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"Instead of being really good at doing some particular thing, companies must be really good at learning how to do new things" [1]. This ability to do new things involves both the identification and the mastery of the next 'new thing' as well as the ability to align the rest of the company with this new direction. This paper focuses on the alignment of innovation activities with the overall business strategy and infrastructure. An innovation strategic alignment model is presented that supports alignment in a company by identifying the driver of change and its impact on other areas of the business. "Instead of being really good at doing some particular thing, companies must be really good at learning how to do new things" [1]. Die vermoë om iets nuut te doen berus op beide die identifisering en bemeestering van die nuutheid, sowel as die belyning van die bestaande maatskappy met hierdie nuwe wending. Hierdie artikel belig die belyning van innovasie aktiwiteite binne die onderneming met die algemene besigheidstrategie asook infrastruktuur. 'n Innovasiestrategie belyningsmodel word voorgestel. Hierdie model ondersteun belyning deur identifisering van die drywer van verandering en die impak daarvan op ander besigheidsareas.

Our purpose in this study is to view theories of psychotherapy from a general social-political context, especially insofar as they pertain to values. Beginning with Weisskopf-Joelson’s (1980) thesis that theories of psychotherapy may be “perceptual houses” with their own unique value structures, we studied the values of psychoanalytic psychotherapists within the framework of Rokeach’s ( 1968) system. Through the Rokeach Value Survey, we examined the values held by a group of psychoanalytic trainees in 1979 and those held by a group of practicing psychoanalysts in 1993. Because neither group of subjects can be regarded as randomly representative of the universe of psychoanalysts, we regard the resultant data as evocative and informative rather than definitive. Nonetheless, we examined the extent to which value profiles for the psychoanalytic trainees of 1979 were similar or dissimilar to those of practicing psychoanalysts in 1993. Such comparisons at the least provide some general indication as to whether values have shifted in the universe within this time period. Findings are presented about specific patterns of values, and implications are discussed. There appears to be more consistency than difference in values among the psychoanalytically-oriented psychotherapists we studied, lending support to this discipline’s designation of a “perceptual house” insofar as its values are concerned.

Theoretical dynamics of ethnic humor are juxtaposed with Jewish wit, showing that there is a distinct factor which operates in the Jewish humor response to oppression. Drawing from Ziv's (1986) rich anthology of research and case studies, this factor is conceptualized as creative pseudo-reality. It is hypothesized that Jewish wit features this element of self-effacing humor besides the factors which it shares with the ethnic humor of other marginal groups. The implicit ability to construct a perceived environment which is bound neither to reason nor to logic, is seen as the last line of defense for an oppressed minority whose other options have been denied. Irony and triumph, suggested as key elements in this factor, are illustrated in annotated stereotypical excerpts of Jewish wit. Throughout the analysis, the dialectic principle—maintaining the co-existence of inconsistent dynamics—is highlighted in contrast to the reductionistic either/or approach commonplace in psychological and sociological discourse.

Abstract Hypertensive complications are relatively common in pregnancy, particularly in the presence of preexisting renal disease. Although the pathogenesis of such complications is still unknown, recent animal studies have suggested that it may be related to impaired synthesis of nitric oxide (NO). Rats with adriamycin nephropathy develop a “preeclamptic-type” pregnant state characterized by elevated blood pressure, lack of hyperfiltration, and enhanced proteinuria. Preliminary studies with this model have implicated inadequate NO synthesis in the development of preeclamptic-like pregnancy. The aim of the present study was to confirm this hypothesis. Pregnant rats, both normal (PREG) and those with adriamycin nephropathy (AN-PREG), received 100 mg/L N ω -nitro- l -arginine methyl ester PO from the middle of gestation to term (day 11, term approximately 22 days). One group of AN-PREG rats received either l -arginine or d -arginine (2 g/L) from midpregnancy. At term, systolic pressure, mean arterial pressure, urinary metabolites of NO, creatinine clearance, and urinary protein were assessed. At term, compared with virgin rats with adriamycin nephropathy, untreated AN-PREG rats had increased systolic pressure, mean arterial pressure, and proteinuria (mean arterial pressure, 124±2.5 versus 99.7±1.6 mm Hg [ P P P =NS). In PREG rats, urinary metabolites of NO increased approximately threefold at term pregnancy compared with control. By contrast, in AN-PREG rats, excretion of urinary metabolites of NO increased only by approximately 1.7-fold ( P N ω -nitro- l -arginine methyl ester enhanced blood pressure and decreased creatinine clearance but did not influence proteinuria. Excretion of urinary metabolites of NO was similarly inhibited in all rats. In AN-PREG rats, l -arginine normalized blood pressure (91±2.15 mm Hg) and lowered proteinuria partially but significantly. d -Arginine had no effect. In summary, AN-PREG rats are unable to adequately increase NO synthesis when physiologically required. Correction of this deficit by l -arginine treatment induced a significant clinical improvement.

First of all, let me thank you, Mr Chairman, and your Council for inviting me to give the Wallace Fenn Lecture on this great occasion. I have pleasant memories of my meetings with Wallace Fenn, whom I admired as a person and as a scientist. I had heard much about his achievements long before we met; I knew about him through our mutual friend and teacher, A.V. Hill, in whose laboratory we both had been working at different periods, and from whom we both learned a great deal, about physiology, about nerves and muscles and about many other things. The subject I want to talk about, neuromuscular and synaptic transmission, is one that has fascinated me and provided me with great fun and entertainment for more than half a century. I was introduced to the field at a time just before Henry Dale and his colleagues discovered the role of acetylcholine as the chemical mediator, the transmitter from motor nerve to muscle fibre. It is probably difficult today to envisage the enormous impact, indeed the shock which this new concept brought to physiologists. The prevailing idea in the 1930s had been that there was direct electric propagation, with some slight delay, at the neuromuscular junction and at central neuronal synapses generally. The thought that a complex sequence of chemical steps should intervene at the contact between nerve and muscle, between two electrical waves of activity which appeared to be a continuous and unfailing process, that seemed strange, and there was prolonged argument going on about it for some 10 years before Dale’s idea and his powerful experimental evidence were generally accepted. And even after the acetylcholine story at the myoneural junction had entered the textbooks, there was a long interval before the idea of chemical transmission was successfully applied and supported by convincing evidence in the central nervous system. I remember discussions at our Physiological Society meetings at which doubts

This literary, textual analysis of the APA Publication Manual reveals a text of extraordinary complexity and intricacy which belies its often presented purpose as being merely a `helpful tool'. In it we examine the characters-for example, authors, editors, typists-involved in the production of a document, the nature of their roles and relationships, and the overt and covert demands of informed and powerful voices who are presented as facilitators and allies. We examine messages inherent in the Manual which potential authors are advised to consider to make their work acceptable for publication. In addition, the process of creativity, construction and ownership of the product is addressed in reference to the standards of professional publishing communities.

The Rokeach Value Survey was administered to two groups of Chinese students: Those residing in the People's Republic of China (P.R.C.) and those who had emigrated to the United States (U.S.A.). Results indicated that the two groups have very different value hierarchies. The traditional stereotypes, which depict the Chinese as dependent and collectivistic in nature, in contrast to the independent and individualistic Americans, were not confirmed; instead the converse appeared. P.R.C. students assigned greater importance to individualistic values, whereas the U.S.A. group deemed collectivistic values more salient. The dimension of class as a meaningful variable was discussed as a tentative explanation of the results. L'Echelle de valeurs de Rokeach a ete administre a deux groupes d'eleves Chinois: ceux residant dans la Republique Populaire de Chine et ceux qui avaient emigre aux Etats Unis d'Amerique. Les resultats indiquent des valeurs hierarchiques tres differentes dans les deux groupes. Les ster...

All commands issued by the brain travel along nerves to respective muscles and there initiate the appropriate contraction. At the junction of nerve and muscle, the neuromuscular junction, the nerve cells and muscle cells are separated by a cleft, across which a chemical, acetylcholine, moves in small quanta at great speed. The mechanism of transmission, the reasons for the transfer of small quantal packets (a process named 'exocytosis' by the author) and the experimental evidence for this, and the size of the miniature potentials responsible are discussed. At present, no final explanation can be given for all the minutiae of this vital process.

THE rate of secretion of a transmitter substance from a nerve terminal is known to be controlled by the membrane potential of the terminal. This has been shown, for example, at the neuromuscular junction by registering the frequency of miniature end-plate potentials when electric currents are sent through the motor nerve endings1. More recently, the use of tetrodotoxin2 has made it possible to eliminate initiation of impulses on either side of the junction, and so to study the graded relation between electrical “input” and “output” of a synapse, undisturbed by any regenerative potential change. With this method it has been found that brief pulses of depolarization, locally imposed on a motor nerve ending, elicit graded end-plate potentials the size of which can reach or even surpass that normally produced by a nerve impulse3. To obtain additional information, it was necessary to use a preparation in which direct measurements of the membrane potential can be made on both sides of the junction. The so-called giant synapse of the squid4 is suitable for this purpose: it is possible to insert microelectrodes in the pre- as well as post-synaptic nerve fibres of this preparation, close to their region of synaptic contact, and there is now good evidence that chemical transmission operates at this synapse5. The experiments reported here were made on the stellate ganglion of the squid Loligo vulgaris at the Naples Zoological Station. Similar work carried out at Woods Hole has been reported by Bloedel, Gage, Llinas and Quastel6.

Sir Bernard Katz established the cellular basis of synaptic transmission at the neuromuscular junction, the contact point between nerve and muscle. With his death, we lost one of the most distinguished biophysicists of our time. He laid the foundations for our understanding of almost every aspect of synaptic transmission. Bernard Katz revealed the existence of key molecules and formally described their interaction. With the benefit of his almost magical intuition, he formulated hypotheses that are now recognized as facts. During his career he pioneered research in three areas. He and Alan Hodgkin elucidated the ionic basis of the action potential overshoot, as formulated in the sodium hypothesis; he unravelled the biophysical mechanisms that generate the endplate potential; and he clarified mechanisms of transmitter release, as detailed in the quantal hypothesis and the vesicle hypothesis. In particular his work on the neuromuscular junction influenced and led several generations of neurophysiologists, and it continues to do so even though research focus has shifted to synapses in the central nervous system. Bernard Katz (or BK, as he was known to colleagues and students) trained several generations of young investigators who have been inspired by his hypotheses, by his impeccable thoroughness as an investigator, and by the straightforward, unpretentious style of his presentations - though some have been dismayed by his occasional unapproachability or his unforgiving nature when confronted with others' mistakes! Perhaps his most valuable and enduring legacy to collaborators and students is that, when data are difficult to interpret and we see only a faint glimmer of light at the end of a long tunnel, we ask ourselves, 'What would BK do now?'

This chapter discusses the role Knowledge Management plays in the management of a radical innovation project. A radical innovation produces a fundamental change in the activities of a company [1]. A company’s capacity to innovate is dependent on its capability to integrate internal processes and to understand the larger market and technological environment [2]. Knowledge Management supports a company’s efforts to understand its internal and external environments. A method for managing a radical innovation project is presented. This method, called the Innovation Implementation Method (IIM) consists of a high-level structure and seven supporting concepts. This chapter highlights the aspects of the IIM which promote Knowledge Management and explains how each aspect supports the successful implementation of a radical innovation. The chapter ends with an overview of a case study in the insurance industry, where the IIM was used to implement a radical innovation project.

Theories of self-effacing ethnic humor are analyzed from the perspectives of psychological defense and acculturation. These processes are contrasted with masochism as explanations of self-directed wit. Developmental paradigms are appealed to in conceptualizing the sociocultural function of humor. Identification with the aggressor is conceptualized as a transitional mechanism to assimilate the minority into the host culture. Turning against the self is developed as an alternate mechanism that uses humor as a means of self-empowerment. Reframing and splitting are posited as integral to the defensive process of ethnic humor. The method of luring the aggressor into a situation that is then used against him is construed as the kamikaze maneuver and conceptualized as an ambush technique in which the role of self-effacement facilitates aggression. The analytic elements of these approaches are explored with reference to Jewish humor as a stereotype of the wit of a transient and oppressed people, and annotated examples are offered from published anthologies. Illustrative vignettes, ranging from the mundane to the clinical, are annotated in the discussion. Directions for further inquiry are outlined for issues unresolved in the research literature.

Background: Pregnancy-induced hypertension is characterized by an increased sympathetic activity and probably by a decreased synthesis/activity of nitric oxide. The aim of the present study is to evaluate whether the beneficial action of the sympathetic antagonist methyldopa (a first-choice hypotensive agent in the treatment of PIH) may be associated to changes in nitric-oxide synthesis. Methods: Forty pregnant Wistar rats received L-NAME (NO synthase inhibitor, 9–10 mg/kg/day) from mid-pregnancy (day 11) through to term. Some rats were treated with daltroban (TxA receptor antagonist, 60 mg/kg/day), diltiazem (calcium channel blocker, 30 mg/kg/day), methyldopa (central adrenergic antagonist, 400 mg/kg/day) or L-arginine (260 mg/kg/day) from mid-pregnancy. The effect of the different treatments on systolic blood pressure (SBP), creatinine clearance (CCR), urine protein excretion (UP) and urinary nitrate excretion (UNO3, representing urine NO metabolite) were evaluated and the results compared with those found in normal pregnancy. Normal pregnant rats receiving similar treatment were used as controls. Results: In normal pregnant (P) rats, SBP values decreased from 94 ± 2 to 83 ± 3 mm Hg at the end of pregnancy (p < 0.01) and CCR augmented significantly. Drug treatment had no significant effect. In NAME-treated rats, at the same period, the SBP augmented from 92 ± 1 to 129 ± 1.8 mm Hg (p < 0.01). At the end of pregnancy, NAME rats had significantly lower CCR values and higher UP excretion when compared with P rats. UNO3 increased significantly in P and in P rats treated with methyldopa. As expected, in NAME rats UNO3 excretion was significantly reduced. Treatment with methyldopa normalized SBP, improved CCR and proteinuria and was associated with an increase in UNO3. Similar results were obtained with L-arginine treatment. Diltiazem lowered SBP significantly but had no effect on renal function or UNO3 and daltroban had no effect. Conclusion: The increased UNO3 found in NAME rats treated with methyldopa suggests that the vasoconstriction secondary to chronic NO inhibition may be partially related to an increased sympathetic activity. The efficient action of the sympathetic antagonist methyldopa may be due not only to its antihypertensive effects but also by its stimulating effect on NO synthesis leading also to an improvement of renal function.

Recent studies have shown that maternal hyperinsulinaemia is a risk factor for the development of hypertension in pregnancy. Experimentally, pregnant rats with chronic exogenously induced hyperinsulinaemia (P-INS rats) have increased blood pressure at the end of gestation. This is associated with a blunted elevation of the excretion of the urinary metabolites of nitrate (UNOx). In the present study, we aimed to evaluate the mechanism(s) of the increase in blood pressure in this model. Four groups were studied: normal pregnant rats (P rats), P-INS rats, P-INS rats treated with l-arginine (2 g/l in the drinking water) (l-ARG rats) and hyperinsulinaemic virgin rats (V-INS rats). Systolic blood pressure (SBP), UNOx excretion (on ingestion of a controlled low-nitrate diet), urine noradrenaline (norepinephrine) and plasma endothelin levels were evaluated. Rats were killed on day 22 of pregnancy. Five P-INS rats were not killed at this time, in order to measure SBP 30 and 60 days after delivery. Fetal number and fetal body weight were evaluated. At the end of pregnancy, a 10±3% increase in SBP was found in P-INS rats, contrasting with a fall of -15±4% in P rats (P < 0.01). In the l-ARG group at the end of pregnancy, SBP values had fallen by -14±2%, to values comparable with those of P rats. The increase in UNOx excretion was 175±38% in P rats, 106±12% in l-ARG rats and 41±8% in P-INS rats (P < 0.01 compared with P and l-ARG groups). No differences were found in the urinary excretion of noradrenaline or in the plasma levels of endothelin-1 between the pregnant groups. Fetal number was similar in all groups, but fetal body weight was lower for P-INS rats compared with P and l-ARG rats. Thus the blood pressure response to l-arginine strongly suggests that a decrease in NO availability may be the main pathogenic mechanism involved in the development of hypertension in this model.

The signs of the times of the 1960s seem very different from those of the 1970s, as different popular movements emphasized different values. Yet there is doubt about the change in values of specific professional groups. In this study students in counselor education at one university were compared regarding values—one group in 1968 and another group in 1978—using the Rokeach Value Survey. Katz and Beech indicate the likenesses and differences in values between the two groups and analyze similarities and dissimilarities of the future counselors with the general population during the 1960s and 1970s.

Recent evidence indicates that curare, in addition to its ‘competitive’ interference with endplate receptors, can block open ionic channels by a ‘non-competitive’ action on the activated acetylcholine-receptor complex. These findings called for further study of the kinetic behaviour of endplate channels and their modification by curare. Examining impulse-evoked endplate currents and acetylcholine-induced current fluctuations, it is found that the lifetime of the open channel is shortened by relatively high concentrations of curare (greater than 5 μM), an effect which shows up most strikingly at hyperpolarized levels of membrane potential (— 130 mV and above). No shortening of this kind is observed when a neuromuscular block of equal or greater intensity is produced by a dose of α-bungarotoxin. Two other neuromuscular blocking agents, gallamine and pancuronium are shown to have an action on channel kinetics which cannot be explained by competitive receptor binding, but conforms to the hypothesis of rapidly repeated blocking and unblocking of individual ion channels, which had been proposed originally to account for the endplate action of local anaesthetics.

A small endplate potential can be recorded in frog muscle fibres, after all acetylcholine-mediated transmission has been eliminated by pre- or postsynaptic blocking agents (botulinum toxin, calcium lack, manganese, curare, α-bungarotoxin). It is usually necessary to hyperpolarize the muscle membrane to detect this ‘non-cholinergic’ endplate potential. Below -100 mV little or no response is seen; a maximum is reached at about -140 mV, when the amplitude can be as large as 100 μV (endplate current up to about 1 nA). Other characteristic features are: the response shows no quantal fluctuations; its amplitude is not facilitated by repetitive impulses; its size and time course are not noticeably affected by prostigmine, curare or α-bungarotoxin; the half-time of decline of the endplate current is approximately 1.7 ms at 20 °C, and is lengthened by lowering the temperature with a Q 10 of about 1.3; the response is abolished by barium. When iontophoretic pulses of potassium are applied to the endplate, local depolarization is recorded whose amplitude varies with membrane potential similarly to that of the nerve-evoked response. These observations strongly indicate that this ‘non-cholinergic’, ‘non-quantal’ endplate potential arises from a rapid synaptic transfer of potassium ions, released by the active nerve terminal into the synaptic cleft and entering the muscle fibre through ‘anomalous rectifier’ channels in the endplate membrane.

Previous experiments have indicated that there is a continuous leakage of acetylcholine (ACh) from resting motor nerve terminals which can produce a small depolarization in anti-esterase treated endplates (Katz & Miledi 1977; Vyskočil & Illés 1978). This leakage might be expected to be intensified during the presynaptic action potential and so lead to a very small non-quantal endplate response. This hypothesis was examined, in frog and mammalian endplates, by stimulating the motor nerve in a calcium-deprived medium and recording the summated average response to several hundred stimuli. The result was completely negative; no trace of a non-quantal endplate potential was ever observed, with the limit of detection being always less than 10 μV, and sometimes as low as 2 μV. These experiments suggest that the leakage of ACh either does not originate predominantly from the synaptic region of the axon terminal, or that it occurs by a mechanism that is not directly influenced by the membrane potential.

Stephen Kuffler who died at his home in Woods Hole, Massachusetts, at the age of 67, was much beloved and admired, as a scientist and as a personal friend, by colleagues and pupils all over the world.

The values of twenty-four drug users were measured using the Rokeach Value Survey (RVS). Their perceptions of the values of society were measured by altering the instructions for the RVS. Background information on drug usage and social economic status was also obtained. The value systems which the drug users espouse and perceive to be in opposition to society's values form three themes: tranquility, aesthetics, and humanism. Although this group of drug users is often perceived by society as deviant, they appear to adhere to the literal meaning of these cultural ideals.

A. V. Hill was born in Bristol, the son of Jonathan Hill (1857-1924) and Ada Priscilla ( née Rumney ) (1861-1943). The father was the second of nine children; the mother one of four sisters. They were married in 1880, and had a son and a daughter, Muriel, who was born in February 1889. She became a biochemist and married Dr T. S. Hele, a colleague who worked in the same field and was later elected Master of Emmanuel College,Cambridge. Muriel died in 1941. A. V. (as he became known to his family and all his colleagues) traced his ancestry to the middle of the eighteenth century. To judge by the family tree which he himself drew, the name ‘Archibald Vivian' must have been a new departure. There were successions of Jameses and Jonathans, several Johns, an occasional Charles, George, Samuel, etc. among them, but apparently no precedent for Archibald or Vivian. A. V.’s forebears all lived in the West Country, mostly in Devonshire and Somerset. On the paternal side he was preceded by five generations of timber merchants at Bristol, carrying on the business which had been founded by James Hill in 1750. James had come from Ireland and later returned there to join a volunteer regiment. He is believed to have been killed during the Irish troubles.

Glutamate-induced potential changes have been recorded with intracellular electrodes in nerve cells of the squid. The responses are accompanied by small voltage fluctuations which resemble postsynaptic ‘membrane noise’ observed at neuromuscular junctions. Certain limitations are discussed in extending the noise analysis to neurons with multiple synaptic inputs.

In anti-esterase treated muscle, repeated nerve impulses give rise to a cumulative depolarization of the endplate which persists for several seconds after the end of the tetanus. It has been suggested that this phenomenon may be due to a side-effect of the esterase inhibitors, namely a stabilization of opened ionic channels in the endplate membrane per­sisting after the transmitter has diffused away, rather than - as pre­viously supposed - to an accumulated residue of acetylcholine which continues to act during the slow depolarization. The question has been studied by intracellular recording of endplate potential and current, in glycerol-pretreated frog sartorius muscle. Noise analysis has been used to distinguish between the alternative explanations. The results show that the post-tetanic depolarization of anti-esterase treated endplates is accompanied by membrane fluctuations which resemble typical ‘acetyl­choline noise’, in size and time characteristics. It is concluded that at least a large part of the prolonged depolarization arises from continued action of a residue of acetylcholine which has accumulated during the tetanus and disappears slowly thereafter.

A possible distinction between ‘extrinsic’ drug receptors and ‘intrinsic’ neuro-receptors at the motor end-plate has been considered, and an experiment described to test the validity of such a differentiation. A dose ofd-tubocurarine is applied ionophoretically to a motor end-plate, and its inhibitory effects are examined on (i) a ‘massive’ local discharge of miniature end-plate potentials (involving ‘intrinsic’ release of acetylcholine) and (ii) artificially produced acetylcholine potentials. Under suitable experimental conditions, curare is shown to suppress both types of depolarization with equal speed and efficacy. It is considered, therefore, that there is no basis for differentiating, in accessibility, location or pharmacological behaviour, between ‘drug- ’ and ‘neuro-receptors’ of the motor end-plate.

At the nerve-muscle junction, a specific process occurs which is not found during the propagation of impulses along nerve or muscle fibres; the nerve impulse causes acetylcholine (Ach) to be released from the motor nerve endings, and this substance depolarizes the end-plate surface of the muscle fibre by a specific chemical reaction. The transient local depolarization of the muscle fibre which is so produced has been called the end-plate potential (e.p.p.). The e.p.p., then, unlike the nerve or muscle impulse, is not itself produced by electric stimulation (direct spread of electric current from nerve to muscle has, in fact, never been demonstrated and appears to be indetectably small). On the other hand, the e.p.p. electrically stimulates the surrounding region of the muscle fibre, and so gives rise to the propagation of a new impulse.

When frog muscles are exposed for several hours to a solution of isotonic calcium chloride, the secretory response of the motor nerve terminals to imposed depolarization ultimately fails and the rate of spontaneous release of acetylcholine also declines towards zero. The failure of depolarization-evoked transmitter release is irreversible while spontaneous release reappears, though in highly abnormal fashion, when the muscle is returned to a normal ionic medium. Examination of motor end-plates, during various stages of calcium treatment, shows that there is gradual intra-axonal agglutination of synaptic vesicles which is only very incompletely reversible. This effect is presumably the consequence of gradual entry and intracellular accumulation of calcium ions. Analogous treatment with isotonic magnesium, while resulting in immediate loss of evoked transmitter release, does not lead to progressive agglutination of synaptic vesicles, nor to irreversible impairment of the secretory response of the nerve terminal. The possible relations between structural and functional changes during calcium and magnesium treatment are discussed.

A micromethod is described by which depolarizing and inhibiting drugs can be applied, ionophoretically, from a common ‘point source’ to sensitive regions of a motor end-plate. The effects of the drugs on the membrane potential of a single end-plate are recorded, in the frog’s sartorius muscle. The antagonism between d -tubocurarine ( DTC ) and acetylcholine (or carbachol) is studied with this method. Close-range application of small quantities of the depolarizing agents (of the order of several times 10 -11 coulombs, or 10 -16 m) sets up transient potential changes of several millivolts amplitude. Application of a somewhat larger quantity of DTC (about 4 x 10 -10 C) produces a transient 50 % inhibition of the acetylcholine (or carbachol) potential. Curare does not alter the resting potential, nor the resistance or capacity of the end-plate or muscle fibre, but specifically interferes with the chemo-receptor properties of the end-plate. The inhibitory effect of DTC is obtained only with external application, but not with intracellular application from the inside of the muscle fibre. The decay of the inhibitory action of DTC is slow compared with the subsidence of the depolarization produced by acetylcholine or carbachol. The reason for this difference in time course is examined; it is probably due to relatively slow dissociation of the curare-receptor complex. Procaine in close-range, short-time application is as potent an inhibitor of acetylcholine action as DTC . The procaine effect subsides, however, much more rapidly than the action of curare.

1. A hyperpolarizing pulse applied through an external microelectrode to a nerve terminal during the falling phase of its action potential can suppress transmitter release; a depolarizing pulse applied during the same period can potentiate the release. 2. The facilitating action of calcium on transmitter release was studied by synchronizing the arrival of the nerve impulse with a rapid increment of the external calcium concentration. Using ionophoretic pulses of calcium, an effect could be produced with very little delay; sometimes the calcium pulse was effective when it preceded the arrival of the nerve impulse by only 1 to 2 ms.