bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of caffeine on the contraction of the frog heart
Authors: Chapman R. A. , Miller D. J. 
Published: December 2014

1. The force of contraction and the membrane potentials have been measured from preparations of frog heart, with methods that also allow the rapid exchange of the extracellular fluid.2. In regularly beating preparations, caffeine induces only weak contractures at temperatures above 15° C, but it does cause a marked potentiation of the twitch responses; longer exposure results in a depression of contraction. The build up and decline of the twitch strength, on addition and on removal of caffeine approximates to a single exponential, time constant 26–45 sec, and this time constant is not altered by variation of the [Ca]o, the stimulus rate or the caffeine concentration. This time course of the change of twitch strength is less complex than the changes seen when either [Ca]o or the stimulus rate is altered, suggesting a more direct action of caffeine on excitation‐contraction coupling.3. Caffeine increases the strength of the contractures initiated by potassium‐rich or sodium‐depleted solutions in isolated atrial trabeculae.4. After the spontaneous relaxation of the contracture, evoked by either sodium‐free or potassium‐rich fluids, the application of caffeine initiates a redevelopment of tension. This caffeine contracture is transient and its strength is dependent on the caffeine concentration. The response in sodium‐free solution can be elicited in the virtual absence of extracellular calcium.5. Local anaesthetics antagonize the caffeine contracture.6. The results suggest that the sarcoplasmic reticulum of frog heart muscle plays an important role in the initiation and control of contraction and relaxation.
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.
Influence of changes in external potassium and chloride ions on membrane potential and intracellular potassium ion activity in rabbit ventricular muscle
Authors: Fozzard Harry A. , Lee Chin Ok 
Published: December 2014

1. The membrane responses of rabbit papillary muscles to rapid changes in [K]o and [Cl]o were measured with open‐tipped micropipettes and with closed micropipettes made from K‐selective glass.2. The muscle cells behaved primarily as a K electrode, and responses to changes in [K]o with constant [Cl]o or with constant [K]o × [Cl]o were substantially the same.3. When [Cl]o was changed at a constant [K]o the membrane potentials changed rapidly and symmetrically by a small value and remained constant for 30 min.4. Measurement of potential with K+‐selective micro‐electrodes in these experiments showed no change in intracellular K activity. In addition to permitting calculation of K permeability, these measurements reassured us that the K+‐selective electrodes were well insulated and not influenced by electrical shunts at the impalement site.5. Although the membrane response to changes in [Cl]o was small, it was possible to calculate that the permeability ratio (PCl/PK), was 0·11. The Cl and K conductances were about 0·015 mmho/cm2 and 0·09 mmho/cm2 respectively, resulting in a conductance ratio (gCl/gK) of about 0·17.6. The time course of depolarization by increase in [K]o was rapid (half‐time 5 sec), but repolarization on return to lower [K]o was much slower (half‐time 50 sec). The depolarization time course was easily fitted by the potential change calculated by assuming the need for K diffusion into the extracellular spaces and taking account of the logarithmic relation between membrane potential and [K]o. These calculations did not fit the time course of repolarization, which was slowed in the fashion expected from an inward‐rectifying membrane.7. The influence of [K]i on membrane potential was investigated by changes in tonicity of the external solution. Hypotonic solution produced a change in intracellular K activity close to that produced by ideal water movement. However, in hypertonic solution, intracellular K activity did not rise as much as predicted, suggesting a change in intracellular activity coefficient.
Reduction of the duration of isovolumic relaxation in the ejecting left ventricle of the dog: residual volume clamping
Authors: Suga Hiroyuki , Yamakoshi Ken-Ichi 
Published: December 2014

1. The individual effects of stroke volume and speed of ejection on the duration of the isovolumic relaxation phase were analysed in the canine left ventricle with a constant end‐systolic residual volume.2. A new technique was employed to maintain the ventricular end‐systolic residual volume at a desired constant value regardless of wide changes in stroke volume and speed of ejection in a given inotropic background.3. The duration of isovolumic relaxation, which was defined to be the time taken for ventricular pressure to fall from its end‐systolic level to its 75, 50 and 25% levels, markedly decreased with increases in stroke volume. The reduction amounted to as much as 30‐50% when stroke volume was increased from zero (isovolumic) to 20‐25 ml.4. The degree of shortening of the duration of isovolumic relaxation was largely independent of changes in speed of ejection which ranged from about 100‐800 ml./sec at a constant stroke volume of 15 ml.5. It was therefore concluded that stroke volume itself could be a major determinant of the duration of isovolumic relaxation.6. It was speculated that the mechanism of the observed phenomenon might be a manifestation of the uncoupling effect of muscle shortening on contractile state.