meyerhof, Bergmann and Schonheimer. Das Neue Israel
(Zurich), 18:826 -33.
Chemical forces controlling permeability changes of excitable
membranes during electrical activity. In: Nerve As A Tissue, ed.
K. Rodahl, pp. 141-61. New York: McGraw-Hill.
Role of acetylcholine in neuromuscular transmission. (Presented
at a symposium on myasthenia gravis.) Ann. N.Y. Acad. Sci.,
135: 136-49.
With H. G. Mautner, E. Bartels, and G. D. Webb. Sulfur and selen-
ium isologs related to acetylcholine and choline. IV. Activity in
the electroplax preparation. Biochem. Pharmacol., 15: 187-93.
With A. K. Prince. Spectrophotometric study of the acetylcholin-
esterase-catalyzed hydrolysis of 1-methyl-acetoxyquinolinium
iodides. Arch. Biochem. Biophys., 113:195-204.
With A. K. Prince. A sensitive fluorometric procedure for the de-
termination of small quantities of acetylcholinesterase. Bio-
chem. Pharmacol., 15:411-17.
With F. C. G. Hoskin. Anaerobic glycolysis in parts of the giant
axon of squid. Nature (London), 210:856 -59.
With S. H. Bryant and M. Brzin. Cholinesterase activity of isolated
giant synapses. J. Cell. Physiol., 68: 107-8.
With P. Rosenberg, W.-D. Dettbarn, and M. Brzin. Acetylcholine
and choline acetylase in squid axon, ganglia, and retina. Nature
(London), 210:858 - 59.
With F. C. G. Hoskin, P. Rosenberg, and M. Brzin. Reexamination
OCR for page 399
DAVID NACHMANSOHN
399
of the effect of DFP on electrical and cholinesterase activity of
squid giant axon. Proc. Natl. Acad. Sci. USA, 55:1231-35.
Properties of the acetylcholine receptor protein analyzed on the
excitable membrane of the monocellular electroplax prepara-
tion. In: Current Aspects of Biochemical Energetics: Lipmann Dedi-
catory Volume, ed. N. O. Kaplan and E. P. Kennedy, pp. 145-72.
New York: Academic Press.
With A. de Roetth, ir., A. Wong, W.-D. Dettbarn, P. Rosenberg,
and i. G. Wilensky. Blood cholinesterase activity in glaucoma
patients treated with phospholine iodide. Am. J. Ophthaln~ol.,
62:834-38.
Chemical control of the permeability cycle in excitable membranes
during electrical activity. Isr. I. Med. Sci., 1:201-19.
With W.-D. Dettbarn and P. Rosenberg. Effect of ions on the efflux
of acetylcholine from peripheral nerve. l. Gen. Physiol., 50:
447-60.
With P. Rosenberg and H. G. Mautner. Similarity of effects of ox-
ygen, sulfur, and selenium isologs on the acetylcholine receptor
in excitable membranes on junctions and axons. Proc. Natl.
Acad. Sci. USA, 55:835-38.
The biochemical basis of cholinergic drugs. In: Biochemistry and
Pharmacology of the Basal Ganglia, ed. E. Costa, L. J. Cote, and
M. D. Yahr, pp. 1-15. Hewlett, N.Y.: Raven Press.
With M. Brzin, V. M. Tennyson, and P. E. Duffy. Acetylcholinester-
ase in frog sympathetic and dorsal root ganglia: A study by
electron microscope cytochemistry and microgassometric anal-
ysis with the magnetic diver. J. Cell Biol., 31:215-42.
With G. D. Webb, W.-D. Dettbarn, and M. Brzin. Biochemical and
pharmacological aspects of the synapses of the squid stellate
ganglion. Biochem. Pharmacol., 15: 1813-19.
With A. Karlin and E. Bartels. Effects of blocking sulfhydryl groups
and of reducing disulfide bonds on the acetylcholine-activated
permeability system of the electroplax. Biochim. Biophys. Acta,
126:525-35.
With T. R. Podleski. Similarities between active sites of acetylcho-
line-receptor and acetylcholinesterase with quinolinium ions.
Proc. Natl. Acad. Sci. USA, 56:1034-39.
With M. Brzin. The localization of acetylcholinesterase in axonal
membranes of frog nerve fibers. Proc. Natl. Acad. Sci. USA,
56: 1560-63.
OCR for page 400
400
BIOGRAPHICAL MEMOIRS
1967
With P. Rosenberg and E. Bartels. Drug effects on the spontaneous
electrical activity of the squid giant axon. I. Pharmacol. Exp.
Ther., 155:532.
With W.-D. Dettbarn.
The acetylcholine system in peripheral
nerve. (Presented at a symposium on cholinergic mechanism.)
Ann. N.Y. Acad. Sci., 144:483.
With M. Brzin and W.-D. Dettbarn. Cholinesterase activity of nodal
and internodal regions of myelinated nerve fibers of frog. I.
Cell Biol., 32:577.
With P. Rosenberg and H. G. Mautner. Acetylcholine receptor:
Similarity in axons and junctions. Science, 155: 1569.
With W. Leuzinger and A. L. Baker. Acetylcholinesterase. I. Large
scale purification, homogeneity, amino acid analysis. Proc. Natl.
Acad. Sci. USA, 57:446.
1968
With }.-P. Changeux, W. Leuzinger, and M. Huchet. Specific bind-
ing of acetylcholine to acetylcholinesterase in the presence of
eserine. FEBS (Fed. Eur. Biochem Soc.) Lett., 2:77.
1969
With W. Leuzinger. Structure and function of acetylcholinesterase.
In: Progress in Brain Research, ed. K. Ackert and P. G. Waser, vol.
31, pp. 241-45. Amsterdam: Elsevier.
With E. Bartels. Organophosphate inhibitors of acetylcholine-
receptor and -esterase tested on the electroplax. Arch. Bio-
chem. Biophys., 133: 1-10.
With W. l. Deal and B. F. Erlanger. Photoregulation of biological
activity by photochromic reagents. III. Photoregulation of bioe-
lectricity by acetylcholine receptor inhibitors. Proc. Natl. Acad.
Sci. USA, 64:1230 - 34.
1970
Proteins in bioelectricity. In: Protein Metabolism of the Nervous System,
ed. A. Lajtha, pp. 313-33. New York: Plenum Press.
Proteins in bioelectricity. In: Colloquium Macromolecules, Biosyn-
thesis and Function, vol. 21, ed. S. Ochoa, C. F. Heredia, and C.
OCR for page 401
DAVID NACHMANSOHN
40
Asensio, pp. 321-28. FEES Proceedings of the Sixth Meeting,
Madrid, April 7-11, 1969. London and New York: Academic
Press.
With E. Bartels, W. Deal, A. Karlin, and H. G. Mautner. Affinity
oxidation of the reduced acetylcholine receptor. Biochim. Bio-
phys. Acta, 203 :568-71.
Proteins in excitable membranes. Their properties and function in
bioelectricity. Science, 168: 1059-66.
With W.-D. Dettbarn, E. Bartels, F. C. G. Hoskin, and F. Welsch.
Spontaneous reactivation of organophosphorus inhibited elec-
troplax cholinesterase in relation to acetylcholine induced de-
polarization. Biochem. Pharmacol., 19:2949-55.
With H. G. Mautner and E. Bartels. Interactions of p-nitrobenzene
diazonium fluoroborate and analogs with the active sites of
acetylcholine-receptor and -esterase. Proc. Natl. Acad. Sci.
USA, 67:74-78.
1971
With E. Bartels. Depolarization of electroplax membrane in cal-
cium-free Ringer's solution. I. Membr. Biol., 5:121-32.
With E. Bartels, N. H. Wassermann, and B. F. Erlanger. Photo-
chromic activators of the acetylcholine receptor. Proc. Natl.
Acad. Sci. USA, 68:1820-23.
With E. Bartels and T. L. Rosenberry. Snake neurotoxins; effects
of disulfide reduction on interaction with electroplax. Science,
174: 1236-37.
Similarity of chemical events in conducting and synaptic mem-
branes during electrical activity. Proc. Natl. Acad. Sci. USA,
68:3170-72.
1972
Bioenergetics and properties and function of proteins in excitable
membranes associated with bioelectrogenesis. In: Molecular
Bioenergetics and Macromolecular Biochemistry (Meyerhof Sympo-
sium, Heidelberg, July 1970), ed. H. H. Weber, pp. 172-93.
Heidelberg: Springer-Verlag.
Biochemistry as part of my life. (Prefatory chapter.) In: Annual
Review of Biochemastry, pp. 1-28. Stanford: Annual Reviews.
With T. L. Rosenberry, H. W. Chang, and Y. T. Chen. Purification
of acetylcholinesterase by a~nity chromatography and deter-
OCR for page 402
402
BIOGRAPHICAL MEMOIRS
mination of active site stoichiometry. I. Biol. Chem., 247: 1555-
65.
With E. Bartels and P. Rosenberg. Correlation between electrical
activity and phospholipid splitting by snake venom in the single
electroplax. J. Neurochem., 19: 1251-65.
With I. Del Castillo, E. Bartels, and }. A. Sobrino. Microelectro-
phoretic application of cholinergic compounds, protein oxidiz-
ing agents and mercurials to the chemically excitable mem-
brane of the electroplax. Proc. Natl. Acad. Sci. USA, 69:2081-
85.
1973
The neuromuscular junction. The role of acetylcholine in excitable
membranes. In: The Structure and Function of Muscle, vol.3, Phys-
iology and Biochemistry, ed. G. H. Bourne, pp.32-117. New York:
Academic Press.
With E. Bartels and T. L. Rosenberry. Modification of electroplax
excitability by veratridine. Biochim. Biophys. Acta, 298:973-
85.
With E. Neumann and A. Katchalsky. An attempt at an interpre-
tation of nerve excitability. Proc. Natl. Acad. Sci. USA, 70:727-
31.
Proprietes et fonction des proteines dans les membranes excitables.
Un modele integrate de l'excitabilite nerveuse. Biochimie, 55:
365-76.
1974
Importance of structure and organization for the chemical reac-
tions in excitable membranes. In: Central Nervous System: Studies
on Metabolic Regulation and Function, ed. E. Genazzini and H.
Herken, pp. 121-37. Heidelberg: Springer-Verlag.
Organophosphate insecticides. A challenging problem of environ-
ment control. Rehovot, 7:4-6.
With E. Neumann. Properties and function of proteins in excitable
membranes. An integral model of nerve excitability. (Presented
at the New York Academy of Sciences Conference on the Mech-
anism of Energy Transduction of Biological Systems. Ann. N.Y.
Acad. Sci., 227:275-84.
With Y. T. Chen, T. L. Rosenberry, and H. W. Chang. Subunit het-
OCR for page 403
DAVID NACHMANSOHN
403
erogeneity of acetylcholinesterase. Arch. Biochem. Biophys.,
161 :479-87.
With H. W. Chang. Purification and characterization of acetylcho-
line receptor-I from Electrophorus electricus. Proc. Natl. Acad.
Sci. USA, 71:2113-17.
With T. L. Rosenberry, Y. T. Chen, and E. Bock. Structure of 11 S
acetylcholinesterase. Subunit composition. Biochemistry, 13:
3068-79.
With E. Neumann. Nerve excitability- towards an integrating con-
cept. In: Biomembranes, ed. L. A. Manson. New York: Plenum
Press.
Biochemical foundation of an integral model of nerve excitability.
(Presented at 25. Mosbacher Colloquium der Gesellschaft fuer
Biologische Chemie, April 25 - 27.) In: Biochemistry of Sensory
Functions, ed. L. Jaenicke, pp. 431-64. Berlin/Heidelberg/New
York: Springer-Verlag.
Chemical and Molecular Basis of Nerve Activity, 2d. rev. ed. including:
Suppl. 1, "Properties and Function of the Proteins of the Ace-
tylcholine Cycle in Excitable Membranes," and suppl. 2 (by E.
Neumann), "Towards a Molecular Model of Bioelectricity." New
York: Academic Press.
1976
Highlights of a friendship. In: Repections on Biochemistry, pp. 405-
11. London: Pergamon Press.
The transduction of chemical into electrical energy. Proc. Natl.
Acad. Sci. USA, 73:82-85.
50 years ago: Acetylcholine its role in nerve excitability. Trends
Biochem. Sci., 1:237-38.
1977
Nerve excitability: Transition from descriptive phenomenology
to chemical analysis of mechanisms. (Herken Festschrift.) Klin.
Wochenschr., 55:715-23.
Nerve excitability: From descriptive phenomenology to molecular
interpretation. In: P. ~ S. Biomedical Sciences Symposia, Arden
House Conference on Neuronal Information Transfer, ed. H. Vogel.
OCR for page 404
404 BIOGRAPHICAL MEMOIRS
FURTHER READINGS
First Conference of Physicochemical Mechanism of Nerve Activity. New
York: Academy of Sciences, 1946.
Metabolism and Function: Anniversary Volume in Honor of Otto Meyer-
hof. Biochim. et Biophys. Acta. Amsterdam: Elsevier Publishing
Co., 1950.
First Conference on Nerve Impulse. New York: Josiah Macy, fir., Foun-
dation, 1950.
Second Conference on Nerve Impulse. New York: Josiah Macy, fir.,
Foundation, 1951.
Fourth Conference on Nerve Impulse. New York: Josiah Macy, Jr.,
Foundation, 1953.
Fifth Conference on Nerve Impulse. New York: Josiah Macy, fir., Foun-
dation, 1954.
Ion Transport Across Membranes. (Symposium at Columbia Univer-
sity.) New York: Academic Press, 1954.
Chemical and Molecular Basis of Nerve Activity. (Monograph.) New
York: Academic Press, 1959.
Second Conference on Physicochemical Mechanism of Nerve Activity. New
York: New York Academy of Sciences, 1959.
Molecular Biology. Elementary Process of Nerve Conduction and
Muscle Contraction. New York: Academic Press, 1960.
OCR for page 405
Representative terms from entire chapter:
nerve activity
