bluuebunny/crossref_metadata_2025 huggingface dataset:
Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat.
Authors: Baker D G , Coleridge H M , Coleridge J C , Nerdrum T
Published: December 2014

1. We have examined the effect of bradykinin on impulse traffic in sympathetic afferent fibres from the heart, great vessels and pleura, and have attempted to identify cardiac nociceptors that on the basis of their functional characteristics might have a role in the initiation of cardiac pain. 2. In anaesthetized cats, we recorded afferent impulses from ‘single‐fibre’ slips of the left 2nd‐‐5th thoracic rami communicantes and associated chain, and selected fibres arising from endings in the heart, great vessels, pericardium and pleura. We applied bradykinin solution (0 . 1‐‐1 . 0 microgram/ml.) locally to the site of the ending; we also injected bradykinin (0 . 3‐‐1 . 0 microgram/kg) into the left atrium. 3. Afferent endings excited by bradykinin (159 of 191 tested) were of two types. The larger group (140) were primarily mechanoreceptors with A delta of C fibres (mean conduction velocity, 7 . 5 +/‐ 0 . 6 m/sec). They were very sensitive to light touch. Those located in the heart, great vessels or overlying pleura had a cardiac rhythm of discharge and were stimulated by an increase in blood pressure or cardiac volume. 4. Bradykinin increased mechanoreceptor firing from 0 . 7 +/‐ to 5 . 0 +/‐ 0 . 3 (mean +/‐ S.E. of mean) impulses/sec. Some endings appeared to be stimulated directly by bradykinin, others sensitized by it so that they responded more vigorously to the pulsatile mechanical stimulation associated with the cardiac cycle. 5. The smaller group of eighteen endings, of which ten were in the left ventricle, were primarily chemosensitive. Most had C fibres, a few had A delta fibres (mean conduction velocity, 2 . 3 +/‐ 0 . 7 m/sec). They were insensitive to light touch. With one exception they never fired with a cardiac rhythm, and even large increases in aortic or left ventricular pressure had little effect on impulse frequency. 6. Chemosensitive endings were stimulated by bradykinin, impulse activity increasing from 0 . 6 to 15 . 6 +/‐ 1 . 3 impulses/sec and remaining above the control level for 1‐3 min. The evoked discharge, which was either continuous or occurred in irregular bursts, was not secondary to mechanical changes in the heart and great vessels. 7. Tachyphylaxis occurred when the interval between successive applications of bradykinin was 20 min or less. It was a feature of the response of both mechanosensitive and chemosensitive endings. 8. Because of their responsiveness to changes in pressure and their sensitivity to light touch, the mechanosensitive endings appear to be unlikely to subserve a primarily nociceptive function, although they may be responsible for evoking some of the components of the pseudoaffective response. By contrast, the chemosensitive endings appear well fitted to act as cardiac nociceptors.
Effects of strontium ions on end‐plate channel properties.
Authors: Miledi R , Parker I
Published: December 2014

1. Changes in end‐plate channel properties resulting from substitution of Sr2+ for Ca2+ in the Ringer solution have been analysed at the voltage clamped frog end‐plate, by recording m.e.p.c.s and ACh induced noise variance. 2. In 2 mM‐Sr2+‐‐Ringer the peak size of m.e.p.c.s showed a very small increase, and the time constant of the decay phase (tau m.e.p.c.), at any given voltage, was increased by a factor of about two compared to control Ringer. The voltage dependence of tau m.e.p.c. was the same in both solutions. 3. Addition of increasing amounts of CaCl2 to 2 mM‐Sr2+‐‐Ringer produced a progressive shortening of tau m.e.p.c., with no change in voltage dependence. 4. Estimates of single channel properties from noise analysis showed that the elementary conductance appeared to be slightly increased in 2 mM‐Sr2+‐‐Ringer, whilst the mean channel life‐time was prolonged by a factor of about two. These changes in single channel properties are sufficient to account for the observed changes in m.e.p.c.s. 5. Following inhibition of cholinesterase activity by neostigmine, similar effects on m.e.p.c.s and single channel properties were still observed on changing to 2 mM‐Sr2+‐‐Ringer. The shapes of m.e.p.c.s in Sr2+ + neostigmine Ringer were often altered, and showed flat ‘plateaus'. 6. The observed effects of Sr2+‐‐Ringer on channel life‐time cannot be explained on the basis of changes in surface charge density on the membrane, and suggest that divalent cations have an additional, and more direct, influence on receptor channel properties.
Excess magnesium converts red cell (sodium+potassium) ATPase to the potassium phosphatase.
Authors: Flatman P W , Lew V L
Published: December 2014

1. The ATPase and phosphatase activities of red cell membranes were measured simultaneously as a function of the magnesium content of the medium. 2. It was found that when the magnesium concentration was greater than that of ATP, magnesium inhibited the ATPase and simultaneously stimulated the phosphatase. The concentrations of magnesium needed for half‐maximal stimulation of the phosphatase and half‐maximal inhibition of the ATPase were similar. 3. It is suggested that increasing the concentration of magnesium directly causes a change in the conformation of the enzyme from one which favours ATPase activity to one which favours phosphatase activity.
Does glial uptake affect GABA responses? An intracellular study on rat dorsal root ganglion neurones in vitro
Authors: Desarmenien M. , Feltz P. , Headley P. M.
Published: December 2014

1. Using single barrel pipettes, intracellular records were obtained from surface neurones of isolated rat dorsal root ganglia (DRG) impaled under microscopic vision.

2. Responses to γ‐aminobutyric acid (GABA) were elicited either by ionophoresis or by placing drops of concentrated GABA solutions directly into the flow of superfusing Ringer. Using this latter method it was estimated that the GABA concentration eliciting threshold (≃ 1 mV) responses was 3‐20 μ
M.

3. Short (≤ 1 sec) ionophoretic or drop administrations of GABA elicited depolarizing responses associated with an increased membrane conductance. With longer applications the initial depolarization was not sustained but decayed to a lower plateau level (desensitization) associated with a minimal conductance change.

4. Low chloride superfusions did not affect subsequent responses to GABA unless GABA was also administered during the low chloride superfusion, in which case responses declined markedly. This suggests that GABA caused appreciable chloride fluxes when it was administered regularly (e.g. for 1 sec every minute).

5. Glial GABA uptake was inhibited by adding 1 m
M‐β‐alanine or 0·25 m
M‐chlorpromazine to the bicarbonate‐Ringer superfusate or by substituting lithium for sodium in a Tris‐Ringer superfusate. Uptake inhibition had no consistent effect on any of the parameters studied, namely membrane potential, input resistance, amplitude and time course of responses to GABA, and GABA desensitization.

6. Muscimol and isoguvacine, which are probably not substrates for the glial GABA carrier, elicited responses with time course and desensitization characteristics indistinguishable from those of responses to GABA.

7. GABA superfused at concentrations as low as 1 μ
M could reduce responses to ionophoretic GABA, i.e. cause a desensitization of GABA receptors.

8. It is concluded firstly that in DRG, glial uptake does not affect the amplitude or time course of responses to GABA when the neurone under study is close to the source of GABA; and secondly that desensitization can occur independently of GABA uptake.

9. The findings are discussed in relation to their possible relevance to GABA systems in the central nervous system.
Fast axonal transport of foreign transmitters in an identified serotonergic neurone of Aplysia californica.
Authors: Goldberg D J , Schwartz J H
Published: December 2014

1. Radioactively labelled compounds, several of which are neurotransmitters, were injected with pressure into the soma of the serotonergic giant cerebral neurone (g.c.n.) of Aplysia californica. The compounds injected were [3H]dopamine, [3H]DL‐octopamine, [3H]histamine, [3H]gamma‐aminobutyric acid and [3H]choline. 2. Substantial amounts of radioactivity appeared in the axons of the g.c.n. with all of the injected compounds. Except for [3H]choline, the amounts were similar to the amount appearing when [3H]serotonin is injected. 3. The biogenic amines, [3H]dopamine, DL‐[3H]octopamine and [3H]histamine, all moved in the axon at velocities similar to that of [3H]serotonin. In contrast, the radioactivity in axons of cells injected with [3H]gamma‐aminobutyric acid and [3H]choline moved much more slowly. In addition, the shapes of the spatial distributions of radioactivity in the axons of cells injected with the biogenic amines resembled that obtained when [3H]serotonin is injected. This distribution is characteristic of fast axonal transport. The spatial distributions of radioactivity in the axons of cells injected with [3H]gamma‐aminobutyric acid and [3H]choline were markedly different. We thus conclude that [3H]dopamine, DL‐[3H]octopamine and [3H]histamine move by fast axonal transport, whereas the radioactivity in the axons of cells injected with [3H]gamma‐aminobutyric acid and [3H]choline does not. 4. Injection of large amounts of dopamine and octopamine reduced the export into the axon of [3H]serotonin injected into the same cell. Large amounts of choline did not reduce export of [3H]serotonin. We conclude that the biogenic amines compete with serotonin for the vesicular storage site and that they move by fast transport because they are sequestered by the serotonergic storage vesicle. 5. The specificity of uptake into the storage vesicle as assayed with this in vivo system is similar to the specificity of uptake into aminergic vesicles as previously studied in vitro.
Porcine muscle responses to carbachol, alpha‐ and beta‐adrenoceptor agonists, halothane or hyperthermia.
Authors: Gronert G A , Milde J H , Taylor S R
Published: December 2014

1. Whole body trans‐section at the level of the first or second lumbar vertebra of stress‐susceptible or normal Poland China swine provided a preparation of isolated perfused caudal muscle that was without nervous or hormonal influences. Metabolic responses to halothane anaesthesia were exaggerated in the susceptible preparation. 2. Carbachol (10(‐4) M) increased O2 consumption threefold and elevated blood lactate levels from 3 to 8 mumole/ml. in susceptible but not in normal muscle preparations. 3. Isoprenaline in a continuous infusion (2.5 micrograms/kg caudal wt. per min for 12 min, subsequently diminished to 1.2 microgram/kg per min) did not increase O2 consumption of susceptible or normal muscle but did increase blood lactate by 2 mumole/ml. in both. 4. Simultaneous administration of carbachol and isoprenaline resulted in additive increases in blood lactate. 5. Incremental increases in temperature above 41 degrees C initiated exaggerated increases in O2 consumption and blood lactate in susceptible but not normal muscle; these were similar to whole body responses. 6. Phenylephrine (0.2‐25 micrograms/kg per min continuous) produced (i) hypertension, (ii) no observed effects upon aerobic or anaerobic metabolism and (iii) progressive tissue oedema; these effects were similar in susceptible and normal muscle. 7. Skeletal muscle from stress‐susceptible swine is evidently inherently capable of metabolic responses to cholinergic agonists and increased temperature; these responses are greater than those in normal muscle. This suggests that initiation of stress responses in intact swine is related to somatic motor and sympathetic stimulation of abnormal skeletal muscle, and not to a disorder of the somatic or sympathetic nervous system.
Action of morphine on the neuro‐effector transmission in the guinea‐pig ileum and in the mouse vas deferens.
Authors: Ito Y , Tajima K
Published: December 2014

Effects of morphine on the neuro‐effector junction of the guinea‐pig ileum or mouse vas deferens were investigated by the micro‐electrode and double sucrose gap methods. 1. Morphine (10(‐8)‐10(‐5) M) did not change the membrane potential, membrane resistance and electrical threshold required to produce the action potential of smooth muscle cells of guinea‐pig ileum or mouse vas deferens. 2. Morphine (10(‐8)‐10(‐7) M) markedly suppressed the amplitude of excitatory junction potential (e.j.p.) of ileum or that of vas deferens. However the same concentration of morphine did not suppress the inhibitory junction potential recorded from the guinea‐pig ileum or the facilitation phenomena observed with repetitive stimulation in the mouse vas deferens. In addition, this opiate (3.5 x 10(‐5) M) did not alter the amplitude or the frequency of miniature excitatory junction potential recorded from the mouse vas deferens. 3. Naloxone (3.5 x 10(‐7) M), itself, exerted no effect on the membrane potential and amplitude of the e.j.p. After pretreatment with naloxone, however, the inhibitory action of morphine on the e.j.p. was suppressed. 4. The extracellularly recorded action potential from the small nerve bundle innervating the mouse vas deferens was not affected by morphine (3.5 x 10(‐5) M). 5. The amplitude of the e.j.p. of the guinea‐pig ileum was dependent on the concentration of [Ca]o. When [Ca]o and the relative amplitude of e.j.p. were plotted on a double logarithmic scale, the above relation yielded a straight line with a slope of 1.7. Application of morphine resulted in a reduction in the slope of the straight line to 1.0. 6. These results indicate that morphine probably suppresses the influx of Ca during spike electrogenesis in the nerve terminal, however, there is no modification of the action of Ca in nerve terminals.
A comparative electrophysiological study of motor end‐plate diseased skeletal muscle in the mouse.
Authors: Weinstein S P
Published: December 2014

1. Experiments using intracellular recording, stimulation, and microionophoretic techniques were performed on extensor digitorum longus nerve‐muscle preparations excised from mice having hereditary ‘motor end‐plate disease'. Control experiments were performed on normal innervated and chronically denervated nerve‐muscle preparations. 2. Two physiologically distinct groups of muscle fibres were found in the diseased muscles. Group I is similar to normal innervated muscle with respect to resting potentials, cable properties, neuromuscular transmission, miniature end‐plate potentials, and extrajunctional acetylcholine sensitivity. Group II is similar to denervated muscle in the above respects except that (i) neuromuscular transmission, though abnormal, was present, and (ii) miniature end‐plate potentials (m.e.p.p.s), often having large amplitudes, were found in these muscle fibres. 3. Large m.e.p.p.s appear to be due to an increase in muscle fibre input resistance and to the quantal release of abnormally large amounts of acetylcholine from motor nerve terminals. 4. Nerve stimulation of group II muscle fibres evoked action potentials with a delayed repolarization phase, suggesting that a prolonged acetylcholine‐induced conductance change occurs at motor end‐plates. 5. Neuromuscular physiology in motor end‐plate disease is similar to that reported for frog nerve‐muscle preparations which have been incubated in high Ca2+ Ringer.
The respiratory role of the ventral surface of the medulla studied in the anaesthetized rat.
Authors: Malcolm J L , Sarelius I H , Sinclair J D
Published: December 2014

1. The respiratory role of the ventral surface of the medulla was studied in rats anaesthetized with a urethane‐chloralose mixture. 2. In fifty‐eight studies on twelve animals, direct superfusion of the medullary surface with artificial c.s.f. made acid by the reduction of bicarbonate content or by the increase of PCO2 produced no significant stimulation of respiration provided that the temperature of the brain surface was unaltered. 3. Superperfusion of the medullary surface with c.s.f. of low bicarbonate content produced an inhibition of respiration in fourteen of thirty‐eight experiments. 4. Electrical stimulation on the surface revealed a localized area lateral to the pyramids and rostral to the XIIth nerve where stimulation at low intensity produced an increase in the frequency and depth of respiration. 5. The application of carbachol to a similar region increased both the frequency and amplitude of ventilation at lower concentrations than were required to obtain effects from surrounding areas. 6. Sudden switching between perfusates at different temperatures produced changes of ventilation within 1‐2 sec of a change of surface temperature. The Q10 for the ventilation/temperature relationship was approximately 6. 7. The experiments confirm that the ventral surface of the medulla contains neural elements which, at least during urethane‐chloralose anaesthesia, have a significant effect on respiration. The stimulus for these effects in the rat does not appear to be a change in H+ concentration. It appears more probable that the primary role of the area lies in the link between thermal and respiratory regulation.
Evidence that the human jaw stretch reflex increases the resistance of the mandible to small displacements.
Authors: Cooker H S , Larson C R , Luschei E S
Published: December 2014

1. Small ‘step’ or sinusoidal displacements were imposed on the mandible while human subjects maintained an average biting force of 10 N. Phase‐related changes in the force resisting sinusoidal displacement were used to determine the mechanical stiffness of the human mandibular system as a function of the frequency of stretching. 2. Jaw‐muscle electromyographic (e.m.g.) responses to ‘step’ stretches were of 8 msec latency and generated a very substantial force response. Jaw‐muscle e.m.g. responses having longer latency were not observed. 3. The mechanical stiffness of the human mandible was relatively constant as a function of the frequency of stretching, having a typical magnitude of about 15 N/mm (+/‐ 200 micrometers stretch) or 10 N/mm (+/‐ 1500 micrometers stretch) at mean biting forces of 10 N. The force resisting displacement was phase‐advanced at all frequencies. 4. Modulation of jaw muscle electrical activity evoked by sinusoidal stretches increased in amplitude as a function of increasing stretch frequency. E.m.g. modulation was 60‐‐100 degrees advanced at frequencies of 1‐‐10 Hz, but the phase decreased at higher frequencies, becoming negative (lagging stretch) at frequencies of 30 Hz and above. These characteristics are consistent with the idea that the jaw stretch reflex is dependent on jaw muscle spindle afferent fibres exciting jaw‐closing motoneurones by relatively direct (but not necessarily monosynaptic) connexions. 5. The relationship between jaw‐muscle activity and voluntary fluctuations of isometric biting force suggests that human jaw muscles can be modelled as a second‐order linear ‘filter’. The corner frequency for human jaw muscle is about 3 Hz; thus it would appear to be considerably slower than jaw muscle of monkeys. 6. The reflex stiffness of the human mandible, estimated quantitatively on the assumption that human jaw muscle stiffness is similar to the intrinsic stiffness of the gastrocnemius of the cat, ranges between 5 and 9 N/mm at frequencies between 1 and 8 Hz. Since this reflex stiffness is about the same as muscle stiffness in this frequency range, we conclude that the stretch reflex of the human mandible contributes functionally to its postural stability. 7. Reflex stiffness appears to be greater in the monkey mandible relative to muscle stiffness than in the human mandible. The difference is argued to be a manifestation of the difference in jaw muscle contraction speed between the two species. 8. The fact that the mandibular stretch reflex appears to be stronger than the stretch reflex of the limbs of intact animals and humans is discussed in terms of the special anatomical and functional features of the mandible.
Current—voltage relations in the rod photoreceptor network of the turtle retina
Authors: Copenhagen D. R. , Owen W. G.
Published: December 2014

1. Electrical coupling between rod photoreceptors was studied in the eyecup preparation of the snapping turtle, Chelydra serpentina, using intracellular micro‐electrodes.

2. The spatial profiles of rod responses to a long narrow slit of light were determined. The peak response amplitudes were found to decline exponentially as the slit was moved from the most sensitive position in the receptive field of each rod. The mean length constant was 55·7 μm.

3. Rods were simultaneously impaled in pairs and electrical coupling was demonstrated between the rods in seventeen of these pairs. No coupling was observed between rods separated by more than 110 μm. The transfer resistance, defined as the ratio of potential in the second rod (coupled potential) to the current injected into the first rod, varied from 0·2 to 13·2 MΩ.

4. The waveform of the coupled potential was time varying, exhibiting a peak and subsequent relaxation phase. The time course of the relaxation phase was voltage‐dependent. At the cessation of current, the coupled potential rebounded beyond the resting potential and then decayed to the dark potential.

5. Plots of input current versus coupled potential showed strong outward‐going rectification, chord transfer resistances being as much as 3·5 times lower for depolarizing currents.

6. Simultaneous impalements were made of pairs of neighbouring red‐sensitive cones, of horizontal cells and rods, and of red‐sensitive cones and rods. No evidence of coupling between cones and rods were found, nor could feed‐back from horizontal cells onto rods be demonstrated; however, coupling between red‐sensitive cones was found. This coupling exhibited neither the marked time‐varying nor voltage‐dependent properties that characterize the rod‐rod coupling.

7. Individual rods were impaled with independent current passing and voltage sensing micro‐electrodes. Pulses of current produced time‐varying potentials having relaxation and rebound phases. Current—voltage measurements showed a strong outward‐going rectification. Input resistances at the resting potential ranged up to 96 MΩ.

8. Square grid and hexagonal lattice models of ohmic electrical coupling were applied to the results. Using the measured values for the length constants and input resistances of single rods, we calculate that the plasma membrane resistance of each rod is approximately 1000 MΩ at the resting potential and that the coupling resistances are 272 and 444 MΩ for the square grid and hexagonal models, respectively.

9. The time‐varying and voltage‐dependent properties observed at the input and in the coupling between rods appear to reflect characteristics of the rod's plasma membrane and not of the coupling pathways between the rods. Both the outward‐going rectification and relaxation phase of the response appear to involve voltage‐dependent conductance increases in the rod's plasma membrane.
Retention of topographic addresses by reciprocally translocated tectal re‐implants in adult goldfish.
Authors: Yoon M G
Published: December 2014

1. The topographic pattern of retinotectal projections re‐established after reciprocal translocation of two tectal re‐implants within a whole tectum was studied in adult goldfish with neurophysiological mapping methods. 2. Reciprocal translocations of tectal re‐implants along the rostrocaudal axis resulted in retinotectal projections on to these re‐implants that showed corresponding reciprocal transpositions of receptive fields along the nasotemporal axis. 3. Similarly, reciprocal translocations of tectal re‐implants along the mediolateral axis resulted in retinotectal projections on to these re‐implants that showed corresponding reciprocal transpositions of receptive fields along the superoinferior axis. Some regenerating optic fibres in the operated tectum abruptly changed the directions of their courses, as if they were taking direct paths towards their displaced, previous target zones in the tectum. 4. Reciprocal translocation of tectal re‐implants either along the rostrocaudal or mediolateral axis, accompanied by 180 degree rotation of the re‐implants about the dorsoventral axis, resulted in retinotectal projections on to the re‐implants that showed not only the corresponding reciprocal transpositions along the nasotemporal or superoinferior axis but also a localized 180 degree rotation in the order of the receptive fields within these re‐implants. The same results were also observed after regeneration of the optic fibres following section of the contralateral optic nerve. 5. These results indicate that translocated pieces of tectal tissue retain not only the topographic polarity indicative of their normal orientation but also the topographic addresses indicative of their original positions in the tectum, with respect to their selective reinnervation by particular groups of optic fibres.
Is excitation by enkephalins of hippocampal neurones in the rat due to presynaptic facilitation or to disinhibition?
Authors: Haas H L , Ryall R W
Published: December 2014

1. Extracellular recordings of postsynaptic potentials (field potentials), population spikes or unitary action potentials and intracellular records of excitatory and inhibitory postsynaptic potentials were obtained from neurons in superfused slices of rat hippocampus, to study the mechanism of the excitatory effect of enkephalins. 2. Most experiments were carried out with a synthetic, stable enkephalin analogue (FK 33‐824) administered either by perfusion or by local administration (ionophoresis or pressure application from micropipettes). Comparisons were made when appropriate with metenkephalin, morphine, 4‐aminopyridine and bicuculline. 3. The enkephalins caused a small increase in extracellular recordings of e.p.s.p.s and a more marked increase in the amplitude and frequency of population spikes. The effect of 4‐aminopyridine on the extracellular e.p.s.p. was more marked than that of enkephalins, indicating that the enkephalins may have an additional effect upon regenerative spike mechanisms in the dendrites, which is not possessed by 4‐aminopyridine. The actions of the enkephalins and morphine were blocked by naloxone, which did not block the action of bicuculline or 4‐aminopyridine. 4. The increase in extracellularly recorded e.p.s.p. was shown to be due to a marked increase in the e.p.s.p. amplitude recorded intracellularly in CA1 and CA3 neurones and dentate granule cells. The augmented e.p.s.p.s evoked more action potentials. 5. The increase in e.p.s.p. amplitude was not accompanied by any marked change in membrane potential or resistance. 6. The inhibition of background firing by appropriate stimulation and recorded as peristimulus histograms was not reduced by FK 33‐824. There was a slight prolongation. 7. Intracellularly recorded i.p.s.p.s were not blocked by FK 33‐824. There was a prolongation of the i.p.s.p.s and an apparent increase in latency due to the unmasking and prolongation of e.p.s.p.s. 8. Dendritic excitability, as tested with ionophoresis of DL‐homocysteic acid locally to the dendrites was unaffected by FK 33‐824. 9. It is concluded that the increase in e.p.s.p.s produced by enkephalins can be explained by an increased release of excitatory transmitter, as occurs with 4‐aminopyridine.
Drinking and antidiuresis in response to reductions in venous return in the dog: neural and endocrine mechanisms.
Authors: Fitzsimons J T , Moore‐Gillon M J
Published: December 2014

1. In order to investigate the mechanisms of hypovolaemic thirst and sodium appetite an inflatable balloon in the upper abdominal inferior vena cava was used to produce acute, graded and reversible reductions in venous return to the heart in conscious dogs. 2. Reducing venous return caused a fall in central venous, arterial and pulse pressures. Heart rate and venous pressure upstream from the point of inflation rose. 3. Within 6‐‐28 min of inflating the balloon the dogs started drinking. The amount drunk in a 1 h experiment was significantly correlated with the changes in central venous and arterial pressures. 4. More prolonged obstruction to venous return led to a sustained increase in water intake and the development of a sodium appetite. 5. Plasma renin activity and concentration rose following caval obstruction. 6. Drinking in response to reductions in venous return was reduced, but not abolished, by simultaneous infusion of the competitive angiotensin II antagonist saralasin acetate. 7. When the left vagosympathetic nerve was blocked at the same time as balloon inflation the response was enhanced. 8. Urine flow fell after partial obstruction of the vena cava. Therefore drinking led to the development of a positive fluid balance. 9. We have shown that hypovolaemia is a potent and quantitatively defined stimulus to drinking in the dog and that the renal renin‐angiotensin system makes an important contribution to it.
The role of prostaglandins in the bronchoconstriction induced by pulmonary micro‐embolism in the guinea‐pig.
Authors: Clay T P , Hughes J M
Published: December 2014

1. Respiratory resistance was measured by a forced oscillation technique in vagotomized guinea‐pigs before and after pulmonary micro‐embolism produced by I.V. injection of 0.5 ml./kg of 10% w/v BaSO4. Changes in quasi‐static inspiratory compliance and arterial platelet count were also measured. 2. Micro‐embolic challenge with BaSO4 increased respiratory resistance by 27%; this was abolished by prior treatment with indomethacin; no change in the control resistance occurred after indomethacin. 3. No change in respiratory compliance or arterial platelet numbers were observed following low dose BaSO4 micro‐embolism. This suggests that pulmonary micro‐embolism produced a decrease in medium or large airway calibre, which was mediated by a prostaglandin‐like substance from lung tissue, and did not require the presence of the vagus nerves.
Release of oxytocin induced by salt loading and its influence on renal excretion in the male rat.
Authors: Balment R J , Brimble M J , Forsling M L
Published: December 2014

1. The present study investigates the nature and magnitude of the renal response to plasma levels of oxytocin which might be induced by salt loading. 2. Increased plasma osmolality induced by loading with NaCl is an effective stimulus for oxytocin release in the unanaesthetized male rat. Plasma oxytocin concentration was positively correlated (r = 0‐.77) with plasma osmolality. Plasma oxytocin (muu./ml.) = 0.37 x (plasma osmolality (m‐osmole/kg) ‐297). 3. In anaesthetized Long Evans rats intra‐atrial administration of oxytocin at rates of 0.05 and 0.15 m‐u./ml. produced plasma hormone concentrations (5 +/‐ 1 and 16 +/‐ 2 mum./ml. respectively) within the range induced by salt loading. 4. Oxytocin administration at 0.15 and 1.5 m‐u./min in Long Evans rats produced dose‐related increases in urine flow and Na+ and Cl‐ excretion. Renal responses to 0.05 m‐u. oxytocin/min were equivocal. 5. Oxytocin administration at 0.15 m‐u./min was ineffective in Brattleboro rats but 1.5 m‐u./min led to increased Na+ and Cl‐ excretion and a reduction in urine flow. 6. Plasma oxytocin levels similar to those induced by severe dehydration or salt loading are effective in increasing renal Na+ and Cl‐ excretion and urine flow. These effects on water and electrolyte excretion appear to be independent of each other and both may be modified by the presence or absence of vasopressin. 7. This study provides no evidence for a major role for oxytocin in the day to day regulation of salt or water balance under conditions of normal hydration in the male rat.
The effect of scorpion venoms on the sodium currents of the squid giant axon.
Authors: Gillespie J I , Meves H
Published: December 2014

1. The effect of externally applied scorpion venoms (0.1‐‐0.5 mg/ml., species Leiurus quinquestriatus and Centruroides sculpturatus) on the Na currents of intracellularly perfused squid giant axons has been studied with the voltage‐clamp method. 2. The venoms from the two species had the same effect. They reduced the size of the peak conductance but had little effect on its kinetics (time to peak, time constant of inactivation) and on its steady‐state inactivation. The venoms increased markedly, however, the maintained conductance and the time constants of its turning‐on and turning‐off. 3. The voltage dependence of the maintained conductance was determined (a) by fitting a modified Hodgkin‐‐Huxley equation to the Na currents and (b) by measuring the tail currents at the end of depolarizing pulses. The maintained conductance rose with increasing depolarization from a minimum at ‐20 mV to a maximum at 40 mV. The peak conductance, by contrast, was constant in the positive potential range. 4. The ratio maintained conductance in venom to maintained conductance in control varied between 2 and 7 (depending on the venom concentration and the time of treatment) and was not significantly dependent on membrane potential. 5. Peak current and maintained current reversed sign at the same potential and were both blocked by tetrodotoxin. 6. During a pulse to ‐2 mV preceded by a pre‐pulse to ‐42 mV the Na conductance showed a rapid initial increase followed by a slower decay and a subsequent slow increase, reflecting the activation and inactivation of the peak conductance and the slow development of the maintained conductance. 7. Many of the observations are compatible with the idea that scorpion venoms increase the number of channels which go from the peak conductance state into the maintained conductance state (open in equilibrium or formed from closed in equilibrium or formed from open transition of the inactivation gate, see Chandler & Meves (1970 a, b)). But the alternative hypothesis that peak conductance and maintained conductance reflect two separate populations of Na channels cannot be ruled out.
Effects of cyclic AMP, ouabain and furosemide on ion transport in isolated canine gastric mucosa.
Authors: Kuo Y J , Shanbour L L
Published: December 2014

1. Cyclic AMP (10 mM), present in the serosal solution of isolated dog gastric mucosa, increased potential difference (p.d.), short‐circuit current (ISC), net flux of Na+ from the mucosal to serosal side, and the unidirectional flux of K+ from the mucosal to serosal side. Cyclic AMP did not stimulate H+ or Cl‐ secretion. 2. Dibutyryl cyclic AMP (DBcAMP, 1 mM) or theophylline (2 mM), present in the serosal solution, stimulated H+ and Cl‐ secretion, decreased p.d., ISC and electrical resistance. These compounds had no effect on Na+ transport. The stimulatory effect of DBcAMP on H+ secretion was still present after pretreatment with cimetidine or atropine. 3. Ouabain abolished both the p.d. and ISC of the histamine‐stimulated gastric mucosa. The mucosal to serosal flux of Na+ and the serosal to mucosal flux of Cl‐ were significantly decreased in the presence of ouabain. Ouabain caused an increase in the serosal to mucosal flux of K+ and high concentrations caused a significant reduction in H+ secretion. 4. Furosemide (10(‐4) M) decreased p.d., ISC and net flux of Na+. Higher concentrations inhibited the net flux of Cl‐ from the serosal to mucosal side. 5. These results suggest that in isolated dog gastric mucosa, (1) both DBcAMP and theophylline may increase intracellular cyclic AMP to stimulate H+ and Cl‐ secretion, (2) cyclic AMP, outside the serosal membrane, stimulates active transport of Na+; in contrast, ouabain inhibits this active process predominantly, (3) the selective action of furosemide on Na+ transport indicates that Na+ and Cl‐ move via separate transport pathways across the serosal border.
Local production of prostaglandins in relation to mammary function at the onset of lactation in the goat.
Authors: Maule Walker F M , Peaker M
Published: December 2014

1. Arterial and mammary venous concentrations of prostaglandins F alpha (PGF alpha), E (PGE) and the PGF alpha metabolite, 13,14‐dihydro‐15‐oxoPGF alpha (DHK‐PGF alpha) were studied during late pregnancy and the onset of lactation in conscious goats. Mammary secretion concentrations of PGF alpha and DHK‐PGF alpha were determined, and mammary blood flow, arterial plasma progesterone concentrations and milk composition were also studied. 2. A significant output of PGF alpha from the mammary gland into mammary venous blood was observed during late pregnancy; this output ceased near term. 3. Mammary output of DHK‐PGF alpha into venous blood began about 6 days prepartum, suggesting an increasing capacity of the gland to metabolize PGF alpha. 4. The concentration of PGF alpha in mammary secretion increased from about 4 days pre‐partum, that of DKH‐PGF alpha from about 12 days pre‐partum. 5. It is concluded that although total mammary output of PGF alpha decreases during late pregnancy and early lactation, the rate of mammary synthesis of PGF alpha increases and the PGF alpha is increasingly secreted into milk and metabolized to DHK‐PGF alpha within the mammary gland. 6. Unilateral treatment of one mammary gland in goats with the PGF 2 alpha analogue, Cloprostenol, at two dose levels from 2‐3 days pre‐partum to 1‐2 days post‐partum prevented the changes in milk [Na] that occur at term in untreated glands. At the higher dose, the normal rise in milk [citrate] was abolished and milk yield was reduced; these effects persisted after cessation of treatment. 7. It is suggested that PGF alpha may play a local inhibitory role in mammary gland function during late pregnancy. It is further suggested that PGF alpha could be the factor, or one of the factors, proposed by Linzell & Peaker (1974) to be responsible for local control of mammary epithelial permeability and possibly also for secretory rate.
Peripheral neural representation of spatial dimensions of a textured surface moving across the monkey's finger pad.
Authors: Darian‐Smith I , Davidson I , Johnson K O
Published: December 2014

1. The responses of single cutaneous mechanoreceptive fibres evoked by a geometrically patterned surface sweeping across the skin were examined. The surfaces used were each a fine diamond‐shaped array of "dots’ in relief against a flat background. The fibres examined were rapidly adapting, slowly adapting and Pacinian fibres innervating the monkey's finger pad skin. 2. Each fibre's response to the two‐dimensioned surface was assessed using a procedure in which the surface was swept across the fibre's receptive field many times, the position of the surface relative to the underlying receptive field being precisely known at any instant in time. Between each successive sweep the stimulus surface was shifted lateral to the direction of movement by a small increment. The response pattern generated by this scanning procedure specified the extent to which a single response of the fibre was dependent on the spatial and temporal dimensions of the stimulus. 3. The invariant spatial features of the moving surface were represented only in the responses of populations of fibres; responses of the constituent fibres always confounded the information relayed about the surface pattern and its rate of movement across the skin. 4. Factors determining the representation of the spatial and temporal characteristics of the moving surface in the responding mechanoreceptive fibre population were examined. These included the response characteristics of the constituent fibres, the innervation density, and the total number of fibres engaged by the moving surface.
Some effects of aliphatic hydrocarbons on the electrical capacity and ionic currents of the squid giant axon membrane.
Authors: Haydon D A , Requena J , Urban B W
Published: December 2014

1. The electrical properties of squid giant axons were examined by means of admittance bridges at frequencies from 0.5 to 300 kHz. A simple equivalent circuit was used to estimate the membrane capacity. 2. The calculated membrane capacities decreased monotonically over the whole frequency range. 3. At 100 kHz and higher frequencies the membrane capacity was independent of potential. 4. At frequencies greater than 20 kHz, exposure of the axons to saturated or 0.9 saturated solutions of n‐pentane (275‐306 micrometer) reduced the capacity per unit area by 0.1‐0.15 micro F cm‐2. 5. At 1 kHz the effect of the saturated pentane solutions depended on the membrane potential. In axons having potentials between ‐60 and zero mV the pentane solutions lowered the capacity, whereas for potentials between ‐160 and ‐60 mV they produced little or no change. 6. Saturated solutions of n‐hexane, n‐heptane and n‐octane exhibited qualitatively similar, but quantitatively smaller influences on the membrane capacity, the changes declining as the chain length increased. 7. Under voltage clamp, the peak inward and steady‐state outward currents were partially suppressed by the hydrocarbons. Saturated solutions of n‐pentane usually reduced the former (reversibly) by 60‐80% and the latter by 20‐40%. Solutions of n‐hexane, n‐heptane and n‐octane appeared to have successively less effect. Except in deteriorating axons, none of the hydrocarbons produced any consistent changes in the passive membrane resistance, the resting potential or in the reversal potential of the transient inward current. 8. Both the changes in the clamp currents and in the membrane capacity were largely, though not usually completely, reversible. In the hydrocarbon solution the axons deteriorated more rapidly than normal. 9. The responses of axons of Doryteuthis plei to the hydrocarbons were very similar to those of Loligo forbesi with the exception that for the former all observed changes were some five times faster. 10. The time courses of the peak inward and steady‐state outward currents on exposure of the axons to n‐pentane resembled the time course of the change in membrane capacity at 100 kHz. 11. The simplest interpretation of the high frequency capacity results is suggested to be that, as for lipid bilayers, the membranes become thicker through adsorption of the hydrocarbon.
Asymmetry of hexose transfer system in erythrocytes of fetal and new‐born guinea‐pigs.
Authors: Aubby D S , Widdas W F
Published: December 2014

1. The asymmetries of affinities of two non‐transportable competitive inhibitors of hexose transfer across fetal and new‐born guinea‐pig erythrocytes have been studied. 2. At 16 degrees C 4,6‐O‐ethylidene‐alpha‐D‐glucopyranose (ethylidene glucose) inhibited 3‐O‐methyl glucose exchange at 20 mM with a K1 oc ca. 52 mM when present inside the cells and with a K1 oc ca. 10 mM when outside. This fivefold asymmetry is qualitatively similar to but smaller than the tenfold asymmetry of human erythrocytes (Baker, Basketter & Widdas, 1978). 3. Methyl‐2,3‐di‐O‐methyl‐alpha‐D‐glucopyranoside (trimethyl glucoside) had K1 values of ca. 120 mM and ca. 160mM for inside and outside inhibition respectively. This is also qualitatively similar to the inhibition in human erythrocytes. 4. The inhibition produced by phlorizin, phloretin and Cytochalasin B was also studied in the erythrocytes of new‐born guinea‐pigs. The results were qualitatively similar to those for human erythrocytes but the inhibitory affinities were different. Thus while phlorizin and phloretin had higher affinities for the inhibition of exchange in new‐born guinea‐pig cells than human cells, the affinity of Cytochalasin B was less for new‐born guinea‐pig cells than for human cells. 5. It is concluded that the hexose transfer system in fetal and new‐born guinea‐pig red cells has asymmetric affinities similar to the system in human red cells but with different values of the inhibitory constants. The differences may represent species variations in a structural protein serving identical functions in the two species. 6. The possibility that fetal red cells with their facilitated transfer system play a role in sugar transport is discussed.
Responses in the posterior lobe of the rat cerebellum to electrical stimulation of cutaneous afferents to the snout.
Authors: Armstrong D M , Drew T
Published: December 2014

1. Responses in the cortex of the posterior lobe of the cerebellum to electrical stimulation of afferent fibres from the skin of the snout have been analysed in decerebrate and pentobarbitone‐anaesthetized rats by means of surface and microelectrode records. Single shocks were applied either to the exposed follicles of the mystachial vibrissae or to the infraorbital branch of the trigeminal nerve. 2. In decerebrate rats responses were mediated only via mossy fibre afferents. Stimulation of one side of the snout yielded responses with mean latency 2.4 ms throughout the uvula (largest ipsilaterally and in lobule IXa). Smaller responses with similar latency were present in both cerebellar hemispheres (largest ipsilaterally). The earliest discharges of Purkinje cells in lobule IXa occurred at latencies between 4.5 and 8.5 ms. 3. All components of the extracellular field potentials generated within the cortex by the mossy fibre input were detectable by surface recording with ball electrodes. 4. The earliest surface potentials had a latency of 0.55 ms (peak latency 0.8 ms); they arose through volume conduction from the brain stem of a potential which signalled arrival of the primary afferent volley. The short delay between this event and the arrival of the mossy fibre volley in the cerebellum suggests that only one synaptic relay occurs in the brain stem. 5. In pentobarbitone‐anaesthetized rats surface responses mediated via mossy fibres persisted and were accompanied at slightly higher threshold by responses shown to be mediated via climbing fibres. The latter were present in descending order of amplitude in three sagittally directed zones, one in contralateral Crus 2 (minimum latency 13 ms), one in the vermis contralaterally near the mid line in lobule IXa (latency 16 ms) and a third in ipsilateral Crus 2 (latency 20 ms) 6. In the hemisphere the responses mediated via climbing fibres occurred within the somewhat larger zones activated via mossy fibres but in the vermis the two types of trigemino‐cerebellar input influenced quite separate areas of cortex.
Influence of vascular flow on amino acid transport across frog small intestine.
Authors: Parsons D S , Sanderson I R
Published: December 2014

1. The vascularly perfused intestine of the frogs, Rana ridibunda and R. pipiens, was used to investigate the transfer of the non‐metabolized amono acids alpha‐amino isobutyric acid (AIB) and 1‐amino‐cyclopentane‐1‐carboxylic acid (cycloleucine) across the intestinal epithelium from the lumen into the portal vein. 2. The steady‐state rate of transfer of cycloleucine was significantly increased with increasing vascular flow rate, both in the presence and absence of Na in the fluid in the intestinal lumen, although at all flow rates the transfer was lower when the Na was replaced by K. The relatively high rate of transfer of cycloleucine seen at high rates of vascular flow when the luminal perfusate was free of Na was almost abolished when leucine was added to the lumen. 3. When the vascular flow is interrupted cycloleucine is taken up from the lumen and accumulates in the tissue. The accumulated amino acid can be measured during the subsequent wash‐out when the vascular flow is resumed. The rates of transfer of accumulated cycloleucine as measured during subsequent wash‐out were lower than those found at continuous flow; it is suggested that there is a limit to the amount of amino acid that the epithelial tissue can retain when the vascular flow is interrupted. A significant accumulation of cycloleucine occurs when Na is present in the lumen, but the accumulation is negligible when Na is replaced by K. 4. The unloading of the amino acids AIB and cycloleucine from the epithelium into the vasculature was investigated. The two amino acids showed markedly different kinetics of exit, that of AIB being monoexponential while that of cycloleucine was biexponential. Moreover, the rate of exit of cycloleucine was influenced by the presence of Na in the intestinal lumen, and by the rate of vascular perfusion. The apparent diffusion coefficients for the exit were smaller than those expected had unloading taken place by unobstructed free diffusion. 5. It is concluded that specific processes for exit from the epithelium play a significant role in amino acid transfer across the small intestine, and that the exit of AIB is more restricted than that of cycloleucine.