bluuebunny/crossref_metadata_2025 huggingface dataset:
Competitive and non‐competitive re‐innervation of mammalian sympathetic neurones by native and foreign fibres.
Authors: Purves D
Published: December 2014

The ability of native (sympathetic preganglionic) and foreign (vagal) nerve fibres to re‐innervate neurones of the guinea‐pig superior cervical ganglion, either alone or in competition with each other, has been studied by means of intracellular recording and electron microscopy. 1. Native fibres make synaptic contacts with nearly all ganglion cells within one month of cervical trunk section; within 6 months the degree of innervation, judged by measurement of excitatory post‐synaptic potential (e.p.s.p.) amplitude and electron microscopical synapse counts, approaches normal. However, even after 15 months innervation was weaker than in normal control ganglia. 2. Vagal fibres are less successful during re‐innervation. Although a similar number of foreign fibres grown into denervated ganglia and make contact with nearly all ganglion cells within a month, after 6‐12 months e.p.s.p. amplitudes in response to foreign nerve stimulation remain relatively small, and counts of synapses are only about 60% as great as in ganglia re‐innervated with the native nerve. 3. When both native and foreign fibres are allowed to re‐innervate ganglion cells simultaneously, about half the neurones in the ganglion receive synapses from both sources after 1 month. The proportion of dually invervated cells remains roughly constant for at least 14 months. Neither set of preganglionic fibres dominates or displaces the other, although neurones generally are re‐innervated more effectively by native than foreign fibres, as is true during non‐competitive re‐innervation. 4. Thus during re‐innervation of mammalian sympathetic neurones native fibres are preferred to foreign ones only in the sense that roughly the same number of native fibres form many more synapses on ganglion cells than do vagal axons. A foreign synapse, once formed, is as stable as a native one, and shows no tendency to be replaced by native terminals. These findings are discussed in relation to other evidence which has suggested specificity and selectivity during re‐innervation of mammalian autonomic neurones.
The potentiating influences of insulin on pancreozymin‐induced hyperpolarization and amylase release in the pancreatic acinar cell.
Authors: Kanno T , Saito A
Published: December 2014

1. Insulin (1 mu./ml.) potentiated the release of amylase from isolated pancreas of rats perfused with erythrocyte‐containing medium and stimulated by 0‐5 m‐u. pancreozymin (Pz)/ml., whereas the same concentration of insulin failed to potentiate the response evoked by or 200 m‐u. PZ/ml. 2. Intracellular measurement of membrane potentials from the acinar cells of the same preparations showed that insulin (1 mu./ml.) simultaneously potentiates the hyperpolarization and amylase release in response to 0‐5 m‐u. PZ/ml. 3. These effects of insulin on the PZ‐induced responses were inhibited by ouabain (3 X 10(‐5) M). 4. The results suggest that insulin, in the concentration studied, has a potentiating action on the activity of an electrogenic Na pump, which maintains the hyperpolarization and amylase release during continuous stimulation with Pz. 5. Insulin in also potentiated the Pz‐induced amylase release in the rat pancreata in situ after vagotomy and ligature of the pyloric region.
Central terminations of muscle afferents on motoneurones in the cat spinal cord.
Authors: Iles J F
Published: December 2014

Intraspinal branches of primary afferent axons in the cat lumbar cord have been revealed by filling then with cobalt, followed by precipitation as cobalt sulphide and silver intensification. 2. Primary afferent collaterals which reached the ventral horn were myelinated and had axon diameters of around 2 mum. Up to four (mean 1) side branches occurred at nodes within the ventral horn. The finest branches were less than 1 mum in diameter. 3. The finest branches formed synaptic boutons on nerve cells. The total observed association between one afferent and a motoneurone (synaptic structure) consisted of up to six boutons (mean 1‐85). The boutons constituting a synaptic structure were usually located close together on the soma or dendrites, but sometimes were spread along more than 60 mum of dendrite. It was assumed that these monosynaptic structures on moto‐neurones were formed by muscle spindle afferents. 4. There was no correlation between the total contact area of a synaptic structure and its location on a motoneurone. 5. A computer model of the motoneurone was used to investigate the effect of multiple synaptic contact on electrophysiological estimates of synaptic location. It was concluded that the observed spread of boutons making up a synaptic structure would not significantly affect distance allocation of distal synapses but could lead to some proximal dendrite structures being incorrectly classified as somatic.
On the receptors which mediate the hyperpolarization of salivary gland cells of Nauphoeta cinerea Olivier.
Authors: Ginsborg B L , House C R , Silinsky E M
Published: December 2014

The actions of sympathomimetics and of catecholamine antagonists have been investigated on the membrane potential and responses to nerve stimulation of acinar cells of the salivary gland of Nauphoeta cinerea Olivier. 2. Hyperpolarizations such as those evoked by nerve stimulation and by low concentrations of adrenaline, noradrenaline and dopamine were not produced by the alpha‐agonists amidephrine and methoxamine. Isoprenaline was active, but only in concentrations above 100 muM. 3. Tyramine, an indirectly acting sympathomimetic, and high concentrations of methoxamine caused an increase in the rate of the small transient hyperpolarizations sometimes seen in the absence of stimulation. 4. The response to nerve stimulation was unaffected by propranolol (20 muM) an alpha‐adrenergic antagonist. Phentolamine, an alpha‐adrenergic antagonist, reduced matching responses to nerve stimulation and to dopamine to about the same extent. 5. As on other systems responsive to low concentrations of dopamine, apomorphine was active, although only in high concentration, and ergometrine and methysergide were antagonistic both to nerve stimulation and to dopamine.
Destruction of the sodium conductance inactivation by a specific protease in perfused nerve fibres from Loligo.
Authors: Rojas E , Rudy B
Published: December 2014

Intracellular perfusion of giant axons from Loligo forbesi with a crude protein extract of Pronase dissolved in a KF solution suppresses the process of fast inactivation of the Na conductance (the h‐process in the Hodgkin‐Huxley terminology). 2. The results with protease inhibitors indicate that the most substrate specific endopeptidase present in pronase, alkaline proteinase b, destroys the h‐process. 3. After destruction of the inactivation the conductance rise upon depolarization followed cube law kinetics. Values of the time constant taum before and after destruction of the h‐process were very similar. 4. After destruction of the inactivation process the following properties were tested: cation selectivity, instantaneous conductance and internal receptor sites for tetrodotoxin (TTX) and tetraethylammonium (TEA). No detectable changes in selectivity or instantaneous conductance were observed. No internal receptors for TTX affecting the Na conductance were found but a TEA receptor is exposed by the protein hydrolysis. 5. TEA derivatives (triethylammonium, TEA‐, with an aliphatic chain, Cn) induce a partial block of the steady‐state sodium current and induce a time‐dependent blockage of the conductance. 6. The first effect of TEA‐Cn could be described in terms of a unimolecular reaction with the following equilibrium constants: 50, 2‐5, 1‐0, 0‐4 and 0‐025 mM for TEA‐C2, TEA‐C4, TEA‐C5, TEA‐C7 and TEA‐C9 respectively. 7. From the dependence of the equilibrium dissociation constant on the length of the alkyl chain we estimated the free‐energy change in 560 cal/mole of CH2. The gain in free energy per CH2 group transferred from aqueous medium to the interior of a non‐polar medium is 1000 cal. 8. Although with the data at hand it is impossible to propose the amino‐acid sequence of the site cleaved by alkaline proteinase b, we propose that an important functional component is arginine (or lysine).
Intracellular pH of single crustacean muscle fibres by the DMO and electrode methods during acid and alkaline conditions.
Authors: Hinke J A , Menard M R
Published: December 2014

1. The intracellular pH of intact single muscle fibres of the giant barnacle was measured directly with a glass micro‐electrode following prolonged (2‐5 hr) equilibration in one of three solutions: normal Ringer, CO2 Ringer and NH4+ Ringer. 2. The intracellular pH of identically‐prepared fibres from the same specimen was measured indirectly from the distribution of DMO following prolonged equilibration in the same solutions. 3. The DMO‐pH compared favourably with the electrode‐pHi provided DMO‐pHi was calculated from the values of the indicator compounds, [14C]DMO and [3H]inulin, obtained by extrapolating the slow uptake phase to time zero. 4. Following prolonged equilibration, the transmembrane H+ ion distribution was found to vary with the membrane potential but not in accordance with a simple Gibbs‐Donnan equilibrium. 5. A model which recognizes the existence of two independent net fluxes for H+ across the membrane in developed to explain the results. One of the fluxes represents passive diffusion and the other represents the so called H+‐pump. The model predicts the H+‐pump rate increases by two orders of magnitude when pHi is reduced from 7‐2 to 6‐7.
Effects of tetracaine on displacement currents and contraction of frog skeletal muscle.
Authors: Almers W , Best P M
Published: December 2014

The kinetics of mechanical activation of intact fibres were examined with a voltage‐clamp technique. Tetracaine (2 mM) increases fifteen‐ to seventyfold the time required to produce a just visible contraction by cell membrane depolarization. 2. Displacement currents thought to be related to contractile activation remain in 2 mM tetracaine. Their characteristics are virtually identical to those found in the absence of the drug. Displacement currents also remain in fibres immobilized by treatment with 10 mM formaldehyde. 3. Despite its effect on contraction of intact fibres, tetracaine does not diminish contraction tension when Ca is applied directly to the contractile proteins of 'skinned' muscle fibres. The sensitivity of the myofilaments to Ca2+ also remains undiminished. 4. When acting on intact fibres the drug must therefore inhibit Ca2+‐release from the sarcoplasmic reticulum. It is estimated that 2 mM tetracaine diminishes more than tenfold the capacity for Ca2+‐release in response to cell membrane depolarization.5. If muscle displacement currents represent events linking depolarization to Ca2+‐release, then tetracaine must be able to block the release without affecting the potential‐sensing portion of the release regulating mechanism. 6. Further experiments on skinned fibres show that tetracaine blocks or greatly diminishes caffeine contractions, but that Cl‐induced contractions of normal amplitude are still possible.
Responses of abdominal vascular capacitance in the anaesthetized dog to changes in carotid sinus pressure.
Authors: Hainsworth R , Karim F
Published: December 2014

1. The abdominal circulation of anaesthetized dogs was vascularly isolated without opening the abdomen, by cutting or tying all structures immediately above the diaphragm and tying the proximal ends of the hind limbs. The region was perfused at constant flow through the aorta and drained at constant pressure from the inferior vena cava. 2. Vascular resistance responses were expressed as the changes in perfusion pressure and capacitance responses were determined by integrating changes in vena caval outflow. 3. Decreasing the pressure in the isolated carotid sinuses over the whole baroreceptor sensitivity range increased mean perfusion pressure from 91 to 149 mmHg (a 67% increase in resistance) and decreased mean capacitance by 111 ml. (5 ml. kg‐1). 4. The range of carotid sinus pressures over which capacitance responses occurred was at a significantly higher level than the corresponding range for resistance responses. 5. Comparison of the reflex responses with the responses to direct stimulation of efferent sympathetic nerves shows that quantitatively similar responses of resistance and capacitance to those induced by a large step decrease in carotid pressure could be produced by stimulating maximally the efferent sympathetic nerves at 5 Hz. These results also suggest that at all levels of carotid sinus pressure there is no difference in the impulse traffic to resistance and capacitance vessels.
Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres.
Authors: Lederer W J , Tsien R W
Published: December 2014

1. Voltage‐clamp experiments were carried out in calf Purkinje fibres to determine the basis of transient depolarizations (TDs) associated with digitalis‐induced arrhythmias. 2. Under the influence of strophanthidin, depolarizing clamp pulses were followed by a transient inward current (TI) which was small or absent in untreated preparations. The TI also appeared in the wake of a train of action potentials. 8. The TI can help generate spontaneous depolarizations in preparations showing the low voltage oscillations which often occur with advanced digitalis toxicity. 8. The TI can help generate spontaneous depolarizations in preparations showing the 'low voltage oscillation' which often occur with advanced digitais toxicity. It was designated TI because its magnitude and timing were appropriate to account for the TD. 3. Longitudinal voltage non‐uniformity during the TI was determined with two voltage‐recording micro‐electrodes. Although the non‐uniformity was not severe, the TI wave form was observed when the voltage difference signal was used to measure membrane current density. 4. Over the diastolic range of potential, the strophanthidin‐induced TI appeared superimposed upon the normal pace‐maker mechanism, the decay of a potassium current, iK2. The TI could be dissociated from iK2, however, by means of its unusual kinetic properties. 5. TIs could also be recorded at holding potentials positive to ‐55 mV, i.e. outside the range where iK2 deactivation occurs. 6. The TI amplitude showed a slow and strongly sigmoid dependence on the duration of the preceding depolarizing pulse. Stronger depolarizing reduced the TI amplitude, while slowing and exaggerating the sigmoid time‐dependence. 7. Two clamp pulses in close succession gave additive effects in evoking a subsequent TI. This finding and the sigmoid time‐dependence fit with previous observations that TDs are most prominent following a series of closely spaced action potentials.
Circadian and other rhythmic activity of neurones in the ventromedial nuclei and lateral hypothalamic area.
Authors: Koizumi K , Nishino H
Published: December 2014

1. The frequency of firing was simultaneously recorded from single neurones of the ventromedial nuclei (VMN) and the lateral hypothalamic area (LHA) in urethane anaesthetized rats for many hours. 2. There were circadian changes of VMN and LHA neurone activity. The pattern of this circadian rhythm is as follows: throughout the day LHA neurones show higher activity than that of VMN, as indicated by higher frequency and more fluctuations in their rates of firing. In late afternoon the discharge rate of LHA neurones increases further, showing oscillations of short duration. In the early evening hours LHA neurone activity gradually goes down, as the VMN neurones become active. Throughout the night, VMN neurones are more active than those of LHA, just the opposite of the day period. In early morning hours VMN neurones gradually become quiet, while LHA neurones begin to show activity. 3. Superimposed on the circadian rhythm, at certain periods of the day, VMN and LHA neurones showed short duration oscillations in rate of firing, roughly every 7‐15 sec and every 3‐5 min. 4. Activities in neurones of the VMN and LHA were reciprocally related; a decrease in firing rate of one was associated with an increase in the other. This phenomenon was shown clearly by analysis of auto‐ and cross‐correlation functions of firing patterns of VMN and LHA neurones. 5. The effects of stimulations of the prefrontal cortex and splanchnic afferents on VMN and LHA neurones depended on the basic firing frequency, thus they varied with the time of day. Definite relationships exist between basic firing frequency of a cell and the magnitude of changes evoked by these stimuli. Reactions of VMN and LHA neurones were the opposite in most instances. Septal stimulations (at more than 10/sec) always produced inhibition of LHA neurone activity. 6. Intravenous injection of glucose inhibited LHA neurones and accelerated firing of VMN cells. This was true during the day period as well as at night when background activities of VMN and LHA neurones were different from that of the day. 7. Stimulation of the septal area with subthreshold pulses at a low rate (1‐0.3/sec) suppressed or altered oscillations in firing frequency of LHA neurones. Severance of connection between LHA and structures caudal thereto had no effect on LHA neurone firing rates or rhythms. Sections between the septal area and LHA, however, abolished or greatly altered the oscillatory rhythms of LHA cell activity, although spontaneous discharges continued at a somewhat lower rate for periods of hours. 8. Stimulation of suprachiasmatic nuclei with weak intensity and low frequency also changed oscillatory fluctuations in firing of LHA neurones. 9. Possible origins of circadian rhythm and oscillations of short duration in firing pattern of VMN and LHA neurones were discussed.
The distribution of GABA sensitivity on crayfish muscle receptor organs.
Authors: Craelius W
Published: December 2014

1. The effectiveness of inhibition of gamma‐aminobutyric acid (GABA) at various points on crayfish abdominal muscle receptor organs (MROs) was investigated by iontophoretic methods that have a spatial resolution of 8 mum. 2. The MROs in the rostral abdominal segments, which receive inhibitory innervation, were always strongly inhibited by focal iontophoretic application of GABA; MROs in the 6th abdominal segment, which do not receive inhibitory innervation, were usually not strongly inhibited. 3. In the rostral MROs, the magnitude of GABA current necessary to abolish stretch induced impulses was least for dendritic points; it increased as a function of distance from the dendrites, over an area extending from the receptor muscle to a point on the axon 200 mum from the cell body. 4. Outward currrents from NaCl‐filled micropipettes had no effect on impulse production when applied to the dendritic region of rostral MROs, but could produce transient inhibition of impulses when applied to the axon. 5. It is suggested that a high degree of GABA sensitivity is localized to the rostral MRO dendrites, where inhibitory synapses are most numerous.
Receptive fields, geometry and conduction block of sensory neurones in the central nervous system of the leech.
Authors: Yau K W
Published: December 2014

1. In segmental ganglia of the leech, the cutaneous mechanosensory neurones responding to to touch innervated the skin of their own segment and of part of the anterior and posterior adjacent segments. Each touch receptive field could be divided into three non‐overlapping areas: a central part innervated by the branches of the cell which ran in the nerve roots of the ganglion containing the cell body, and anterior and posterior parts innervated by its branches which ran in the nerve roots of the anterior and posterior adjacent ganglia. 2. Impulses originating from the anterior and posterior parts of the receptive fields were susceptible to conduction block within the central nervous system when the touch cells fired repetitively at frequencies that could readily be elicited with weak mechanical stimulation. In contrast, impulses originating from the central part of the receptive fields were less susceptible to block. 3. The morphology of touch cells revealed by intracellular injection of horseradish peroxidase suggested that conduction block occurred at specific bifurcation points where small cell processes joined the main process. Different physiological experiments supported this conclusion. 4. In some touch cells, bifurcation points with particularly low safety margins of conduction operated as low‐pass filters, limiting the frequency of impulses capable of invading certain branches. 5. The results suggest that mechanical stimuli which would likely be encountered by the animal can lead to conduction block within its central nervous system and as a result modify its integrative activities.
The thermal sensitivity of the polymodal nociceptors in the monkey.
Authors: Croze S , Duclaux R , Kenshalo D R
Published: December 2014

1. The static and dynamic sensitivities to thermal and mechanical stimuli of polymodal nociceptors in hairy skin of the anaesthetized monkey have been investigated by recording activity in their primary nerve fibres. 2. Polymodal nociceptors responded to skin pricking, pinching and heating to temperatures higher than 40 degrees C. They did not respond to touch, stretch or cold. The conduction velocity of their axons was from 0.6 to 1.1 m/sec. 3. Three types of cutaneous receptive fields have been observed: single spot‐like areas of 1‐2 mm2; multiple spot‐like areas of 1‐2 mm2; and larger areas up to 25 mm2 with heterogeneous sensitivity. 4. Polymodal nociceptors were subjected to heat stimuli that commenced from a 33 or 37 degrees C adapting temperature. A series consisted of heating their receptive fields to 43, 45, 47 and 50 degrees C from one or the other adapting temperatures at a constant rate of 0.2 degrees C/sec. Each heat stimulus intensity was maintained for 4 min after which the skin was returned to the adapting temperature. Immediately after the first series the identical series was repeated in order to determine the effect of prior heating upon the dynamic responses to re‐heating. The dynamic responses were characterized by three phases: an initiation of a discharge at a threshold level of skin temperature; a dynamic discharge during the suprathreshold change, that reached a peak frequency when the temperature reached its maximum; and an adaptation phase while the temperature remained at the high intensity. Adaptation was rapid initially, and then slowed during the final minutes at the high intensity. 5. Adapting the receptive field to either 33 degrees C or to 37 degrees C before the heat stimuli did not affect the sensitivity and the discharge pattern of the polymodal nocicpetors. 6. During the first series of stimulations, the threshold at which the individual polymodal nociceptors began to discharge to heat stimuli varied from 40 to 46.5 degrees C. The mean threshold of the population was 42.5 degrees C. 7. No change in the threshold was observed when responses to 0.2 and 1.5 degrees C/sec rates of heating were compared...
Acid and pepsin secretion of separated gastric pouches during perfusion of antral pouches with cholinergic stimulating and blocking agents and lignocaine.
Authors: McLeay L M , Titchen D A
Published: December 2014

1. Secretion of HCl and pepsin from abomasal fundic pouches was studied in sheep during perfusion of antral pouches with cholinergic blocking and stimulating agents and lignocaine. 2. Resting secretion was reduced to about 50% of control levels and secretory responses to feeding were largely or completely blocked during antral pouch perfusions with atropine (0‐01‐0‐16%) and hexamethonium (1%). 3. Antral pouch perfusions with lignocaine (2%) reduced fundic pouch resting secretion to about 60% of control values but did not block secretory responses to feeding. 4. Perfusions of acetylcholine (0‐1%) and carbachol (0‐0037 and 0‐005%) through antral pouches characteristically stimulated increases in the concentration of acid, outputs of acid and pepsin, but not concentration of pepsin. 5. The mechanisms involved in the release of gastrin in the sheep are discussed. 6. It is concluded that antral secretion of gastrin contributes both to the maintenance of resting secretion of acid and the secretory responses of fundic pouches of sheep when they eat freshly provided food.
The influence of immobilization and stretch on protein turnover of rat skeletal muscle.
Authors: Goldspink D F
Published: December 2014

1. Changes in muscle size have been studied as a function of time after immobilization and in relation to the functional length of the muscle. 2. When immobilized in a shortened position the soleus and extensor digitorum longus muscles underwent atrophy, showing net losses of tissue protein. This atrophy appears to be caused by decreases in protein synthesis and increases in protein break‐down. Average rates of protein synthesis and degradation were measured in immobilized and unrestrained control muscles by sensitive in vitro methods. 3. When the two muscles were held in a lengthened position they grew compared with internal controls. This rapid growth was primarily due to increased rats of protein synthesis, which possibly arise from a more active involvement of ribosomes in translation. In keeping with these situations of growth, DNA synthesis, DNA and RNA concentrations were found to be higher in the immobilized tissues. 4. Passive stretch and the development of isometric tension via the stretch reflux are suggested as factors stimulating protein synthesis, and hence inducing the growth of muscles held in the lengthened state. Probably neither of these factors will be experienced appreciably in the shortened position of restraint, and the lower level of activity in these immobilized muscles leads to their atrophy.
Kinetics of the inhibition of the Na‐K pump by external sodium.
Authors: Sachs J R
Published: December 2014

1. When the ouabain‐sensitive K influx or the ouabain‐sensitive Cs influx is measured as a function of the extracellular concentration of K or Cs in Na‐free solutions the resulting saturation curve at first rises more rapidly than a rectangular hyperbola, i.e. the curve is antisigmoid. 2. If the ouabain‐sensitive K influx or the ouabain‐sensitive Cs influx is measured in Na‐free solutions at a fixed low concentration of K or Cs and at varying concentrations of Li, the influx decreases monotonically as the Li concentration rises and there is no evidence of competitive activation. 3. These findings can be accounted for by a model which proposes that there are two binding sites for K or Cs and that both the singly loaded and doubly loaded pump is capable of transport. 4. Extracellular Na changes the shape of both the K and the Cs saturation curve from antisigmoid to sigmoid. Dixon plots (1/ouabain‐sensitive influx versus Na concentration at fixed K or Cs concentration) are linear at intermediate concentrations of K or Cs. 5. Na does not change the rate of K influx if the measurements are made at nearly saturating K concentrations using cells with nearly saturating internal Na concentrations. The effect of outside Na cannot therefore be explained by any mechanism which requires that Na alter the Vmax of the pump. 6. Measurement of the ouabain‐sensitive Cs influx as a function of the external Cs concentration in solutions with different fixed Na concentrations results in curves which change from antisigmoid in Na‐free solutions to sigmoid as the Na concentration rises. Dixon plots are linear at all but the lowest and highest Cs concentrations. 7. The resulting curves are best fit by equations which result from a model which proposes that Na acts both as a dead‐end competitive inhibitor and as a heterotropic allosteric effector. Simpler models which propose either that Na acts solely as a dead‐end competitive inhibitor or as a heterotropic allosteric effector do not fit as well as the more complicated model. 8. The combined competitive inhibition and allosteric effector model also describes adequately the relation between the ouabain‐sensitive K influx and external K concentration measured at different external Na concentrations.
The hepatocellular uptake of glucose, galactose and fructose in conscious sheep.
Authors: Hooper R H , Short A H
Published: December 2014

1. Surgical techniques for chronic catheterization of hepatic and portal veins in the sheep are described. These catheters remained usable for 2‐6 months and did not alter hepatic morphology. 2. Hepatocellular uptake of monosaccharides was estimated from their ability to pass the boundaries of the sucrose space in a double indicator dilution procedure in conscious fed sheep. 3. A large proportion (81%) of D‐glucose carried in the portal blood was found to enter an hepatic cellular compartment. 4. The radioactive label of D‐glucose infused in the portal vein remained associated with D‐glucose in hepatic venous blood samples during the experimental period. 5. A large proportion (74%) of an infused trace of D‐galactose, a smaller proportion (33%) of D‐fructose, and negligible amounts of L‐glucose were taken up in a single passage through the liver. 6. Raised blood concentrations of sucrose or of methyl‐alpha‐D‐glucoside (Me‐alpha‐DG) significantly diminished the proportional uptake of D‐glucose. Raised blood concentrations of glucose, galactose or Me‐alpha‐DG diminished the proportional uptake of D‐galactose. Raised blood concentrations of fructose diminished the proportional uptake of fructose. 7. Neither total hepatic blood flow changes nor competitive effects within the cell could account for these findings. 8. It is concluded that these monosaccharides enter the liver cell by facilitated diffusion, and share at least some of the membrane elements that mediate this process. It seems likely that only a proportion of the glucose‐transporting apparatus is accessible to galactose.
Tension in mechanically disrupted mammalian cardiac cells: effects of magnesium adenosine triphosphate.
Authors: Best P M , Donaldson S K , Kerrick W G
Published: December 2014

1. Maximum and submaximum Ca‐activated tension in mechanically disrupted rat ventricular fibres was examined in solutions containing 30 micron, 100 micron and 4 mM‐MgATP and either 50 micron or 1 mM ionized Mg. 2. In the absence of added Ca, significant amounts of base‐line tension (up to 50% of maximum) develop in solutions containing less than 30 micron‐MgATP. This effect is Mg‐dependent; more tension is produced with 50 micron‐Mg than with 1 mM. 3. Increasing the MgATP concentration shifts the pCa‐% maximum tension relationship in the direction of increasing Ca required for activation. At 50 micron‐Mg the pCa which produces 50% maximum tension is 5‐8, 5‐3 and 5‐5 for the 30 micron, 100 micron and 4 mM‐MgATP solutions. The effect of MgATP on position is relatively independent of the Mg concentration. 4. The steepness of the pCa‐% maximum tension curve increases as MgATP is elevated to the millimolar range. The Hill coefficients for the different MgATP curves at 50 micron‐Mg are 1‐1, 1‐3 and 3‐0. This change in steepness accounts for the slightly lower Ca concentration needed for half‐maximum tension as the MgATP concentration is increased to millimolar levels. Raising the Mg concentration to 1 mM greatly diminishes the effect of MgATP on the slope of the pCa‐tension relationship. 5. The maximum tnesion a fibre bundle can produce decreases as the amount of MgATP is raised from micromolar to millimolar levels. For 50 muM‐Mg, maximum tension drops about 35% as MgATP is raised from 30 micronM to 4 mM. For any concentraiton of MgATP, maximum tension is higher at 1 mM‐Mg than at 50 micron‐Mg. 6. Existing theories of interaction between myosin heads and the thin filament are sufficient to account for the effects of MgATP on the position of the pCa‐tension curves and on maximum tension. The effects on slope are less satisfactorily explained.
Microcalorimetric determination of energy expenditure due to active sodium‐potassium transport in the soleus muscle and brown adipose tissue of the rat.
Authors: Chinet A , Clausen T , Girardier L
Published: December 2014

1. The resting heat production rate (E) of soleus muscles from young rats and brown adipose tissue from adult rats was measured by means of a perfusable heat flux microcalorimeter in the absence and presence of ouabain. In the soleus muscle, the acute response of E to ouabain was compared with the ouabain‐suppressible components of 22Na‐efflux and 42K‐influx. 2. In standard Krebs‐Ringer bicarbonate buffer, ouabain (10(‐3)M) induced an immediate but transient decrease in E of around 5%. Both in muscle and adipose tissue this was followed by a progressive rise in heat production rate. 3. When the medium was enriched with Mg (10 mM), ouabain produced a sustained decrease in E of the same magnitude as in the standard medium and the secondary rise was less marked or abolished. Under these conditions, in the soleus muscle, ouabain inhibited E by 5% (i.e. by 1‐76 +/‐ 0‐22 mcal.g wet wt.‐1.min‐1), 22Na‐efflux by 58% (0‐187 +/‐ 0‐013 micronmole. g wet wt.‐1.min‐1) and 42K‐influx by 34% (0‐132 +/‐ 0‐028 micronmole. g wet wt.‐1.min‐1). 4. When the muscles were loaded with Na by pre‐incubation in K‐free Mg‐enriched medium, the addition of K (3mM) induced an immediate ouabain‐suppressible increase in E of 2‐98 +/‐ 0‐33 mcal. g wet wt.‐1.min‐1 and a concomitant stimulation of 22Na‐efflux of 0‐388 +/‐ 0‐136 micronmole. g wet wt.‐1.min‐1. 5. Maximum Na/ATP ratios for the active Na‐K transport process were computed, with no assumption as to the in vivo free energy of ATP hydrolysis. These were 2‐1, 1‐9 and 2‐3 under the conditions described in paragraphs (2), (3) and (4) respectively. 6. The calculated reversible thermodynamic work associated with active Na‐K transport corresponded to 34% of the measured ouabain‐induced decrease in E. On the premise that the maximum efficiency of the cellular energy conservation processes is 65%, this estimate indicates that the minimum energetic efficiency of ATP utilization by the active Na‐K transport process in mammalian muscle is 52%.
Effects of applied currents on turtle cones in darkness and during the photoresponse.
Authors: Byzov A L , Cervetto L
Published: December 2014

1. The voltage changes, produced by pulses of current of various intensities and polarities into turtle cones, were examined both in darkness and during the photoresponse. 2. Depolarizing pulses of current produced voltage deflexions which, during the photoresponse, were increased to a greater extent than those produced by pulses of current of the same intensity and opposite polarity. 3. Voltage‐current relationships were measured both in darkness and during illumination. During illumination they display a non‐linear behaviour, the curve being steeper for positive than for negative currents. 4. These non‐linearities are greatly attenuated following exposure of the retina to a solution containing 5 mM‐CoCl2 which is known to block synaptic transmission. The effects of CoCl2 are readily reversible when the retina is returned to normal conditions. 5. By comparing the effects produced by pulses of current injected into individual cones with those observed in horizontal cells following stimulation with a radial current, it is observed that the non‐linear behaviour of the cone membrane during the photoresponse can be, at least in part, accounted for by events occurring in post‐synaptic elements (i.e. horizontal cells).
Three pharmacologically distinct potassium channels in molluscan neurones.
Authors: Thompson S H
Published: December 2014

1. Potassium currents were studied under voltage‐clamp conditions in nerve cell bodies of the nudibranch Tritonia diomedia. 2. Potassium currents could be separated into three distinct components on the basis of their sensitivity to 4‐aminopyridine (4‐AP), tetraethyl‐ammonium (TEA) and to Co2+ and Mn2+ ions. 3. A transient potassium current, similar to the fast outward current described by Connor & Stevens (1971b) and Neher (1971), was blocked by externally applied 4‐AP but was much less sensitive to TEA or to Co2+ or Mn2+. A single 4‐AP ion binds each receptor with an apparent dissociation constant of 1‐5 X 10(‐3) M. 4‐AP decreases the rates of activation and inactivation and reduces the maximum conductance of transient current channels. 4. Delayed outward current was not effected by 4‐AP at concentrations which blocked the transient current, but it could be divided into two components by external application of TEA and Co2+ or Mn2+. 5. A voltage‐dependent component of delayed current, termed K‐current, was blocked by TEA. Each K‐current receptor binds a single TEA ion with an apparent dissociation constant of 8 X 10(‐3) M. Co2+ and Mn2+ have little or no effect on K‐current. 6. A second component of delayed outward current, termed C‐current, depends on Ca2+ entry for its activation. It is similar to the Ca2+ dependent potassium current reported by Meech & Stranden (1975) in Helix cells. C‐current is essentially blocked by 30 mM external Co2+ or Mn2+. It is little affected by TEA, however, being reduced by about 20% at a TEA concentration of 100 mM. 7. It is concluded that three sets of potassium selective channels contribute to the outward current and that these channels can be separated pharmacologically.
Utilization of blood‐borne and intramuscular substrates during continuous and intermittent exercise in man.
Authors: Essén B , Hagenfeldt L , Kaijser L
Published: December 2014

1. Substrate utilization in the legs during bicycle exercise was studied in five subjects when performing intermittent intense exercise (15 sec work‐‐15 sec rest) as well as continuous exercise during 60 min, with an almost identical average power output and oxygen uptake in both situations. 2. Muscle biopsies were obtained from vastus lateralis at rest, during, and after exercise in order to determine intramuscular lipid and carbohydrate utilization. The contribution from blood‐borne substrates to total oxidative metabolism was determined by arterial‐femoral venous (a‐fv) differences for oxygen, FFA, glucose, and lactate and leg blood flow. 3. Intermittent and continuous exercise revealed a similar glycogen depletion and the intramuscular lactate accumulation was rather small. A similar uptake of blood‐borne substrate (FFA, glucose) was found in both situations whereas a release of lactate only was observed in intermittent exercise. 4. ATP and CP levels oscillated between work and rest periods in intermittent exercise but were not resynthesized to resting levels at the end of the rest periods. The mainly aerobic energy release during each work period in intermittent exercise is partly caused by myoglobin functioning as an oxygen store; this factor was calculated to be more important than ATP and CP or lactate level oscillations. 5. The metabolic response to intermittent exercise was found to be similar to that found in continuous exercise with approximately the same average power output and oxygen uptake. This indicates that some factor in the intermediary metabolism, for instance citrate, functions as a regulator retarding glycolysis and favouring lipid utilization and an aerobic energy release in intermittent exercise.
The permeability of the skin of a neotenous urodele amphibian, the mudpuppy Necturus maculosus.
Authors: Bentley P J , Yorio T
Published: December 2014

1. The permeability of the isolated skin of a neotenous urodele amphibian, the mudpuppy Necturus maculosus, to Na, Cl, urea and water was measured. 2. Unidirectional transcutaneous flux measurements and the action of ouabain and amiloride, showed that there was normally no active Cl or Na transport, nor a Cl/Cl exchange diffusion process. 3. Amphotericin B initiated a transcutaneous potential difference and short‐circuit current, which could be inhibited by ouabain. 4. The short‐circuit current was nearly equivalent to the net Na Transport and this was also inhibited by ouabain. 5. A transcutaneous active Na transport mechanism thus appears to be incipient in the mudpuppy but is limited by a low permeability of the outer barrier of the cells. 6. Vasotocin increased the skin's diffusion permeability for water but had no effect on the influx of Na or urea. 7. The function of Necturus skin is in several respects unique compared to that of other amphibians.
Slow bleach‐induced birefringence changes in rod outer segments.
Authors: Kaplan M W , Liebman P A
Published: December 2014

1. Time resolved birefringence measurements reveal complex structural changes in rod outer segments following a bleaching flash. 2. The detailed character of the observed changes depends upon osmotic integrity of the outer segment envelope membrane. Rod outer segments with intact envelope membranes show a fast initial loss of intrinsic birefringence simultaneous with the formation of metarhodopsin II followed by a slower secondary loss. A subsequent birefringence increase to higher than the dark‐adapted level is partially correlated with the formation of retinol. Rod outer segments with ruptured envelope membranes show the initial and secondary losses, but the subsequent recovery only reaches the dark‐adapted level. Retinol does not form in such organelles. 3. The slow birefringence changes in intact rod outer segments were qualitatively different when Na+ salts were replaced by equimolar K+ salts in the bathing medium. 4. Glycerol appears to influence both the rate and magnitude of metarhodopsin III formation, and of the spectrally silent secondary birefringence loss.
Responses of isolated Golgi tendon organs of the cat.
Authors: Fukami Y , Wilkinson R S
Published: December 2014

1. The responses to stretch have been studied in living, isolated Golgi tendon organs (GTOs) from tail muscles of cat. Experiments were performed in vitro and consisted of subjecting single GTOs to controlled ramp‐and‐hold stretch while recording the response from their sensory axons raised in oil. 2. The threshold force required for sustained afferent discharge was measured directly, and found to be between 8 and 170 dynes at 24 degrees C for nine GTOs tested. Beyond threshold, the discharge frequency is approximately proportional to applied static tension over a wide range. Sensitivy to tension varies among different GTOs and appears to be inversely correlated with mechanical stiffness. 3. With impulse activity blocked by tetrodotoxin, graded receptor potentials could be recorded whose amplitude varied in proportion to applied static tension. All GTOs examined showed in addition a dynamic response, which became larger with increasing velocity of ramp stretch. This dynamic sensitivity appears in the receptor potential and is then augmentd by an apparent accommodative process at the impulse initiating site. 4. Based on the above findings, possible mechanical models are discussed for the sensory transduction mechanism.
Placental transport of sodium in the guinea‐pig.
Authors: Stulc J , Svihovec J
Published: December 2014

1. The mechanism of placental transport of Na was studied in guinea‐pigs in placentae with intact umbilical blood circulation or in the preparation of the placenta perfused in situ. 2. A constant level of 22Na was maintained in maternal plasma for 60 min, and from the quantity of 22Na recovered from the foetus at the end of this period the influx of Na from mother to foetus was calculated. Ligation of the omphalomesenteric vessels (supplying the everted yolk sac with blood) had no effect on the influx, the corresponding values of influx in the control and treated foetuses being 0‐235 +/‐ 0‐020 and 0‐247 +/‐ 0‐029 micron‐mole/min. g foetal weight (n = 6, the limits are S.E. of mean). The specific activity of Na in amniotic fluid was below that of the maternal or foetal plasma Na by two orders of magnitude. These observations indicate that the extraplacental transport of Na into the foetus is negligibly low. 3. The electrical potential difference (p.d.) and unidirectional fluxes of Na across the placenta perfused in situ were measured by means of 22Na and 24Na administered to the opposite sides of the placental barrier. The fluxes varied with the weight of the foetuses whose placentae were perfused. The flux from the maternal to the foetal side was 0‐270 +/‐ 0‐017 micronmole/min.g foetal weight, the flux from the foetal to the maternal side was 0‐340 +/‐ 0‐018 micronmole/min.g foetal weight (n = 38). The corresponding p.d. was ‐ 20‐7 +/‐ 1‐2 mV (foetal side negative). 4. The active component of Na transport across the placenta was calculated from the unidirectional fluxes and the p.d. The active transport was directed from the foetal to the maternal side, and its rate was 0‐211 +/‐ 0‐015 micronmole/min.g foetal weight (n = 38). During perfusion of the placenta with KCN (10(‐3) M) the active transport decreased by approximately one third. 5. The flux of Na from the foetal to the maternal side of the perfused placenta was higher than the flux from the maternal to the foetal side. A similar asymmetry of Na fluxes was observed in the non‐perfused placenta, the flux from mother to foetus being 0‐180 +/‐ 0‐013 micronmole/min.g foetal weight and the flux from foetus to mother 0‐235 +/‐ 0‐024 micronmole/min.g foetal weight (n = 12). This indicates that the asymmetry of Na fluxes is caused by the anaesthesia and/or by the trauma of the operation rather than by the perfusion of the placenta. 6. The permeabilities of the perfused placenta to Na and sucrose measured simultaneously from the maternal to the foetal side were 0‐0767 +/‐ 0‐0183 and 0‐324 +/‐ 0‐0094 cm3/min (n = 7y, respectively. The permeability values bear the same relation to each other as the respective coefficients of free diffusion in water, suggesting that the passive transport of Na across the placenta takes place as simple diffusion through wide aqueous channels. 6...
Effect of implantation of an extra nerve on the recovery of neuromuscular transmission from botulinum toxin.
Authors: Tonge D A
Published: December 2014

1. The common peroneal nerve was implanted into soleus in the mouse and 2 weeks later a sublethal dose of botulinum toxin injected causing a block of neuromuscular transmission at the terminals of the soleus nerve. Most muscle fibres became innervated by the common peroneal nerve. 2. Recovery of neuromuscular transmission at the soleus nerve terminals was delayed in the common peroneal nerve implanted muscles. 3. Stimulation of the soleus nerve after botulinum‐evoked subthreshold end‐plate potentials (e.p.p.s) in virtually every fibre tested in unoperated muscles. In common peroneal nerve‐implanted muscles stimulation of the soleus nerve failed to evoke e.p.p.s in about 40% of fibres tested and where e.p.p.s were recorded their amplitudes were generally smaller. 4. When the common peroneal nerve was cut 2 months after botulinum, neuromuscular transmission at soleus nerve terminals occurred after 4 weeks. When the common peroneal nerve was cut 6 months after botulinum, transmission was found at soleus nerve terminals within 1 week. 5. Recovery of transmission at soleus nerve terminals from the effects of botulinum toxin is delayed if the muscle fibres become innervated by the common peroneal nerve and a proportion of soleus nerve terminals cease to release acetylcholine (ACh) until after the peroneal nerve has been cut.