bluuebunny/crossref_metadata_2025 huggingface dataset:
Reserpine, vagal adrenergic activity and stress‐induced acute gastric mucosal injury in the rat.
Authors: Salim A S
Published: December 2014

1. Stress activates the hypothalamus causing central adrenergic discharge and stimulation of the autonomic sympathetic system. Reserpine produces the same effect and, therefore, its acute gastric mucosal injury is stress‐induced. This injury was employed in the gastric diversion rat, a model for determining gastric acid secretion under basal conditions, to examine the relationship of the vagus nerve to the autonomic sympathetic system in the mechanism of stress‐induced acute gastric mucosal injury. 2. After 6 h of reserpine (5 mg/kg I.P.), all rats developed oval or round lesions confined to the glandular stomach and of no constant relationship to rugal crests (lesion score 29 +/‐ 2.7 mm2, mean +/‐ S.E., n = 10). Microscopically, these lesions were vascular in origin, developing as intramural foci of haemorrhage or necrosis and expanding to communicate with the lumen. Pre‐treatment with potent antisecretory doses of the anticholinergic atropine (5 mg/kg I.P.) or the H2‐receptor antagonist cimetidine (40 mg/kg I.P.) did not influence this reserpine action (28 +/‐ 3 mm2 and 27.5 +/‐ 2.3 mm2, respectively, mean +/‐ S.E., n = 10). Protection against the reserpine lesions by the alpha‐adrenoceptor blocking drugs phenoxybenzamine or phentolamine given in a dose of 10 mg/kg I.P. was significantly (P less than 0.01) more than that afforded by the 5 mg/kg I.P. dose. However, the 15 mg/kg I.P. dose was completely protective against the lesions. Vagotomy had a similar protective effect. Interruption of autonomic sympathetic delivery to the stomach by coeliac ganglionectomy had no influence on the macroscopic or microscopic effects of reserpine on the stomach (30.5 +/‐ 3.4 mm2, mean +/‐ S.E., n = 10). 3. The H+ output associated with 6 h of gastric diversion (61 +/‐ 4.5 mumol, mean +/‐ S.E.) was significantly (P less than 0.001) depressed by reserpine alone (26 +/‐ 2 mumol) or with atropine (19 +/‐ 1.8 mumol) or cimetidine (21 +/‐ 2 mumol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dose‐dependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 +/‐ 4.1 mumol and 60.3 +/‐ 2.8 mumol vs. 61 +/‐ 4.5 mumol). Vagotomy protection was associated with an H+ output significantly (P less than 0.001) lower than that with reserpine alone (14 +/‐ 1.4 mumol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Burst kinetics of sodium channels which lack fast inactivation in mouse neuroblastoma cells.
Authors: Quandt F N
Published: December 2014

1. The kinetics of the slow inactivation process of Na+ channels were examined by recording single‐channel currents from cultured neuroblastoma cells. 2. In order to directly examine slow inactivation, fast inactivation was first removed irreversibly by briefly exposing the internal surface of excised membranes to papain. Following treatment, the time constant for the inactivation of averaged membrane Na+ current increased by over two orders of magnitude, while the open time of individual channels increased by a factor of three. The two effects are consistent with the idea that papain can selectively remove fast inactivation of Na+ channels. 3. In the absence of fast inactivation, Na+ channels continued to open during maintained depolarization of the membrane to potentials less negative than ‐60 mV. Under these conditions, the opening occurred in bursts 50 ms to hundreds of milliseconds long, followed by silent periods lasting many seconds. The average burst length was found to be equal to the time constant of the decline in average evoked current measured at the same potential, indicating that a burst was terminated by entry of the channel into the slow inactivated state. 4. Histograms of open times revealed two populations of open states at any potential. Bursts could also be classified as either short or long bursts. Bursts appeared to be due to the gating of a single channel, and long bursts contained both types of open states, suggesting that a Na+ channel could have more than one open state. 5. The kinetics of bursts of Na+ channels were voltage dependent. As the membrane was depolarized, the burst length, interval between bursts, and open time all increased. Although the probability of an open channel during a burst increased to almost 1.0 with depolarization, any channel was open less than 0.5% of the time when measured throughout the depolarization. The increase in burst duration with depolarization would occur if the rate of slow inactivation is faster from closed states of the channel than from open states. 6. Records of membrane current evoked by a series of step depolarizations were clustered into those with openings of Na+ channels and those without openings. Records in which a channel did not inactivate during the depolarization were less likely to lead to hibernation, suggesting that this phenomenon is caused by the slow inactivation process.
Ganglion cell performance at absolute threshold in toad retina: effects of dark events in rods.
Authors: Copenhagen D R , Donner K , Reuter T
Published: December 2014

1. The performance of ganglion cells in detecting flashes of light near the absolute threshold was studied in an isolated eye‐cup preparation of toad retina. Retinal ganglion cells, through which all visual information from the rods must flow to the brain, are in a key position for evaluating the still unproven hypothesis that the absolute light sensitivity is limited by rod noise (Barlow, 1956). 2. The dark‐adapted threshold intensity for these cells, which were selected on the basis of their high sensitivity, averaged 0.029 Rh* flash‐1 (range 0.008‐0.062), where Rh* signifies one photoisomerization per rod. On average, 46 photoisomerizations were needed per receptive field per flash to evoke a threshold response (range 16‐84). 3. In the threshold region, frequency of responses versus mean flash intensity was determined. Threshold performance could be described by theoretical frequency of response curves, allowing intrinsic noise to be estimated in terms of an equivalent rate of photoisomerization‐like (dark) events. In two completely characterized cells the rate of dark events corresponded to 0.03 and 0.06 Rh*DS‐1, where Rh*D signifies one dark event per rod. 4. Threshold elevations produced by dim backgrounds were studied. The results of these experiments are consistent with a dark event rate equivalent to 0.046 Rh*DS‐1, or 0.037 Rh*DS‐1 after correcting for a probable decrease in summation time. 5. The rate of actual dark events (0.028 Rh*DS‐1, 20 degrees C) measured in Bufo rods (Baylor, Lamb & Yau, 1980) is close to the equivalent rates determined here. Thus, for the ganglion cells signalling the dimmest lights, the dark events in rods appear to be the most significant intrinsic retinal noise source limiting detection.
Optical recording of electrical activity from parallel fibres and other cell types in skate cerebellar slices in vitro.
Authors: Konnerth A , Obaid A L , Salzberg B M
Published: December 2014

1. A reliable and simple fish brain slice preparation was obtained from the cerebellum of the skate, and its properties were described. 2. A potentiometric oxonol dye, RH‐482, and multiple site optical recording of transmembrane voltage (MSORTV) were used to reveal the electrophysiological properties of the parallel fibre action potential and to measure its conduction (0.13 m/s). The parallel fibre action potential was blocked in the presence of tetrodotoxin (TTX) and prolonged by tetraethylammonium (TEA), suggesting that the upstroke depends upon sodium entry and the repolarization upon potassium efflux. An after‐hyperpolarization results from a calcium‐dependent potassium conductance. 3. A second potentiometric dye, RH‐155, differing only slightly from RH‐482, exhibited a high affinity for glial cell membrane, and could be used to monitor changes in extracellular potassium concentration by detecting changes in glial membrane potential. 4. Calcium channel blockers such as cadmium ions blocked the optical signal that reflected the extracellular accumulation of potassium. 5. Interventions that modified the extracellular volume, and thereby affected the accumulation of potassium, produced large changes in the optical signal that monitored glial depolarization. Hypertonic and hypotonic bathing solutions resulted in decreases and increases, respectively, in the magnitude of the extrinsic absorption change that tracked potassium accumulation. 6. Blocking sodium‐potassium pump activity by means of ouabain prolonged the time course of the optical signal that was related to potassium accumulation in the extracellular space. 7. Extracellular potassium accumulation was revealed to be critically dependent upon intracellular calcium ions.
The nutritional regulation of plasma prostaglandin E concentrations in the fetus and pregnant ewe during late gestation.
Authors: Fowden A L , Harding R , Ralph M M , Thorburn G D
Published: December 2014

1. The effects of nutrient availability on the plasma concentrations of prostaglandin E (PGE) were investigated in chronically catheterized ewes and their fetuses during late gestation by varying dietary intake and by experimental manipulation of the fetal plasma concentration of glucose. The aim of the study was to determine whether varying the glucose level altered the fetal and maternal concentrations of plasma PGE. 2. Basal plasma concentrations of PGE increased with increasing gestational age in both the fetus and ewe. Fetal plasma concentrations of PGE were positively correlated with the corresponding uterine venous concentrations throughout the period of study. There was also a significant venous‐‐arterial difference in plasma PGE concentration across the uterus at all gestational ages studied. 3. Withdrawal of food but not water for 48 h increased the plasma PGE concentration in all the fetuses studied irrespective of gestational age. In the pregnant ewe, the effects of fasting depended on gestational age. Before 130 days, fasting only increased the uterine venous concentration of plasma PGE, while after 130 days there were significant increases in both maternal arterial and uterine venous concentrations of plasma PGE. There was also a significant widening of the uterine venous‐‐arterial difference in plasma PGE concentration during fasts begun after 130 days of gestation. Refeeding the fasted animals restored the plasma PGE levels to normal values within 24 h in both the fetus and ewe. 4. The normal daily feeding regime had no apparent effect on plasma PGE concentrations before 130 days of gestation. However, in animals nearer to term, there were significant reductions in plasma PGE in the fetus and uterine vein in the 3‐6 h period after feeding. 5. The changes in plasma PGE levels during fasting and in response to the normal daily feeding regime were correlated to the changes in plasma glucose level observed in the fetus. The slope of the line relating the changes in the fetal concentrations of plasma PGE and glucose was significantly steeper in animals older than 130 days than earlier in gestation. 6. Fetal hypoglycaemia induced by fetal infusion of insulin increased fetal concentrations of plasma PGE without any apparent change in maternal plasma PGE values. In contrast, fetal hyperglycaemia produced by infusion of glucose into the fetus had little effect on plasma PGE levels in utero. 7. The results demonstrate that nutrient availability can influence uterine output and plasma concentrations of PGE in the fetus and pregnant ewe.(ABSTRACT TRUNCATED AT 400 WORDS)
The electrophysiological effects of vasoactive intestinal polypeptide in the guinea‐pig inferior mesenteric ganglion.
Authors: Love J A , Szurszewski J H
Published: December 2014

1. The effects of vasoactive intestinal polypeptide (VIP) on the inferior mesenteric ganglion of the guinea‐pig were studied in vitro. 2. In 67% of the neurones tested, application of VIP (1‐7.5 X 10(‐5) M) by pressure ejection caused a depolarization of the membrane potential which averaged 8.6 +/‐ 0.4 mV. 3. In 52% of the cells that were responsive to VIP, the membrane depolarization was accompanied by a decrease in membrane input resistance. In another 48% of the cells tested, there was an increase in membrane input resistance. 4. Membrane depolarization caused by VIP enhanced the excitability of post‐ganglionic neurones and converted subthreshold electrotonic and subthreshold synaptic potentials to action potentials. 5. The effects of VIP persisted during nicotinic and muscarinic synaptic blockade. The effects of VIP also persisted in a low‐Ca2+, high‐Mg2+ solution. Thus, the site of action of VIP was on the postsynaptic membrane. 6. Electrical stimulation of the lumbar colonic nerves evoked a slow noncholinergic depolarization of the membrane potential. 7. VIP appeared to be one of the transmitters involved in the electrically evoked e.p.s.p. because both prior desensitization with exogenous VIP and VIP antiserum reduced the amplitude of the slow, non‐cholinergic e.p.s.p. 8. Radial distension of a segment of colon attached to the inferior mesenteric ganglion (i.m.g.) evoked a non‐cholinergic depolarization of the membrane potential in neurones in the i.m.g. 9. The distension‐induced non‐cholinergic depolarization was reduced by VIP antiserum. 10. The data support the hypothesis that a population of the mechanosensory afferent nerves running between the colon and the i.m.g. utilize VIP or a VIP‐like peptide as a transmitter to modulate reflex activity between the colon and the i.m.g.
Saccadic eye movements evoked by microstimulation of lobule VII of the cerebellar vermis of macaque monkeys.
Authors: Fujikado T , Noda H
Published: December 2014

1. Oculomotor responses to microstimulation of the cerebellar vermis were studied on macaque monkeys by measuring eye position with a magnetic search‐coil method. 2. Vermal microstimulation resulted in conjugate eye movements. Analyses of amplitude‐velocity and amplitude‐duration relationships revealed that although the peak velocities were slightly faster, the durations of these responses were comparable to those of spontaneous and visually guided saccadic eye movements (saccades). 3. Systematic mapping with microstimulation revealed that the low‐threshold sites were localized in the white matter of a limited number of folia in the posterior vermis. The low‐threshold region from which saccades could be evoked with stimulus intensities less than 10 microA was confined to lobule VII in seven monkeys; in the other five monkeys it included a posterior part of lobule VI (folium VIc). This region coincided with the distribution of saccade‐related neural activity observed in the present study and corresponded to the vermal folia from which we previously recorded the burst mossy fibre units and the oculomotor Purkinje cell activity (Kase, Miller & Noda, 1980). 4. Microstimulation of most sites in the oculomotor vermis evoked saccades in oblique directions and the horizontal component of the saccade was always ipsilateral to the stimulation side. In penetrations through the paramedian vermis, the direction of the saccade changed gradually from upward oblique to downward oblique as the electrode was advanced vertically across lobule VII. The vertical component was dominant in these saccades. When the stimulation track was systematically shifted from the medial to the lateral part of the vermis, the horizontal component of the saccade increased and the vertical component decreased gradually until the saccade became almost horizontal. 5. The direction of saccades changed with the stimulus intensity; thus the topographical change in the direction of a saccade was consistent only when the stimulus intensity was adjusted to the threshold for every stimulus site. When stimulated with near threshold intensities, the evoked saccades were very seldom straight: the trajectories were curved in the responses observed at most vermal sites. The horizontal and vertical components of these saccades showed different onset latencies, durations, and peak‐velocity latencies. Increasing the stimulus current produced differing effects on the two components of the saccades.(ABSTRACT TRUNCATED AT 400 WORDS)
Respiratory interneurones in the thoracic spinal cord of the cat.
Authors: Kirkwood P A , Munson J B , Sears T A , Westgaard R H
Published: December 2014

1. The discharges of spontaneously firing neurones, whose activity was modulated in phase with the central respiratory cycle, were recorded in the thoracic ventral horn (T3‐T9) of anaesthetized, paralysed cats. 2. Out of 310 neurones, forty‐six were positively identified as motoneurones by antidromic activation or spike‐triggered averaging, fifty‐four were positively identified as interneurones by antidromic activation from other spinal cord segments and ninety were indirectly identified as interneurones by virtue of their positions or firing rates as compared to the motoneurones. 3. Units were classified as inspiratory (64%), expiratory (25%) or post‐inspiratory (7%) according to the times of their maximum firing rates. The remaining 4% consisted of units whose discharges were either strongly locked to the respiratory pump cycle or did not fit into the other categories. All but one of the motoneurones were classified as inspiratory or expiratory. 4. Inspiratory and expiratory units were further classified as early, late or tonic according to the starting times of their discharges in the respiratory cycle. The interneurones (both positively and indirectly identified) included more of the early and tonic categories and more fast‐firing units than did the motoneurones in both the inspiratory and expiratory groups. 5. The locations of the motoneurones corresponded to the known positions of the intercostal and interchondral motor nuclei, including clear segregation of inspiratory and expiratory populations. The locations of neither the interneurones nor the unidentified units were segregated according to their firing patterns. These neurones were concentrated in the medial half of the ventral horn and were found generally more dorsally than the positions of the motoneurones, though their positions overlapped considerably with this group. 6. The axons of the positively identified interneurones were identified from one to five segments caudally and mostly contralaterally, but were not traced to their terminations. Some axons were located by microstimulation and found to run in the ventral or ventromedial white matter. Conduction velocities covered a wide range, 8 to around 100 m/s, mean 53 m/s. 7. Preliminary calculations indicate that there may be almost 10 times more respiratory thoracic interneurones as respiratory bulbospinal neurones.(ABSTRACT TRUNCATED AT 400 WORDS)
The influence of intracellular calcium concentration on degranulation of dialysed mast cells from rat peritoneum.
Authors: Neher E
Published: December 2014

1. Mast cells, isolated from rat peritoneum, were studied under tight‐seal, whole‐cell recording conditions. Membrane conductance, membrane capacitance and the concentration of free intracellular Ca2+, [Ca2+]i, were measured simultaneously. 2. [Ca2+]i could be accurately buffered to values between 0 and 1.5 microM only if relatively high concentrations of calcium buffers (in the millimolar range) were added to the pipette filling solution against which the cytoplasm was dialysed. At lower buffer concentrations [Ca2+]i was markedly increased by hyperpolarizing the membrane. 3. When added to the pipette, guanosine‐3‐thio‐triphosphate (GTP‐gamma‐S), a nonhydrolysable analogue of guanosine triphosphate, stimulated a 3.3‐fold increase in membrane capacitance, which is indicative of mast cell degranulation (Fernandez, Neher & Gomperts, 1984). 4. In weakly buffered cells, GTP‐gamma‐S also induced a transient increase in [Ca2+]i which, usually, preceded degranulation. Calcium buffers at 1‐5 mM concentration suppressed this transient. 5. High [Ca2+]i alone did not induce degranulation. However, it markedly accelerated GTP‐gamma‐S‐induced degranulation. When [Ca2+]i was buffered to zero, an appreciable fraction of cells degranulated in response to GTP‐gamma‐S, but very slowly, and only after a long lag phase. 6. Transient increases in [Ca2+]i, evoked either by GTP‐gamma‐S, or by voltage changes, did not elicit capacitance changes during the lag phase, but accelerated the GTP‐gamma‐S‐induced degranulation response at later times. 7. Internally applied inositol 1,4,5‐trisphosphate (IP3) also induced transient increases in [Ca2+]i which did not lead to secretion in the absence of GTP‐gamma‐S. 8. It is concluded that an increase in [Ca2+]i is neither necessary nor sufficient for secretion from dialysed mast cells. [Ca2+]i, however, acts synergistically with other stimuli to promote secretion. It is the more efficient the more time the other stimulus had been allowed for priming the cell.
The influence of the sympathetic outflow on aortic chemoreceptors of the cat during hypoxia and hypercapnia.
Authors: Anand A , Paintal A S
Published: December 2014

1. An attempt has been made to reconcile differing observations, made by different groups of investigators, on the responses of aortic chemoreceptors of cats during normoxia, hypoxia and hypercapnia. 2. In cats anaesthetized with sodium pentobarbitone it was observed that during hypoxic stimulation of twelve chemoreceptors, an intravenous injection of about 20 mg sodium pentobarbitone produced hypotension which was accompanied by an initial fall in chemoreceptor activity instead of the expected increase that invariably occurred in all the receptors when hypotension was produced mechanically by distending a balloon in the right atrium (twenty‐six during normoxia, eleven during hypoxia and eight during hypercapnia). 3. In twelve receptors a reflex fall in blood pressure produced by injecting 8‐25 micrograms veratridine (Bezold‐Jarisch reflex) yielded results qualitatively similar to those following injection of sodium pentobarbitone. 4. In sixteen out of twenty‐five chemoreceptors it was observed that ventilating the cat with 5.6‐6.7% CO2 produced either no or little increase in activity; in nine receptors there was a clear increase in activity, which fell initially or was abolished after injecting a single dose of 20 mg sodium pentobarbitone. 5. In all seven chemoreceptors tested in seven deeply anaesthetized cats it was found that a larger dose (about 50‐60 mg) of sodium pentobarbitone had no direct depressant effect on aortic chemoreceptor activity. It followed that the initial depressant effect of the much smaller doses of sodium pentobarbitone observed during hypoxic and hypercapnic stimulation (see above) must be due to reduction in the sympathetic outflow to the aortic bodies. This conclusion was supported by the results following injections of veratridine. 6. By comparing the present results with those reported previously it was concluded that the variations in the responses of aortic chemoreceptors during hypoxia and hypercapnia reported by different investigators could be partly due to variations in the level of sympathetic activity prevailing under different experimental conditions.
The transport and metabolism of naturally occurring pyrimidine nucleosides by isolated rat jejunum.
Authors: Bronk J R , Hastewell J G
Published: December 2014

1. Uridine perfused through the lumen of isolated loops of rat jejunum over a concentration range of 0.1‐1.0 mM gave rise to higher serosal concentrations of uracil than the equivalent luminal concentration of uracil (P less than 0.001). No serosal uridine could be detected. 2. Luminal thymidine over a concentration range of 0.1‐0.5 mM gave rise to the same serosal concentration of thymine as the equivalent luminal concentration of thymine (P greater than 0.1). Low concentrations of serosal thymidine were detected. Both luminal thymidine and thymine gave rise to elevated levels of serosal uracil. 3. Luminal cytidine at concentrations of 0.1‐0.5 mM was poorly transported and yielded low serosal concentrations of cytidine. No serosal cytosine was detected, although elevated levels of uracil were found in the serosal secretions. 4. Cytosine over a luminal concentration range of 0.1‐0.5 mM gave rise to low concentrations of cytosine in the serosal secretions. These results were consistent with a passive diffusion model for cytosine transport. No increase in serosal uracil was detected. 5. The cleavage of uridine and thymidine to their respective pyrimidine bases occurred via a cytoplasmic nucleoside phosphorylase, which had a similar Michaelis constant (Km), (61.0 +/‐ 4.4 and 97.1 +/‐ 5.7 microM for uridine and thymidine, respectively) but a maximal velocity (Vmax) for uridine cleavage (320 +/‐ 32 nmol min‐1 (mg protein)‐1) 13 times that for thymidine cleavage (24.7 +/‐ 1.4 nmol min‐1 (mg protein)‐1). 6. The differences between the three pyrimidine nucleosides are discussed with reference to the interactions between their epithelial transport and metabolism.
Free‐calcium and force transients during depolarization and pharmacomechanical coupling in guinea‐pig smooth muscle.
Authors: Himpens B , Somlyo A P
Published: December 2014

1. Fura2 was loaded by permeation and hydrolysis of the acetoxymethyl ester into smooth muscle cells of intact thin sheets of the longitudinal layer of the small intestine of the guinea‐pig, to record Ca2+ transients during contraction. 2. Cytoplasmic Ca2+ ([Ca2+]i) was monitored by computing the ratio of the fluorescence signal excited at 340 and 380 nm wavelengths. The dye loading and the exposure to UV light required for the experiments had no significant effect on the contractile parameters observed. 3. Spontaneous, rhythmic increases in [Ca2+]i were often observed, preceding the onset of force. Removal of extracellular Ca2+ caused a very transient increase in [Ca2+]i accompanied by a phasic force transient; this was followed by a decline in [Ca2+]i and tension below control levels. Elevated Ca2+ from 1.2 to 15 mM also caused a fall in [Ca2+]i and a relaxation of basal tension. 4. Elevation of [K+]o increased [Ca2+]i. Graded concentrations of K+ caused graded changes in both fluorescence ratio and tension. 5. Carbachol evoked a transient increase in [Ca2+]i and contraction. Thereafter, in spite of the continued presence of the drug, both signals declined, presumably as the result of cholinergic desensitization. The initial phasic force response to carbachol was usually followed by an 'after‐contraction', that was only occasionally accompanied by a similar (small) secondary rise in the fluorescence signal. 6. In depolarized smooth muscle, both in the presence and in the absence of extracellular Ca2+, carbachol induced a transient increase in [Ca2+]i, indicating that Ca2+ release from intracellular stores is a major mechanism of pharmacomechanical coupling. 7. In some preparations an applied stretch caused, after a few seconds, a rise in [Ca2+]i and force development.
Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.
Authors: Rayner V C , Robinson I C , Russell J A
Published: December 2014

1. Acutely, opioids inhibit oxytocin secretion. To study the responses of oxytocin neurones during chronic opioid exposure, forty‐five lactating rats were infused continuously from a subcutaneous osmotically driven mini‐pump via a lateral cerebral ventricle with morphine sulphate solution from day 2 post‐partum for 5‐7 days; the infusion rate was increased 2‐ or 2.5‐fold each 40 h from 10 micrograms/h initially up to 50 micrograms/h; controls were infused with vehicle (1 microliter/h, twenty‐eight rats) or were untreated (eight rats). 2. Maternal behaviour was disrupted in 27% of the morphine‐treated rats; in rats that remained maternal morphine did not affect body weight or water intake but increased rectal temperature by 0.82 +/‐ 0.14 degrees C (mean +/‐ S.E.M.) across the first 4 days. 3. Weight gain of the litters of maternal morphine‐treated rats was reduced by 32% during 7 days, predominantly in the first day of treatment when milk transfer was also reduced. Observation of pup behaviour during suckling showed decreased frequency of milk ejections on only the second day of morphine treatment. Plasma concentration of prolactin after 6 days was similar in maternal morphine‐treated and control rats, but reduced by 90% in non‐maternal morphine‐treated rats, indicating normal control of prolactin secretion by suckling in morphine‐treated rats. 4. Oxytocin and vasopressin contents, measured by radioimmunoassay, in the supraoptic and paraventricular nuclei and in the neurohypophysis were similar between fourteen maternal morphine‐treated, twelve vehicle‐treated and eight untreated lactating rats; thus exposure to morphine did not involve increased production and storage of oxytocin. 5. Distribution of [3H]morphine infused intracerebroventricularly into six virgin female rats for 6 days was measured by scintillation counting of tissue extracts. Morphine concentration in the hypothalamus and neurohypophysis was 2.7 and 12.8 micrograms/g, respectively, and in blood plasma 0.75 micrograms/g. Tolerance was not due to failure of morphine infusion. In addition, naloxone (5 mg/kg s.c.) provoked typical withdrawal reactions ('wet dog' shakes, defaecation, burrowing) in lactating rats infused with morphine for 5 days. 6. Pups were suckled onto seven maternal morphine‐infused and five vehicle‐infused rats anaesthetized with urethane for recording of intramammary and arterial blood pressures after treatment for 5 days. The incidence and pattern of milk ejections, and mammary gland sensitivity to oxytocin were similar in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)
Human adaptation to repeated cold immersions.
Authors: Golden F S , Tipton M J
Published: December 2014

1. The present investigation was designed to examine human adaptation to intermittent severe cold exposure and to assess the effect of exercise on any adaptation obtained. 2. Sixteen subjects were divided into two equal groups. Each subject performed ten head‐out immersions; two into thermoneutral water which was then cooled until they shivered vigorously, and eight into water at 15 degrees C for 40 min. During the majority of the 15 degrees C immersions, one group (dynamic group) exercised whilst the other (static group) rested. 3. Results showed that both groups responded to repeated cold immersions with a reduction in their initial responses to cold. The time course of these reductions varied, however, between responses. 4. Only the static group developed a reduced metabolic response to prolonged resting immersion. 5. It is concluded that repeated resting exposure to cold was the more effective way of producing an adaptation. The performance of exercise during repeated exposure to cold prevented the development of an adaptive reduction in the metabolic response to cold during a subsequent resting immersion. In addition, many of the adaptations obtained during repeated resting exposure were overridden or masked during a subsequent exercising immersion.
Ionic basis of tetanic and post‐tetanic potentiation at a mammalian neuromuscular junction.
Authors: Nussinovitch I , Rahamimoff R
Published: December 2014

1. The ionic basis of tetanic and post‐tetanic potentiation (TP and PTP) was studied at the rat soleus neuromuscular junction (NMJ), using the miniature endplate potential (MEPP) frequency as an index for transmitter release. Conventional intracellular recording and computer‐assisted data analysis were employed. 2. The experimental results in this study indicate that contrary to previous suggestions, there is a substantial similarity in the ionic basis of TP and PTP at the mammalian and amphibian motor nerve terminals which can be subdivided into [Ca2+]o‐dependent and [Ca2+]o‐independent parts. 3. Tetanic and post‐tetanic increase in MEPP frequency at the rat soleus NMJ is similar to that at the frog NMJ in the following aspects: (i) Tetanic potentiation is substantially larger in calcium‐containing solutions than in calcium‐deficient solutions. About 90% of tetanic potentiation is contributed by extracellular calcium. (ii) Increase in [Mg2+]o reduces tetanic potentiation in calcium‐containing solutions and enhances TP in calcium‐defient solutions. Elevated [Mg2+]o prolongs the post‐tetanic potentiation both in calcium‐containing and in calcium‐deficient solutions. (iii) A post‐tetanic jump in MEPP frequency was observed in 44% of the experiments performed in calcium‐deficient solutions. (iv) The augmentation phase of post‐tetanic potentiation, evident in calcium‐containing solutions, is completely abolished by removal of [Ca2+]o. (v) Tetanic and post‐tetanic potentiations are enhanced by increasing the rate and duration of tetanic stimulation in calcium‐containing solutions. 4. The [Ca2+]o‐independent part of tetanic potentiation is presumably due to entry of sodium ions and their accumulation in the nerve terminal, since it is increased by measures known to inhibit the sodium pump: reduction in [K+]o and partial substitution of sodium by lithium. 5. Sodium ions contribute substantially to the [Ca2+]o‐independent part of posttetanic potentiation, since its duration is markedly prolonged by ouabain, reduction in [K+]o and partial substitution of sodium by lithium. 6. Tetanic potentiation is manifested earlier in calcium‐containing media than in calcium‐deficient media. This difference may indicate that sodium entry into the terminal during tetanic stimulation is at locations remote from the releasing sites. Alternatively, this time difference may be due to the delay between intracellular sodium accumulation and the increase in transmitter release.
Intrinsic properties of neurones in the dorsal cochlear nucleus of mice, in vitro.
Authors: Hirsch J A , Oertel D
Published: December 2014

1. Intracellular recordings were made from the dorsal cochlear nucleus (DCN) in slices of the cochlear nuclear complex. Probably the larger and most frequent cells were impaled. 2. The steady‐state current‐voltage (I‐V) properties of all cells impaled were nonlinear. The I‐V curve was steepest in the voltage range depolarized from the resting potential and most shallow when the cell was hyperpolarized from rest by more than about 10 mV. Thus, the inwardly rectifying I‐V characteristics of cells in the DCN distinguish them from those of ventral cochlear nuclear neurones (Oertel, 1983). 3. When depolarized with current, most cells fired trains of large, all‐or‐none action potentials. The undershoot after single spikes comprised an initial, fast component followed by a second, slower wave. A few cells (15%) generated bursts of smaller, graded spikes in addition to the large ones. 4. Repetitive firing evoked by depolarizing pulses of current was followed by an after‐hyperpolarization whose magnitude depended on the strength and duration of the preceding current pulse. 5. Blocking the large action potentials with tetrodotoxin (TTX) revealed Ca2+‐dependent spikes in all cells examined. 6. The steady‐state I‐V relationship became linear in the presence of TTX, suggesting that a persistent Na+ conductance probably mediates the inward rectification seen above the resting potential. 7. Muscarine at micromolar concentrations excited cells and increased their input resistance.
Chemoreceptor control of heart rate and behaviour during diving in the tufted duck (Aythya fuligula).
Authors: Butler P J , Stephenson R
Published: December 2014

1. The role of chemoreceptors in the control of heart rate and behaviour during diving activity in the tufted duck was investigated in two ways. In a closed‐loop experiment, ducks were exposed to ambient gas mixtures of varied composition during diving activity in an indoor tank. Characteristics of diving behaviour, heart rate and deep body temperature were monitored under hypoxic, hyperoxic and hypercapnic conditions and compared with those in air. Secondly, in an open‐loop experiment the role of the carotid body (CB) chemoreceptors in the control of the responses to altered inspired gas composition and in the cardiac responses to extended and enclosed dives (Stephenson, Butler & Woakes, 1986) was investigated by chronic bilateral denervation of these receptors. 2. Heart rate during submersion was unaffected by inspired gas composition in control (data from intact and sham‐operated ducks combined) and CB‐denervated ducks, though diving behaviour was significantly modified in both groups of animals in response to altered inspired gas composition. Hypoxia and hypercapnia resulted in an increase in the proportion of total diving time spent breathing at the surface. The main effect of hypoxia (9‐10% O2) was to reduce dive duration in control ducks and this effect was almost completely abolished after CB denervation. Hypercapnia (5‐6% CO2) reduced dive duration less markedly than hypoxia but it greatly increased the duration of the inter‐dive interval, effects which were not significantly influenced by CB denervation. Hyperoxia (40‐45% O2) had very little effect on either behaviour or heart rate during diving, although deep body temperature was significantly elevated in this gas mixture during diving activity. There was also a less marked, but nevertheless significant, apparent hyperthermia during diving activity in air on an indoor tank but not on an outdoor pond. Conversely, there was a significant apparent hypothermia during diving activity under hypoxic conditions. 3. The CB chemoreceptors were shown to play a role in cardiac control during diving under certain circumstances. The duration of pre‐dive tachycardia was significantly increased in hypoxia and this increase was abolished after CB denervation. The rate of development of bradycardia during extended and enclosed dives was slowed following CB denervation, though the initiation of the responses in extended and enclosed dives and the eventual attainment of sub‐resting heart rates in enclosed dives were not prevented, indicating that other, as yet unidentified, sensory inputs are involved in cardiac control under these conditions.
The morphology and projections of dorsal horn spinocerebellar tract neurones in the cat.
Authors: Edgley S A , Gallimore C M
Published: December 2014

1. The morphology of dorsal horn neurones located in the mid‐lumbar segments of the spinal cord and which have an axonal projection to the cerebellum has been investigated. The neurones were identified by antidromic activation from the cerebellum and by their characteristic input from group II afferents as described in the preceding paper (Edgley & Jankowska, 1988). 2. The cell bodies of the neurones were distributed across the width of the spinal cord in laminae IV and V, but particularly at the border between these laminae. Most were in the caudal half of the fourth lumbar segment (L4), caudal to Clarke's column. However, neurones of this type were encountered as far caudal as the middle of the fifth lumbar segment (L5) and as far rostral as the middle of the third lumbar segment (L3). 3. The morphology of the neurones was investigated following intracellular staining with horseradish peroxidase (HRP). Fourteen well‐filled cells were recovered. They had large somata and extensive dendritic arborizations within the dorsal horn which could extend more than 2 mm rostro‐caudally. The most dense arborization was in laminae III and IV, just dorsal to the cell bodies. 4. The axons of all fourteen cells could be followed well into the white matter. All of them passed into the dorsal part of the ipsilateral lateral funiculus where they ascended. All followed a similar indirect course through the grey matter. Despite careful inspection, initial axon collaterals were never found. 5. All of the neurones were antidromically activated by low‐intensity electrical stimulation of the dorsolateral part of the ipsilateral lateral funiculus in the thoracic region and from the cerebellum. The conduction velocities of the axons ranged from 62 to 112 m s‐1 (mean 84.2 (S.D. +/‐ 10.1) m s‐1). 6. The axonal terminations of some neurones were investigated by mapping the most effective locations for antidromic activation from the cerebellar cortex. Most neurones were activated with lowest stimulus intensities from the rostral part of the anterior lobe. A second effective area was found in the posterior lobe, deep to the paramedian lobule. The majority of neurones were activated from both locations, suggesting that their axons branched to terminate in both areas. 7. On the basis of their projection and termination, it is proposed that the axons of these dorsal horn spinocerebellar tract neurones contribute to the dorsal spinocerebellar tract (DSCT).
Changes in perceived heaviness and motor commands produced by cutaneous reflexes in man.
Authors: Aniss A M , Gandevia S C , Milne R J
Published: December 2014

1. This study examined the relationship between the perceived heaviness of a weight and reflexes acting on the motoneurones required for the contraction. The perceived heaviness of low (100 g) and high (500 g) reference weights lifted by the first dorsal interosseous muscle was estimated using a matching task. Weights were also lifted during stimulation of the digital nerves of the index finger at two times and four times sensory threshold (T). Averages of force and EMG were also made when isometric forces of 100 and 500 g were maintained. 2. Stimuli at 4T produced a significant increase in perceived heaviness in each subject for both reference weights. Averages of EMG made under isometric conditions showed a short‐latency inhibition with a reflex reduction in force following single stimuli. This inhibition was also observed during weight lifting when trains of stimuli were given. 3. Stimuli at 2T produced less‐marked changes in EMG, averaged force, and perceived heaviness for individual subjects. However, for the group of subjects, perceived heaviness declined significantly with 2T stimuli for the 500 g but not the 100 g weight. This decrease in perceived heaviness was associated with evidence of short‐latency facilitation within the motoneurone pool. 4. Inhibition of the motoneurone pool was associated with an increase and facilitation with a decrease in perceived heaviness. These observations favour a role for a signal of centrally generated motor command in the sensation of heaviness and provide insight as to how this signal must change when reflex inputs change and when high‐threshold motoneurones are recruited.
Membrane current responses of NG108‐15 mouse neuroblastoma x rat glioma hybrid cells to bradykinin.
Authors: Brown D A , Higashida H
Published: December 2014

1. Membrane current responses to focal application of bradykinin (BK) were recorded in voltage‐clamped NG108‐15 neuroblastoma x glioma hybrid cells. 2. BK produced sequential outward and inward currents at clamp potentials between ‐60 and ‐30 mV, designated IBK(out) and IBK(in), respectively. 3. The outward current IBK(out) was accompanied by an increased membrane conductance. Ramp current‐voltage (I‐V) curves yielded a reversal potential (VBK) of ‐80 +/‐ 5.6 mV (mean +/‐ S.D., n = 9) in 5.4 mM [K+]o. VBK showed a positive shift on raising [K+]o, compatible with a primary increase in K+ conductance. Subtracted I‐V curves indicated that the underlying conductance was not strongly voltage dependent between ‐120 and ‐40 mV. 4. IBK(out) was inhibited by d‐tubocurarine (dTC, 0.1‐0.5 mM) but was insensitive to tetraethylammonium (TEA) below 5 mM. 5. The inward current IBK(in) was accompanied by a fall in membrane conductance. This was associated with the inhibition of a time‐ and voltage‐dependent K+ current, IM. In consequence, IBK(in) was strongly voltage dependent and dissipated, usually without reversal, on hyperpolarizing the cell beyond ‐70 mV in 5.4 mM [K+]o. Reversal to an outward current negative to ‐40 mV could be obtained on raising [K+]o to 54 mM. 5. Both IBK(in) and IBK(out) persisted when ICa was blocked with Co2+ or Cd2+. IBK(out) slowly diminished in Ca2+‐free, Mg2+‐substituted solution. 6. The Ca2+ spike current ICa and the Ca2+‐activated K+ current IAHP were inhibited during IBK(out) or after Ca2+ injections. BK did not affect the voltage‐activated K+ current IK(V) recorded in Co2+ solution. 7. It is concluded that the dual response to BK results from opposing effects on two different species of K+ current. IBK(out) results from activation of a Ca2+‐dependent, voltage‐insensitive K+ conductance, probably mediated by a transient rise in intracellular Ca2+. It is suggested that the Ca2+ is released from an intracellular store. IBK(in) results primarily from inhibition of the Ca2+‐independent, voltage‐gated K+ current, IM. This effect is not replicated by a rise of intracellular Ca2+ and must therefore be generated by another mechanism.
Dynamic characteristics of optokinetically controlled eye movements following inferior olive lesions in the brown rat.
Authors: Hess B J , Savio T , Strata P
Published: December 2014

1. The inferior olive was destroyed by the drug 3‐acetylpyridine in brown rats. Spontaneous and optokinetic eye movements in response to constant‐velocity rotation (5‐80 deg/s) or sinusoidal oscillations (0.05 and 0.1 Hz with 15 deg/s peak velocity and 0.3, 0.5, 1.0 and 2 Hz with 5 deg/s peak velocity) of the visual surround were recorded 4‐6 days, 40‐50 days and 3‐4 months after the lesion using the magnetic search coil technique. 2. Persistent oculomotor deficits were observed in rats with a lesion of more than 97% of inferior olive neurones. In cases with a less complete lesion, no or only transient deficits were observed. In these latter cases the bulk of surviving neurones was located in the caudal half of the inferior olive, which includes the dorsal cap of Kooy. 3. Eye position holding after saccadic gaze shifts in the light was strongly deficient, showing pronounced postsaccadic centripetal drift for several hundred milliseconds. Similar deficits were observed in slow‐phase components following quick phases of optokinetic nystagmus. In the dark, eye position holding was also deficient. 4. Closed‐loop gains of optokinetic step responses obtained from rats with inferior olive lesions could be as good as those obtained from control animals. There was, however, a trend towards smaller gain values over the range of stimulus velocities tested. The duration of optokinetic after‐nystagmus was not changed. 5. The initial fast rise of slow‐phase velocity of optokinetic step responses was reduced by about 30‐50%, showing no recovery in the follow‐up experiments up to 3‐4 months after the lesion. 6. Optokinetic responses to sinusoidal oscillations of the visual surround exhibited an increasing drop in gain for frequencies between 0.1 to 0.5 Hz. In the range of 0.5‐2.0 Hz gain was only about 0.2 compared to 0.7‐0.8 in control animals. Phase lag of sinusoidal responses was shifted to larger values by about 25‐35 deg for frequencies increasing from 0.1 to 0.5 Hz. At 1.0 Hz phase shift was reduced to about 15 deg and at 2.0 Hz no significant change in phase was observed. Both gain and phase of sinusoidal responses showed some recovery when tested 3‐4 months after inferior olive lesion. 7. The results suggest that inferior olive lesions impair velocity‐to‐position integration, mainly as a consequence of the missing climbing fibre input to the cerebellar flocculi.(ABSTRACT TRUNCATED AT 400 WORDS)