bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure‐activity relations for caffeine: a comparative study of the inotropic effects of the methylxanthines, imidazoles and related compounds on the frog's heart
Authors: Chapman R. A. , Miller D. J.
Published: December 2014

1. The ability of several groups of compounds, related to caffeine, to induce contractures in isolated frog auricular trabeculae has been tested.

2. Of the methylxanthines, theophylline, theobromine and paraxanthine are of similar potency to caffeine. This applies to contractures produced in either high‐potassium or in sodium‐free solution, and to the twitch responses in normal Ringer.

3. Xanthines in which the 9‐position nitrogen is combined and is, therefore, without an ethylene bond do not affect contraction.

4. The hypothesis is put forward that a double‐bonded nitrogen, in an imidazole ring, is required for activity of the methylxanthine. This hypothesis is supported by the ability of imidazole and several close derivatives (e.g. histamine), as well as imidazolines, to evoke contractures. As predicted by the hypothesis, imidazolidines and imidazolidones, in which all the nitrogen atoms have single bonds, fail to initiate tension development.

5. The activity of histamine and histidine is only demonstrable at high pH (≏ 9·0).

6. Raising the pH in sodium‐free solution induces a transient contracture.

7. Several arguments suggest that cyclic AMP is probably not an intermediate in the response to the methylxanthines. The activity of cyclic AMP (and adenosine) in eliciting contractures is predicted by the hypothesis because they contain an imidazole moiety as part of their molecular structure.
Absorption and catabolism of histamine in sheep
Authors: Kay R. N. B. , Sjaastad Ø. V.
Published: December 2014

1. The fate of dietary histamine in sheep has been studied. When 200 mg histamine diphosphate was administered into a rumen with normal contents the average time taken for the biological activity to disappear from the rumen was about 4 hr. In sheep starved for 60 hr the activity disappeared much more slowly.

2. When 0·9% NaCl solution was substituted for the normal rumen contents and the rumen was isolated in situ under anaesthesia, the disappearance of histamine was scarcely detectable. About 1% of the radioactivity introduced into such rumen preparations as [14C]histamine was recovered in the urine during a 6 hr period.

3. When both [14C]histamine and 200 mg unlabelled histamine diphosphate were administered into the rumen, between 4 and 15% of the radioactivity and 2 and 11% of the biological activity reached the duodenum.

4. When jejunal loops isolated between two pairs of re‐entrant cannulas were perfused with 0·9% NaCl solution containing histamine a considerable fraction of the histamine was absorbed from the loops.

5. When [14C]histamine and 200 mg histamine diphosphate were administered into the rumen an average of 9% of the radioactivity appeared in the urine. When histamine was given into the abomasum the corresponding figure in a single experiment was 25%.

6. Between 11 and 34% of the radioactivity administered into the rumen as [14C]histamine was exhaled as 14CO2. Most of the 14CO2 seemed to stem from metabolism of [14C]histamine in the ruminoreticulum whereas the contribution of the intestines to 14CO2 was very small.

7. When [3H]histamine was administered into the rumen most of the radioactivity in the urine a few days after administration was in the form of tritiated water. The formation of 3H2O is probably a result of histamine metabolism in the fore‐stomach, analogous to the formation of 14CO2.
Inhibition within the trigeminal nucleus induced by afferent inputs and its influence on stimulus coding by mechanosensitive neurones
Authors: Carmody John , Rowe Mark
Published: December 2014

1. In decerebrate, unanaesthetized cats two thirds of slowly adapting mechanosensitive neurones sampled in the trigeminal nucleus oralis exhibited inhibition in response to conditioning mechanical stimulation applied beyond their excitatory receptive fields. The influence of this inhibition was examined over the response range of these neurones using controlled, reproducible natural stimulation procedures.

2. The extent of the inhibition was graded according to the intensity of the conditioning stimulus. It was evoked most strongly by vibratory skin indentation which very effectively excites rapidly adapting afferent fibres. Tonic conditioning inputs associated with steady skin indentation were less effective.

3. The slope of stimulus—response relationships constructed from responses to inputs from the excitatory receptive field was reduced in 42% of trigeminal nuclear cells in the presence of afferent‐induced inhibition. In the remainder the slope was unchanged.

4. There was no evidence, in the neurones subject to inhibition, of an expansion of their dynamic range defined as the range of stimulus intensities over which a neurone exhibited a graded responsiveness.

5. The variability in responses of an individual neurone at a given stimulus intensity was unchanged by this inhibition.

6. Analysis of the stimulus—response data using information theory statistics revealed that neurones which underwent a reduction in the slope of their stimulus—response relationship in the presence of inhibition displayed a reduced capacity for defining the intensity of skin indentation. This capacity was not modified in those neurones where the slope was unchanged by the peripherally evoked inhibition.
Sodium transport by the small intestine of new‐born and suckling pigs
Authors: de Jesus C. Henriques , Smith M. W.
Published: December 2014

1. Sodium transport has been measured across in vitro preparations of pig ileum taken at birth or during the first 10 days of post‐natal life.

2. Both the unidirectional and net fluxes of sodium fell shortly after colostrum was ingested by the new‐born piglet. These changes were associated with falls in short‐circuit current, open‐circuit voltage and tissue conductance and with the appearance of protein‐filled vacuoles within the mucosal epithelium.

3. Overnight fasting of piglets following a period of suckling caused all sodium fluxes to revert to values similar to those found in the new‐born animal. The short‐circuit current also increased on fasting but the magnitude of this effect decreased with age.

4. The suckling‐dependent inhibition of sodium transport was not associated with any change in the level of adenine nucleotides within the mucosa. However the rate at which sodium entered the intestinal mucosa of suckled pigs was found to be only half that of the new‐born.

5. It is suggested that pinocytosis might use up or chemically modify the microvillar membrane making it less permeable to sodium. Subsequent fasting would, by replenishment or further modification of existing membrane surface, allow the epithelium to recover its original permeability to sodium and possibly regain the ability to undergo a further cycle of pinocytotic activity.
Protein and glucose‐induced changes in sodium transport across the pig small intestine
Authors: de Jesus C. Henriques , Smith M. W.
Published: December 2014

1. The effect of glucose and of bovine γ‐globulin on short‐circuit current and sodium transport was measured using new‐born pig ileum before and after suckling.

2. Glucose increased the short‐circuit current with an apparent Km of 1·9 and 19·5 m
M for new‐born unsuckled and suckled intestines respectively. The Vmax was about 80 μA cm−2 in each case.

3. Bovine γ‐globulin applied to new‐born pig ileum caused a 20% increase in sodium chloride influx without change of short‐circuit current. The tissue conductance was also greater in the presence of globulin. These effects were not seen in ileum taken from suckled pigs.

4. p‐Chloromercuriphenyl sulphonic acid (PCMPS) inhibited the globulin induced increase in sodium influx in new‐born pig ileum without changing the measured short‐circuit current. 0·1 m
M‐PCMPS also changed the characteristics of the glucose‐dependent increase in short‐circuit current, so that this response came to resemble that seen in ileum taken from suckled pigs. Dithioerythritol reversed this effect of PCMPS.

5. The suckling‐dependent difference in results is explained in terms of a change in microvillar function taking place as a consequence of long‐term pinocytosis in vivo. The ability of PCMPS to simulate some of these changes suggests that sulphydryl groups might be important regulators of microvillar membrane stability.
The organization of visual processing in the pigeon cerebellum
Authors: Clarke P. G. H.
Published: December 2014

1. Visual responses were sought in the cerebella of decerebrate pigeons using extracellular micro‐electrodes, and were found in folia VIc—IXb, especially folia VII and VIII. The responses were mainly, but not exclusively, from the ipsilateral eye. Four binocular units were recorded.

2. In the anterior and posterior walls of folium VII the organization was clearly, though rather crudely, retinotopic. The temporal field was represented laterally, on the ipsilateral side, and the nasal field medially; the superior field was represented superficially, and the inferior field towards the base of the folium. In the lateral wall of folium VII there was a small anomalous region innervated by the contralateral eye.

3. The visual input arrived via the mossy fibre system.

4. Units exhibited a strong preference for moving targets, 20–60°/sec being the range of optimal speeds. About three quarters of the units responded most strongly to a particular direction of target motion. The preferred direction was most frequently upwards or backwards.

5. Units in the granule layer were to some extent clustered according to their direction‐preference, which tended to change gradually as the electrode advanced along the granule layer.

6. Units were classified as Gr‐units (granule cells or mossy fibre rosettes) or P–units (Purkinje cells) or were left unclassified. Receptive fields of Gr‐units were usually 5‐30° across; they were much larger for P‐units in folium VIII, but not obviously so for those in folium VII. Gr‐units were more frequently direction‐sensitive than were P‐units.
Cervical branching of lumbar vestibulospinal axons
Authors: Abzug C. , Maeda M. , Peterson B. W. , Wilson V. J. , Bean C. P.
Published: December 2014

1. We have investigated the possibility that individual lateral vestibulospinal tract (LVST) axons branch so as to innervate more than one spinal cord level.

2. LVST cells in Deiters' nucleus were activated antidromically by means of electrical stimulation applied through fine metal electrodes inserted into the spinal cord. Both by directly measuring the spread of effect of stimulus current, and from theoretical considerations (Appendix), we determined that in most cases an estimate of spread of effect of stimulus current was 10 μm/μA. From the magnitude of the threshold stimulus and from the location of the stimulus point we could often exclude the possibility that the stimulus was spreading to the LVST instead of activating local branches.

3. Movable stimulating electrodes, or multi‐electrode arrays placed in fixed position, were used to activate 115 LVST neurones antidromically by stimulation of local branches in the lower cervical or upper thoracic cord. Of these cells, 50% were also fired antidromically by stimulation of the LVST at levels ranging from L1 to L4 (Lc cells). The remaining cells were not activated by the lumbar stimulus (C cells). An additional group of cells was only fired by the lumbar tract stimulus (L cells).

4. The distribution of locations of Lc cells within Deiters' nucleus more closely resembles that of L cells than that of C cells. In addition the median conduction velocity of Lc cells is similar to that of L cells, but higher than that of C cells.

5. Much of the information reaching the lower cervical level from neurones of the LVST is information that is also simultaneously being passed downward to the lumbar region. Such integration makes it possible for a single neurone to be used to co‐ordinate widespread motor activity.

6. A theory is presented in a separate section (Appendix) to account for the spread of effect of stimulus current upon a myelinated axon submerged in an isotropic medium. The threshold for stimulation of a node by a nearby monopolar electrode is predicted to be proportional to the electrode‐node spacing. The constant of proportionality is given in a closed form that depends on the electrical properties of both the neurone and the surrounding medium. The predictions of the theory are shown to be in good accord with the experimental results.
Calcium influxes and tension development in perfused single barnacle muscle fibres under membrane potential control
Authors: Atwater I. , Rojas E. , Vergara J.
Published: December 2014

1. Single giant barnacle muscle fibres from Megabalanus psittacus (Darwin) were used to measure the Ca entry and the development of tension in the fibres under membrane potential control.

2. Fibres bathing in 60 m
m‐MgCl2 sea water, free of Ca, did not develop tension with sudden displacements of the membrane potential towards more positive values. This failure to develop tension with depolarizations was observed with and without the internal application of Ca buffers.

3. Fibres bathing in artificial sea water with either 10, 20, 60 or 100 m
m‐CaCl2 developed tension with depolarization even after 60 min of internal perfusion of the fibres with solution containing no Ca buffers. In this case the maximum tension recorded during a voltage clamp run decreased with time from nearly 2·5 to 0·2 kg/cm2. However, addition of 10 m
m‐Tris‐EGTA (ethyleneglycol‐bis (β‐aminoethyl ether) N, N′ — tetraacetic acid) to the perfusing solution rapidly eliminated the development of tension; after 10 min of internal perfusion with Ca buffers no tension could be elicited by electrical stimulation.

4. Ca‐influx determinations were carried out only in the fibres in which the outward K+ currents were blocked by internal application of TEA (tetra‐ethylammonium). The ratio of ‘measured extra Ca influx/computed ionic flux of divalent cations during the inward current’ was 1·06 ± 0·41.

5. For fibres bathed in either natural sea water or in artificial sea water with various concentrations of Ca, the temporal course of development of isometric tension was similar to the temporal course of the integral of the inward current due to Ca2+.

6. In a fibre from M. psittacus bathing in natural sea water the calculated extra entry of Ca required to increase its internal concentration to about 50 μ
m was 500 p‐mole per depolarization (60 mV); while the corresponding average influx calculated from the inward current record in natural sea water is 474 p‐mole.

7. Evidence was obtained for the accumulation of Ca in an internal compartment.
Transmembrane potentials in guinea‐pig hepatocytes
Authors: Heller Philip , van der Kloot William
Published: December 2014

1. In pieces of guinea‐pig liver with an intact capsule, the mean resting potential (E) is −49·8 mV, close to the value for in vivo hepatocytes and significantly higher than a similar preparation of rat liver. E is considerably less than the calculated K equilibrium potential of about −90 mV.

2. Changes in [K+]o in the range of 0–10 m
M produce almost no change in E. At [K+]o above 20 m
M, a tenfold increase produces only a 33 mV depolarization. The results with changing [K+]o are the same in Cl− free solutions (isethionate substitution) or when the [K+]o[Cl−]o product is kept constant. E rapidly returned to normal in liver pieces returned to Ringer after prolonged soaking in high K+ solution.

3. Changes in [Na+]o, [Cl−]o, [H+]o, [Ca2+]o or [Mg2+]o have little effect on E. Simultaneous variation of [Na+]o and [Cl−]o in opposite directions to maximize predicted changes in E also has only a minimal effect on E.

4. Cyanide (5 m
M) or ouabain (10−4
M) cause depolarization, so there is no reason to believe that pumps sensitive to these poisons are normally lowering resting potential. Part of the normal E may be produced by an electrogenic ouabain‐sensitive ion pump.

5. The data is interpreted by using a form of the constant field equation developed by Brading & Caldwell (1971). Application of this method yields PNa/PK less than 0·04, PCl/PK approximately 0·3. Additional terms, x and y, are required to account for the behaviour of E. Their physical basis remains undetermined.

6. Suggestions are presented for further study and for the application of the method of Brading & Caldwell to other non‐excitable cells and to excitable cells in low [K+]o, in which E is poorly understood.
A core‐conductor model of the cardiac Purkinje fibre based on structural analysis
Authors: Hellam D. C. , Studt J. W.
Published: December 2014

1. Structural analysis of voltage clamp preparations of sheep cardiac Purkinje fibres was carried out using methods based on light and electron microscopic observations. Results demonstrate the marked structural variability in preparations that appear, outwardly, simple.

2. The length of the cell aggregate was measured in vitro, and the mean area of cross‐section, by light microscopic methods in serially sampled transverse sections. The number of intercellular clefts and path lengths of cell profiles distributed at the lateral surface and along clefts were determined from photomicrographs. Accuracy of these estimates was improved by obtaining, electron microscopically, values representing the degree of membrane folding in longitudinal and transverse planes.

3. Cleft width was evaluated from electron micrographs. Measurements made on sections that there tilted through wide arcs with a goniometer indicate that cleft width is quite variable and, on average, somewhat greater than 400 Å.

4. A three‐dimensional core‐conductor model is presented to aid in quantitative interpretation of electrophysiological experiments. Application of the model to individual preparations requires evaluation of the length and perimeter of cross‐section of cell aggregates and of the mean number, width and depth of intercellular clefts, with appropriate corrections for fine sarcolemmal folding. Methods are given for estimating these structural parameter values from measurements of external dimensions of cell aggregates.

5. The core‐conductor model is applied in an accompanying analysis of the linear electrical characteristics of Purkinje membrane.
Motor control of nuclear bag and nuclear chain intrafusal fibres in isolated living muscle spindles from the cat.
Authors: Boyd I A , Ward J
Published: December 2014

1. The behaviour of nuclear bag and nuclear chain intrafusal fibres in isolated cat muscle spindles was studied by direct observation during repetitive stimulation of the muscle nerve at different stimulus strengths. Contraction of intrafusal fibres and stretch of sensory endings was recorded on film. 2. Tenuissimus spindles are usually operated by a total of four or five fusimotor axons, and the individual action of all of them was studied in many cases. 3. The great majority of fusimotor axons produce activity at one spindle pole only. 4. In about 60% of spindles nuclear bag and nuclear chain intrafusal fibres are selectively controlled by different fusimotor axons, while in one third of these spindles the individual nuclear bag fibres are themselves controlled independently. The remaining 40% of spindles, in addition to some selective innervation, receive one non‐selective axon which operates both nuclear chain and nuclear bag fibres though usually only one of the nuclear bag fibres is involved. Selective control is demonstrated in photographs. 5. The thresholds of fusimotor axons selectively innervating nuclear bag and nuclear chain fibres, and of non‐selective fusimotor axons are not significantly different. 6. It is suggested that in spindles in which the nuclear bag fibres are controlled by the same axon, it is a ‘dynamic’ gamma, or occasionally beta, axon. Where one nuclear bag fibre is operated along with the nuclear chain fibres it is controlled by ‘static’ gamma axon(s), and the other nuclear bag fibre is selectively controlled by ‘dynamic’ gamma, and perhaps beta, axon(s). Where two nuclear bag fibres are separately operated one may be controlled by ‘dynamic’ axon(s) and the other by ‘static’ gamma axon(s). Nuclear chain fibres are always controlled by ‘static’ gamma axons.
Changes in non‐electrolyte permeability of alveoli and the absorption of lung liquid at the start of breathing in the lamb.
Authors: Egan E A , Olver R E , Strang L B
Published: December 2014

1. Experiments were done on mature foetal lambs, 135–145 days in gestation, exteriorized at Caesarean section, and on new‐born lambs aged 12–60 hr. In the foetal lambs, test substances were added to lung liquid and then spontaneous ventilation was induced or the lungs were statically inflated with gas or saline. In the new‐born lambs, the left lung was ventilated in order to maintain respiratory gas‐exchange, while foetal lung liquid, taken from previous experiments and containing test substances, was introduced into the right lung, which was then inflated with gas and used for permeability measurements. In both foetuses and new‐borns, the gas used was O2 or N2O and, at 20 min intervals, ventilation or static inflation was interrupted, the gas in the lungs absorbed into the circulation and the remaining liquid sampled through the trachea. The following test substances were used in various combinations: [14C]‐erythritol, [3H]sucrose, [14C]inulin, [131I]albumin, and the polymer [131I]‐PVP. The last of these was separated, after the experiments, by gel filtration with Sephadex G200 or G50, into fractions of defined molecular radius. [131I]albumin, or a large molecule fraction of [131I]PVP, was used as a volume marker. 2. Spontaneous ventilation was associated with the absorption of liquid and with an alteration in the foetal pattern of non‐electrolyte permeability that could be characterized by postulating an opening up of water‐filled cylindrical pores to 34–56 A in radium. In the new‐born lambs, the results suggested pores 7–14 A in radius. 3. Static inflation of the foetal lungs with gas, to pressures of 25–35 cmH2O, gave permeabilities appropriate for pores 5‐5–12 A in radius. Static inflation with gas, to pressures of 41–49 cmH2O, produced changes appropriate for much larger channels, more than 125 A in radius and possibly much larger. With one exception, expansion with saline produced changes similar to those obtained by gas inflation to 25–35 cmH20. 4. It was concluded that in the initial stages of pulmonary ventilation a change takes place in alveolar epithelial cells. The increase in size would be sufficient to allow for rapid liquid absorption, but is not so great as to permit significant penetration by plasma albumin. The results obtained in the lung of the new‐born lamb statically inflated to 25–32 cmH2O suggest that, following the initial adaptation, alveolar permeability returns towards the foetal pattern, although the pores remain larger than in the foetus. The change in permeability pattern at birth appears to depend on the degree of lung expansion with gas.
The influence of aortic baroreceptors on venous tone in the perfused hind limb of the dog.
Authors: Hainsworth R , Karim F , Stoker J B
Published: December 2014

1. The aortic arch and both carotid sinuses were vascularly isolated and perfused. A hind limb was vascularly isolated and blood was pumped at constant flows into the femoral artery and the central end of a superficial metatarsal vein. 2. Large increases in aortic arch pressure resulted in decreases in arterial blood pressure, heart rate and femoral arterial perfusion pressure. The average response of the vein was a decrease of 11% in the pressure gradient between the perfused vein and the femoral vein. Similar responses were obtained when carotid sinus pressure was increased. 3. Crushing or cooling the lumbar sympathetic trunk caused responsed similar to those induced by increasing baroreceptor perfusion pressure. Stimulation at 1 HZ resulted in venous responses four times as great as the average reflex response, whereas frequencies of 2‐5 Hz were required to produce changes in arterial resistance as great as those induced reflexly. 4. These experiments indicate, that although the large superficial veins of the dog's hind limb participate in the baroreceptor reflexes, the activities in the nerves supplying arterioles and veins must have been different.
The interaction of ATP‐analogues possessing a blocked gamma‐phosphate group with the sodium pump in human red cells.
Authors: Simons T J
Published: December 2014

1. The (Na++K+)‐ATPase of red cell membranes is unable to hydrolyse ATP‐analogues in which the oxygen atom linking the beta‐ and gamma‐phosphate groups is replaced by a minusCH2minus or minusNH‐bridge. 2. In resealed ghosts both these ATP‐analogues support K:K exchange but not Na:K exchange. ATP supports both modes of operation of the sodium pump, whereas neither occurs without any nucleotide. 3. These results support the hypothesis that ATP is needed as a cofactor for K:K exchange to occur, and make it extremely unlikely that phosphorylation from ATP is involved.
Comparative effects of sodium taurodeoxycholate and sodium taurocholate on bile secretion in the rat, dog and rabbit.
Authors: Rutishauser S C , Stone S L
Published: December 2014

1. The biliary effects of sodium taurodeoxycholate and sodium taurochloate were investigated in anaesthetized dogs and rats, and in the isolated perfused rat liver. 2. Both bile salts had similar qualitative and quantitative effects on the flow and composition of bile in the dog. 3. In the rat, the bile salts had similar effects on the ionic compoistion of bile, but differed in that bile flow was not always directly related to the rate of bile salt secretion in bile, in the experiments with sodium taurodeoxycholate. 4. Sodium taurodeoxycholate is hydroxylated form sodium taurocholate by the liver of the rat but not by that of the dog. 5.The biliary effects of sodium taurodexoycholate in the rat and in the dog are contrasted with its effects in the rabbit, and the differences between the three species are discussed.
Pancreatic islet cells: electrogenic and electrodiffusional control of membrane potential.
Authors: Mattews E K , Sakamoto Y
Published: December 2014

1. Responses of the membrane electrical characteristics of mouse pancreatic islet cells to ionic environmental changes have been used to assess the role of [Na]0 and [K]0 in the control of membrane potential, i.e. by electrodiffusion or via an electrogenic sodium pump. Islet cell electrical properties were measured in vitro with intracellular glass micro‐electrodes. 2. Substitution of LiCl for extracellular NaCl did not change the islet cell membrane potential significantly in low (2.8 mM) glucose solutions, but readmission of NaCl caused a transient hyperpolarization (membrane potential maximum: −70 mV) in high glucose; when choline chloride was substituted for NaCl no hyperpolarization was observed on NaCl re‐admission. 3. Superfusion with K‐free solution gave no marked change in membrane potential during 30 min incubation in either low (2–8 mM) or high (28 mM) glucose concentrations but longer periods of exposure to K‐free solutions caused progressive depolarization. 4. Readmission of K+ induced a transient hyperpolarization of up to 30 mV magnitude and 10 min duration in the presence of high (28 mM) but not low glucose (2–8 mM) concentrations. At the level of maximum hyperpolarization the membrane potential reached −60 mV, the electrical activity induced by the high glucose concentration being concurrently completely blocked. Replacement of [Cl]0 by isethionate accentuated these effects. 5. Ouabain, 10(−3) M, or a decrease in temperature from 37 to 7 degrees C depolarized the islet cells and blocked the transient hyperpolarization induced by readmission of K+. 6. Diphenylhydantoin, 1–5 times 10(−4) M, caused a significant hyperpolarization of the islet cells in low glucose (2–8 mM) and inhibited the electrical activity induced by high glucose (28 mM) or tolbutamide (0–7 mM). 7. It is concluded from these results that both an electrogenic and ionic component contribute to the membrane potential of the mouse pancreatic islet cell although electrodiffusional control normally predominates; acceleration of the Na‐K exchange pump by diphenylhydantoin inhibits glucose‐induced electrical activity. These findings are discussed in relation to the permeability characteristics of the islet cell membrane and the mechanism of insulin release.
The requirements of the brain for some amino acids.
Authors: Baños G , Daniel P M , Moorhouse S R , Pratt O E
Published: December 2014

1. A constant specific activity of radioactively labelled amino acids was maintained in the circulation by means of a new technique devised for this purpose. This has made it possible to measure accurately the entry rates of amino acids into the brain in vivo. 2. The rates of entry into the brain of seven nutritionally non‐essential amino acids were measured. 3. Glycine and proline enter the brain relatively slowly, at rates comparable to those of amino acids which are not normally found in the blood. Thus their entry is due mainly if not entirely to passive diffusion. 4. Serine (which is used by the brain to make glycine) and alanine (which is used to make glutamate and aspartate) enter the brain as rapidly as the essential amino acids and thus, although not essential for the body as a whole, appear to be essential for the brain. 5. It is suggested that those amino acids that the brain is able to synthesize have low rates of entry, even though they are present at high concentrations in the plasma, but that the transport systems for those amino acids that are not synthesized in the brain ensure rapid entry at rates that are related to the rates of cerebral utilization.
The relation between the surface electromyogram and muscular force.
Authors: Milner‐Brown H S , Stein R B
Published: December 2014

1. Motor units in the first dorsal interosseus muscle of normal human subjects were recorded by needle electrodes, together with the surface electromyogram (e.m.g.). The wave form contributed by each motor unit to the surface e.m.g. was determined by signal averaging. 2. The peak‐to‐peak amplitude of the wave form contributed to the surface e.m.g. by a motor unit increased approximately as the square root of the threshold force at which the unit was recruited. The peak‐to‐peak duration of the wave form was independent of the threshold force. 3. Large and small motor units are uniformly distributed throughout this muscle, and the muscle fibres making up a motor unit may be widely dispersed. 4. The rectified surface e.m.g. was computed as a function of force, based on the sample of motor units recorded. The largest contribution of motor unit recruitment occurs at low force levels, while the contribution of increased firing rate becomes more important at higher force levels. 5. Possible bases for the common experimental observation that the mean rectified surface e.m.g. varies linearly with the force generated by a muscle are discussed. E.m.g. potentials and contractile responses may both sum non‐linearly at moderate to high force levels, but in such a way that the rectified surface e.m.g. is still approximately linearly related to the force produced by the muscle.
Fluorescence intensity changes associated with contractile activation in frog muscle stained with Nile Blue A.
Authors: Bezanilla F , Horowicz P
Published: December 2014

1. Extrinsic fluorescence intensity changes were studied in frog semitendinosus muscles stained with Nile Blue A in response to electrical stimulation. Muscles were stretched and put into hypertonic solutions to prevent movement. The muscles were illuminated at 90 degrees to their long axis with a narrow beam of light at a central wave‐length of 6250 . Fluorescence emission was measured at 90 degrees to the exciting light using a filter which absorbed light of wave‐lengths shorter than 6400 . 2. In response to a single stimulus the fluorescence intensity increases briefly. The fluorescence response is propagated at a constant velocity of about 1.5 m/sec. The average ratio of the maximum fluorescence intensity change to the resting fluorescence is 4.5 times 10‐3 for supramaximal shocks. The fluorescence intensity change starts early in the falling phase of the action potential. 3. The fluorescence intensity change increases when nitrate replaces chloride and decreases when D2O replaces H2O. The rates of rise and fall of the fluorescence change was unaffected by nitrate replacement of chloride but are slowed where D2O replaces H2O. The rates of rise and fall of the fluorescence change increase with increasing temperature for all solutions used. The peak fluorescence intensity change, however, goes through a maximum at about 17 degrees C for aqueous chloride and nitrate solutions in the range of 10–25 degrees C. With D2O solutions, the peak fluorescence intensity increases monotonically in this range of temperatures. 4. The fluorescence intensity change in response to trains of action potentials are not additive. 5. Depolarization of muscles treated with tetrodotoxin using triangular‐shaped fluid electrodes produces an increase in fluorescence at about the same threshold values required to elicit tension in preparations that are not fully stretched. The fluorescence intensity change precedes in time tension development. Near threshold depolarizations, the delay in onset of the fluorescence response can be 80 msec or longer. Byond threshold, delays become shorter and peak responses larger. During maintained depolarization, after the peak response, fluorescence declines to a plateau value. 6. The results suggest that the fluorescence intensity changes are associated with excitation‐contraction coupling, possibly with changes in the transmembrane potential of the sarcoplasmic reticulum.
The relationship of adenosine triphosphatase activity to tension and power output of insect flight muscle.
Authors: Pybus J , Tregear R T
Published: December 2014

1. On a simple model of actomyosin interaction, the tension cost (ATP hydrolysed/unit tension) and the frequency of low amplitude oscillation optimum for work production are both determined by the rate of detachment from the actin filament of the myosin crossbridge. To test this model, the two parameters were measured under different conditions using glycerol‐extracted Lethocerus cordofanus dorsal longitudinal flight muscle fibres. 2. The ATPase activity of the static muscle rose by an amount approximately proportional to the rise in tension as the muscle was stretched. 3. When the muscle fibres were sinusoidally oscillated at 5‐10 Hz by 2% of their resting length they produced a large amount of mechanical power and hydrolysed approximately twice as much ATP per unit mean tension as they did when static. The ATPase activity was linearly related to the mean tension during oscillation. 4. The experiments were repeated at temperatures between 12 and 30 degrees C and the tension cost and the optimal frequency of oscillation of the fibres were found to rise with temperature. 5. Removal of phosphate from the incubating medium reduced both the tension cost and the optimal working frequency. Addition of pyrophosphate or sulphate reduced both parameters still further. 6. From these results the tension cost of static muscle was shown to be proportional to its optimal working frequency. 7. ATPase activity rose monotonically with power production at work‐producing frequencies and at moderate degrees of stretch. A high absolute efficiency was found under a wide range of conditions. 8. The proportionality between tension cost and optimal frequency is evidence for the proposed model of actomyosin interaction.
Heterosynaptic facilitation in the giant cell of Aplysia.
Authors: Shimahara T , Tauc L
Published: December 2014

1. Heterosynaptic facilitation, defined as an increase of the efficacy of synaptic transmission between a test interneurone and a post‐synaptic neurone, produced by the stimulation of a separate pathway, was studied in the left pleural ganglion. The experimental procedure consisted of detecting the effects of a brief tetanus, applied to tentacular and tegumentary nerves, on the amplitude of monosynaptic and unitary post‐synaptic potentials (p.s.p.s) recorded in the left giant cell and generated by stimulating the test interneurone every 10 sec. The membrane potential of the test interneurone was simultaneously recorded. 2. Following heterosynaptic stimulation, the amplitude of the test p.s.p. increased, after a delay of about 30 sec, up to 250% of its original size; this increase subsided after 2‐3 min or more. 3. Only the interneurones producing in the giant cell the e.i.p.s.p. (excitatory‐inhibitory post‐synaptic potential) were affected by hetero‐synaptic facilitation. Other interneuronal types showed no changes in their synaptic transmission on the giant cell after heterosynaptic stimulation. 4. Heterosynaptic stimulation did not produce either orthodromic or antidromic spikes in the test interneurones clearly indicating that facilitation of test p.s.p. did not result from increased spike activity in the test interneurone. 5. Often heterosynaptic facilitation of the test p.s.p. was observed due to spontaneous activity in the heterosynaptic pathway, demonstrating the normal occurrence of the phenomenon. 6. Iontophoretic injection of 5‐HT at critical, presumably synaptic, sites in the neuropil, evoked a facilitation of the test p.s.p. similar to heterosynaptic facilitation. Only the e.i.p.s.p.s. were so affected by 5‐HT. On the contrary, other p.s.p. types were depressed by 5‐HT as a result of conductance changes in the left giant cells. 7. Both heterosynaptic facilitation and 5‐HT facilitation were suppressed by the presence in the bath of 5‐HT (10(−5) M) and of LSD‐25 (3 X 10(−4) M). The action of injected 5‐HT on the membrane conductance of the left giant cell was also depressed in the pressence of 5‐HT in the bath, but was unaffected by LSD‐25 (3 X 10(−4) M). 8. From the parallelism of properties of heterosynaptic and 5‐HT facilitation, it is suggested that 5‐HT is the probable transmitter mediating heterosynaptic facilitation. It seems likely that 5HT is released from the heterosynaptic pathway at the level of the synaptic ending of the test interneurone on to the giant cell and that it increases the efficacy of this synapse, probably acting on the quantity of synaptic transmitter liberated.
Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.
Authors: Blaustein M P
Published: December 2014

1. 45‐Ca uptake by pinched‐off nerve terminals (synaptosomes) of rat brain incubated in standard physiological saline (including 132 mM‐Na + 5mM‐K + 1–2 mM‐Ca) at 30 degrees C averages about 0–5 mumole Ca per g protein per minute. This may be equivalent to a Ca influx of about 0–03 p‐mole/cm−2 sec. 2. The rate of 45‐Ca uptake is increased when the concentration of K in the medium is increased above 15–20 mM, K replacing Na isosmotically. Maximum stimulation, a three‐ to six‐fold increase in the rate of Ca uptake, occurs when [K]o is about 60 mM. The effect of increased [K]o is reversible. 3. The K‐stimulated Ca uptake is associated primarily with the nerve terminal fraction of brain homogenates. The entering Ca is not accompanied by extracellular markers such as mannitol or inulin. Replacement of external chloride by methylsulphate or sulphate does not prevent the stimulation by K. 4. The effects of external K are quantitatively mimicked by Rb. Caesium also stimulates Ca uptake, but is only about one fifth as effective as K or Rb; Li is ineffective. 5. Two other depolarizing agents also stimulate Ca uptake by synaptosomes: veratridine (7–5 times 10− minus 6 to 7–5 times 10− minus 5 M) and scorpion (Leirus quinquestriatus) venom (6–7 times 10− minus 7 to 6–7 times 10− minus g/ml.). The stimulatory effects of veratridine and scorpion venom, but not of increased [K] are blocked by 2 times 10− minus 7 M tetrodotoxin. 6. Internal K also influences the rate of 45‐Ca uptake by synaptosomes: lowering [K]i reduces the stimulatory effect of external K and veratridine. 7. Replacement of external Na by choline markedly inhibits the response to veratridine, but has a much smaller effect on the response to increased [K]o. 8. The Ca uptake mechanism has an apparent dissociation constant for Ca (KCa) of about 0–8 mM. Increasing [K]o increases the maximal rate of Ca uptake, but has no effect on KCa. The K‐induced 45‐Ca uptake is competitively inhibited by Mg‐2+, Mn‐2+ and La‐3+. 9. The release of acetylcholine and noradrenaline was also studied. Increasing [K]o stimulates external Ca‐dependent acetylcholine release. Scorpion venom stimulates noradrenaline release from synaptosomes; this effect could be prevented by adding tetrodotoxin or removing external Ca. 10. These results indicate that synaptosomes may increase their permeability to Ca, accumulate Ca and release neural transmitter substances, when stimulated by depolarizing agents under appropriate physiological conditions.
The influence of sodium on calcium fluxes in pinched‐off nerve terminals in vitro.
Authors: Blaustein M P , Oborn C J
Published: December 2014

1. The influence of internal and external Na concentrations on Ca movements have been measured in pinch‐off presynaptic nerve terminals (synaptosomes). Ca uptake is enhanced when external Na (Nao) is replaced by Li, choline or dextrose, in Na‐loaded synaptosomes. Depletion of internal Na (Nai) abolishes the stimulatory effect of external Na removal. 2. Ca uptake from Na‐depleted media is proportional to [Na]i −2, and averages about 1–5 mumole Ca/g synaptosome protein per minute when [Na]i is approximately 137 mM. This may correspond to a Ca influx of about 0–1 p‐mole/cm‐2 sec. 3. External Na is a competitive inhibitor of the Nai‐dependent Ca uptake. The interrelationship between [Na]o, [Ca]o and Ca uptake indicate that two external Na ions may compete with one Ca at each uptake site. 4. The distribution of particles with Nai‐dependent Ca uptake activity parallels the distribution of synaptosomes in the preparative sucrose gradient. Thus, this Ca uptake activity is probably a property of the pinched‐off nerve terminals per se, and not of the mitochondria which may contaminate the synaptosome fraction. 5. The Nai‐dependent Ca uptake mechanism requires an intact surface membrane, since synaptosomes subjected to osmotic lysis lose the ability to accumulate Ca by this route. 6. Ca efflux into Ca‐free media is largely dependent upon the presence of external Na. The curve relating Ca efflux to [Na]o is sigmoid, and suggests that more than one external Na ion (perhaps 2 or 3) is needed to activate the efflux of each Ca ion. 7. The net Ca gain exhibited by Na‐loaded synaptosomes incubated in Na‐depleted media can be accounted for by the increased Ca uptake and decreased Ca loss observed under these conditions. 8. Treatment of synaptosomes with cyanide or 2,4‐dinitrophenol decreases Ca uptake and enhances Ca efflux into Na‐containing media. This results in a net loss of Ca from the terminals, even in the presence of external Ca. 9. In contrast to the Ca efflux from synaptosomes, the Ca efflux from brain mitochondria is not dependent upon external Na, and is reduced by succinate, a substrate which is known to fuel mitochondrial respiration. 10. The temperature coefficient (Q10) of the Nai‐dependent Ca uptake is about 3. 11. The Nai‐dependent Ca uptake is reduced at low pH. The relationship between this Ca uptake and pH approximates a titration curve with a pKa of about 5‐6. 12. The data indicate that Ca transport in rat brain presynaptic terminals may involve a carrier‐mediated Na‐Ca exchange mechanism, and that some of the energy required for Ca extrusion may come from the Na electrochemical gradient across the surface membranes.
Visual evoked responses in humans with abnormal visual experience.
Authors: Freeman R D , Thibos L N
Published: December 2014

1. The visual evoked response to a grating target of varying spatial frequency was examined for normal subjects and for subjects with meridional amblyopia. This condition, reduced visual resolution for specific target orientations, is associated with, and thought to result from, marked ocular astigmatism. 2. For normal subjects, the general relation between spatial frequency and the evoked response is similar to psychophysical contrast sensitivity data. Evoked response amplitudes to oblique gratings are typically reduced and this is analogous to the lower acuity for oblique compared to horizontal and vertical detail. 3. In addition to the oblique effect, the magnitude of the evoked response for meridional amblyopes depends upon grating orientation over most of the spatial frequency range tested (0‐5‐16 cycles/deg). The lowest evoked amplitude is found when stimulus grating orientation matches that for which acuity is reduced. 4. The evoked potentials spatial frequency response functions are qualitatively similar to contrast sensitivity functions determined with the same abnormal subjects. 5. From these results, it may be concluded that the physiological locus of meridional amblyopia is confined primarily to structures at or prior to the site of evoked potential generation.
The interaction between foreign and original motor nerves innervating the soleus muscle of rats.
Authors: Frank E , Jansen J K , Lono T , Westgaard R H
Published: December 2014

1. The fibular nerve was transplanted on to the soleus muscle of the rats. Interruption of the original soleus nerve then permitted cross‐innervation, and subsequently, over a period of weeks, re‐innervation by the original nerve. 2. Individual muscle fibres were often innervated by both the original and the foreign nerve. The original and foreign end‐plates were located in separate regions of the muscle. There were no indications that the original nerve could displace or repress the foreign innervation. 3. The extent of re‐innervation by the original nerve depended upon the method of denervation. A single crush of the nerve was followed by virtually complete re‐innervation, even of muscle fibres already innervated by the foreign nerve. When re‐innervation was delayed by resection of a segment of the nerve only muscle fibres without foreign nerve innervation were re‐innervated. Denervation by a simple nerve cut gave an intermediate result. 4. Re‐innervation by the original nerve can take place without measurable extrajunctional sensitivity to ACh. 5. The original end‐plate region could retain high and localized sensitivity to ACh for several months despite degeneration of its motor nerve terminal and activity of the muscle fibre. 6. Established foreign end‐plates were re‐innervated by the foreign nerve on muscle fibres with intact original innervation. 7. The factors controlling synapse formation in skeletal muscles are discussed.