bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced ATP concentration as a basis for synaptic transmission failure during hypoxia in the in vitro guinea‐pig hippocampus
Authors: Lipton Peter , Whittingham Tim S. 
Published: December 2014

1. Experiments were performed to determine whether a decrease in tissue ATP contributes to the rapid failure of cerebral synaptic transmission during hypoxia. Transmission between the perforant path and the dentate granule cells in the in vitro hippocampus was studied.2. Hippocampal slice ATP is decreased by ∼ 15% at the time that the evoked response begins to diminish in standard Krebs bicarbonate buffer. This is about 2 min after the onset of hypoxia.3. When transmission failure is accelerated by increasing extracellular K+ from 4·4 to 13·4 mM, the evoked response begins to decay about 30 sec after exposure to hypoxia. There is no decrease in hippocampal slice ATP at this time.4. However, ATP in the molecular layer (the synaptic region of the tissue) is decreased by ∼ 15% at the time the evoked response begins to decay in the slices exposed to elevated K+ concentration.5. Exposing the hippocampal slice to 25 mM‐creatine for 3 hr elevates molecular layer phosphocreatine fourfold. Synaptic transmission during hypoxia survives three times as long as it does in the absence of creatine.6. In the creatine fortified medium, molecular layer ATP no longer declines within 30 sec of hypoxia. However the molecular layer ATP does decline within 90 sec of hypoxia, the time at which the evoked response begins to decay in this creatine‐fortified buffer.7. The results establish that ATP in the region of the active synapses is lowered when the first signs of electrophysiological failure appear during hypoxia. They also show that maintaining ATP for longer than normal during hypoxia is associated with a prolonged maintenance of the evoked response. They thus suggest that a decline in ATP is one factor causing hypoxic block of synaptic transmission.8. It is further suggested that the very rapid failure of the electroencephalogram during anoxia may also result from a decline in ATP.
The effects of atropine on [3H]acetylcholine secretion from guinea‐pig myenteric plexus evoked electrically or by high potassium
Authors: Alberts P. , Bartfai T. , Stjärne L. 
Published: December 2014

1. The myenteric plexus‐longitudinal muscle preparation of the guinea‐pig ileum was incubated with [3H]choline (1·125‐1·5 μM), and then superfused with Tyrode solution containing hemicholinium‐3 (10 μM). Secretion of [3H]acetylcholine ([3H]ACh) was evoked either (a) by electrical field stimulation (0·5‐15 Hz, 150 shocks per period, 0·5 msec), used to ‘indirectly’ depolarize the varicosities of nerve terminals, or (b) by high potassium (40 mM with 1 μM‐tetrodotoxin, for 6 min, or 80 mM without tetrodotoxin, for 1 min), to ‘directly’ depolarize varicosities.2. With these stimulation parameters, which yielded about the same fractional secretion of [3H]ACh, and with eserine (10 μM) present in the medium, atropine (1 μM) enhanced the ‘indirectly’, electrically evoked secretion 3·65±0·34 (n = 6) fold, and that caused by 40 mM or 80 mM‐potassium 1·82±0·06 (n = 6) or 1·55±0·09 (n = 10) fold, respectively. Atropine thus enhanced ‘indirectly’, electrically evoked secretion 4‐fold more than that caused by ‘direct’ depolarization of varicosities with high potassium (P < 0·001).3. This difference is not likely to be caused by depression of the sensitivity of the presynaptic muscarinic receptors to ACh released by nerve stimulation, caused by the hypertonicity of the medium in the potassium stimulation experiments. The medium made hypertonic by addition of Tris‐HEPES (80 mM) did lower the binding affinity of membrane preparations of (pre‐ and post‐synaptic) muscarinic receptors, to carbamylcholine, and also the contractile responsiveness of the longitudinal muscle to this agent, in both cases to about one half. But it did not appear to alter the responsiveness of either pre‐ or post‐synaptic muscarinic receptors to endogenous ACh, released by nerve stimulation.4. The results support a dual‐mode model for the muscarinic negative feed‐back control of ACh secretion from the nerve terminals of this preparation, mainly operating by restriction of the invasion of terminals, and only secondarily by depression of the efficiency of depolarization—secretion coupling in invaded varicosities.5. Since this model has earlier been proposed to apply for the control of secretion of [3H]noradrenaline from the micro‐anatomically similar nerve terminals of noradrenergic nerves, the present findings suggest that the model may have a wider biological significance, and possibly apply to the control of the secretory activity of boutons‐en‐passant nerve terminals in general.
Control scheme governing concurrently active human motor units during voluntary contractions
Authors: de Luca C. J. , LeFever R. S. , McCue M. P. , Xenakis A. P. 
Published: December 2014

1. The electrical activity of up to eight concurrently active motor units has been recorded from the human deltoid and first dorsal interosseous muscles. The resulting composite myoelectric signals have been decomposed into their constituent motor‐unit action potential trains using a recently developed technique.2. A computer cross‐correlation analysis has been performed on motor‐unit firing rate and muscle‐force output records obtained from both constant‐force and triangular force‐varying isometric contractions performed by normal subjects, and three groups of highly trained performers (long‐distance swimmers, powerlifters and pianists).3. The temporal relationships between firing rate activity and force output have provided evidence that the deltoid of long‐distance swimmers has a significantly higher percentage of slowly fatiguing fibres than that of normal subjects.4. Results showed that both muscles are incapable of producing a purely isotonic contraction under isometric conditions. Small, possibly compensatory force variations at 1‐2 Hz result from a common drive to all active motoneurones in a single muscle pool.5. Rapid force reversals during triangular, force‐varying isometric contractions appear to be accomplished through a size‐related motor‐unit control scheme. All firing rates decline prior to the force peak, but small motor units with slow‐twitch responses tend to decrease their firing rates before large, fast‐twitch motor units. This mechanism is not visually controlled, and does not depend on force rate in non‐ballistic contractions.
Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: an in vitro study
Authors: Crepel F. , Dhanjal S. S. , Sears T. A. 
Published: December 2014

1. The responses of Purkinje cells to short duration (pulse) ionophoretic applications of L‐aspartate (L‐asp), L‐glutamate (L‐glu), N‐methyl DL‐aspartate (NMDLA) and quisqualic acid in their dendritic fields were studied in vitro on sagittal slices of lobules IX and X of the adult rat cerebellum.2. Pulse application of L‐asp or L‐glu evoked transient and dose‐dependent increases in the firing rate of the simple spikes recorded extracellularly as single units. When the ionophoretic electrode was positioned in the dendritic field of the Purkinje cells, the lowest thresholds for L‐glu and L‐asp mediated excitations of the cells were as low as 25 and 35 pC respectively, with a latency for maximal responses as brief as 7 ms.3. In intracellular recordings these excitatory responses consisted of depolarizations of up to 18 mV in amplitude and with depolarizing slopes up to 0·52 mV/ms. They were generally unaccompanied by changes in cell input resistance in contrast to the marked decrease which occurred in response to steady applications of large doses of L‐asp and L‐glu.4. The spatial distribution of the excitatory sites confirmed that the dendritic sensitivity to L‐glu was greater than that of the soma and showed that the same was true for L‐asp. In 34% of cells the sensitivity for L‐asp declined markedly in the upper region of the molecular layer, whereas it remained high for L‐glu; no such differential sensitivity was detected in the remaining 66% of cells.5. Inhibitory responses, antagonized by 10−5 M‐bicuculline in the bath, were also induced in Purkinje cells by L‐glu and L‐asp when the ionophoretic electrode was withdrawn from the excitatory sites by as little as 8 μm and up to 40 μm upward or downward along the track of parallel fibres or positioned as far as 250 μm laterally.6. Whenever it was applied in the molecular layer, the pulse application of NMDLA elicited no excitatory response in Purkinje cells recorded extra or intracellularly. However, slow depolarizations accompanied by a slight increase in cell input resistance were obtained with steady applications of 20‐50 nA of the drug for 20‐30 s.7. In contrast, pulse application of quisqualic acid appeared to have the same type of fast excitatory effect on Purkinje cells as L‐asp and L‐glu, but its potency was greater and its action more prolonged. Furthermore, its steady application led to an abrupt and marked decrease in cell membrane resistance.8. The excitatory effects of L‐asp, L‐glu and quisqualic acid were antagonized by L‐glutamic acid diethyl ester more consistently than by D‐α‐aminoadipate, suggesting together with previous observations that L‐asp and L‐glu act on Purkinje cells via quisqualic acid rather than via NMDLA receptors.
The effects of substance P on histamine and 5‐hydroxytryptamine release in the rat
Authors: Fewtrell C. M. S. , Foreman J. C. , Jordan C. C. , Oehme P. , Renner H. , Stewart J. M. 
Published: December 2014

1. Substance P (SP) induces histamine release from isolated rat peritoneal mast cells at concentrations of 0·1‐10 μM.2. Inhibitors of glycolysis and oxidative phosphorylation prevent the release of histamine induced by SP.3. Cells heated to 47 °C for 20 min release histamine when treated with an agent causing cell lysis but fail to release in response to SP.4. SP does not release histamine by interacting with cell‐bound IgE.5. Histamine release by SP is rapid, with more than 90% of the response occurring within 1 min of the addition of the peptide to mast cells at 37 °C.6. Substance P, unlike antigen—antibody or compound 48/80, does not show enhanced release of histamine when calcium (0·1‐1 mM) is present in the extracellular medium but calcium increases the response to SP when the ion is added after the peptide. Extracellular calcium (0·1‐1 mM), magnesium (1‐10 mM) and cobalt (0·01‐0·1 mM) all inhibit SP‐induced histamine release when added before the peptide. Pre‐treatment of the cells with EDTA (10 mM) and washing in calcium‐free medium inhibits the histamine release induced by SP.7. Histamine release induced by SP was optimum at an extracellular pH of 7·2.8. A number of peptides structurally related to SP were examined for histamine‐releasing activity. At the concentrations tested, the N‐terminal dipeptides Lys‐Pro and Arg‐Pro, tuftsin, physalaemin, eledoisin, SP3-11, SP4-11 and [p‐Glu6, p‐amino Phe7]‐SP6-11 were all found to be inactive. The relative activities of the other peptides were: [Formula: see text]9. Rat basophilic leukaemia cells (RBL‐2H3) fail to respond to SP at concentrations which activate rat mast cells. Release of 5‐hydroxytryptamine by immunological activation of RBL cells is not changed by the presence of SP.10. The mechanism of action of SP on mast cells and the nature of the SP receptor on mast cells is discussed in relation to SP receptors in other cell types.
Forces generated at the thumb interphalangeal joint during imposed sinusoidal movements
Authors: Brown T. I. H. , Rack P. M. H. , Ross H. F. 
Published: December 2014

1. A method is described for driving the interphalangeal joint of the thumb through repeated sinusoidal flexion—extension movements, while immobilizing other joints of the wrist and hand.2. The joint met the sinusoidal movement with a force that fluctuated in an approximately sinusoidal manner. This paper is concerned with the relationship between the position and force sinusoids.3. When the thumb was relaxed the forces were small, but when the flexor pollicis longus was tetanically stimulated there was a large force change in response to each cycle of the movement. In either case, the maximum resistance to extension occurred during the later part of the extension movement, some 20°‐45° in advance of maximum extension. A similar result was obtained when the subject exerted a maximal voluntary flexing force.4. The resistance to movement can conveniently be displayed as a stiffness vector, the amplitude of which is the force/displacement, and the phase is the angle by which the force sinusoid leads the position sinusoid.5. When the subject maintained a continuous, though sub‐maximal, flexing effort the timing of the force fluctuations changed with changing frequency of movement in a characteristic way, and the stiffness vectors described a C‐shaped or spiral path. With increasing frequency the stiffness vectors moved round this path in a clockwise direction.6. For descriptive purposes the resistance to movement can usefully be regarded as the vector sum of a reflex and a non‐reflex component. Since the reflex pathway involves significant conduction delays, the reflex force can be expected to appear later in the cycle of a higher frequency movement, and give rise to a vector which moves round in a clockwise direction as the frequency increases. The non‐reflex stiffness, however, changes much less with frequency.7. It is concluded that the size of the C‐shaped or spiral vector path gives an indication of the strength of the reflex activity, while the position of the high frequency points gives an indication of the non‐reflex resistance to the movement.
Denervation changes in normal and myasthenia gravis human muscle fibres during organ culture
Authors: Cull‐Candy S. G. , Miledi R. , Uchitel O. D. 
Published: December 2014

1. Human intercostal nerve‐muscle obtained from normal and myasthenia gravis affected patients has been organ cultured for up to 5 weeks at 23 °C. In addition normal nerve‐muscle has been cultured for up to 2 weeks at 36 °C. Muscle fibres had normal resting and overshooting action potentials. Input resistances dropped markedly after 21 days at 23 °C or 10 days at 36 °C.2. Muscle fibre action potentials became partially resistant to tetrodotoxin (10−7 g/ml.) after culturing for 8 days at 36 °C.3. Extrajunctional acetylcholine (ACh) sensitivity was compared in fresh and cultured muscle. Fresh normal fibres possessed extrajunctional ACh sensitivity covering several hundred micrometres around the end‐plate and at the muscle—tendon junction. Myasthenia gravis affected fibres had reduced extrajunctional sensitivity at the end‐plate and no detectable ACh sensitivity near the tendon.4. Less than one third of normal muscle bundles showed an increased area of ACh sensitivity after several days in organ culture. Under the same conditions myasthenic muscle bundles did not show an increase in extrajunctional ACh sensitivity,5. M.e.p.p.s were present for 2‐4 days in normal fibres cultured at 36 °C. In normal and myasthenic muscles cultured at 23 °C m.e.p.p.s disappeared after 6‐8 days and re‐appeared in some fibres (50%) after approximately two weeks in organ culture. These m.e.p.p.s were abolished by curare and increased in frequency by hypotonic solution suggesting they are due to the release of ACh‐packets from Schwann cells.6. Electron microscopic examination of cultured human muscle indicates that the disappearance of m.e.p.p.s corresponds with degeneration of nerve terminals.7. In muscle bundles shown to possess m.e.p.p.s after 13‐14 days, the synaptic gutter, which had been vacated by the nerve terminal, was usually occupied by a Schwann cell or projections of Schwann cell cytoplasm. This indicates that the Schwann cell at denervated human end‐plates may be capable of releasing packets of ACh.8. It is concluded that the organ culture system described here is suitable for studying normal and diseased human muscle fibres. Using this system we find that the denervation changes which follow nerve transection appear to be similar in most respects at normal and myasthenic end‐plates.
Effects of sarcomere length on the force—pCa relation in fast‐ and slow‐twitch skinned muscle fibres from the rat
Authors: Stephenson D. G. , Williams D. A. 
Published: December 2014

1. Steady‐state force—pCa relations were determined for mechanically skinned fibres of fast‐ and slow‐twitch rat skeletal muscle, extensor digitorum longus (e.d.l.) and soleus respectively, at varied sarcomere lengths and temperatures (3‐35 °C).2. This relation was different for the two fibre types at all sarcomere lengths, with soleus fibres having lower Ca2+ concentration threshold for activation and requiring a wider Ca2+ concentration range to reach force saturation.3. An increase in sarcomere length within the range 2·2‐3·6 μm reversibly shifted the steady‐state force—pCa curves for both fast‐ and slow‐twitch fibres toward lower Ca2+ without affecting the steepness of the curves.4. The results are consistent with the idea that the sensitivity of the contractile apparatus to Ca2+ is increased with increasing sarcomere length.5. The change in apparent Ca2+ sensitivity (measured as the change in pCa corresponding to 50% Ca‐activated force (ΔpCa50)) was approximately proportional to the change in sarcomere length (ΔSL) at all temperatures for both types of muscle fibre.6. The proportionality coefficient (ΔpCa50/ΔSL) was higher for slow‐twitch fibres than for fast‐twitch fibres by a factor of 1·5‐2·0 at all temperatures investigated.7. The force—pCa relation was less affected by changes in sarcomere length at lower (3‐5 °C) than at higher temperatures (22‐35 °C).8. The sarcomere length—maximum force relation obtained with skinned fibres for sarcomere lengths between 2·10 and 4·05 μm was similar for both fibre types at all temperatures despite large temperature dependent variations in maximum Ca‐activated force response. Maximum force decreased linearly to zero between ca. 2·8 and 3·95 μm; remained high and essentially constant between ca. 2·40 and 2·80 μm, and decreased significantly below 2·40 μm.9. Myofilament‐generated tension oscillations produced by partially activated soleus skinned fibres are highly length dependent, disappearing completely when sarcomere length is increased above 3·15 μm.
The signal‐to‐noise characteristics of rod—cone interaction
Authors: Bauer G. M. , Frumkes T. E. , Nygaard R. W. 
Published: December 2014

1. The influence of rods on cone‐mediated vision was assessed in eight human observers. To this end, increment threshold functions were obtained by determining thresholds of a cone‐detected test flash (25 ms duration, 655 nm wave‐length, 13′ diameter) as a function of the illuminance of larger, 500 ms duration, rod‐detected masking flashes. The type of photoreceptor influenced by each stimulus was carefully checked by means of a series of control procedures involving action spectra and selective rod adaptation.2. When the rod mask was 512 nm in wave‐length, 40′ in diameter, and less than one scotopic td in illuminance, increment threshold functions show that [Formula: see text], where ICth is cone test threshold, IR is rod mask illuminance, and D is a dark noise term similar to that used by Barlow (1956). Further increases in IR have no additional influences on cone test threshold until threshold is influenced by the combined action of the mask on both rods and cones. If IR is expressed in terms of scotopic flux rather than illuminance, the functional relationship obtained with all rod masks ≤ 40′ diameter and ≤ 580 nm wave‐length is identical.3. Over the range of illuminance where a square‐root relationship is obtained, probability of seeing functions show that a signal‐to‐noise mechanism limits the detectability of the cone test flash. These findings suggests a quantitative model in which cones produce a signal in a detector which is proportional to the illuminance of the cone test flash. Within a neural locus designated E (excitatory spatial summator), a response is produced which over at least a 40′ diameter area, is proportional to the scotopic flux of the rod mask. E, however, feeds into a gain box, S, which saturates at illuminance levels at least 3 log10 units less than usual estimates of rod saturation. Other than saturation, S behaves in a linear fashion.4. As diameter increases beyond 60′, rod masks of equal scotopic illuminance have progressively less influence on cone test threshold; rod masks > 2° have negligible influence on cone test threshold. We propose that I (inhibitory spatial summator), a neural locus which responds to scotopic flux provided over a very large area, attenuates the activity of E. The combined action of E and I is designated a rod channel. The response of cones and the rod channel summate at a detector. Within the detector, cone signals are distinguished from rod‐related activity and intrinsic dark noise on the basis of signal‐to‐noise discriminations.5. The neural substrate for this rod channel most probably involves the combined action of several neurones which synapse within the inner plexiform layer of the retina. The relationship of this rod channel to other perceptual phenomena is discussed.
Neurotrophic control of channel properties at neuromuscular synapses of rat muscle
Authors: Brenner H. R. , Sakmann B. 
Published: December 2014

1. Ectopic neuromuscular synapses formed when the fibular nerve was implanted into the proximal part of rat soleus muscle and the soleus nerve was cut. The gating properties of acetylcholine (ACh) receptor channels in the newly formed ectopic and in the denervated original end‐plates were examined at various stages of ectopic synapse formation.2. At ectopic end‐plates the apparent mean open time of ACh receptor channels changes during synaptic development. Channels in immature ectopic end‐plates, examined 1 week after cutting the soleus nerve, have apparent mean open times of ∼4 ms (at ‐70 mV, 22 °C), similar to those of the extrasynaptic ACh receptor channels of completely denervated fibres. The channel gating of mature ectopic end‐plates, examined 3‐7 weeks after nerve section, is characterized by a mean open time of ∼1 ms and resembles that found in normal end‐plates of adult fibres.3. The conversion of end‐plate channel gating occurs during the second and third week of synapse formation. During this period two discrete classes of channels with different gating behaviour are present in the ectopic end‐plate.4. Examination of ectopic end‐plates in the electron microscope reveals that junctional folds begin to appear in the subsynaptic membrane during the period of channel conversion.5. At the denervated original end‐plates of ectopically innervated fibres the apparent mean open time of ACh receptor channels remains similar to that of normally innervated end‐plates. Original end‐plates retain the normal synaptic class of channel for at least 42 days after denervation. At this time, most of the ACh receptors present originally in the membrane have been replaced by newly inserted receptors.6. At former end‐plates of completely denervated fibres ACh activates two classes of channels, even when most of the ACh receptors originally present in the end‐plate have been replaced by new receptors.7. The results show that during synapse formation a neurally controlled conversion of ACh receptor channels occurs about 2‐3 weeks after establishment of the nerve muscle contact. Thereafter end‐plate channel properties are independent of neural influences. These observations are consistent with a mechanism of channel conversion whereby the nerve modifies not the ACh receptor channel itself, but another constituent of the end‐plate membrane which determines the gating properties of end‐plate channels.