bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuromuscular transmission in a mammalian preparation in the absence of blocking drugs and the effect of D‐tubocurarine
Authors: Hubbard J. I. , Wilson D. F. 
Published: December 2014

1. Neuromuscular transmission in the presence and absence of
D‐tubocurarine was examined in cut muscle preparations of the rat diaphragm using intracellular recording techniques. The method of localizing the end‐plates is described and evidence is presented indicating that end‐plate potential (e.p.p.) recordings were made close to the end‐plate region and that reliable estimates of the quantum content of e.p.p.s could be made.2. During repetitive nerve stimulation at rates between 2 and 10 Hz, e.p.p. amplitudes declined in response to the first 6–8 stimuli to reach a plateau level which was maintained for 1500 stimuli. At higher rates of stimulation some 500–700 stimuli were needed before a plateau level of amplitude was reached. It was demonstrated that these amplitude changes reflected similar changes in the quantal release of ACh.3. Tubocurarine in a concentration of 4 × 10−8 g/ml. had no effect on quantal release but did reduce quantal size. In the presence of tubocurarine, 8 × 10−8 g/ml., small reductions in the quantum content of the first e.p.p. in response to a train of stimuli and the maintained quantal release were observed. In the presence of tubocurarine 4 × 10−7 g/ml., the quantum content of the first e.p.p. and the maintained release were further reduced, to the level previously described for curarized preparations. At this concentration a significant effect of tubocurarine upon the presynaptic measurements could be detected (t test). Studies on single junctions revealed that the post‐ and presynaptic effects of tubocurarine developed with different time courses.4. Neuromuscular preparations in vivo have been reported to be much more resistant to maintatined stimulation than curarized neuromuscular preparations in vitro. It is suggested that this disparity is explained by the presynaptic action of tubocurarine.5. From the quantal release rates of the present investigation and reports of ACh release/stimulus/end‐plate in previous investigations it can be calculated that a quantum of ACh contains between 12,000 and 21,000 molecules.
The specific effect of potassium on transmitter release by motor nerve terminals and its inhibition by calcium
Authors: Cooke J. D. , Quastel D. M. J. 
Published: December 2014

1. There exist two distinct effects of potassium on the transmitter release system, one which develops rapidly and another which becomes maximal much more slowly. The fast effect is inhibited by raised Ca2+, which does not inhibit transmitter release evoked by depolarizing pulses. Thus the fast effect is not secondary to nerve terminal depolarization.2. The fast effect of K+ was found to consist in an increase in the slope of the linear relation between log m.e.p.p. frequency and nerve terminal depolarization. This effect is complete within a few seconds, is inhibited by raised Ca2+, and is not produced by prolonged focal or electrotonic depolarization, which instead tends to reduce the slope of log m.e.p.p. frequency vs. depolarization.3. A slope change effect like that of K+ was not found with ouabain or ethanol, nor did these agents depress the slope change effect of K+. The specific action of K+ was not exerted on release evoked in the absence of Ca2+ by ethanol, chloral hydrate, or raised osmotic pressure.4. It is suggested that the specific action of K+ is to increase the lability of nerve terminal Ca permeability with respect to depolarization of the nerve terminal membrane, while the slow effect of K+ simply reflects nerve terminal depolarization, slow to become maximal because of diffusion barriers limiting access of raised K+ to the Ranvier nodes of motor axons.
Effect of sodium and sodium‐substitutes on the active ion transport and on the membrane potential of smooth muscle cells
Authors: Casteels R. , Droogmans G. , Hendrickx H. 
Published: December 2014

1. The changes of the ion content and of the membrane potential of taenia coli cells have been studied during prolonged exposure to Na‐deficient solutions containing either Li or choline.2. A K‐free solution containing either 71 m
M‐Na‐71 m
M‐Li or 71 m
M‐Na‐71 m
M choline causes a slower loss of cellular K than a 142 m
M‐Na solution. In both these Na‐deficient solutions the membrane hyperpolarizes to about −100 mV for periods up to 6 hr. This hyperpolarization is partially abolished by 2 × 10−5
M ouabain.3. Replacing all extracellular Na by Li and maintaining 5.9 m
M‐K causes a fast loss of all Na and a progressive replacement of K by Li. These changes of the intracellular ion content are accompanied by a depolarization of the cells, suggesting that intracellular Li cannot substitute for Na in activating the ion pump.4. Exposing K‐depleted cells to a K‐free 71 m
M‐Na‐71 m
M‐Li solution results in a ouabain sensitive transport of Na and Li against their electro‐chemical gradient.5. The K‐uptake by K‐depleted cells from a solution containing 0.59 m
M‐K is increased by reducing [Na]o to half of its normal value. This finding indicates that external Na inhibits the active Na‐K exchange.6. In Na‐enriched tissues half of the Na efflux is due to a ouabain insensitive Na‐exchange diffusion. If Li is used as a Na substitute, the Na‐Li exchange compensates for the diminution of the Na‐exchange diffusion unless ouabain is added.
Spontaneous activity in isolated bovine mesenteric lymphatics
Authors: Mawhinney H. J. D. , Roddie I. C. 
Published: December 2014

1. Longitudinal tension was measured in isolated segments (approximately 20 mm in length and 2 mm in diameter) of bovine mesenteric lymphatic vessels.2. Seventeen out of thirty‐nine vessels showed regular spontaneous rhythmic contractions, the most common frequency being about 2/min.3. The strength of each contraction was related to the duration of the preceding pause, a longer pause being associated with a stronger contraction.4. Noradrenaline increased the frequency and decreased the amplitude of the contractions. This effect was abolished by α‐receptor blockade with phentolamine.5. Isoprenaline slowed the frequency of the contractions. This effect was abolished by β‐receptor blockade with propranolol.6. Acetylcholine had little effect on the rate of spontaneous contractions.
Prostaglandin E2 and gastric acid secretion in man
Authors: Bennett A. , Stamford I. F. , Unger W. G. 
Published: December 2014

1. Extracts of human stomach homogenized in Krebs solution had more PGE2‐like activity than tissue homogenized in acid/ethanol or in the presence of indomethacin, indicating that the tissue can synthesize PGE2.2. The distribution and synthesis of PGE2‐like substance in human stomach was determined by extracting frozen sections cut parallel to the mucosal surface. Peak levels usually occurred at a depth of 0–600 μm in the mucosa.3. Small amounts of a PGE2‐like substance were present in basal gastric juice, and its concentration was usually even lower in secretion stimulated by pentagastrin or histamine.4. Submaximal acid secretion produced by I.V. infusion of pentagastrin generally fell slightly when indomethacin was administered rectally to inhibit PG synthesis.5. These experiments, together with the findings that orally administered PGE compounds do not inhibit human gastric acid secretion, seem to argue against a possible inhibitory role for PGE2 in gastric acid secretion in man.6. If this is so, it would follow that gastric bleeding caused by aspirin‐like drugs is not due to increased acid secretion. A hypothesis is presented that tissue damage following vasoconstriction and ischaemia, due to inhibition of PG synthesis in blood vessels, contributes to the bleeding.
Metabolic aspects of the synthesis and intra‐axonal transport of noradrenaline storage vesicles
Authors: Banks P. , Mayor D. , Mraz P. 
Published: December 2014

1. Constricted cat hypogastric nerve/inferior mesenteric ganglion preparations have been maintained for 24 hr in vitro, in either test‐tubes or a two compartment box, and used to study the roles of energy metabolism, protein synthesis and calcium ions in the synthesis and transport of noradrenaline storage vesicles in sympathetic neurones.2. When preparations were incubated so that the nerve trunks but not the ganglia were made anoxic, dense‐cored vesicles lost their store of noradrenaline and did not accumulate above the ligature. This was accompanied by profound ultrastructural damage to the nerves.3. When in contact with the ligated nerve trunks, sodium fluoride inhibited the intra‐axonal movement of dense‐cord vesicles but did not deplete them of their stored noradrenaline. When sodium fluoride and pyruvate were present in the medium bathing the nerve trunks the movement of noradrenaline storage vesicles was unaffected.4. Whilst a reduction of the calcium ion concentration in the incubation medium and the inhibition of protein synthesis by cycloheximide prevented the synthesis of dense‐cored vesicles in the neuronal perikaryon they had no effect on the movement of preformed dense‐cored vesicles along non‐myelinated axons.
Blood pressure effects obtained by drugs applied to the ventral surface of the brain stem
Authors: Guertzenstein P. G. 
Published: December 2014

1. In cats anaesthetized with pentobarbitone sodium the effect on arterial blood pressure was examined of substances applied bilaterally to the exposed ventral surface of the brain stem by means of Perspex rings placed lateral to the pyramids and caudal to the trapezoid bodies. Routinely, atropine methyl nitrate, which does not pass the blood—brain barrier, was injected I.V.2. The cholinomimetic substances carbachol and physostigmine, and the amino acids glycine and GABA, caused a fall in arterial blood pressure.3. Atropine produced a small but definite rise in arterial blood pressure, antagonized the depressor effects of the cholinomimetic substances, but not those of the amino acids.4. Strychnine, leptazol and tubocurarine, caused a rise in arterial blood pressure.5. The depressor and pressor effects are due to changes in vasomotor tone. They are central effects brought about by penetration of the substances into the brain tissue from the ventral surface of the brain stem. They are not due to their absorption into the blood stream.6. The depressor effects of the cholinomimetic substances may imitate the action of cholinergic neurones, and those of the amino acids that of central inhibitory neurones ending on cells near the ventral surface of the brain stem and exerting an inhibitory influence on vasomotor tone. The pressor effects of strychnine and tubocurarine may in part result from ‘disinhibition’, i.e. from an antagonistic action produced by these drugs on the amino acids released from the central inhibitory neurones.
Calcium and potassium systems of a giant barnacle muscle fibre under membrane potential control
Authors: Keynes R. D. , Rojas E. , Taylor R. E. , Vergara J. 
Published: December 2014

1. Single barnacle muscle fibres from Megabalanus psittacus (Darwin) were internally perfused and the effects of various internal and external solutions on voltage clamp currents were examined.2. The usual internal solution was 180 m
M‐K+ aspartate (osmotic pressure adjusted to 1000 m‐osmole by adding sucrose). Fibres perfused with this solution gave an average resting potential of −55 ± 5 mV (all potentials are referred to the external solutions as ground). Further increase in internal K concentration depolarized the fibres.3. With membrane current control the total capacitance, referred to apparent membrane surface area, was 21·2 ± 2·4 μF/cm2.4. Under normal conditions, with demonstrably good longitudinal space clamp control, voltage clamp currents associated with certain depolarizing pulses showed oscillations. These oscillations were reduced in frequency and magnitude by lowering the temperature from 20 to 10° C, by eliminating the inward currents with external Ca‐free saline or by reducing the outward currents with internal tetraethylammonium (TEA) or replacement of internal K by Cs.5. With a Na‐ and Ca‐free, 60 m
M‐MgCl2 solution outside depolarizing voltage clamp pulses produced only outward currents. On repolarization the current tail reversed direction at about −70 mV for pulses of less than 50 msec duration. For longer pulses this reversal potential was less negative, suggesting an accumulation of external, or depletion of internal K.6. Both the size of the outward currents and the rate at which they reached their maximum value increased with temperature. The activation energy for the rate constant was about 63 kJ/mole.7. Fibres bathed in Na‐ and Mg‐free, 60 m
M‐CaCl2 saline were excitable. After replacement of the internal K+ with Cs+ or adding 60 m
M‐TEA to the internal solution only sustained inward currents were recorded with depolarization.8. Sustained inward currents could be reduced by external application of 5 m
M‐LaCl3. Tetrodotoxin was not effective even at a concentration of 1000 n
M.9. The rate at which these inward currents reached a maximum value increased with increase in temperature of the bathing solution with an activation energy of the order of 42 kJ/mole.10. The reversal potential of the inward currents changed with the level of internal Ca ions. For a fibre perfused without ethyleneglycol‐bis (β‐aminoethyl ether) N,N′‐tetraacetic acid (EGTA) this reversal potential was 175 mV (internal free Ca 5 × 10−7
M), and was 196 mV for a fibre perfused with 20 m
M‐Tris EGTA (internal free Ca 0·26 × 10−8
M).11. We propose an electrical equivalent circuit to account for most of the observed electrical properties of barnacle muscle fibres. In this model the Ca and the K system are located at different anatomical places and they interact through a series resistance.
Studies on micellar fatty acid uptake by rat intestine in vitro with reference to the role of bile
Authors: Rampone Alfred J. 
Published: December 2014

1. The uptake and esterification to trigylceride of oleic acid in micellar form was studied in rat intestine in vitro. Sacs of the upper half of the everted intestine taken from bile fistula rats were incubated in a buffered solution containing mono‐olein, 14C‐labelled oleic acid and bile salt (sodium taurocholate (NaTch) in concentrations exceeding the critical micellar concentration).2. At 37° C incubation temperature increasing the NaTch concentration enhanced both uptake and esterification. Adding whole rat bile caused uptake to decrease at all NaTch concentrations but had only a slight and variable effect on esterification.3. Lowering the incubation temperature to 0° C suppressed esterification but had no effect on uptake.4. At 0° incubation temperature adding whole bile still decreased fatty acid uptake but had no effect on esterification.5. It is concluded that intestinal fatty acid uptake from micelles is a non‐energy requiring process and that a non‐bile salt component in bile exists which can suppress this process.6. It is suggested that lecithin may be the non‐bile salt component and that it suppressed uptake by interacting either with the micelles or with the epithelial membrane to reduce fatty acid permeability.
DNP‐induced dissipation of ATP in anoxic ventricular muscle
Authors: McDonald Terence F. , MacLeod Don P. 
Published: December 2014

1. During aerobic incubation in 5 mM glucose medium, 10−5 M‐DNP reduced the action potential duration and amplitude and the developed tension of guinea‐pig ventricular muscle more rapidly and to a greater extent than anoxia.2. The DNP effect on electrical and mechanical activity was even more pronounced following prolonged anoxic incubation. Since the action potential duration and developed tension of anoxic ventricular muscle have previously been shown to be dependent on glycolytic ATP, and since the effects of DNP could not be duplicated with NaCN, it was concluded that DNP was exerting an effect in addition to its uncoupling of oxidative phosphorylation.3. Anoxic muscle was incubated with 10−4 M‐IAA or with 10−4 M‐IAA + 10−4 M‐DNP. The ATP content of IAA‐treated muscle was significantly lower than control but in the presence of both IAA and DNP there was a further reduction in ATP and an increased lactate production.4. Sodium azide (10−2 M), a potent inhibitor of mitochondrial ATPase, did not prevent the reduction of ATP in DNP‐treated anoxic muscle.5. Ouabain (10−7 M) partially prevented the rapid decline of action potential duration and developed tension of DNP‐treated anoxic muscle. In addition, the glycoside partially blocked the DNP‐induced break‐down of ATP and stimulation of lactate production.6. Oligomycin (10 μg/ml.) partially prevented the reduction in action potential duration and developed tension of DNP‐treated anoxic muscle.7. It was concluded that DNP induces an ‘energy leak’ by actively promoting the hydrolysis of an high energy glycolytic intermediate at least one step beyond the sites of ATPase inhibition by ouabain and oligomycin.
Pre‐ and post‐ junctional effects of 1‐fluoro‐2,4‐dinitrobenzene at the frog neuromuscular junction
Authors: Edelson Alan M. , Nastuk William L. 
Published: December 2014

1. FDNB increased by 60–90% the depolarization of the end‐plate produced by applied carbachol in frog sciatic nerve‐sartorius muscle preparations.2. In partially curarized preparations, FDNB (0·4 mM) increased the amplitude of the end‐plate potential by a factor of 1·8.3. The quantal content of end‐plate potentials was increased by FDNB (2 mM) as determined by the method of failures.4. After approximately 25–35 min, neuromuscular transmission was blocked by 0·4 mM‐FDNB, as evidenced by abolition of neurally elicited end‐plate potentials. At this stage miniature end‐plate potentials could still be recorded, which indicates that the neuromuscular block was presynaptic.5. FDNB (0·4 mM) increased miniature end‐plate potential frequency several hundred‐fold when the Ringer solution contained normal calcium concentration (1·8 mM) or 0·45 mM calcium and 5·4 mM magnesium.6. During the first 60 min of exposure to 0·4 mM‐FDNB there was a slight drop (4–6 mV) in resting potentials of muscle fibres. During this period directly initiated action potentials showed a marked decrease in the rate of repolarization and a small decrease in the amplitude and rate of rise.7. Using the technique of point voltage clamping in tetrodotoxin‐treated muscles, it has been found that FDNB almost completely abolished the active increase in gK during stepwise depolarization of the nonjunctional muscle fibre membrane from −90 to 0 mV. The passive outward leakage current appeared unaffected by FDNB.
Electrophysiological identification of cell bodies of the tubero‐infundibular neurones in the rat
Authors: Sawaki Yukiko , Yagi K. 
Published: December 2014

1. Electrical stimulation of the median eminence induced unit responses in the suprachiasmatic, the ventromedial and the arcuate nuclei of the hypothalamus in the female rat anaesthetized with urethane.2. Arcuate units with constant latency responded in one to one fashion to repetitive stimuli up to 286 Hz.3. A conditioning stimulus just above threshold increased the threshold and latency for responses produced by a test stimulus given within 6 msec after the conditioning stimulus. Absolute refractory period was 1·4–2·0msec.4. A conditioning stimulus just below threshold did not alter the threshold and latency of the responses to test stimuli at any interval.5. A stimulus given within a time period following a spontaneously occurring spike failed to induce a unit response.6. It is concluded that the arcuate nucleus of the hypothalamus includes cell bodies of origin of the tubero‐infundibular axons in the rat.
The inotropic effect on the heart of stimulating the vagus in the dog, duck and toad
Authors: Furnival C. M. , Linden R. J. , Snow H. M. 
Published: December 2014

1. The chronotropic and inotropic effects of stimulating the vagus on the hearts of the dog, duck and toad were studied.2. The maximum rate of rise of pressure in the left ventricle (dP/dt max) measured at a constant heart rate and mean aortic pressure was used as an index of the inotropic changes.3. The sensitivity of dP/dt max as an index of inotropic changes brought about by stimulating the vagus was established in the toad where a 49% reduction in heart rate was associated with a 30% reduction in dP/dt max.4. In the dog stimulation of the vagus resulted in a reduction in heart rate of 38% and only a small reduction in dP/dt max of 6%.5. Results similar to those found in the dog were obtained in the duck where the reduction in heart rate of 44% was associated with reduction in dP/dt max of only 3%.6. It is concluded that the vagus has only a small and negligible negative inotropic effect on the ventricles of the dog and duck.
Changes in firing rate of human motor units during linearly changing voluntary contractions
Authors: Milner‐Brown H. S. , Stein R. B. , Yemm R. 
Published: December 2014

1. Human subjects generated approximately linearly increasing or decreasing voluntary, isometric contractions using the first dorsal interosseus muscle of the hand.2. Single motor units began firing at 8·4±1·3 impulses/sec (mean ±
S.D. of an observation) and increased their firing rate 1·4±0·6 impulses/sec for each change of 100 g in voluntary force. These values were independent of the threshold force for recruiting motor units.3. At intermediate rates of increasing and decreasing voluntary force (one complete cycle every 10 sec) the firing rate of single motor units varied linearly with force over the entire range of forces studied. However, during slow increases in voluntary force, the firing rate tended to reach a plateau, while during rapid increases an initial train of impulses at a roughly constant rate was observed.4. The relative importance of recruitment and increased firing rate, as mechanisms for increasing the force of voluntary contraction, was determined. Only at low levels of force is recuitment the major mechanism. Increased firing rate becomes the more important mechanism at intermediate force levels and contributes the large majority of force if the entire physiological range is considered.
Influence of chronic neostigmine treatment on the number of acetylcholine receptors and the release of acetylcholine from the rat diaphragm
Authors: Chang C. C. , Chen T. F. , Chuang Sing‐Tai 
Published: December 2014

1. Rats were treated twice daily for 7 days with neostigmine and the diaphragm was isolated for study of its acetylcholine content, release upon nerve stimulation and the number of receptors in the end‐plate.2. While the content of total acetylcholine was unchanged, the release of acetylcholine on stimulation with trains of 500 pulses at 100 Hz every 20 sec was reduced by about 50%. Five days after the end of neostigmine treatment the release of acetylcholine recovered to normal.3. The total number of acetylcholine receptors in the end‐plate as measured from the binding of N, O‐di[3H]acetyl α‐bungarotoxin was reduced from 2·1 × 107 to 1·2 × 107 per end‐plate.4. The above‐mentioned changes are not due to acute pharmacological effects of neostigmine, nor to an immediate effect of cholinesterase inhibition but presumably due to chronic accumulation of acetylcholine at the neuromuscular junction.