bluuebunny/crossref_metadata_2025 huggingface dataset:
A morphological study of the axons and recurrent axon collaterals of cat alpha‐motoneurones supplying different functional types of muscle unit.
Authors: Cullheim S , Kellerth J O
Published: December 2014

1. Cat alpha‐motoneurones supplying muscle units of the soleus S type and gastrocnemius S, FR and FF types were injected intracellularly with horseradish peroxidase. 2. Ten alpha‐motoneurones of each motor unit type were collected for morphological analysis of the intramedullary parts of their axonal systems including the recurrent axon collaterals. 3. The alpha‐motor axon diameters in the spinal cord white matter were significantly smaller for the soleus motor units (mean = 5.2 micrometer) than for the gastrocnemius S units (mean = 6.4 micrometer), which in turn differed significantly from those of the gastrocnemius FR (mean 7.4 micrometer) and FF (mean = 7.3 micrometer types. 4. The number of axon collateral outbulgings, interpreted as synaptic terminals, which originated from the soleus motor axons (mean = 27.8) was significantly smaller, white that of the gastrocnemius FF motor axons (mean = 98.1) was significantly larger, than the number of outbulgings from the gastrocnemius S (mean = 44.4) and FR (mean = 53.8) motor axons. The latter two types were not significantly different. 5. In transverse sections the axon collateral outbulgings were found not only in the classical Renshaw cell area ventromedial to the main motor nuclei but also within the homonymous motor nucleus. However, only some of the neurones projected to the latter area. Rostrocaudally, the outbulgings were distributed within a distance of less than 1 mm around the position of the parent cell bodies. 6. Some physiological implications of the observed differences between axon collateral systems of various functional types of alpha‐motoneurones were discussed in relation to the present knowledge of the effects of the recurrent axon collaterals during different types of involuntary and voluntary activation of the alpha‐motoneurones.
Kinetic properties of normal and perturbed axonal transport of serotonin in a single identified axon.
Authors: Goldberg D J , Schwartz J H , Sherbany A A
Published: December 2014

1. The axonal transport of pulses of [3H]serotonin was studied in an axon of the serotonergic giant cerebral neurone (GCN) of Aplysia californica. 2. [3H]serotonin was transported as a discrete peak which was followed by a relatively low, smooth trail. 3. The peak broadened as it moved along the axon, sometimes skewing in the proximal direction. 4. The velocity of the transport was highly dependent on temperature, but the rate of peak broadening was not. The velocity was 130 mm per day at 23 degrees C and 48 mm per day at 14 degrees C. The rate of broadening was 143 micrometer per mm transport at 23 degrees C and 156 micrometer per mm transport at 14 degrees C. 5. In another series of experiments, almost the entire length of the lip nerve, which contained the axon of GCN, was maintained at 1‐‐3 degrees C to block transport. The GCN's cell body and the proximal few millimetres of the nerve were maintained at 23 degrees C. As a result, the amount of [3H]serotonin in the proximal segment of the nerve increased manyfold during periods of up to 4 hr. The concentrated pulse of [3H]serotonin resulting from this treatment was transported more slowly than normal after the cooling was terminated. Sometimes, a minor peak split from the major peak of radioactivity and was transported a normal velocity. 6. Incubation of the cerebral ganglion and nerves for 16 hr in the presence of anisomycin, an inhibitor of protein synthesis, reduced by nearly fourfold the amount of [3H]serotonin subsequently exported into the axon of the GCN. The transport velocity at this reduced concentration was less than half the normal value. If the concentration of [3H]serotonin in the axon was restored to normal in the presence of anisomycin, the velocity of transport was also returned to normal. 7. We conclude that the velocity of transport of serotonergic vesicles in the axon of the GCN is positively dependent on the local concentration of vesicles, except at very high concentrations, where the dependence is negative. The results are interpreted in the context of a model for transport in which the serotonergic vesicle is translocated along the axon in an intermittent fashion, alternating between moving and stationary states. The local concentration of the vesicles along the axon would control the observed velocity of transport by altering the partitioning between the two states, that is, by changing the percentage of time vesicles spend in each state.
Discrimination between different entry mechanisms for neutral amino acids in rabbit ileal mucosa.
Authors: Sepúlveda F V , Smith M W
Published: December 2014

1. Influx of neutral and basic amino acids into the mucosal epithelium of the rabbit ileum was measured in the presence of high and low concentrations of Na. Uptake measured at an amino acid concentration of 1 mM varied from 10 to 16 nmole . cm‐2 . min‐1. Removal of Na inhibited the uptake of short‐chain amino acids more than long‐chain amino acids. 2. Inhibition of uptake of glycine, alanine, leucine and phenylalanine by a selection of non‐radioactive amino acids was found to follow a particular pattern. Long‐chain amino acids inhibited the uptake of all test amino acids; short‐chain amino acids inhibited preferentially the uptake of glycine. 3. The maximum inhibition serine could cause to the uptake of other amino acids was found to vary. Serine inhibited completely the uptake of glycine but a portion of uptake of long‐chain amino acids was found to persist, even in the presence of high concentrations of serine. This is taken as evidence for the presence of an amino acid uptake mechanism having no affinity for serine. 4. The apparent affinities of neutral amino acids for the serino‐inhibitable system (system 1) varied from about 0.5 mM (for long‐chain amino acids) to about 3 mM (for short‐chain amino acids). The total uptake of individual amino acids by system 1 was essentially similar when compared at an amino acid concentration of 1 mM. 5. The serine‐resistant uptake of neutral amino acids (system 2) constituted up to two fifths of total uptake for long‐chain amino acids, measured at amino acid concentrations of 1mM. The affinities of long‐chain amino acids for system 2 is thought to be less than for system 1. Serine appears not to interact with system 2. 6. A second component to serine uptake was found to be related linearly to the concentration of serine in the medium. A similar component may contribute to the total uptake of phenylalanine. The possibility that such a component could arise as a space marker artifact is discussed. 7. An independent kinetic analysis of phenylalanine uptake by rabbit ileal mucosa showed that it could not be accounted for on the basis of a single entry system. However uptake could be described kinetically, assuming two systems of mediated entry to be present. The possible presence of a third non‐saturable component to uptake does not affect these conclusions. 8. It is concluded that least two systems exist for the mediated entry of neutral amino acids into rabbit ileal mucosa. This fact should be taken into account in any future mechanistic interpretation of carrier‐mediated amino acid transport in the small intestine.
Destruction of a single cell in the central nervous system of the leech as a means of analysing its connexions and functional role
Authors: Bowling D. , Nicholls J. , Parnas I.
Published: December 2014

A method has been devised for killing an individual neurone in the
C.N.S. of the leech by injecting it with Pronase. The technique has been used to examine the role of individual sensory and motor cells involved in producing reflex movements.

1. After a neurone was injected with Pronase, either in an intact animal or an isolated ganglion, its cell body lost its resting and action potentials. Some hours later the injected cell's axons in the periphery failed to conduct impulses. In the intact animal the cell body could no longer be discerned after a few weeks.

2. To test for destruction of processes within the neuropile, cells were injected first with the enzyme horseradish peroxidase (HRP) and then several hours later with Pronase. Absence of the characteristic HRP reaction product indicated that Pronase had spread throughout the arborization of the cell.

3. Injection of Pronase into one cell did not produce overt electrophysiological or anatomical changes in other cells in the ganglion including neurones that were originally electrically coupled to the killed cell.

4. Evidence that an individual cell was the only motoneurone supplying particular muscles was provided by destruction of that cell in otherwise intact animals, which resulted in a characteristic motor deficit in the area supplied by the killed cell. Over a period of months, functional recovery of the affected muscles occurred by way of homologous cells in adjacent ganglia.

5. A further application of the technique was to trace the connexion that a particular sensory neurone makes onto two motoneurones that are electrically coupled. Normally, the sensory neurone gives rise to excitatory potentials in both post‐synaptic cells. Synaptic potentials could still be recorded in one motor cell after the other had been destroyed by Pronase, indicating that synapses were made directly onto both of the motoneurones.
Fever and survival in rabbits infected with Pasteurella multocida
Authors: Kluger M. J. , Vaughn L. K.
Published: December 2014

1. Fever and survival rate of New Zealand white rabbits, injected with two doses of live Pasteurella multocida, were compared to determine if the relation between fever and survival observed in reptiles is also seen in a mammal. Since it is known that fever is beneficial in infected reptiles, our experiments were viewed as an initial step in the investigation of a similar potentially beneficial effect in mammals.

2. There was a statistically significant correlation between the fever magnitude and survival. As fever increased up to 2·25 °C, the survival rate increased. Fevers above this level were associated with a decreased survival rate.

3. Antipyretic drugs were administered to half the rabbits. The drugs were ineffective in reducing the fevers produced by injections of large doses of bacteria. Rabbits infused with antipyretics had a decreased mortality rate. The decreased mortality rate may be due to some action of the drugs other than their antipyretic effect.

4. In vitro growth of P. multocida at normal (39 °C) and febrile (42 °C) temperatures was not significantly different. This suggests that the increased survival rate associated with higher fevers was not due to a direct inhibition of the growth of the bacteria by the increased temperature. It may be due to an enhancement of some aspect of the rabbits' immunological defences.

5. It remains to be determined whether fever causes a higher survival rate or whether fever is only correlated with survival rate.
Measurements of muscle stiffness and the mechanism of elastic storage of energy in hopping kangaroos.
Authors: Morgan D L , Proske U , Warren D
Published: December 2014

1. A kangaroo hopping above a certain speed appears to consume less oxygen than a quadrupedal mammal, of similar weight, running at the same speed (Dawson & Taylor, 1973). This is thought to be achieved by storage of elastic energy in tendons and ligaments. 2. Energy can be stored in a tendon by stretching it, but only if the muscle fibres in series with it are stiff enough to resist most of the length change. We have measured length and tension changes in the contracting gastrocnemius muscle of the wallaby Thylogale during rapid, controlled stretches, and from this determined the amount of movement in muscle fibres and tendon (method of Morgan, 1977). 3. When the muscle was developing close to its maximum isometric tension, up to eight times as much movement occurred in the tendon as in the muscle fibres. This is made possible by the wallaby having a long and compliant tendon. 4. Measurement of work absorption by the muscle with a full length of free tendon and when the tendon had been shortened, showed that with the shortened tendon a larger proportion of movement occurred in the muscle fibres, producing a steep rise in work absorption by the muscle and a consequent increase in energy loss.
The inhibitory effects of vasoactive intestinal polypeptide on the mechanical and electrical activity of canine antral smooth muscle.
Authors: Morgan K G , Schmalz P F , Szurszewski J H
Published: December 2014

1. The inhibitory effects of vasoactive intestinal polypeptide (VIP) on the electrical and mechanical activity of canine antral smooth muscle were investigated. 2. In concentrations ranging from 5 X 10(‐9) to 1 X 10(‐7) M, VIP decreased the force of spontaneous contractions but had no measurable effect on spontaneous action potential complexes. 3. VIP had no effect on the increase in the amplitude and duration of the plateau potential and on the amplitude of contraction caused by a maximally effective concentration of acetylcholine. 4. VIP caused a significant decrease in the force of contraction caused by ED50 and threshold concentrations of acetylcholine. However, VIP had no measurable effect on the increase in the size of the action potential plateau caused by either concentration of acetylcholine. 5. VIP antagonized the increase in the amplitude of the plateau potential and the force of contraction induced by pentagastrin. It had no consistent effect on the pentagastrin‐induced increase in frequency. 6. The data indicate that VIP acts as an inhibitor in this tissue in two distinct ways. It uncouples electromechanical coupling during spontaneous and acetylcholine‐induced electrical and mechanical activity, and antagonizes pentagastrin‐induced increases in electrical and mechanical activities.
Adaptive properties of olfactory receptors analysed with odour pulses of varying durations.
Authors: Getchell T V , Shepherd G M
Published: December 2014

1. The adaptive properties of salamander of olfactory receptors have been analysed in extracellular unit recordings. Stimulation has been by step pulses of odour of varying durations for 1‐‐10 sec. 2. The most common response was a prolonged impulse discharge that continued throughout the duration of the pulse and terminated abruptly within 1 sec of the end of the pulse. The interval for termination was relatively independent of the pulse duration. Pulses were frequently followed by a period of impulse inactivity lasting 1‐‐3 sec, usually independent of previous pulse duration. 3. The impulse discharges were typically slowly adapting. Initially, during the first 1‐‐2 sec, the frequency rose to 5‐‐10 impulses/sec, at threshold concentration. In some cases, the initial level was maintained throughout the pulse, with little or no adaptation. More commonly, there was a distinct initial phasic peak, followed by decay to a lower level of 4‐‐8 impulses/sec, which was maintained during the pulse. It was concluded that most olfactory receptors are slowly adapting, with variable phasic responsiveness dependent on odour concentration and other factors. 4. Reductions in impulse activity, compared with background, during a pulse were rarely seen. Methods for increasing the level of background activity and the use of very long duration pulses were necessary in order to bring out this type of response. Uniformly reduced activity throughout a pulse was seen clearly in only one case. A pattern consisting of a waning and then recovery of impulse frequency during a pulse was also observed in rare cases. 5. The results have shown that olfactory receptor discharges characteristically have a relatively precise relation to step pulses of odour of varying duration. The properties of the response have implications for the steps involved in the overall processes of activation and inactivation of receptor mechanisms at the olfactory mucosa.
The central control of shivering and non‐shivering thermogenesis in the rat.
Authors: Banet M , Hensel H , Liebermann H
Published: December 2014

1. To test whether the preoptic area controls only non‐shivering and the spinal cord only shivering thermogenesis, ten rats were chronically implanted with a preoptic and a spinal cord thermode each. The following were then studied: (a) the effect of propranolol (8 mg/kg.hr) on the metabolic response to cooling the preoptic area, and the spinal cord, (b) the effect of exogenous noradrenaline (0.5 mg/kg) on the metabolic response to cooling the preoptic area, and the spinal cord, and (c) the effect of warming the preoptic area on the metabolic response to cooling the spinal cord, and vice versa. 2. Administration of propranolol inhibited the metabolic response to cooling each of the thermosensitive areas, but the response to cooling the preoptic area was more strongly inhibited than that to cooling the spinal cord. 3. Administration of exogenous noradrenaline did not prevent the metabolic response to cooling either the preoptic area or the spinal cord. 4. Warming the spinal cord completely inhibited the metabolic response to cooling the preoptic area, and warming the preoptic area fully inhibited the metabolic response to cooling the spinal cord. 5. It is concluded that exogenous noradrenaline underestimates the capacity for non‐shivering thermogenesis, and that both thermosensitive areas can control both forms of thermogenesis, but that the preoptic area threshold of non‐shivering thermogenesis is probably lower than that of shivering, while the spinal cord threshold of shivering is probably lower than that of non‐shivering thermogenesis.
Influence of rate of induction of hypoxia on the ventilatory response
Authors: Mahutte C. K. , Rebuck A. S.
Published: December 2014

1. We have studied the influence of rate of induction of hypoxia on the duration of the phases of the respiratory cycle in seven conscious healthy subjects.

2. Nine hypoxic procedures were performed on each subject, comprising three different rates of induction of hypoxia each at three different levels of PCO2. Ventilation vs. arterial O2 saturation plots were constructed and patterns of response were analysed in terms of ventilation vs. tidal volume and tidal volume vs. inspiratory duration (TI) and vs. expiratory duration (TE).

3. The highest ventilatory responses were observed during steady‐state hypoxia when PCO2 was held at a level similar to the control mixed venous level; progressive hypoxia at this PCO2 failed to stimulate ventilation to comparable levels. The ventilatory response was not influenced by rate of induction of hypoxia when PCO2 was maintained at an end‐tidal PCO2 close to the control level.

4. As tidal volume increased in response to hypoxia, TI and TE shortened. The progressive decrease in cycle duration occurred at all levels of PCO2 and at all rates of induction of hypoxia, but was most marked under eucapnic conditions during steady state.

5. It is concluded that steady‐state hypoxia may produce a higher ventilatory response than progressive, non‐steady‐state hypoxia. Inspiratory time shortens as tidal volume increases irrespective of the rate of induction of hypoxia.
Facilitation of synaptic transmission by general anaesthetics.
Authors: Morris M E
Published: December 2014

1. The actions of five structurally different intravenous and inhalation anaesthetics (alphaxalone/alphadolone, halothane, ketamine, methohexitone, and pentobarbitone) have been studied on synaptic transmission through the cuneate nucleus of the dorsal column‐lemniscal afferent pathway in the decerebrate cat. 2. Synaptic input and output were estimated from antidromic and orthodromic potentials, which were evoked by either afferent volleys from the periphery or micro‐electrode excitation of the presynaptic fibre terminals in the cuneate and recorded at forelimb nerves and the medial lemniscus. 3. Each of the anaesthetic agents potentiated the efficiency of synaptic transmission, as shown by the elevation of input‐output curves constructed from the integrals of the potentials evoked by varying intensities of either peripheral or cuneate stimulation. 4. The excitability of the afferent terminals, as measured at the peripheral nerves by the antidromic responses to micro‐electrode stimulation, was depressed by the anaesthetics. Post‐synaptic excitability, which was assessed from the direct lemniscal response to intra‐nuclear stimulation, did not appear to change. 5. Hypotensive states (mean arterial levels less than 60 torr) produced depolarization of presynaptic terminals and depression of synaptic efficiency and transmission; these changes opposed the primary effects of the general anaesthetics. 6. It is concluded that anaesthetics do not depress activity at all synapses of the central nervous system. Their facilitatory action on cuneate transmission is attributed to an enhanced release of excitatory transmitter; the underlying mechanism may be hyperpolarization of the primary afferent terminals, secondary to an increase in K+ conductance.
Variability of transmitter quanta released during incorporation of a false transmitter into cholinergic nerve terminals
Authors: Large W. A. , Rang H. P.
Published: December 2014

1. Electrophysiological techniques have been used to investigate the variability of quanta released during various stages of the incorporation of acetylmonoethylcholine (AMECh) into the transmitter store at the neuromuscular junction.

2. Stimulation of the rat phrenic nerve—diaphragm preparation at 3 Hz for 15‐25 min reduced the time constant of decay τm.e.p.c. of miniature end‐plate currents from 1·61 ± 0·08 (mean ±
S.E. of mean) msec to 1·32 ± 0·09 msec; this represents 45% replacement of acetylcholine (ACh) by AMECh. Total replacement of ACh was achieved by a further 30‐60 min stimulation which reduced τm.e.p.c. to 0·93 ± 0·06‐msec.

3. At the intermediate stage of exchange, the coefficient of variation c.v.τ of τm.e.p.c. increased from the control value of 0·094 ± 0·005 to 0·154 ± 0·012. The latter value was less than the value (0·29) calculated for two distinct populations of quanta (i.e. pure ACh and pure AMECh quanta). Moreover, frequency distribution histograms of τm.e.p.c. did not reveal a bimodal distribution. Total replacement of ACh by AMECh achieved by the second period of stimulation decreased c.v.τ towards the control value.

4. Pre‐incubation of muscles with MECh (to replace any stored choline) or stimulation in the presence of a cholinesterase inhibitor (to prevent ACh destruction and hence re‐uptake of choline) did not produce any greater degree of heterogeneity than was seen in the absence of these procedures.

5. The increase in c.v.τ observed at the intermediate stage of replacement disappeared spontaneously with a half‐time of about 1 hr at 20 °C.

6. These results are discussed in terms of the vesicle hypothesis.
Properties of synaptic linkage from long ranging afferents onto dorsal horn neurones in normal and deafferented cats.
Authors: Mendell L M , Sassoon E M , Wall P D
Published: December 2014

1. In intact cats, dorsal horn cells sometimes respond to afferents entering the cord three or four segments more rostral. If dorsal roots near a segment have been cut for at least 4 weeks, many more cells respond to these long ranging afferents. Using extra‐ and intracellular recording, we examined the change in the nature of the connectivity of the long ranging afferents from dorsal roots L3 and L4 onto cells in L7. 2. In intact animals 33% of all cells in L7 recorded extracellularly and 48% of those recorded intracellularly exhibited responses to electrical stimulation of skin whose afferents entered the spinal cord over dorsal roots L3 and L4. Most of these responses had a long latency and followed high frequency stimulation poorly. 3. Thirty‐eight to fifty‐one days after cutting dorsal roots L5‐S2, 76% of cells recorded intracellularly in L7 responded to long ranging afferents, in contrast to 48% in the intact cord. In these preparations 48% of all cells responded in less than 5 msec versus 12% in intact cats. Furthermore, 21% of the cells had natural receptive fields in the distant dermatome versus 1% in intact animals. 4. Chronic deafferentation of a segment increased the number of cells responding to afferents arriving over distal dorsal roots and increased the speed and power of the responses.
The metabolic and endocrine effects of circulating catecholamines in fetal sheep.
Authors: Jones C T , Ritchie J W
Published: December 2014

1. Adrenaline and noradrenaline have been infused into the fetal sheep to produce plasma concentrations comparable to those seen during hypoxia. The effects have been compared with those of isoprenaline and methoxamine and the sensitivity to beta‐ and alpha‐adrenergic antagonists has been followed. 2. Adrenaline caused an alpha‐mediated increase in blood glucose that is associated with a fall in plasma insulin concentration. It also caused a beta‐mediated increase in plasma lactate, free fatty acid and amino acid concentrations. 3. Noradrenaline was much less effective than adrenaline at eliciting metabolic responses. It had not cause a significant change in plasma glucose concentration, although this was associated with a small increase in plasma insulin concentration. It caused a small rise in the concentration of lactate and free fatty acids in fetal plasma but had no effect on plasma amino acids. 4. The beta‐ and alpha‐adrenergic antagonists propranolol and phentolamine alone were without effect on any of the plasma metabolites or hormones assayed. Isoprenaline increased plasma glucose, lactate, free fatty acid, alanine and insulin concentrations, while methoxamine only increased plasma glucose and lactate, and this was associated with a fall in insulin concentration. 5. The concentration of ACTH in fetal plasma was increased by adrenaline and to a lesser extent by noradrenaline and methoxamine; these were blocked by phentolamine. Isoprenaline also caused a small increase in ACTH. There were no corticosteroid changes associated with the increase in ACTH. 6. The results have been discussed in relation to the adrenergic and pancreatic control of metabolism in the fetal sheep.
Crossed disynaptic inhibition of sacral motoneurones.
Authors: Jankowska E , Padel Y , Zarzecki P
Published: December 2014

1. Intracellular recording was made from motoneurones in lower sacral (S2 and S3) segments of the spinal cord in cats, to analyse the neuronal organization of the inhibition evoked in these motoneurones from contralateral afferents. 2. It was confirmed that stimulation of the lowest threshold afferents of contralateral dorsal roots evokes i.p.s.p.s with latencies similar to those of disynaptic i.p.s.p.s. evoked from group Ia muscle spindle afferents in limb motoneurones. 3. The crossed disynaptic i.p.s.p.s in sacral motoneurones were found to be mediated by interneurones which are themselves inhibited by Renshaw cells, these interneurones and Renshaw cells being activated from the dorsal and ventral roots respectively, on the side of the body opposite to the location of the inhibited motoneurones. 4. In unanaesthetized decerebrate preparations crossed recurrent facilitation of sacral motoneurones was evoked with a time course similar to that of recurrent facilitation of lumbar motoneurones. It was taken to indicate a tonic inhibition of sacral motoneurones by interneurones responsible for their crossed disynaptic inhibition, and a disinhibition following stimulation of contralateral ventral roots. 5. In anaesthetized preparations crossed recurrent inhibition appeared, instead of the recurrent facilitation, in more than one half of the tested motoneurones. 6. A comparison of the input from ipsilateral and contralateral afferents to identified motoneurones of tail muscles with the input to pudendal motoneurones led to the conclusion that crossed disynaptic inhibition is evoked specifically in tail motoneurones. 7. Intracellular staining of sacral motoneurones with horseradish peroxidase revealed that the tail motoneurones and others with crossed disynaptic inhibition differ from the pudendal motoneurones in their location and in a number of morphological features; tail motoneurones are larger, they have differently directed dendrites and they show more extensively branched initial axon collaterals which appeared to ramify only within the ventral and lateral parts of the ipsilateral ventral horn. 8. One Renshaw cell which was stained with horseradish peroxidase was found to project contralaterally, after giving a number of axon collaterals ipsilaterally.
Tissue and plasma catecholamines and dopamine beta‐hydroxylase activity of various animal species after neurogenic sympathetic stimulation.
Authors: Arnaiz J M , García A G , Horga J F , Kirpekar S M
Published: December 2014

1. The effects of reserpine and exposure to a stressing atmosphere containing 20% CO2 for 5 hr on catecholamine (CA) levels and dopamine beta‐hydroxylase (DBH) activity of adrenal, spleen and plasma of cat, rabbit, rat and guinea‐pig were studied. 2. Twenty‐four hr after an I.P. injection of reserpine, the CA contents of the adrenals and spleens were markedly reduced in all the four species studied. Adrenal and splenic DBH activity was unchanged in reserpine treated cats and rats. The enzyme activity decreased by 28 and 36% in adrenals of rabbits and guinea‐pigs, and a 33% diminution was observed in the spleens of both species. 3. A marked rise in guinea‐pig plasma DBH activity was obtained 24 hr after reserpine, while plasma DBH activity was unchanged in the rat. 4. Exposure of rats to a stressing atmosphere containing 20% CO2 for 5 hr increased the circulating noradrenaline (NA) levels by 600%, but plasma DBH activity remained unchanged. CO2 exposure caused both, an increase in plasm NA levels and DBH activity in the guinea‐pig (950% and 100%, respectively). 5. The combined treatment with reserpine plus immediate exposure to CO2 produced a 230% rise in rat plasma NA with no concomitant change in DBH activity. A similar treatment caused a 75% fall of NA levels and an increase in DBH activity of 600% in the guinea‐pig. 6. The ratios of total DBH activity to CA in the spleen and adrenal were much higher in the guinea‐pig than in the rat. The fraction of the total DBH activity that can be solubilized by osmotic shock of purified adrenomedullary chromaffin granules was 28% in the rat and 71% in the guinea‐pig. If one makes the assumption that 'soluble' and 'releasable' DBH may be equated, the amount of 'releasable' DBH into the circulation is much greater in the guinea‐pig than in the rat. 7. The results suggest that the guinea‐pig is a better model than the rat to study circulating DBH activity as an index of exocytotic CA release from adrenergic neurones and adrenal medulla, and therefore of sympathetic activity. The results also indicate that previous data trying to correlate sympathetic activity with circulating DBH activity carried out in the rat have to be reconsidered in the light of data obtained in the guinea‐pig.
The excitation of mammalian central neurones by amino acids.
Authors: Hall J G , Hicks T P , McLennan H , Richardson T L , Wheal H V
Published: December 2014

1. The relative potencies of a number of analogues of L‐glutamate as excitants of thalamic neurones in the rat have been compared. The most powerful compounds were kainate, ibotenate and (+/‐)cis‐1‐amino‐1,3‐dicarboxycyclopentane. The D‐ and L‐isomers of glutamate and aspartate were also compared. Whereas D‐glutamate is approximately one‐half as active as the L‐form, D‐aspartate is more potent than L‐aspartate. 2. Computer analysis has indicated that ibotenate and cis‐1‐amino‐1,3‐dicarboxy‐cyclopentane have relatively fixed and similar C alpha‐N, Comega‐N and C alpha‐Comega interatomic distances which can also be achieved by glutamate in certain conformations of the molecule, but not by aspartate. 3. Parallel examination of the antagonists glutamate diethylester and D‐alpha‐aminoadipate has shown that the former preferentially reduces L‐glutamate effects while the latter blocks the actions of other amino acid excitants more readily than those of L‐glutamate. 4. The evidence is consistent with the hypothesis that at least two populations of neuronal receptors for the excitatory amino acids exist.
Immobilization of intramembrane charge in Myxicola giant axons.
Authors: Bullock J O , Schauf C L
Published: December 2014

1. Immobilization of gating charge was examined in Myxicola giant axons dialysed with Cs+. 2. With increasing pulse durations the ratio QOFF/QON decreases to as little as 0.25 with a time constant of 3.2 msec determined from composite data. Na inactivation time constants measured in the same axons ranged from 0.8 to 1.5 msec. A slow component of QOFF tends to appear as QOFF/QON decreases. 3. Both QON and QOFF may be decreased by a prepulse with no change in their time course. In this case the time course of the decrease is similar to that observed for INA. 4. The normalized steady‐state charge immobilization curve is shifted in the depolarized direction by 15‐‐20 mV from the normalized Na inactivation curve.
Field potentials and excitation of primate spinothalamic neurones in response to volleys in muscle afferents.
Authors: Foreman R D , Kenshalo D R , Schmidt R F , Willis W D
Published: December 2014

1. In anesthetized monkeys, stimulation of muscle afferents results in a sequence of cord dorsum potentials. These include a group I volley followed by several negative potentials called here the NI, NII and NIII waves. 2. Evidence based on the effects of graded stimulus strengths, measurements of latencies, and the results of anodal blockade of large muscle afferents indicate that the NI, NII and NIII waves are evoked, respectively, by group I, II and III muscle afferents. 3. The NII and NIII waves appear to be confined to the lumbosacral enlargement when evoked by hind limb muscle afferents. However, the group I volley and NI wave can be detected at least as far rostrally as L 3. 4. The NII and NIII waves were mapped in the depth of the cord. The maxima for these waves were found in the neck of the dorsal horn. The waves reversed to become positive in the ventral horn. 5. Using graded electrical stimulation of muscle nerves it was possible to demonstrate that a few spinothalamic tract neurones could be activated monosynaptically by group I volleys; other spinothalamic cells may have been activated polysynaptically by group I volleys. The lack of any substantial excitation of spinothalamic neurones by intra‐arterial injections of succinylcholine suggests that these group I actions may have been due to group Ib afferents from Golgi tendon organs. 6. The most potent excitation of spinothalamic tract cells was due to the action of middle sized and small muscle afferents. Evidence was obtained for an excitatory action of group II, III and IV afferents. There was a good correlation between the effects of graded stimulation in evoking discharges in separate bursts associated with the arrival of volleys in group II and group III afferents and the generation of the NII and NIII waves. 7. Some spinothalamic neurones, including several located in lamina I, were unaffected by the muscle afferent volleys used. It is suggested that such neurones might help to signal well localized pain, whereas the cells which respond to a variety of cutaneous and muscle afferents might be involved in signalling poorly localized pain which is subject to referral.
The depolarizing afterpotential of crab muscle fibres. A sodium‐dependent process mediated by intracellular calcium.
Authors: Suarez-Kurtz G
Published: December 2014

1. A study was made of the depolarizing afterpotential (d.a.p.) which follows the initial graded electrogenesis of crab muscle fibres. 2. Increasing the strength, duration or amplitude of the stimulating current pulses enhanced both the d.a.p. and the local contractions. 3. Arsenazo III was injected intracellularly and changes in light absorbance by the dye were used to monitor the increase in free sarcoplasmic Ca concentration during excitation‐contraction (E‐C) coupling. The onset of the absorbance changes occurred during the depolarizing phase of the initial electrogenesis and the maximum value coincided with the peak of the d.a.p. An exponential decay of the absorbance signal occurred during the repolarizing phase of the d.a.p. 4. Ionophoretic injection of EGTA into the sarcoplasm did not affect the initial electrogenesis but did reduce changes in dye absorbance, blocked tension development and abolished the d.a.p. 5. Caffeine (0.1‐‐0.4 mM) markedly enhanced both the d.a.p. and the local contractions, but had no effect on the initial electrogenesis. 6. Replacement of extracellular Na ions with Li, Tris or choline abolished the d.a.p. The initial electrogenesis was enhanced in the choline‐containing medium, but was not affected by Li or Tris. The rate of relaxation of the local contractions and the rate of decay of the light absorbance changes were slowed in Na‐free saline. 7. Tetrodotoxin (10(‐5) g/ml.) had no effect on either the membrane responses or tension development. 8. For initial graded responses of comparable peak amplitude a threefold reduction of [Ca‐a1o shortened the d.a.p., but had little effect onits peak amplitude. A fivefold increase in [Ca]o reduced both the amplitude and duration of the d.a.p. 9. Changes in [Mg]o had little effect on the d.a.p., but both Mn (4‐‐10 mM) and La (0.1 mM) blocked the initial electrogenesis and the d.a.p. 10. It is concluded that distinct ionic mechanisms give rise to the initial electrogenesis and the d.a.p. While the former is due to activation of Ca conductance, the d.a.p. is a Na‐dependent phenomenon that is tetrodotoxin‐insensitive, and mediated by the rise of intracellular Ca concentration during E‐‐C coupling.
Prolonged changes in excitability of pyramidal tract neurones in the cat: a post‐synaptic mechanism.
Authors: Bindman L J , Lippold O C , Milne A R
Published: December 2014

1. Prolonged changes in the excitability of cortical neurones can be produced by altering their firing rates for brief periods. In the anaesthetized cat, increased firing of pyramidal tract cells induced by trains of antidromic conditioning shocks led to increases in cell excitability, as measured by the size of the mass response at the medullary pyramid to test shocks applied to the cortical surface. We have shown in two ways that post‐synaptic mechanisms could be responsible. 2. In one experimental design, MgCl2 solution (1 mole/l.) was applied to the cortical surface in order to block synaptic activity throughout the cortical depth. Following antidromic conditioning trains, cell excitability was increased; the size of the mass response was up to 30% larger than the control values. This persisted undiminished for up to 3 hr. 3. In the second experimental design, synaptic activity was not blocked, but we compared the effects of antidromic plus synaptic activation of pyramidal tract cells with the effects of synaptic activation alone. Antidromic plus synaptic activation was obtained by applying conditioning trains to the pyramidal tract at the medulla ipsilateral to the cortical test shock; prolonged increases in the ipsilateral response to the test shock were produced. Synaptic activation alone was obtained by the same conditioning trains, but in those cells whose axons projected into the contralateral pyramidal tract; prolonged increases in the contralateral response to the cortical test shock were never seen. In many instances prolonged decreases in excitability were found. 4. We conclude that prolonged increases in excitability of pyramidal tract cells can occur in the absence of any synaptic input, demonstrating that the underlying mechanism is post‐synaptic; this does not preclude the action of synaptic mechanisms when synaptic transmission is not blocked.
Different mechanisms for neutral amino acid uptake by new‐born pig colon
Authors: Sepúlveda F. V. , Smith M. W.
Published: December 2014

1. Mucosal amino acid uptake by pig proximal colon, measured independently for fourteen different amino acids each used at a concentration of 1 m
M, ranged from 0·6 to 8·6 n‐mole. cm−2. min−1 in the new‐born to 0 to 0·3 n‐mole. cm−2. min−1 in the 2‐day‐old animal. Long chain amino acids entered the mucosa of new‐born pig proximal colon much more readily than did short chain amino acids.

2. Glycine was used extensively to inhibit the uptake of other neutral amino acids. The degree of maximal inhibition produced depended on the amino acid used. The relative inability of glycine to inhibit the uptake of long chain amino acids suggested that these compounds could cross the brush border on a carrier inaccessible to glycine. The glycine‐sensitive uptake remained more or less constant for all amino acids tested (1‐2 n‐mole.cm−2.min−1); the glycine‐insensitive uptake varied from 0 to 7 n‐mole.cm−2.min−1 (glycine and methionine respectively).

3. It is suggested that at least two mechanisms exist for the entry of neutral amino acids into pig proximal colon, one showing specificity for hydrophobic amino acids and the other having broad specificity. The mechanism responsible for the uptake of long chain essential amino acids predominates over the less specific mechanism.

4. These results are discussed in relation to previous work carried out on the rabbit ileum where two similar systems for neutral amino acid entry have been shown to be present. Both tissues transport hydrophobic amino acids on their own specific carrier at approximately the same rate; the ability of the pig colon to transport amino acids on the broad specificity carrier is eight times less than in the rabbit ileum. The possibility is raised that this system is subject to regulation.
Catecholamine secretion in a rat pheochromocytoma cell line: two pathways for calcium entry.
Authors: Ritchie A K
Published: December 2014

1. The pathways for Ca entry during stimulus‐secretion coupling were studied by measuring carbamylcholine and KCl activated dopamine (DA) release from PC12, a clonal cell line originated from a rat pheochromocytoma. Various conditions were used to establish the existence of two independent pathways for Ca entry, i.e. a voltage dependent Ca channel and the acetylcholine (ACh) receptor linked channel. 2. DA release from PC12 was stimulated by activation of nicotinic ACh receptors with carbamylcholine. Release was dependent on external Ca, but not Na, and was insensitive to tetrodotoxin. 3. High concentrations of external KCl (15‐‐56 mM) also stimulated the release of dopamine from PC12. This release required external Ca, but not Na, was insensitive to tetrodotoxin and was diminished by high concentrations of Ca. 4. Ni, Co and, to a lesser extent, Mg inhibited both the carbamylcholine and KCl stimulated release of DA in normal and Na‐free media. 5. In the absence of Ca and Na, Mn supported DA release stimulated by either carbamylcholine or KCl. 6. The divalent cation ionophore A23187 stimulated DA release when Ca or Mn, but not Co, Ni or Mg, was the only divalent cation present in the medium. 7. Conclusions can be summarized as follows, (a) KCl stimulates DA release by activation of voltage dependent Ca channels. (b) Carbamylcholine probably stimulates DA release by Ca influx through both the ACh channel and voltage dependent Ca channels. (c) Mn ion is a suitable substitute for Ca ion as regards permeation of the Ca and the ACh channels and activation of the secretory process. (d) Na flux through voltage dependent Na channels is not necessary for stimulation of release by either KCl or carbamylcholine.
End‐plate currents and acetylcholine noise at normal and myasthenic human end‐plates.
Authors: Cull-Candy S G , Miledi R , Trautmann A
Published: December 2014

1. The amplitudes and time courses of miniature end‐plate currents (m.e.p.c.s) have been compared at normal and myasthenic (MG) human end‐plates studied under voltage clamp. The m.e.p.c. amplitude at MG end‐plates is reduced to about one third normal; mean m.e.p.c. (normal) = 2.6 +/‐ 0.2 nA, mean m.e.p.c. (MG) = 1.0 +/‐ 0.1 nA. The decay time constant of m.e.p.c.s (tau m.e.p.c.) is very similar at normal and MG end‐plates; tau m.e.p.c. (normal) = 1.70 +/‐ 0.1 msec, tau m.e.p.c. (MG) = 1.80 +/‐ 0.13 msec (Vm = ‐ 80 mV. T = 23 degrees C). 2. The equilibrium potential of the end‐plate current (e.p.c.) at normal and myasthenic human end‐plates is close to 0 mV. 3. Decay time constants tau e.p.c. and tau m.e.p.c. increase exponentially with membrane hyperpolarization. The voltage sensitivity of the time constants was similar at normal and MG end‐plates. 4. Both normal and myasthenic e.p.c.s are greatly prolonged in the presence of neostigmine (10(‐6) g/ml.). At the same time the voltage sensitivity of tau e.p.c. is slightly reduced. 5. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end‐plates were smaller than the normal under similar conditions. 6. Analysis of end‐plate current noise obtained during the steady application of acetylcholine (ACh) to voltage clamped normal and MG human end‐plates showed that the amplitude of the elementary current event (gamma) and the average channel life‐fime (tau noise) was similar at the two sites: tau noise (normal) ‐ 1.54 +/‐ 0.04 msec, tau noise (MG) = 1.60 +/‐ 0.11 msec; gamma(normal) ‐ 22.3 +/‐ 1.57 PS, gamma (MG) = 20.25 +/‐ 1.93 pS (Vm = ‐ 80 mV, T = 23 degrees C). The voltage sensitivity of the channel life time, measured from end‐plate current noise, was similar at normal and MG end‐plates. 7. At normal human end‐plates a packet of transmitter opens about 1500 channels whereas at MG end‐plates a packet opens only about 600 channels. It is calculated that the size of the transmitter packets released from MG‐terminals is at least as large as the packet of the ACh released from normal human nerve terminals.
Comparison of the temperature‐dependence of rapid axonal transport and microtubules in nerves of the rabbit and bullfrog.
Authors: Brimijoin S , Olsen J , Rosenson R
Published: December 2014

1. The average velocity of transport of dopamine‐beta‐hydroxylase, an enzyme confined to unmyelinated adrenergic nerves, was measured in rabbit and bullfrog sciatic nerves or branches incubated in vitro at various temperatures. In parallel experiments, the number and density of microtubules were measured in cross‐sections of randomly selected unmyelinated axons from another set of nerves incubated under the same conditions. 2. Average transport velocity was exponentially related to temperature over a wide range, but it fell abruptly towards zero at temperatures below 13 degrees C in the case of rabbit nerves and 10 degrees C in the case of frog nerves. 3. The number of microtubules per unmyelinated axon had declined considerably before the transport of dopamine‐beta‐hydroxylase was impaired. At 13 degrees C, axons in rabbit nerves lost 30% of their microtubules. Axons in bullfrog nerves were, if anything, more sensitive to cold, losing 35% of their microtubules at 15 degrees C and 65% of them at 10 degrees C. 4. Since the temperature‐dependence of the axonal transport of dopamine‐beta‐hydroxylase is probably typical of rapid axonal transport in general, it was concluded that transport in unmyelinated axons can continue unaffected when a substantial fraction of the microtubular population has been lost. 5. Although these results could imply that microtubules are not essential for transport, they are equally compatible with the view that these organelles determine the capacity of the transport system and are normally present in excess.