bluuebunny/crossref_metadata_2025 huggingface dataset:
Action potentials reconstructed in normal and myotonic muscle fibres.
Authors: Adrian R H , Marshall M W
Published: December 2014

1. Muscle fibres from goats with myotonia congenita show characteristic responses to stimulation with intracellular currents (Adrian & Bryant, 1974). To test whether the reduced surface chloride conductance can account for these myotonic discharges, we have calculated responses of a model 'muscle fibre' to intracellular current of long duration (greater than 100 msec), assuming that the current is applied at the end of the fibre, that the fibre is of finite length, that a regenerative action potential occurs in the transverse tubular system as well as the surface, and that the potassium current in the wall of the transverse tubular system raises the potassium in the tubular lumen. In the absence of information about the kinetic parameters of the ionic currents in mammalian muscle we have used numerical values from frog muscle (Adrian, Chandler & Hodgkin, 1970). 2. In calculations with a normal surface chloride conductance a long maintained current gives only one action potential. Reduction of the chloride conductance to a half produces repetitive firing during the current; reduction to a tenth produces repetitive firing during and a small number of action potentials after the end of the current. Elimination of the tubular potassium accumulation from the calculation reduces the number but does not eliminate action potentials arising after the end of the applied current. 3. With a tenth of the normal chloride conductance calculated responses show maintained firing following a constant current if the deactivating rate of the sodium channels (betam) is reduced by 25%. As before, eliminating potassium accumulation reduces the number of post‐stimulus action potentials, but it does not eliminate them altogether. 4. We conclude that in the absence of a surface chloride conductance tubular potassium accumulation could certainly contribute to the instability of the membrane, but it is clear that potassium accumulation is not the only reason for the instability of myotonic muscle fibres. The kinetics of the sodium channels are important and we do not know that they are the same in normal and myotonic fibres. Nevertheless the presence of a surface chloride conductance does stabilize the response of a fibre to constant current or to repetitive stimulation, and its absence could be a sufficient condition for myotonic behaviour.
Disynaptic inhibition of spinal motoneurones from the motor cortex in the monkey.
Authors: Jankowska E , Padel Y , Tanaka R
Published: December 2014

1. The neuronal mechanism of disynaptic inhibition of spinal motoneurones by the corticospinal tract was investigated in Macaca irus. Surface stimulation or weak intracortical stimulation was used in order to evoke the inhibition. Intracellular records were taken from motoneurones in lumbar segments. 2. Both the disynaptic i.p.s.p.s evoked from group Ia afferents and the disynaptic i.p.s.p.s evoked from corticospinal fibres were found to be depressed by conditioning stimulation of motor axons to antagonistic muscles. Mutual facilitation of the actions from these two fibre systems occurred when nerve impulses set up in them reached the explored spinal segment synchronously. These observations led to the conclusion that disynaptic i.p.s.p.s from group Ia afferents and from the motor cortex are mediated by common interneurones. 3. No evidence either for or against projections of the same pyramidal tract cells to motoneurones of one motor nucleus and to interneurones interposed between group Ia afferents and motoneurones of an antagonistic muscle could be obtained by comparing cortical areas from which monosynaptic e.p.s.p.s and disynaptic i.p.s.p.s were evoked in the different motor nuclei. 4. The areas from which the disynaptic i.p.s.p.s were evoked in individual motoneurones appeared to be similar in size to the areas of cortical monosynaptic projections to motoneurones and showed similar degrees of overlap, indicating that the projections of pyramidal tract cells to Ia inhibitory interneurones are as extensive as to motoneurones and that they are similarly organized.
Release of peptide hydrolases during incubation of intact intestinal segments in vitro.
Authors: Silk D B , Kim Y S
Published: December 2014

1. Rat intestinal segments have been incubated in isotonic saline in vitro and release of peptide hydrolase enzymes into the incubation media examined over a 90 min study period. 2. Chemical assay data, as well as analysis of electrophoretic mobilities of release enzymes on starch gel, indicate that peptide hydrolase enzymes in the incubation media originate predominantly from the cytoplasm of the mucosal cells. 3. Peptide hydrolases were released rapidly from intact intestinal segments. Release occurred from the start of the in vitro incubations and was not affected by temperature and shaking. 4. It is concluded that compared to the in vivo situation, cytoplasmic peptide hydrolases are released from intestinal tissue very rapidly in vitro. Caution is therefore required when comparing results of in vivo and in vitro peptide absorption experiments.
Identification of the pace‐maker current in frog atrium.
Authors: Brown H F , Clark A , Noble S J
Published: December 2014

1. The nature and interactions of the membrane currents underlying induced pace‐maker activity in frog atrial muscle have been investigated using a double sucrose gap technique. 2. The membrane current which controls the speed of the atrial pacemaker depolarization (the pace‐maker current, ip), is shown to be an outward current activated within the plateau potential range of a normal action potential. The subsequent deactivation of ip at more negative potentials unmasks the depolarizing action of time‐independent inward membrane currents so that a pace‐maker potential can result. 3. The deactivation of ip over a limited potential range (between about ‐30 and ‐60 mV) can be reliably recorded by switching on the voltage clamp during an induced pace‐maker depolarization. 4. Investigation of the time and voltage‐dependent behaviour of ip over a much wider potential range is less straightforward. How ip can be separated from other components of outward current present in the decay tails following square voltage clamp depolarizations is described. 5. The majority of such current decay tails contain three components of outward current. It appears that two of these components, one of which is ip, are true Hodgkin‐Huxley conductance systems chiefly carrying potassium ions. 6. The nature of the third current, which decays very slowly at moderate membrane potentials (about ‐40 mV), is discussed and reasons are briefly given for considering it to result from the accumulation of potassium ions in extracellular spaces. Preliminary evidence that potassium depletion occurs at potentials negative to the resting potential of the trabeculum is also presented. 7. Because of the obvious complexities involved, a quantitative analysis of the atrial outward currents is not attempted here but forms the subject of a following paper (Brown, Clark & Noble, 1976a).
Properties of motor units of the frog sartorius muscle.
Authors: Luff A R , Proske U
Published: December 2014

1. The mechanical properties of single motor units in the sartorius muscle of the frog Litoria aurea were examined during single shock and repetitive stimulation of motor axons. 2. The tetanic tension developed by motor units lay in the range 1‐40% of whole muscle tension with two peaks in the distribution, in the range 5‐10% and 25‐30%. The large units had briefer times‐to‐peak for the twitch than the small units and were more readily fatigued during prolonged repetitive stimulation. 3. Histological examination of the muscle gave a count of 620 muscle fibres with a diameter range of 28‐128 mum. Cholinesterase stained preparations showed that the majority of muscle fibres had several nerve terminals (mean 3, range 1‐5). 4. Muscle fibres received their multiple innervation from different axons (polyneuronal) or branches of the same axon (multiterminal). The presence of polyneuronal innervation of muscle fibres was confirmed by a comparison of the tensions when each of a pair of motor units was stimulated alone and when they were stimulated together. The tension excess, or overlap, was up to 60% when expressed in terms of the tension developed by either unit alone. Motor units developing similar amounts of tension tended to show more overlap in their innervation than units with very different tensions. 5. An estimate of the amount of multiterminal innervation gave variable results but could account for up to 60% of a motor unit's tension. No correlation could be detected between the values for multiterminal innervation and any other measured parameter. However, it is argued that because of the limitations of the measurements the existence of a relationship between the extent of multiterminal or polyneuronal innervation and the mechanical properties of the motor unit cannot be excluded.
Effects of the ionophore X‐537A on acetylcholine release at the frog neuromuscular junction.
Authors: Kita H , Van Der Kloot W
Published: December 2014

1. X‐537A is an ionophore that can carry cations across cell membranes. We studied its effects on spontaneous and stimulated quantal acetylcholine (ACh) release at the frog neuromuscular junction. 2. When neuromuscular transmission was blocked with high Mg2+ or with curare, X‐537A markedly increased the end‐plate potential (e.p.p.) amplitude. Then a few minutes later the e.p.p. disappeared. 3. When neuromuscular transmission was blocked with hypertonic saline solution, X‐537A did not increase e.p.p. amplitude; it did produce many transmission failures. 4. X‐537A decreased the depolarization of the end‐plate produced by iontophoretically applied ACh. this may account in part for the disappearance of the e.p.p. in solutions containing the ionophore. 5. X‐537A depolarized muscle fibres by about 15 mV. 6. When the extracellular divalent cation concentration was very low, X‐537A had little or no effect on miniature end‐plate potential (min.e.p.p.) frequency. 7. When a divalent cation was present in the extracellular fluid, X‐537A increased the frequency of the min.e.p.p.s. The sequence of effectiveness of the divalent ions we have tested is: Ba2+ greater than Sr2+ greater than Ca2+ greater than Mn2+ congruent to Co2+ congruent to Ni2+ greater than Mg2+. There is a rough parallel between these results and the reported affinity of X‐537A for various divalent ions. 8. The increase in min.e.p.p. frequency caused by X‐537A was transitory, following the increase min.e.p.p. frequency fell to a very low rate or to zero. Then nerve stimulation did not cause quantal release. A second application of X‐537A was without effect. 9. X‐537A decreased min.e.p.p. amplitude, in accord with the effect on the sensitivity of the end‐plate to ACh. 10. The results support the idea that increases in intracellular divalent cation concentrations trigger quantal release from nerve terminals and are involved in the disensitization of end plate receptors to ACh.
Reflex activation of sympathetic pathways to vesical smooth muscle and parasympathetic ganglia by electrical stimulation of vesical afferents.
Authors: de Groat W C , Theobald R J
Published: December 2014

1. Activation of the sympathetic input to the urinary bladder by electrical stimulation of afferent fibres in the pelvic nerve evoked three responses: (1) an initial transient rise in intravesical pressure, (2) an inhibition of neurally evoked bladder contractions and (3) an inhibition of transmission in vesical parasympathetic ganglia. Similar responses were elicited by stimulation of the hypogastric nerve. 2. The reflex responses were observed in acute spinal preparations (T10‐T12) and in cats with intact spinal cords, but were abolished by bilateral transection of the hypogastric nerves. 3. The inhibition of bladder contractions was antagonized by the administration of propranolol (200‐400 mug, I.A.), a beta‐adrenergic blocking agent. The inhibition of ganglionic transmission was antagonized by dihydroergotamine (30‐75 mug, I.A.), an alpha‐adrenergic blocking agent. The initial rise in intravesical pressure was not antagonized by either agent. 4. Electrical stimulation of other afferents (carotid sinus nerve and sciatic nerve) did not consistently elicit responses in the urinary bladder. However, stimulation of these afferents as well as pelvic nerve afferents evoked reflex firing in nerve filaments on the surface of the urinary bladder. The firing was abolished by transection of the ipsilateral hypogastric nerve. 5. It is concluded that stimulation of vesical afferents activates a spinal sympathetic reflex which results in closing of the internal urethral sphincter and a depression of bladder activity. The latter occurs by a direct depression of detrusor smooth muscle as well as a block of the neural input to the bladder. This vesico‐sympathetic reflex represents a negative feed‐back mechanism which may have an important role in the maintenance of urinary continence.
Evidence that brain prostaglandin synthesis is not essential in fever.
Authors: Cranston W I , Duff G W , Hellon R F , Mitchell D , Townsend Y
Published: December 2014

1. We have tested the hypothesis that a fever caused by pyrogen depends upon the synthesis of prostaglandin E in the brain and that the prostaglandin in turn acts on the hypothalamus to produce fever. 2. In rabbits, fever was produced by the injection of leucocyte pyrogen in a lateral cerebral ventricle. The latency, rate of rise and magnitude of the fever was unaffected by the simultaneous intraventricular injection of two prostaglandin antagonists, SC 19220 and HR 546. 3. Both antagonists effectively attenuated the fever caused by the intraventricular injection of prostaglandin E2. 4. This evidence is not consistent with the hypothesis that prostaglandin E is the principal mediator of fever.
An octopus toxin, maculotoxin, selectively blocks sodium current in squid axons.
Authors: Gage P W , Moore J W , Westerfield M
Published: December 2014

1. A low molecular weight, stable, cationic neurotoxin (maculotoxin, MTX) extracted from the posterior salivary glands of the octopus Hapalochlaena maculosa, blocked sodium current in voltage‐clamped squid axons without affecting potassium current. 2. The effectiveness of MTX was increased by repetitive, brief, depolarizing pulses but not by a single prolonged depolarization. 3. The potency of MTX decreased at pHs from 8 to 9. Effectiveness could be restored be restored by lowering the pH to 7‐1 again. It was concluded that MTX is active in its cationic form. 4. MTX affected sodium conductance kinetics, slowing the turn‐on of sodium current. This effect was most noticeable with small deploarizations but became progressively less with larger depolarizations. Neither the turn‐off of sodium current nor sodium inactivation kinetics were affected by the toxin. 5. MTX inhibited sodium current without inhibiting sodium gating current. 6. The effectiveness of MTX was not detectably changed when calcium concentration was varied from 50 to 10 mM, or sodium concentration was varied from 225 to 750 mM.
Respiratory modulation of barareceptor and chemoreceptor reflexes affecting heart rate and cardiac vagal efferent nerve activity.
Authors: Davidson N S , Goldner S , McCloskey D I
Published: December 2014

1. Brief stimuli were delivered to the carotid chemoreceptors or baroreceptors in dogs anaesthetized with chloralose. Chemoreceptor stimulation was achieved by rapid retrograde injection of 0.2‐0.5 ml. CO2 equilibrated saline through a cannula in the external carotid artery. Baroreceptor stimulation was achieved by forceful retrograde injection of 2‐5 ml. air‐equilibrated saline into the external carotid artery after first clamping the common carotid artery. 2. prompt decreases in heart rate were elicited by brief sudden chemoreceptor or baroreceptor stimuli when these were delivered during the expiratory phase of respiration. The stimuli did not modify the control heart rate pattern when delivered in the inspiratory phase of respiration. This respiratory modulation of reflex effectiveness persisted when the animals were completely paralysed and the phase of the respiratory cycle was monitored through a phrenic electroneurogram. 3. single cardiac vagal efferent nerve fibres were dissected from the cut central end of the right cervical vagus nerve. They were classified as cardiac efferents by their cardiac and respiratory rhythmicity, and by their increased activity in response to stimulation of a carotid sinus nerve or to mechanical elevation of the systemic arterial pressure. These efferent fibres increased their activity in response to brief chemoreceptor or baroreceptor stimuli delivered in expiration, but did not respond to stimuli delivered in inspiration. This respiratory modulation of both reflexes persisted after bilateral cervical vagotomy.
Calcium‐sodium antagonism on the frog's heart: a voltage‐clamp study.
Authors: Benninger C , Einwächter H M , Haas H G , Kern R
Published: December 2014

1. In double sucrose‐gap voltage‐clamped frog atrial fibres the influence of [Ca]o and [Na]o on membrane current and contraction was investigated. 2. The slow (secondary) inward current varied with [Ca]o but was almost insensitive to changes in [Na]o. In contrast, the phasic (transient) contraction initiated by the slow inward current was affected by both [Ca]o and [Na]o. 3. With moderate changes of [Ca]o and [Na]o from normal, the strength of phasic contraction at a given depolarization followed the [Ca]o/[Na]2o ratio approximately. This was best seen at membrane potentials near zero level. 4. Under the same conditions, tonic (sustained) contractions associated with prolonged depolarizations were strictly correlated to the [Ca]o/[Na]2o ratio at any potential. No interrelation between tonic tension and steady‐state current was found. 5. With extensive changes in [Ca]o and [Na]o, the sensitivity of both phasic and tonic tension to the [Ca]o/[Na]2o ratio declined, the negative effect of [Na]o becoming smaller than was expected from this ratio. 6. In Na‐free choline‐Ringer, a strong contracture developed followed by a spontaneous relaxation. Starting from the relaxed state, application of depolarizing clamps gave rise to phasic contractions with a very slow relaxation while tonic contractions were apparently lacking. 7. The results are interpreted in terms of an energy‐dependent carrier mechanism exchanging one Ca for two Na ions across the cell membrane. The model implies a strong asymmetry in the rate constants governing the chemical reactions on both sides of the membrane. The system is thought to operate close to equilibrium at any potential, thereby determining the steady level of myoplasmic Ca. The equilibrium itself is considered to shift upon depolarization. Assuming that [Na]i is constant, the steady level of [Ca]i is expected to be proportional to the [Ca]o/[Na]2o ratio, the scale factor being a function of membrane potential. 8. The carrier model suggests the occurrence of a depolarization‐induced inward transfer of Ca which might be involved in the generation of tonic contractions. 9. The apparent lack of tonic contractions in the absence of external Na ions may be explained by a suppression of carrier‐mediated Ca influx normally occurring upon depolarization. 10. The antagonistic effects of [Ca]o and [Na]o on phasic contraction are understood as being due to alterations of the Ca pumping system rather than changes in slow inward current.
Non‐quantal fluctuations and transmission failures in charge transfer at Ia synapses on spinal motoneurones.
Authors: Edwards F R , Redman S J , Walmsley B
Published: December 2014

1. The origins of fluctuations in charge transfer during the generation of Ia e.p.s.p.s have been investigated. The discrete components which make up the fluctuating e.p.s.p. have been separated. 2. Some e.p.s.p.s fluctuate between two different amplitudes and time courses. These fluctuations have been analysed to show that charge transmission always occurs at one synaptic location, but not always at a second synaptic location. 3. The failures in transmission were study by stimulating the afferent fibre at different frequencies. Although different probabilities of failure were obtained at different frequencies, there was no systematic change in probability with increasing frequency. 4. Single afferents were tetanized and histograms of charge transfer computed during post‐tetanic potentiation (p.t.p.). Only half of the units studied showed any p.t.p. In those that did, evidence was found for a decrease in the probability of failure during potentiation. 5. The results could not be used to distinguish between failure of the impulse to always propagate into the terminals, and failure of the terminals to release transmitter following adequate depolarization. 6. The fluctuations in transmission at a single synapse can be described by a binomial process with n = 1 and p less than or equal to 1. Junctional mechanisms consistent with this description are discussed. Alternative mechanisms which associate failures with failure of impulse transmission at afferent fibre branch points are also suggested.
Calcium exchange in vascular smooth muscle, action of noradrenaline and lanthanum.
Authors: Godfraind T
Published: December 2014

1. The Na, K, Ca and Mg content and the 45Ca uptake and loss were determined in rat aortae incubated in physiological solution or in solution containing LaCl3 instead of CaCl2. 2. Aortae washed in La‐solution contained less Ca and Na than controls in physiological solution, the K content was not modified and the Mg content was slightly decreased. 3. In 50 mM‐La solution the 45Ca diffusion space was intermediate between the values found for the [14C]sorbitol space and the [14C]inulin space, indicating that there was no Ca entry within the cell nor Ca binding at superficial sites. 45Ca loss from the tissue was directly related to the La concentration. 4. Noradrenaline increased the rate of uptake of 45Ca into the Ca fraction resistant to displacement by La. This increase was dose dependent, a response of 50% of the maximum being produced by 2 x 10(‐8) noradrenaline as for the contraction. In the presence of phentolamine, the dose‐effect curves for the action of noradrenaline on 45Ca uptake were displaced in a manner characteristic of competitive antagonism. The rhoA2 for phentolamine was 7‐8. 5. In physiological solution, the rate of loss of 45Ca, from the Ca fraction resistant to displacement by La, was increased by noradrenaline the ED50 was 2 x 10(‐8) M, and the effect was abolished by phentolamine. 6. In view of the similarity of phentolamine rhoA2 estimated by measuring noradrenaline sensitive 45Ca uptake or noradrenaline evoked contraction, it is likely that the activation of alpha‐adrenergic receptors is responsible for both effects.
Effects of prostaglandin E2 and oxytocin on the electrical activity of hormone‐treated and pregnant rat myometria.
Authors: Kuriyama H , Suzuki H
Published: December 2014

The effects of prostaglandin E2 (PGE2) and oxytocin on the electrical activity of rat myometrium at various stages of gestation and following hormonal treatment have been investigated. 1. PGE2 and oxytocin produce an excitation of the myometrial membrane under all experimental conditions. The sensitivity of the myometrium markedly increases during the last stage of gestation, and at parturition is more than one thousand times greater than in the mid‐pregnant rat. The sensitivity of the myometrium to oxytocin increases rapidly during the last stage of gestation but to PGE2 the increase is gradual, beginning in the late middle stage of gestation. 2. During the early middle stage of gestation, the sensitivity of the myometrium to PGE2 and oxytocin is lower than in the non‐pregnant myometrium. 3. After oestradiol treatment, the sensitivity to PGE2 and oxytocin increases but the sensitivity is much weaker than that during the parturition. On the other hand, after progesterone treatment, the sensitivity is reduced below that of the castrated rat. 4. Differences in the sensitivity of progesterone‐treated and oestradiol‐treated myometria to PGE2 and oxytocin are compared to those of the pregnant and post‐partum myometrium. The results show that the sensitivity of the myometrium to PGE2 and oxytocin during the early and early‐middle stages of gestation can be simulated by progesterone treatment, but that the sensitivity during the last stage of gestation and during parturition cannot be simulated by oestradiol and progesterone treatment.
Conduction velocity along the afferent vagal dendrites: a new type of fibre.
Authors: Duclaux R , Mei N , Ranieri F
Published: December 2014

1. We systematically calculated the conduction velocity along the peripheral extensions of sensory vagal neurones in cats (the dendrites). In addition, a study of excitability cycle and light microscopic investigation were also conducted on these neurones. 2. The conduction velocity of the three known types of fibres (A, B and C) remains uniform along the dendrites. 3. Another mixed type of fibres exists with a C conduction velocity (mean value 1‐5 m/sec) along its distal pathway and a B conduction velocity (mean value 6 m/sec) along its proximal pathway. The change in conduction velocity progressively occurs in the thoraco‐cervical portion of the vagus nerve at least 20 mm from the receptor and at least 40 mm from the T cell. 4. The mixed fibres exhibited a C type excitability cycle in their peripheral pathway and a B type excitability cycle in their central pathway. 5. The histological study using the teasing method demonstrated the existence of unmyelinated fibres, in the thoraco‐cervical region of the vagus nerve, becoming progressively myelinated from the periphery to the nodose ganglion. These fibres are likely to be the ones showing mixed electrophysiological properties. They represent (approximately) 10% of the vagal nerve population. 6. We propose to call the mixed fibres BC because they present electrophysiological and morphological properties of C fibres in their distal part and properties of B fibres in their proximal part.
Identification of pathways mediating cardiovascular responses elicited by stimulation of the septum in the rat.
Authors: Calaresu F R , Ciriello J , Mogenson G J
Published: December 2014

1. Experiments were done in rats anaesthetized with sodium pentobarbitone to localize pathways mediating the cardiovascular responses elicited by electrical stimulation of the septum. The major efferent projections from the septum were first identified anatomically by the Fink‐Heimer II technique and these pathways were subsequently lesioned in acute experiments to establish their role in the mediation of the cardiovascular responses elicited by septal stimulation. 2. Electrical stimulation of histologically localized sites in the lateral septum elicited hypotension and bradycardia whereas stimulation of sites in the medial septum elicited hypertension and bradycardia. 3. Selective lesions of cardiovascular responsive sites in either the lateral or medial septum produced a pattern of degeneration essentially similar to that of previous anatomical studies, i.e. the main efferent projections were localized to the fornix, stria medullaris and the medial forebrain bundle. 4. Stimulation of the fornix did not elicit cardiovascular changes and lesions of this pathway did not alter cardiovascular responses to septal stimulation. 5. Stimulation of the stria medullaris elicited hypotension and bradycardia whereas stimulation of the medial forebrain bundle elicited hypertension and bradycardia. Ipsilateral lesions of the stria medullaris, signicicantly attenuated the hypotension and bradycardia elicited by stimulation of the lateral septum but did not affect the responses to stimulation of the medial septum. Bilateral lesions of the medial forebrain bundle in the region of the lateral hypothalamus abolished the hypertension but did not affect the bradycardia elicited by medial septum stimulation. Cardiovascular, reponses elicited by stimulation of the lateral septum were not affected by medial forebrain bundle lesions. 6. It is suggested that the cardiovascular responses elicited by stimulation of the lateral septum are mediated via the stria medullaris and that the hypertension elicited by stimulation of the medial septum is mediated via the medial forebrain bundle. On the other hand, the bradycardia elicited by stimulation of the medial septum is probably mediated by a pathway presently unknown.
Sodium‐dependent influx of orthophosphate in mammalian non‐myelinated nerve.
Authors: Anner B , Ferrero J , Jirounek P , Jones G J , Salamin A , Straub R W
Published: December 2014

1. The rate of uptake of radiophosphate was measured in desheathed vagus nerves of rabbits mounted in an apparatus where the incubating solution flowed along the preparation. 2. Replacement of the Na of the Locke by either choline or Tris slowed the rate of uptake to about 10% of its value in Na; with K it was slowed to 20%; and with Li to 50%. 3. Measurements of the rate of uptake at different extracellular phosphate concentrations showed that in choline‐Locke the influx of phosphate was proportional to the extracellular phosphate concentration, while in Locke the rate of inward flow showed a tendency to saturation with increasing phosphate concentrations. 4. Extracts of nerves after 45 min exposure to labelled solutions showed for different phosphate concentrations a slowing of the labelling of ATP, ADP and creatine‐phosphate (CrP) and inorganic phosphate (Pi) when Locke was replaced by choline‐Locke. 5. A similar slowing was found when, at 0‐2 mM phosphate, the labelling of these compounds was measured at different times: application of choline‐Locke reduced the rate of incorporation of 32P to about 15% of the rate in Locke. 6. In preparations that were loaded with radiophosphate and then washed with inactive solution, and the effluent fractionated, over 90% of the radioactivity was found in the inorganic phosphate fraction. 7. The efflux of 32P showed an initial exponential phase with a time constant of 20‐30 min and a much slower one. The slow efflux had a rate constant of 0‐0014 min‐1 in 0‐2 mM external phosphate. 8. Increasing the external phosphate concentration increased the efflux. 9. Prolonged incubation in choline‐Locke reduced the efflux. 10. The influx of phosphate was calculated for different external phosphate concentrations using the rate of uptake of radiophosphate measured 45 min after the application of isotope and the corresponding efflux rate coefficient and the intracellular specific activities of the labelled compounds. 11. A correction was also introduced for diffusion, using the "limited biophase model". 12. The Na‐sensitive influx, i.e. the difference between influx in Locke and influx in choline‐Locke, showed saturation kinetics. 13. A Lineweaver‐Burk plot for Na‐sensitive uncorrected influxes gave a vmax of 16‐7 mumole/kg wet wt. min and an apparent Km of 0‐42 mM; for the corrected fluxes these values were 18‐2 and 0‐36. 14. It is concluded that a large part of phosphate influx and some of the phosphate efflux is mediated by a specific Na‐dependent phosphate transport system. 15. This system seems to be present also in other types of nervous tissues and probably in many types of animal cells.
The effect of noradrenaline, injected into the hypothalamus, on thermoregulation in the cat.
Authors: Cooper K E , Jones D L , Pittman Q J , Veale W L
Published: December 2014

1. Noradrenaline (NA) was microinjected into the anterior hypothalamic/preoptic area(AH/POA) of unanaesthetized cats held at ambient temperatures of 10, 22 or 35 degrees C. Loci in which injection of NA caused body temperature changes were also found to be sensitive to the febrile action of PGE1. 2. At all ambient temperatures, NA caused a dose‐dependent fall in body temperature. However the mechanisms by which these temperature changes were brought about varied at different ambient temperatures. In cats maintained at the higher ambient temperature, NA activated heat loss mechanisms whereas in the cats maintained in the 10degrees C environment, the major effect of NA injection was an inhibition of heat conservation and heat production mechanisms. 3. We conclude that NA acts in cats not only as an inhibitor of heat conservation and production, but also acts in an excitatory manner on an active heat loss pathway within the AH/POA.
Release of noradrenaline from the cat spleen by nerve stimulation and potassium.
Authors: Garcia A G , Kirpekar S M , Sanchez-Garcia P
Published: December 2014

1. Release of noradrenaline from the perfused cat spleen, or from isolated spleen slices, in response to prolonged nerve stimulation or maintained depolarization by potassium was measured. 2. Prolonged stimulation of the splenic nerves at 2, 10 and 30 Hz for 10 min evoked release, which was maximum during the first 2 min, and then declined during the remaining period of stimulation. When noradrenaline release was induced by high potassium from the perfused spleen or from isolated slices, it followed a similar time course to nerve stimulation. Similar results were obtained from phenoxybenzamine‐treated spleens, using both modes of stimulation. 3. Stimulation of the splenic nerves in calcium‐free Krebs solution did not release noradrenaline. If calcium was introduced at a later stage during stimulation, the release was markedly diminished. In phenoxybenzamine‐ or phentolamine‐treated spleens, stimulation of the nerves in the presence of calcium evoked a secretory response which was comparable to the one produced by introduction of calcium after a few minutes of nerve stimulation. 4. Simultaneous application of calcium plus high potassium always produced a much greater secretion of noradrenaline than application of calcium after a few minutes of potassium depolarization. Release of noradrenaline by potassium from phenoxybenzamine‐treated spleens was also much greater if calcium and potassium were added simultaneously than addition of calcium after a few minutes of potassium depolarization. 5. In the presence of maintained depolarization by potasssium, tyramine was effective in causing release of noradrenaline.
The passive permeability of the skin of anuran amphibia: a comparison of frogs (Rana pipiens) and toads (Bufo marinus).
Authors: Bentley P J , Yorio T
Published: December 2014

1. Efflux of Na across dorsal skin, in vitro (bathed on both sides with Ringer solution), of frogs and toads were similar, but it was greater in ventral skin from the latter. 2. The efflux of Na declined, in both species, when the external surface of ventral, but not dorsal, skin was exposed to hyposmotic solutions with a low Na concentration. This change in Na permeability was influenced by the low osmotic concentration as well as the low Na concentration. 3. Efflux of Cl was similar in both the dorsal and ventral skin preparations (Ringer on both sides) from frogs and toads. 4. Chloride efflux declined in all skin preparations exposed on the external surface to dilute Ringer solution. Solute replacement with sucrose or choline or Na2SO4 showed that the decreased Cl efflux was principally due to the low Cl concentration, though Na may also contribute. This observation suggests the presence of Cl‐/Cl‐ exchange diffusion mechanism. 5. Cutaneous urea permeability was less in toads than frogs and the dorsal and ventral skin was similar with respect to this solute in each species. 6. The presence of external hyposmotic solutions reduced the efflux, but not the influx, of urea across frog, but not toad, skin and it appeared that solvent 'drag' may contribute to this change. 7. Diffusion permeability to water was greater in frogs than toads and in the latter the ventral skin was more permeable than the dorsal. 8. The passive permeability of amphibian skin shows considerable interspecific and regional differences to various molecules which do not necessarily parallel each other. The control of passive cutaneous permeability appears to involve a variety of specific mechanisms, the distribution of which may have evolved during their adaptation to different environments.
Brain stem afferents to the rat medial septum.
Authors: Segal M
Published: December 2014

1. Activity of neurones in the medial septal nucleus and the diagonal band was recorded from urethane anaesthesized rats. Responses of the cells to electrical stimulation of the raphe nuclei and nucleus locus coeruleus (LC) were measured. 2. LC stimulation caused a long latency, 30‐100 msec, and long duration, 100‐300 msec cessation of spontaneous activity of most recorded neurones. When bursting‐type neurones were recorded, the stimulation occasionally caused a synchronized repetitive bursting firing pattern. 3. Pre‐treatment with drugs which interfere with catecholamine neurotransmission, i.e. reserpine and 6OHDA, prevented the appearance of cellular responses to LC stimulation. 4. Stimulation of the dorsal or the median raphe nuclei generated more complex and less clear‐cut responses. These included several types of long (20‐50 msec) and short (2‐5 msec) latency responses. These responses were also accompanied in some cells by synchronized repetitive bursting. 5. Interference with serotonin neurotransmission with PPCA or reserpine reduced the detection of long latency responses. 6. Short latency responses accompanied by evoked field potentials were recorded also after stimulation of dorsal tegmental nucleus. 7. Rates of spontaneous firing cells were augmented after monoamine neurotransmission interruption whereas after fornix lesion, when there is supposedly an increased monoamine innervation of the septum, cells fire at lower rates than normal. 8. It is suggested that noradrenaline and serotonin may serve as neurotransmitters in the medial‐septum‐diagonal band areas.
Inhibitory effects of acetylcholine on neurones in the feline nucleus reticularis thalami.
Authors: Ben-Ari Y , Dingledine R , Kanazawa I , Kelly J S
Published: December 2014

1. Short iontophoretic pulses of acetylcholine (ACh) inhibited almost every spontaneously active cell encountered in the nucleus reticularis thalami of cats anaesthetized with a mixture of halothane, nitrous oxide and oxygen. On 200 cells the mean current needed to eject an effective inhibitory dose of ACh was 67 +/‐ 2 nA. When the ACh‐evoked inhibition was mimicked by gamma‐aminobutyric acid (GABA) or glycine on the same cell, the current required to release ACh was found to be approximately twice as great as that required to release an equally effective dose of GABA or glycine. 2. ACh inhibitions developed with a latency which was very much shorter than that for ACh excitation in cells of the ventrobasal complex. The latency of the ACh‐evoked inhibition was as rapid as the onset and offset of the excitation of the same cells glutamate and their inhibition by GABA or glycine. 3. The firing pattern of ACh‐inhibited neurones in the nucleus reticularis was characterized by periods of prolonged, high frequency bursts, and their mean firing frequency was 22 Hz. Raster dot displays and interspike interval histograms showed that whereas ACh suppressed the spikes that occurred between bursts much more readily than those that occurred during bursts, all spikes were equally sensitive to the depressant action of GABA and glycine. Large doses of ACh provoked or exaggerated burst activity. 4. ACh‐evoked inhibition was extremely sensitive to blockade by short iontophoretic applications of atropine, which had no effect on the inhibitions evoked on the same cell equipotent doses of GABA or glycine. The ACh‐evoked inhibitions were also antagonized by dihydro‐beta‐erythroidine released with slightly larger currents. When tested on the same cell, small iontophoretic applications of picrotoxin and bicuculline methoiodide blocked the inhibition evoked by GABA but had no effect on that evoked by ACh. Iontophoretic strychnine only rarely affected the inhibition evoked by ACh, while readily blocking the inhibition evoked on the same cell by an equipotent dose of glycine. In two cats, intravenous strychnine (1‐2 mg/kg) had no effect on the ACh‐evoked inhibition, while greatly reducing the sensitivity of the cell under study to glycine. 5. Only four out of forty‐eight ACh‐inhibted cells tested were inhibited by iontophoretic applications of either guanosine or adenosine 3':5'‐phosphate. 6. Cells of the nucleus reticularis have been shown to have an inhibitory action on the thalamic relay cells, which are excited by ACh. It is suggested that the presence of both ACh excited and inhibited cells in different nuclei of the thalamus could be of considerable functional significance in gating sensory transmission through the thalamus.
The responses of human muscle spindle endings to vibration of non‐contracting muscles.
Authors: Burke D , Hagbarth K E , Löfstedt L , Wallin B G
Published: December 2014

1. In micro‐electrode recordings from the human peroneal and tibial nerves, the responses of thirty‐two primary spindle endings, thirteen secondary spindle endings and three Golgi tendon organs were studied during vibration of the tendons of the receptor‐bearing muscles in the leg. The amplitude of the applied vibration was 1‐5 mm and the frequency was varied from 20 to 220 Hz. As checked with e.m.g. and torque measurements, the muscles of the leg were relaxed during the sequences analysed. 2. Providing that the vibrator was accurately applied, all endings responded with discharges phase‐locked to the vibration cycles, the discharge rates being at the vibration frequency or at subharmonics of that frequency. The response to vibration was of abrupt onset and offset, was maintained for the duration of vibration, and was not subject to fluctuation with changes in attention or with remote muscle contraction. 3. The maximal discharge rate that could be achieved varied from one ending to the next, and increased with the length of the receptor‐bearing muscle. For endings driven at their maximal rate an increase in vibration frequency produced a decrease in discharge rates as the ending changed to a subharmonic pattern of response. The converse occurred on decreasing vibration frequency. 4. For any given muscle length, primary endings could generally be driven to higher rates than secondary endings but there was a wide range of responsiveness within each group and a significant overlap between the groups. At medium muscle length, the most responsive primary endings could be driven up to 220 Hz but secondary endings did not reach discharge rates higher than 100 Hz. 5. With combined vibration and passive movements, primary endings exhibited maximal vibration responsiveness during the stretching phases, sometimes firing twice per vibration cycle. During the shortening phases, however, they usually ceased responding to the vibratory stimulus. The vibration responsiveness of secondary endings was not potentiated to the same extent by on‐going muscle stretch or reduced to the same extent by on‐going muscle shortening. Thus, during shortening, secondary endings may be more responsive than primary endings. 6. The responses of primary endings to tendon taps were reduced during muscle vibration, a reduction which probably contributes to vibration‐induced suppression of tendon jerks. Additionally, as the muscle shortened after tendon percussion, there was a transient pause in the response to vibration.
The arrangement of collagen fibrils in the iridescent cornea of the scorpion fish, Taurulus (Cottus) bubalis, and the transparency of vertebrate corneal stroma.
Authors: Lythgoe J N
Published: December 2014

The iridescent layer in the corneal stroma of the scorpion fish, Taurulus (Cottus) bubalis (Scorpaeniformes), is composed of alternating thin lamellae of normal stroma containing collagen fibrils and lamellae of an amorphous dense‐staining material. 2. Iridescence is lost after conventional resin embedding procedures, but is retained after embedding in urea‐glutaraldehyde polymer. 3. The retention of iridescence and the absence of gross thickness changes during embedding in urea‐glutaraldehyde polymer are an indication that the fine structure of the cornea is less altered than by conventional resin embedding. 4. It is believed that in life the collagen fibrils in the cornea of the scorpion fish and the cornea of the frog and rabbit are slightly larger and much more closely packed than is revealed by conventional resin‐embedded sections.
Relationship between internal calcium and outward current in mammalian ventricular muscle; a mechanism for the control of the action potential duration?
Authors: Bassingthwaighte J B , Fry C H , McGuigan J A
Published: December 2014

In sheep and calf ventricular bundles, increasing the internal calcium by increasing the frequency of voltage‐clamping to plateau range potentials increased the time‐independent outward current. This effect was more marked with higher [Ca]o, and was reduced if the Ca current blockers Verapamil or D 600 were used. 2. If the internal Ca was increased by the addition of cyanide and reduction of external sodium the outward current was also increased. The frequency‐dependent increase in outward current also occurred in this Na‐poor (12 mM) solution. 3. Tension measurement on the ventricular bundles showed that a Na‐free solution with cyanide did not cause a contracture. On changing from Tyrode to a Na‐free solution containing cyanide, and on changing back to Tyrode there was a potentiation of the twitch. 4. In Na‐poor solution with cyanide, although no contracture was found, ECa was less positive, suggesting that under these circumstances Ca accumulates at the inner side of the membrane, but not around the myofibrils. 5. The prolongation of the action potential in Cl‐free solution is frequency‐dependent. A greater prolongation is seen at lower frequencies suggesting that Cl current is relatively more important for repolarization at lower frequencies of stimulation. 6. It is suggested that calcium at the inner side of the membrane sets the level of the background outward current. A feed‐back mechanism on this basis is proposed for the control of the action potential duration. Various factors that could influence this basic mechanism are discussed.