bluuebunny/crossref_metadata_2025 huggingface dataset:
Ontogeny of the circadian rhythm of plasma corticosterone in blind infantile rats.
Authors: Hiroshige T , Honma K , Watanabe K
Published: December 2014

1. Post‐natal manifestation of plasma corticosterone rhythm was followed by individual pups until the end of 12 weeks of life. Results obtained were analysed by both visual inspection and a least squares spectrum method. The validity of the approaches used was evaluated. 2. Circadian rhythm of plasma corticosterone in sighted pups under light‐dark cycle (LD) first appeared at around the third post‐natal week, accompanied often with a bimodal pattern: a second peak being counterphased to the first main peak. The second peak became obscure at the fourth week, disappearing as pups matured. 3. The hormone rhythm in blinded pups whose eyes were removed within 16 h of birth was free‐running under LD with a period of 24.40 +/‐ 0.02 h (mean +/‐ S.E.M.). The free‐running period was stable until at least the end of the twelfth week of life. 4. The acrophase of the circadian rhythm in blind pups born and reared under LD was 180 degrees out of phase to that born and reared under DL, a reversed light‐dark condition. In each case, the acrophase shifted about 8 h from that of sighted pups at the fourth week of life. 5. It is suggested that an underlying oscillator for the hormone rhythm starts to oscillate earlier than the fourth week of life and the environmental light‐dark cycle prior to the fourth week determines the phase angle of the circadian rhythm in blind pups.
Somatic motor axons can innervate autonomic neurones in the frog heart
Authors: Proctor William , Roper Stephen , Taylor Barbara
Published: December 2014

1. The effects of sympathetic and parasympathetic stimulation on the heart rate in frogs were tested after hearts were reinnervated with a somatic motor nerve. When frogs were vagotomized and hypoglossal axons were redirected to the heart for 8 or more weeks, stimulating the redirected hypoglossus nerve produced a parasympathetic‐like inhibition of the heart. Stimulating sympathetic rami of the anastomosed hypoglossus nerve produced cardiac acceleration.

2. Individual parasympathetic neurones received synaptic input from hypoglossal terminals. The excitatory post‐synaptic potentials evoked by hypoglossal stimulation were much smaller than those evoked by vagal stimulation in control or vagal‐reinnervated ganglia. However, hypoglossal axons innervated most (71%) of the ganglion cells and this level of innervation persisted for at least 60 weeks.

3. Hypoglossal axons formed networks of varicose terminals within cardiac ganglia and established axo‐axonic synapses with parasympathetic neurones. Hypoglossal terminals did not reinnervate the neuronal perikarya, in contrast to vagal axons in control or vagal‐reinnervated ganglia.

4. Axo‐axonic synapses from redirected hypoglossal axons were identified in cardiac ganglia by bathing isolated hearts in horseradish peroxidase (HRP) and stimulating the redirected nerve. Electron micrographs showed that axo‐axonic synapses contained HRP‐labelled presynaptic vesicles.

5. The source of foreign innervation in experimental cardiac ganglia was confirmed to be hypoglossal motoneurones (a), by comparing the conduction velocity of the redirected presynaptic axons (1·32 m/sec) with regenerating vagal preganglionic fibres (< 0·3 m/sec), and (b), by retrograde HRP‐labelling of large motoneurones in the hypoglossal nucleus after applying peroxidase to the axons which had grown into the heart.
Effects of the oestrous cycle on the metabolism of arachidonic acid in rat isolated lung.
Authors: Bakhle Y S , Zakrzewski J T
Published: December 2014

1. The metabolism of exogenous arachidonic acid perfused through the pulmonary circulation was investigated in lungs taken from rats at different stages of the oestrous cycle. 2. Following perfusion with [14C]arachidonic acid there was more radioactivity associated with cyclo‐oxygenase products in general at pro‐oestrus than at any other stage of the cycle. 3. Production of 6‐oxo‐prostaglandin F1 alpha and hence of prostacyclin (PGI2) was also highest at pro‐oestrus. 4. Production of thromboxane B2 was highest at pro‐oestrus although it was never greater than PGI2 production at any stage. 5. Radioactivity retained in lung tissue was mostly present in phospholipid and free fatty acid fractions with the distribution at pro‐oestrus being different from the other stages. 6. Following perfusion with [14C]oleic acid (which is not a substrate for cyclooxygenase), variations in the distribution of label in radioactivity in lung were also observed. However, these were not related to the stages of the oestrous cycle in the same way as those associated with arachidonic acid. 7. We conclude that both pathways of arachidonic acid metabolism in lung‐‐oxidation via cyclo‐oxygenase and incorporation into phospholipid ‐ are affected by the progress of the oestrous cycle. 8. Altered arachidonate metabolism appeared to be associated chiefly with pro‐oestrus and may be linked to those hormones involved in this stage of the oestrous cycle.
The role of vagal and intramural inhibitory reflexes in the regulation of intragastric pressure in the ferret
Authors: Andrews P. L. R. , Lawes I. N. C.
Published: December 2014

1. The step inflation technique combined with nerve section and pharmacological receptor blockade was used to determine the gastric distribution of the vagal inhibitory fibres and their role in the regulation of intragastric pressure in the anaesthetized ferret.

2. Under the conditions described the predominant effect of the vagus was inhibitory. The dorsal abdominal vagus mediated more inhibition than the ventral vagal trunk. There was partial overlap in the inhibitory effects of the two trunks but, in contrast to excitatory effects, this overlap was less than complete.

3. No evidence was found to indicate that the intramural inhibitory neurones (demonstrated pharmacologically) could be activated by a local distensive stimulus or that local inhibitory reflexes played an independent role in the regulation of intragastric pressure. The vago—vagal inhibitory reflexes play the major (possibly the only) part in the over‐all regulation of intragastric pressure.

4. After a step gastric inflation (50 ml. in < 3 sec) the time taken for the intragastric pressure to fall to 1/e of the peak pressure was a function of the number of inflations; the time decreased with increased number of inflations. It was apparently unaffected by nerve lesions.

5. The intragastric pressure in response to an inflation, besides being a function of the neural reflexes evoked, was also related to the gastric weight and hence the size of the animal.

6. The sum of the prevailing intragastric pressure and the response to vagal stimulation (10 Hz, 10 sec) was similar, irrespective of the intragastric fluid volume (10‐80 ml.).

7. The volume of fluid in the corpus was shown to be a major determinant of the contraction produced in response to vagal stimulation: as the corpus volume increased the corpus contraction decreased but the relaxation that follows the contraction increased. A similar effect was observed with intra‐arterial ACh which implies that the response to stimulation was modified directly by the degree of stretch of the smooth muscle cells. Inhibitory effects were not apparent unless the stomach was moderately inflated.

8. The relative roles of the vagal reflexes, intramural reflexes and the smooth muscle in the regulation of intragastric pressure are discussed in the light of the above observations.
Mammary development in mice: effects of hemihysterectomy in pregnancy and of litter size post partum
Authors: Knight C. H. , Peaker M.
Published: December 2014

1. Mice were hemihysterectomized on day 8 of pregnancy to reduce the number of feto‐placental units.

2. Fetal mortality was not affected by hemihysterectomy; mean single‐pup weight at birth was increased when compared with sham‐operated controls.

3. Pregnant sham‐operated and hemihysterectomized animals were killed on days 13 and 18 of gestation, and their mammary glands were analysed for total DNA (DNAt) and RNA (RNAt). Both were significantly lower in the hemihysterectomized group on day 18, but not on day 13.

4 Milk yield was assessed, by daily weighing of the litter, in groups of sham‐operated and hemihysterectomized lactating animals suckling nine pups each. There was no difference in yield between the two groups.

5. One group of sham‐operated mice suckling nine pups, one of hemihysterectomized mice suckling nine pups and one of hemihysterectomized mice suckling four pups were killed on day 5 of lactation for mammary gland analysis. There was no significant difference in mammary weight or DNAt between the sham‐operated and hemihysterectomized animals suckling nine pups, although RNAt was still reduced in the latter. Mammary weight, DNAt and RNAt were all significantly lower in the hemihysterectomized group suckling four pups than in either of the other two groups.

6. It is concluded that the less well developed mammary glands of mice which give birth to small litters are capable of compensatory growth during the first few days of lactation if a sufficiently strong suckling stimulus is given.

7. It is suggested that control of mammary development by the fetus during gestation and by the suckling young during early lactation are both mechanisms designed to ensure that milk yield is appropriate to the needs of the young.
Variations in the time course of the synchronization of intercostal motoneurones in the cat
Authors: Kirkwood P. A. , Sears T. A. , Tuck D. L. , Westgaard R. H.
Published: December 2014

1. Synchronization of intercostal motoneurones was studied by the construction of cross‐correlation histograms which related the firing times of paired groups of efferent inspiratory or expiratory discharges recorded from filaments of the external or internal nerves of anaesthetized or decerebrate cats.

2. The principal feature of the histograms was always a central peak but the time course of the central peak showed considerable variation. Three forms of synchronization were defined on the basis of the time course of the central peak: (i) short‐term synchronization (Sears & Stagg, 1976), where the peak was narrow, extending over about ±3 ms but sometimes with weak shoulders to about ±5 ms; (ii) broad‐peak synchronization where the peak was wider than this (often ±20 ms or more) but where there were no strong periodicities; (iii) high‐frequency oscillation (h.f.o) synchronization, which was named from the related phenomena in medullary and phrenic recordings (Cohen, 1979), where there were periodic peaks on either side of the central peak with a frequency in the range 60‐120 Hz. Combinations of these forms of synchronization were seen in some histograms.

3. When different animals were compared, broad peak synchronization was seen in association with light anaesthesia and with polysynaptic excitation of the motoneurones from muscle spindle afferents.

4. In individual animals, additional anaesthesia depressed both broad peak and h.f.o. synchronization.

5. Raising PA, CO2, which increased the respiratory drive to the motoneurones, favoured short‐term or h.f.o. synchronization at the expense of broad‐peak synchronization.

6. In three decerebrate animals only short‐term or h.f.o. synchronization was seen.

7. Spinal cord lesions above or below the segments of interest promoted broad‐peak synchronization, even with high PA, CO2 or deep anaesthesia.

8. We conclude: (i) that short‐term synchronization, due mainly to the branching of presynaptic axons, is generated mainly by those axons which transmit the respiratory drive, that drive providing most of the excitation of the motoneurones in moderately deep anaesthesia; (ii) that h.f.o. synchronization arises from the periodic synchronization of the discharges in these same presynaptic axons; (iii) that broad‐peak synchronization is generated by the activity of other presynaptic neurones whose discharges are also synchronized, but aperiodically, these neurones most likely including spinal cord interneurones which are active in light anaesthesia or when released by spinal cord lesions.

9. These conclusions are supported by comparisons between intracellular recordings from inspiratory motoneurones in animals showing different forms of motoneurone synchronization, the comparison including the measurements of ‘average common excitation’ (a.c.e.) potentials (Kirkwood & Sears, 1978).
Immunohistochemical studies on the development of prochymosin‐ and pepsinogen‐containing cells in bovine abomasal mucosa.
Authors: Andrén A , Björck L , Claesson O
Published: December 2014

1. Prochymosin‐ and pepsinogen‐containing cells in abomasal mucosa were simultaneously localized by means of an indirect immunofluorescence technique with specific rabbit antibodies. 2. In the young milk‐fed calves all the chief cells and several mucous neck cells produced both prochymosin and pepsinogen. 3. By elution of the first antibody and restaining of the same section it was demonstrated that the same cells were producing both prochymosin and pepsinogen. 4. In concentrate‐fed calves and older cattle all chief cells and almost all mucous neck cells produced pepsinogen, while prochymosin was produced only from the chief cells situated in the upper part of the base in the gastric gland. 5. The number of prochymosin‐containing cells was highly correlated to the milk‐feeding of the animal. 6. The present data suggest that the non‐differentiated cell in the neck region is initially capable of producing both prochymosin and pepsinogen during the proliferation phase to a mature chief cell, via mucous neck cell. The ability to produce prochymosin is however only retained if the mucosa is stimulated by milk‐feeding. Dietary factors may thus be of importance for the differentiation of the gastrointestinal epithelium.
Effects of the autonomic system on insulin release in response to exogenous glucose in weaned lambs.
Authors: Bloom S R , Edwards A V
Published: December 2014

1. The role of the autonomic innervation to the pancreas in mediating the release of insulin in response to exogenous glucose has been investigated in conscious weaned lambs 4‐5 months after birth. 2. The incremental rise in mean plasma insulin concentration was consistently lower in lambs with cut splanchnic nerves, which had been pre‐treated with atropine (0.2 mg kg‐1), than in normal control lambs, although the differences did not achieve statistical significance. 3. Pre‐treatment with propranolol (0.25 mg kg‐1) effectively suppressed release of insulin in response to exogenous glucose in atropinized lambs with intact splanchnic nerves, but not in atropinized lambs with cut splanchnic nerves. 4. The rise in mean plasma insulin concentration was significantly greater in lambs pre‐treated with atropine (0.2 mg kg‐1) and phentolamine (0.1 mg kg‐1 initially, followed by 0.02 mg kg‐1 min‐1) than in atropinized lambs with cut splanchnic nerves. 5. It is concluded that release of insulin in response to exogenous glucose is normally modified by both sympathetic alpha‐adrenergic inhibition and beta‐adrenergic excitation in this species.
The properties of single cones isolated from the tiger salamander retina
Authors: Attwell David , Werblin Frank S. , Wilson Martin
Published: December 2014

1. The properties of isolated single cones were studied using the voltage‐clamp technique, with two micro‐electrodes inserted under visual control.

2. Single cones had input resistances, when impaled with two electrodes, of up to 270 MΩ. This is probably lower than the true membrane resistance, because of damage by the impaling electrodes. The cone capacitance was about 85 pF.

3. The cone membrane contains a time‐dependent current, IB, controlled by voltage, and a separate photosensitive current.

4. The gated current, IB, is an inward current with a reversal potential around ‐25 mV. It is activated by hyperpolarization over the range ‐30 to ‐80 mV, and at constant voltage obeys first order (exponential) kinetics. The gating time constant is typically 50 ms at the resting potential of ‐45 mV, rises to 170 ms at ‐70 mV, and decreases for further hyperpolarization.

5. The spectral sensitivity curve of the cone light response peaks at 620 nm wave‐length, and is narrower than the nomogram for vitamin A2‐based pigments. The light responses of isolated cones are spectrally univariant.

6. Voltage‐clamped photocurrents were recorded at various membrane potentials, for light steps of various intensities. The photocurrent reversed at around ‐8 mV. The time course of the photocurrent, for a given intensity, was approximately independent of voltage (although its magnitude was voltage‐dependent). The shape of the peak current—voltage relation of the light‐sensitive current was independent of light intensity (although its magnitude was intensity‐dependent).

7. These results can be explained if: (a) light simply changes the number of photosensitive channels open, without altering the properties of an open channel; (b) the reactions controlling the production of internal transmitter, the binding of internal transmitter to the photosensitive channels, and the closing and opening of the channels are unaffected by the electric field in the cone membrane, even though at least some of these reactions take place in the membrane.

8. IB plays only a small role in shaping the cone voltage response to light.
On the pyrogenic action of intravenous lipid A in rabbits.
Authors: Kenedi E , Laburn H , Mitchell D , Ross F P
Published: December 2014

1. Previous evidence purporting to show that lipid A is the pyrogenic moiety of endotoxin is demonstrably inconclusive. 2. We have extracted lipid A from endotoxin of Salmonella typhosa and tested the pyrogenic action of the lipid A, the residual polysaccharide and the parent endotoxin, by intravenous injection in conscious rabbits. 3. Lipid A dissolved in an aqueous solution of rabbit serum albumin induced a significant pyrexia of short latency, while neither rabbit serum albumin alone, nor the polysaccharide from S. typhosa, affected body temperature. The physical presence in the injectate of the polysaccharide from S. typhosa did not enhance the pyrogenicity of the lipid. 4. Dose‐response curves for lipid A and the parent endotoxin, over the dose range 10 ng‐20 micrograms, showed that lipid A incorporated in endotoxin was much more pyrogenic than pure lipid A in solution. When separated from the polysaccharide component of endotoxin, lipid A lost more than 99.9% of its pyrogenic activity, at threshold doses.
The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog
Authors: Cross Brenda A. , Davey A. , Guz A. , Katona P. G. , Maclean M. , Murphy K. , Semple S. J. G. , Stidwill R.
Published: December 2014

1. The ventilatory response to electrically induced ‘exercise’ was studied in six chloralose‐anaesthetized dogs. The on‐transient and steady‐state responses to ‘exercise’ were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions.

2. Phasic hind limb ‘exercise’ was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact.

3. Cord transection produced no significant change in either the resting values of ventilation (V̇I) and CO2 production (V̇CO2) or the ventilatory equivalent for CO2 during ‘exercise’ (△ V̇I/ △ V̇CO2).

4. During the steady state of exercise Pa, CO2 was on average significantly lower than at rest with the cord intact (mean △Pa, CO2, ‐ 2·1 mmHg; range ‐ 5·7 to + 1), and higher, though not significantly, with the cord cut (mean Pa, CO2, + 1·2 mmHg; range ‐ 1·5 to + 4·3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO2 sensitivity; the △ V̇I/ △Pa,CO2 obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO2 inhalation (true sensitivity) both before and after cord section.

5. V̇I and V̇CO2 increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection.

6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on‐transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced ‘exercise’ was free of artifact.

7. It was concluded that spinal cord transmission is not necessary for the steady‐state ventilatory response to electrically induced exercise of the hind limbs.

8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise.
Micropuncture study of changes in glomerular filtration and ion and water handling by the rat kidney during pregnancy
Authors: Garland H. O. , Green R.
Published: December 2014

1. In rats receiving 200 μl. min−1 sodium chloride, glomerular filtration rate, single nephron glomerular filtration rate, and fractional reabsorption were measured at various points along the nephron, and ionic concentrations measured in early distal tubular fluid in virgin and 6, 12 and 19 day pregnant rats.

2. Glomerular filtration increased progressively until the twelfth day of pregnancy. At 19 days of pregnancy the glomerular filtration rate, while still above virgin levels, was reduced below 12 day pregnant levels.

3. Single nephron glomerular filtration rates measured in proximal and distal tubules were different at both 12 and 19 days of pregnancy, indicating an alteration of tubuloglomerular feed‐back.

4. A change in the ratio of glomerular filtration rate: distal single nephron filtration rate indicated a redistribution of glomerular filtrate to juxtamedullary nephrons by the sixth day of pregnancy.

5. Fluid reabsorption is similar up to the early distal tubule but it is not possible to say whether reabsorption is the same in proximal tubules. More fluid is reabsorbed by late distal tubules and collecting ducts in 12 and 19 day pregnant animals than in the virgin and 6 day pregnant animals.

6. Changes in ion reabsorption by the loop of Henle occurred during pregnancy; sodium reabsorption was increased by the sixth day of pregnancy and potassium reabsorption by the twelfth day.
Calcium‐ and length‐dependent force production in rat ventricular muscle
Authors: Hibberd M. G. , Jewell B. R.
Published: December 2014

1. Trabeculae from the right ventricles of rat hearts were ‘skinned’ by immersion for 30 min in a solution containing the non‐ionic detergent Brij‐58 at a concentration of 1%.

2. The average sarcomere length in the central region of the relaxed preparation was estimated by laser diffraction and set at pre‐determined values within the range of 1·9‐2·4 μm by adjustment of muscle length. Isometric contractions were then induced by raising the Ca2+ concentration under carefully controlled chemical conditions.

3. The dependence of Ca2+‐activated force production on sarcomere length over the ascending limb of the length—force relation was examined at Ca2+ concentrations giving partial and full activation of the contractile system of the muscle.

4. The dependence of Ca2+‐activated force on Ca2+ concentration was compared at sarcomere lengths on the ascending limb and plateau of the length—force relation.

5. The results obtained from both kinds of experiment showed that the sensitivity of the contractile system to Ca2+ increases with sarcomere length over the ascending limb of the length—force relation.

6. Possible explanations for this observation have been discussed.
The effects of intracochlear cyanide and tetrodotoxin on the properties of single cochlear nerve fibres in the cat.
Authors: Evans E F , Klinke R
Published: December 2014

1. Tuning properties and spontaneous discharge rate of single cochlear fibres in the anaesthetized cat were determined under conditions where millimolar concentrations of KCN were instilled into the scala tympani. 2. Short‐term effects on the tuning properties were obtained, in which the threshold of the low threshold sharply tuned tip segment of the frequency‐threshold ('tuning') curve (f.t.c.) was elevated by up to 40 db, without changes in the threshold of the low frequency ‘tail’ segment of the f.t.c., or necessarily changes in the spontaneous and maximally evoked activity. These changes were accompanied by a shift of the characteristic frequency tip segment towards lower frequencies. All these effects could be reversed. 3. The long‐term effects of repeated KCN instillations produced irreversible changes similar to the short‐term effects. 4. These changes correlated well with depression of the amplitude of the gross cochlear action potential but not with the cochlear microphonic potential, both recorded at the round window. 5. Instillations of tetrodotoxin (TTX) rapidly reduced and blocked the cochlear fibre discharges without effects on their tuning, in contrast to the effects of KCN.
Uptake, localization and release of serotonin in the chick retina.
Authors: Osborne N N
Published: December 2014

1. High pressure liquid chromatography and electrochemical detection have shown that serotonin exists in the chick retina (127 ng/g wet weight). No other indoleamine was identified. 2. Immunofluorescent histological studies showed that the endogenous serotonin was localized apparently in those cell bodies and processes which took up exogenous [3H]serotonin as revealed by autoradiography. These serotonergic neurones can be destroyed by injecting kainic acid into the eye. 3. Isolated chick retina accumulated exogenous [3H]serotonin. Kinetic analysis revealed the presence of two saturable uptake systems: a ‘high affinity’ mechanism with an apparent Km of 5.9 X 10(‐8) M and a Vmax of 0.143 X 10(‐13) mol/mg wet weight . min and a low affinity mechanism with an apparent Km2 of 1.8 X 10(‐3) M and Vmax of 0.12 X 10(‐9) mol/mg wet weight . min. 4. The uptake of serotonin was temperature‐sensitive and sodium‐dependent and Lilly 110140 and chlorimipramine were potent inhibitors of the amine uptake. 5. Autoradiographic studies indicated that neuronal processes associated with the innermost and outermost areas of the inner plexiform layer and perikarya situated in the inner nuclear layer are the sites which accumulated exogenous [3H]serotonin. 6. [3H]Serotonin accumulated in the retina was released by increasing the external K+ concentration. This release was Ca2+‐dependent. Additionally, autoradiographic studies show that [3H]serotonin taken up by the serotonin neurones was also released by Ca2+‐dependent K+ depolarization of the retina.
Comparative effects of external monovalent cations on sodium pump activity and ouabain inhibition rates in squid giant axon.
Authors: Hobbs A S
Published: December 2014

1. A number of external monovalent cations were compared with regard to their effects on Na pump rate and the rate of ouabain inhibition of the pump in squid giant axon. 2. External ions which stimulate active Na efflux (K, Rb, and Cs) were found to decrease the rate at which low concentrations of ouabain inhibit the pump, and those ions which inhibit the pump externally (Na and Li) to increase the rate of inhibition. 3. In Na‐ and Li‐containing solutions, pump rate appeared to be the major factor in determining the rate of ouabain inhibition regardless of whether K, Cs, or Rb was used to stimulate active Na efflux. 4. When choline was substituted for external Na, ouabain inhibition rates were more than twice as rapid when Cs was used as the pump‐stimulating cation than when K was activating the pump to a similar level. 5. These results suggest that external monovalent cations modulate ouabain inhibition in squid axon at two classes of sites: pump activation sites, and also separate regulatory sites, whose occupation can significantly increase the rate of ouabain inhibition independent of pump turnover rate.
Glucose‐sensitive afferent nerve fibres in the hepatic branch of the vagus nerve in the guinea‐pig.
Authors: Niijima A
Published: December 2014

1. Afferent discharges were recorded from nerve filaments dissected from the hepatic branch of the vagus nerve in the guinea‐pig in situ. 2. A significant decrease in the discharge rate was observed following the administration of D‐glucose into the portal vein but not after the administration of D‐mannose, D‐fructose, D‐galactose, L‐glucose, D‐xylose or D‐arabinose. 3. The mean discharge rate of these fibres was inversely related to the concentration of glucose in the portal blood. 4. These results suggest the existence of D‐glucose ‘sensors’ in the liver which monitor the glucose concentration of portal blood.
The electrogenic sodium—potassium pump of mouse pancreatic B‐cells
Authors: Henquin J. C. , Meissner H. P.
Published: December 2014

1. The contribution of the sodium pump to the membrane potential of mouse pancreatic B‐cells was studied with micro‐electrodes.

2. In 0 or 3 mM‐glucose, ouabain rapidly (within 2 min) depolarized the B‐cell membrane by an average of 7 mV, whereas K omission hyperpolarized it markedly.

3. In 6 or 7 mM‐glucose, ouabain still produced depolarization, but K omission had no consistent effect. Both induced electrical activity in certain cells.

4. In 10 mM‐glucose, withdrawal of ouabain or K re‐introduction caused a transient hyperpolarization with suppression of electrical activity. Duration and amplitude of the hyperpolarization increased with the time of pump blockade and with the concentration of ouabain.

5. The hyperpolarization following K re‐admission was abolished by ouabain and that following ouabain withdrawal was prevented by K omission. Re‐admission of various K concentrations showed that the hyperpolarization was not due to depletion of K just outside of the membrane.

6. In 10 mM‐glucose, the membrane potential of B‐cells exhibited repetitive slow waves with bursts of spikes on the plateau. These electrical events were modified by ouabain in a dose‐dependent manner. The frequency of the slow waves augmented markedly because of an increase in the slope of the pre‐potential and a shortening of the intervals; the slope of their repolarization phase decreased, but their duration was not changed.

7. Omission of K increased the slope of the pre‐potential and the frequency of the slow waves. It also accelerated their repolarization phase and reduced their duration, likely because of the increase in driving force for K efflux. Increasing K concentration to 8 mM slowed the repolarization phase and lengthened the slow waves without changing their frequency.

8. Even when K permeability of the B‐cell membrane was increased by high extracellular Ca, ouabain and K omission augmented the frequency of the slow waves.

9. In 0 or 10 mM‐glucose, ouabain increased 86Rb+ efflux from perifused islets, whereas K omission decreased it. In 10 mM‐glucose, a marked decrease in 86Rb+ efflux accompanied ouabain withdrawal and K re‐introduction. The hyperpolarization is thus not due to an increase in K permeability.

10. It is concluded that, in pancreatic B‐cells, the sodium pump is truly electrogenic, contributes to the resting potential and modulates the slow waves of membrane potential induced by glucose. Rapid changes in insulin release occurring upon inhibition or activation of the sodium pump may thus be due to the changes in B‐cell membrane potential.
Muscarinic presynaptic inhibition of synaptic transmission in myenteric plexus of guinea‐pig ileum.
Authors: Morita K , North R A , Tokimasa T
Published: December 2014

1. The effect of oxotremorine (300 pM to 30 nM) on synaptic transmission in isolated myenteric ganglia of guinea‐pig ileum was investigated with intracellular recording techniques. 2. These low concentrations of oxotremorine had no effect on the resting membrane potentials or on the membrane conductance. 3. Oxotremorine reduced the amplitude of the fast excitatory post‐synaptic potential (e.p.s.p.) but did not reduce the amplitude of nicotinic responses to ionophoretic application of acetylcholine (ACh). This effect of oxotremorine on the fast e.p.s.p. was dose‐dependent; the amplitude was reduced by about 45% by 30 nM‐oxotremorine. 4. Non‐cholinergic slow e.p.s.p.s evoked by repetitive presynaptic nerve stimulation were reduced in amplitude by oxotremorine. 5. Hyoscine or atropine (1 nM) completely antagonized both these effects of oxotremorine (30 nM). 6. Muscarinic antagonists alone increased the amplitude of second and subsequent fast e.p.s.p.s when these were evoked at intervals of 1 s, and increased the amplitude and duration of the slow e.p.s.p. evoked by repetitive presynaptic nerve stimulation. 7. The results indicate that muscarinic receptor activation inhibits the release of the transmitters which mediate both the fast and the slow e.p.s.p.s and that this can occur with physiologically released ACh during repetitive presynaptic nerve activity.
Visualization of the spread of electrical activity in rat hippocampal slices by voltage‐sensitive optical probes
Authors: Grinvald A. , Manker A. , Segal M.
Published: December 2014

1. Voltage‐sensitive membrane‐bound dyes and a matrix of 100 photodetectors were used to detect the spread of evoked electrical activity at the CA1 region of rat hippocampus slices. A display processor was designed in order to visualize the spread of electrical activity in slow motion.

2. The stimulation of the Schaffer collateral‐commissural path in the stratum radiatum evoked short latency (2‐4 msec) fast optical signals, followed by longer latency (4‐15 msec) slow signals which decayed within 20‐50 msec. Multiple fast signals were frequently detected at the stratum pyramidale; they propagated toward the stratum oriens with an approximate conduction velocity of 0.1 m/sec.

3. The fast signals were unaltered in a low Ca2+ high Mg2+ medium but were blocked by tetrodotoxin. These signals probably represent action potentials in the Schaffer collateral axons. Their conduction velocity was about 0.2 m/sec and their refractory period about 3‐4 msec.

4. The slow signals were absent in a low Ca2+ medium and probably represent excitatory post‐synaptic potentials (e.p.s.p.s) generated in the apical dendrites of the pyramidal cells. They were generated in the stratum radiatum, where the presynaptic signals were seen, and spread into somata and basal dendrites (the stratum pyramidale and oriens, respectively).

5. The timing of the signals with fast rise‐time, which were detected at the statum pyramidale, approximately coincided with the timing of the extracellularly recorded field potentials. These multiple discharges probably represent action potentials of the pyramidal cells. They spread back into the apical dendrites but with significant attenuation of the amplitudes of the high frequency components of the pyramidal action potentials.

6. Hyperpolarizing potentials could be detected when strong stimuli were applied to the stratum radiatum or alveus. The net hyperpolarizations were detected only in the stratum pyramidale and the border region between the stratum pyramidale and radiatum. Frequently the inhibition was masked by the large e.p.s.p.s. However, its existence could be demonstrated by treatment of the slice with picrotoxin or a low Cl− medium. Under these conditions a long‐lasting depolarization of the apical dedrites was evoked by the stimulation. This was associated with an increase of the multiple discharges in the stratum pyramidale and oriens.

7. These studies illustrate the usefulness of voltage‐sensitive dyes in the analysis of passive and active electrical properties, pharmacological properties and synaptic connexions in mammalian brain slices, at the level both of small neuronal elements (dendrites, axons) and of synchronously active neuronal populations.
Effect of sodium, deoxycorticosterone and duration of hypertension on pressor responses in rats
Authors: Bing Robert F. , Russell Gavin I. , Swales John D. , Thurston Herbert
Published: December 2014

1. Enhanced pressor responsiveness to angiotensin II and noradrenaline has been demonstrated in the hypertension that follows deoxycorticosterone (DOC) and salt administration in the rat. The present studies were carried out to assess the importance of factors common to both pressor agents and those specific to individual agents such as receptor availability.

2. Accordingly pressor reponses to angiotensin II and noradrenaline have been studied in normotensive salt‐loaded and sodium depleted rats with and without DOC, and in rats with DOC‐salt hypertension of short and long duration. These responses have been related to the plasma renin levels in the animals studied.

3. Pressor reponses to angiotensin II were increased, dose‐response curve (d.r.c.) shifted to the left, in salt‐loaded rats and the administration of DOC produced a further increase. DOC‐salt hypertension of short duration was associated with an even greater responsiveness. Sodium depletion, however, reduced responsiveness (d.r.c. shifted to the right) and concurrent DOC administration did not alter this. Angiotensin II responses were closely correlated with plasma renin concentration over a wide range of values (p.r.c, r = ‐0·77, P < 0·001). The differences between the groups could be explained therefore by the number of unoccupied angiotensin II receptors available.

4. On the other hand only sodium loaded rats that were also receiving DOC showed any change in noradrenaline responsiveness, when the dose‐response curve was shifted to the left. Noradrenaline responses showed no linear relationship to plasma renin concentration.

5. The presence of hypertension did not significantly alter noradrenaline responses and the increase observed in angiotensin II responsiveness could be explained by the greater suppression of plasma renin in this group. Duration of hypertension had no effect on responsiveness to either agent.

6. These results point to important differences in the pressor responsiveness to angiotensin II and noradrenaline with variation of salt intake and DOC administration.
Existence of a sodium‐induced calcium release mechanism of frog skeletal muscle fibres.
Authors: Potreau D , Raymond G
Published: December 2014

1. The electrical and the mechanical activity of isolated frog muscle fibres have been simultaneously recorded in a physiological solution which allows the development of a large tubular sodium current. 2. Under such experimental conditions, fibres develop long‐lasting action potentials and strong mechanical responses. 3. In voltage‐clamp experiments a slow inward current is revealed for depolarizations higher than +20 mV from the resting potential. This current increases until +40 to +50 mV and then decreases to reverse near +90 mV. The amplitude of the mechanical response increases with the potential to reach an optimum value between +40 and +50 mV and then decreases to stabilize when the depolarization is near +90 mV. 4. In the presence of picrotoxin the slow inward current is reversibly inhibited and the tension‐depolarization curve has an S‐shape as found in normal physiological conditions. 5. The dependence of a part of the contraction upon the slow inward current is reinforced by the fact that in a 50% sodium solution the amplitude of the current and that of the contraction are reduced in the same proportion. 6. Detubulated fibres failed to generate such a sodium inward current. 7. When sodium ions are replaced by lithium ions a slow inward lithium current develops but it does not induce a mechanical response. 8. Tetracaine reversibly inhibits the current‐dependent component of the contraction without affecting the potential‐dependent one. 9. It is concluded that the contraction recorded in the present experimental conditions is the sum of two components: one is potential‐dependent and the other depends on a sodium‐induced calcium release mechanism.
Excitatory amino acids in synaptic transmission in the Schaffer collateral‐commissural pathway of the rat hippocampus.
Authors: Collingridge G L , Kehl S J , McLennan H
Published: December 2014

1. The effects of excitatory amino acids and some antagonists applied by ionophoresis to stratum radiatum in the CA1 region of rat hippocampal slices were examined on the locally recorded field e.p.s.p. evoked by stimulation of the Schaffer collateral‐commissural projection. 2. L‐glutamate, L‐aspartate and the more potent and selective excitatory amino acids quisqualate, kainate and N‐methyl‐DL‐aspartate (NMA) depressed the e.p.s.p., presumably through depolarization and/or a change in membrane conductance. 3. The depression induced by kainate considerably outlasted the period of ejection whereas NMA depressions were rapidly reversible and were often followed by a potentiation of the e.p.s.p. In higher doses NMA also depressed the presynaptic fibre volley. The possible involvement of these effects in neurotoxicity and synaptic plasticity is raised. 4. The selective NMA antagonist, DL‐2‐amino‐5‐phosphonovalerate (APV) applied in doses which abolished responses to NMA, had no effect on the e.p.s.p. but prevented long term potentiation (l.t.p.) of synaptic transmission evoked by high frequency stimulation of the Schaffer collateral‐commissural pathway. Other antagonists which had little or no effect on normal synaptic transmission included D‐alpha‐aminoadipate (DAA), the optical isomers of 2‐amino‐4‐phosphonobutyrate (APB) and L‐glutamate diethylester (GDEE). 5. In contrast, gamma‐D‐glutamylglycine (DGG), applied in amounts which affected quisqualate and kainate actions as well as those of NMA, was an effective synaptic antagonist whilst having no effect on the presynaptic fibre volley. 6. These results indicate that the synaptic receptor in the Schaffer collateral‐commissural pathway may be of the kainate or quisqualate type. Although NMA receptors do not appear to be involved in normal synaptic transmission in this pathway they may play a role in synaptic plasticity. The interaction of L‐glutamate and L‐aspartate with these receptors is discussed.
Electrophysiological properties of rat spinal dorsal horn neurones in vitro: calcium‐dependent action potentials.
Authors: Murase K , Randić M
Published: December 2014

1. The electrophysiological properties of dorsal horn neurones have been investigated in the immature rat in vitro spinal cord slice preparation. 2. Intracellular recordings from dorsal horn neurones show that direct or orthodromic stimulation generates action potentials followed by a brief after‐hyperpolarization. Synaptic potentials were elicited by the activation of primary afferent fibres in the dorsal root. 3. Input resistance for dorsal horn neurones ranged from 48 to 267 M omega, and the membrane time constant was in the range of 4‐19 ms. 4. In response to strong depolarizing currents dorsal horn neurones perfused with TTX and TEA frequently exhibit a slow regenerative depolarizing potential followed by a slow after‐hyperpolarization. The depolarizing potential probably results from an influx of Ca. It is blocked by low concentration Ca, Co or Mn, and enhanced by high levels of extracellular Ca. 5. There is, in addition, a low‐threshold Ca‐dependent response which is activated at membrane potentials more negative than ‐65 mV and has a maximum rate of rise at the polarization level of about ‐80 mV. 6. The addition of Ba or TEA to the perfusing medium provided support for the Ca‐dependence of the low‐ and high‐threshold responses, and the lack of fast inactivation of the high‐threshold Ca potential.
Breathing in fetal lambs: the effect of brain stem section.
Authors: Dawes G S , Gardner W N , Johnston B M , Walker D W
Published: December 2014

The effects of section of the brain stem caudally (through the upper pons or mid‐collicular) or rostrally (through the caudal hypothalamus or anterior commissure‐suprachiasmatic nucleus) were studied in fetal lambs from 118 days gestation, after recovery in utero. In lambs sectioned caudally, breathing movements and electrocortical activity were dissociated. After some days recovery breathing tended to become continuous, with an abnormal prolongation of inspiratory time. Isocapnic hypoxia caused an increase in the rate and amplitude of breathing. After carotid denervation hypoxia still caused an increase in the amplitude of breathing. In lambs sectioned rostrally, there was also dissociation between breathing movements and electrocortical activity. Breathing remained episodic, with an incidence similar to that of intact fetal lambs. In two lambs after 10 days of recovery the breathing and electrocortical rhythms returned, from time to time, to their normal phasic relationship. Isocapnic hypoxia caused a diminution or arrest of breathing, as in intact lambs. The cardiovascular effects of transection were examined. Baroreflex sensitivity was normal in those lambs sectioned caudally and enhanced in those sectioned rostrally. It is concluded first that as a result of rostral section, independent episodic rhythms of fetal breathing and electrocortical activity can be dissociated. Secondly, moderate isocapnic hypoxia causes arrest of fetal breathing indirectly, requiring the integrity of a suprapontine mechanism. And thirdly, after caudal section of the brain stem, hypoxia causes enhancement of fetal breathing efforts, independently of the carotid chemoreceptors. Possible mechanisms are discussed.
Temperature‐dependent transitions in isometric contractions of rat muscle.
Authors: Ranatunga K W , Wylie S R
Published: December 2014

The effect of temperature on tetanic tension development was examined in extensor digitorum longus (fast‐twitch) and soleus (slow‐twitch) muscles of the rat, in vitro and with direct stimulation. The temperature range was from 35 to 10 degrees C. 2. The maximum tetanic tension decreased slightly on cooling from 35 to 25 degrees C. Cooling below 20 degrees C resulted in a marked depression of tetanic tension. The results were similar in the two muscles. 3. Analysis (in the form of Arrhenius plots) of the rate of tetanic tension development and relaxation clearly showed the occurrence of two phases in their temperature dependence, due to an increased temperature sensitivity below about 25 degrees C. Arrhenius activation energy estimates for temperatures lower than 21 degrees C were around twice as high as those for temperatures higher than 24 degrees C in both muscles.