bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in the changes in sympathetic nerve activity when arterial pressure is raised by infusion of angiotensin and noradrenaline
Authors: Morrison J. F. B. , Pickford Mary
Published: December 2014

1. In cats and dogs impulse frequency was studied in single and few‐fibre preparations of the cervical sympathetic nerves when blood pressure was raised in steps to about 200 mm Hg by infusions of noradrenaline and angiotensin. Two forms of frequency/blood pressure relationships were found which differed in their distribution between the sexes.

2. In females, both normal and ovariectomized, there was an inverse linear relationship between spike frequency and blood pressure over the whole range of blood pressure studied. The same was true in castrated males and normal males pretreated with oestrogens.

3. In normal males the inverse linear relationship held to a pressure of about 150 mm Hg. At higher pressures the sympathetic discharge rate remained steady or increased. This was also found in castrated males pretreated with testosterone. There was a statistically significant difference between the responses of these animals and those of normal females and castrated or oestrogen treated males.

4. The sex difference originates peripherally since the responses of both sexes were similar following baroreceptor and chemoreceptor denervation. During ventilation with oxygen instead of air the male pattern of response becomes like that of the female. The latter observation implicated the chemoreceptors.

5. α adrenoceptor blockade with phenoxybenzamine and phentolamine localized to the region of the carotid bifurcation in male cats abolished the increase in sympathetic discharge rate at high blood pressure induced by noradrenaline, but did not alter the response to angiotensin.

6. Records of spike frequency in single and few‐fibre preparations of chemoreceptor units in the sinus nerves of cats also showed an inverse relationship between frequency and blood pressure in females. In males at the higher pressures, the discharge rate was steady or increased. The increased chemoreceptor discharge at high pressures in males was abolished by ventilation with oxygen instead of air.

7. The sex difference in behaviour of chemoreceptor units could not be explained by differences in either total carotid body blood flow or arterial oxygen tension.

8. It is tentatively concluded that the observed sex difference is related to the state of the blood supply to the chemoreceptors and that, in males, testosterone sensitizes the blood vessels to vasoconstrictors, so that at high pressures blood is diverted through shunts and the chemoreceptors are subjected to a stagnant hypoxia.
Pepsin secretion, gastric motility and mucosal blood flow in the anaesthetized cat
Authors: Reed J. D. , Sanders D. J.
Published: December 2014

1. There is a weak relationship between pepsin output and gastric mucosal blood flow (MBF) during vagal stimulation. When compared with the strong relationship between H+ output and MBF, this suggests little dependence of pepsin secretion on MBF.

2. Gastric MBF per unit H+ output was significantly greater during vagal stimulation, when H+ secretion was accompanied by pepsin secretion, than during pentapeptide stimulation when no pepsin was secreted.

3. Pepsin output was not reduced during splanchnic stimulation whereas MBF and acid output were, when blood pressure was kept constant.

4. Splanchnic stimulation did not produce any pepsin secretion.

5. Gastric motor responses to vagal stimulation and to
I.A. injections of acetylcholine were equally reduced by splanchnic stimulation.
On the presynaptic acetylcholine receptor in sympathetic ganglia of the frog
Authors: Ginsborg B. L.
Published: December 2014

1. Action potentials have been recorded extracellularly from individual preganglionic nerve terminals in the lumbar sympathetic chain of frogs (cf. Koketsu & Nishi, 1968).

2. The action potentials were unaffected by changes in external Mg2+ or Ca2+ concentration, but were attenuated or even abolished by acetylcholine or carbachol. The effect on the presynaptic action potential was transient, in contrast to the blockade of synaptic transmission caused by these drugs, which as is well known persists indefinitely in their presence.

3. In the presence of tubocurarine (5 × 10−5
M), acetylcholine and carbachol had no effect on the presynaptic action potential.

4. The action potentials were reduced by an increase in external K+ concentration and abolished at between 9 and 16 m
M K+. Synaptic transmission persisted until the amplitude of the action potential was reduced to less than one third of its control value.

5. It is concluded that although the presynaptic nerve is endowed with acetylcholine receptors, they are not the source of the long lasting blockade of synaptic transmission caused by cholinergic substances.
Evidence against adrenergic motor transmission in the guinea‐pig vas deferens
Authors: Ambache N. , Zar M. Aboo
Published: December 2014

1. Field stimulation of desheathed preparations of guinea‐pig vas deferens, treated with a ganglion‐blocking agent, has revealed the presence of two tetrodotoxin‐susceptible components in the motor response, suggesting the existence of two sets of post‐ganglionic motor nerve fibres of different excitability: one set responding maximally to pulses of 0·1–0·4 msec; the other, to pulses of 2 msec. No distinction could be made pharmacologically between the two components.

2. Cooling potentiated that component in the twitch‐responses which was due to stimulation of the more excitable fibres.

3. The sensitivity of the longitudinal muscle to the motor action of noradrenaline was low and was subject to considerable animal variation. But normal responses to post‐ganglionic field stimulation were elicited in noradrenaline‐insensitive preparations, in which the twitches elicited by 5 pulses could not be matched with noradrenaline, even 100–125 μg/ml.

4. In some forty experiments, small doses of noradrenaline inhibited the twitch‐responses evoked by either set of motor fibres. This inhibition differed from that produced by isoprenaline in two respects. Firstly, propranolol did not antagonize the noradrenaline inhibition, thus excluding an action on β‐adrenoceptors; and secondly, noradrenaline did not depress contractions elicited by muscarine or by 5‐methylfurmethide.

5. Phenoxybenzamine, 10−6 g/ml., produced a thousandfold reduction in the sensitivity of the muscle to the motor action of noradrenaline, without any decrease in the height of the twitches elicited by 0·1 or 1 msec pulses.

6. The twitch‐responses were not affected by combined α + β adrenoceptor blockade with phentolamine and propranolol.

7. Tyramine, amphetamine, tranylcypromine and prostaglandin E2 inhibited the twitches but potentiated the contractile effect of noradrenaline.

8. The twitch‐responses and their inhibition by noradrenaline were present in preparations taken from reserpinized animals.

9. Although the twitch‐responses could be paralysed by bretylium or guanethidine, the foregoing results excluded adrenergic transmission at the motor endings. Cholinergic transmission was also excluded by negative findings with anticholinesterases, atropine, nicotine and (+)‐tubocurarine.

10. Motor transmission by histamine, 5‐hydroxytryptamine, γ‐aminobutyric acid or ATP was also excluded.
Stimulation of amylase secretion from the perfused cat pancreas by potassium and other alkali metal ions
Authors: Argent B. E. , Case R. M. , Scratcherd T.
Published: December 2014

1. In the isolated cat pancreas, stimulated maximally with secretin, increasing the perfusate potassium concentration (at the expense of sodium ions) caused a copious secretion of amylase from the gland, reduced the volume rate of secretion and caused vasoconstriction.

2. Rubidium and caesium had similar effects to potassium: lithium, though depressing secretory rate, had no effect on enzyme secretion or vasoconstrictor action.

3. Amylase secretion was detected at potassium concentrations of 30 m
M and was maximal at 80–90 m
M, output declining as the concentration was raised to 120 m
M.

4. Amylase secretion was maximal during the first few minutes of exposure to excess potassium, but remained above basal levels throughout the test period. Secretory rate was depressed by a constant amount during the test period.

5. Atropine sulphate blocked the effect on enzyme secretion without affecting the reduction in secretory rate.

6. During perfusion with excess potassium a vasodepressor material with the properties of acetylcholine was detected in the effluent from the gland.

7. The reduction in secretory rate, when perfusate sodium was replaced by potassium, was equal to that obtained when sodium was replaced by sucrose.

8. It is concluded that potassium stimulates amylase secretion indirectly by releasing acetylcholine from nerve terminals in the gland, and that the reduction in secretory rate is due not to excess potassium but to sodium deficiency.
Studies on the translocation of noradrenaline‐containing vesicles in post‐ganglionic sympathetic neurones in vitro. Inhibition of movement by colchicine and vinblastine and evidence for the involvement of axonal microtubules
Authors: Banks P. , Mayor D. , Mitchell Mary , Tomlinson D.
Published: December 2014

1. Methods are presented for studying axonal transport mechanisms in preparations of constricted hypogastric nerve/inferior mesenteric ganglia maintained in vitro for periods up to 48 hr. Under these conditions the ultrastructure of the tissue is excellently preserved.

2. The proximo‐distal movement of noradrenaline and noradrenaline storage vesicles in the non‐myelinated axons of these preparations is inhibited by both colchicine (10 μg/ml.) and vinblastine sulphate (1 μg/ml.) whilst the movement of mitochondria appears to be unaffected.

3. Neither colchicine nor vinblastine sulphate depletes accumulated dense‐cored vesicles of their stores of noradrenaline.

4. These drugs reduce the accumulation of noradrenaline and densecored vesicles against a constriction when they are in contact with the nerve trunks only, and are denied direct access to the nerve cell bodies in the ganglion.

5. The only other morphological change that can be attributed to the action of colchicine and vinblastine is a marked reduction in the number of axonal microtubules.

6. The experiments provide strong support for the view that the axonal system of microtubules is closely involved in the proximo‐distal movement of noradrenaline storage vesicles within noradrenergic neurones. The microtubular system does not appear to be involved in mitochondrial movement.
The hyperpolarization of frog skeletal muscle fibres induced by removing potassium from the bathing medium
Authors: Akiyama T. , Grundfest H.
Published: December 2014

1. The time course of changes in resting potential after removing K0 was studied in twenty‐four single fibres and in 136 fibres from small bundle (two to four fibres) preparations of frog semitendinosus muscles.

2. The initial resting potentials in the control saline ranged between −88 and −98 mV. The potentials returned to nearly the initial values when control conditions were reinstated after 3‐8 hr of experimentation. All the fibres twitched at the end of the experiment.

3. Only about one third of the fibres hyperpolarized for any length of time on exposure to a K‐free saline at room temperature (20–28° C). The hyperpolarization was reversed to depolarization after a variable delay. The resting potential could fall to −50 or −40 mV.

4. The remainder of the fibres depolarized with little or no prior hyperpolarization.

5. Both patterns of response could be replicated in the different fibres.

6. Hyperpolarization induced by K‐free solution was reduced or abolished on cooling to ca 10°C; on substitution of Tris or Li for Na; and upon inhibition of the Na pump with DNP (0·025–0·2 m
M) or ouabain (0·05 m
M). The latter agent was not as effective as the other conditions.

7. Only small, slowly developing depolarization occurred when Na was replaced with Tris or Li.

8. The various effects in K‐free solutions were reversed on returning to the control conditions.

9. It is suggested that removal of K0 itself has little or no direct effect on the resting potential and that the initial hyperpolarization is due to the pumped efflux of Na without a compensatory influx of K. Block of the pump electrogenesis is manifested by depolarization of the fibres as K1 is depleted and Na1 increased.

10. The Na pump appears to be dependent upon the nutritional status of the frogs and variations of the latter probably cause the different responses of fibres to removal of K0.
Methyl histamines and gastric secretion
Authors: Code C. F. , Maslinski S. M. , Mossini F. , Navert H.
Published: December 2014

1. The previous findings that N‐methylhistamine and N‐dimethylhistamine are more potent stimulators of gastric secretion than histamine have been confirmed in dogs with Heidenhain pouches or gastric fistulas.

2. In cats with gastric fistulas, doses of N‐methylhistamine of 0·25 or 0·5 μmole/hr produced 1·4–1·6 times as much HCl as equimolar doses of histamine.

3. The maximal HCl outputs of dogs with Heidenhain pouches to histamine, N‐methylhistamine, and N‐dimethylhistamine were not significantly different, though lesser doses of the N‐methyl derivatives were required to produce the maxima. At the one‐half maximal level, N‐dimethylhistamine showed a twofold greater potency than histamine.

4. When given slowly or quickly via arteries supplying blood to the stomach of dogs or cats with gastric fistulas or via the artery to a Heidenhain pouch in a dog, 0·1–1·0 μmole N‐methylhistamine or N‐dimethylhistamine produced 4·1–13·9 times as much HCl as equimolar doses of histamine.

5. Injection of histamine or N‐methylhistamine via the portal vein in two dogs with gastric pouches stimulated less secretion of HCl than injection of the same doses via a systemic vein.

6. The results allow the conclusion that N‐methylhistamine and N‐dimethylhistamine are more potent stimulators of acid gastric secretion than histamine in dogs and cats, particularly when delivered directly via the arterial route to the gastric mucosa, and support the prospect that N‐methylhistamine or N‐dimethylhistamine or both are natural chemostimulators of the parietal cells.
Some properties of a preparation of rat colon perfused in vitro through the vascular bed
Authors: Parsons D. S. , Powis G.
Published: December 2014

1. A technique is described for the perfusion of the isolated colon of the rat, involving the infusion of an appropriate fluid through both the inferior and the superior mesenteric arteries. During neither the preparation nor the subsequent perfusion is the colon without an adequate supply of oxygen. The preparation remains histologically intact and metabolically viable and is capable of actively transporting ions for up to 5 hr.

2. The addition of at least 3 g albumin/100 ml. perfusate is necessary to prevent the formation of large quantities of serosal exudate. With erythrocytes added to the vascular perfusate the preparation appears to be adequately oxygenated as judged by measurements of the rate of glycolysis. The mean rate of oxygen utilization over 4 hr is 9·2 ± 0·3 (4) μmole. hr−1.g−1 fat free dry weight.

3. Ion transport rates approaching those found in vivo are found only after the administration of an antihistamine substance to the colon donor rat before operation. In the absence of an antihistamine substance there appears to be an ultrafiltration of the plasma fluid into the lumen.

4. Vasodilatory substances accumulate in the recycled perfusate. In a ‘single pass’ perfusion, the transport capacity of the preparation decreases at high perfusion pressures. It is suggested that this is due to some form of autoregulation whereby perfusate is shunted away from the epithelium into deeper layers as the pressure is increased.

5. With CO2 absent from the vascular infusate there is an increase in the net lumen to blood flux of total CO2. This increased flux is accompanied by an equivalent amount of cation, comprising Na+ and K+ in the ratio of 12:1.

6. The presence of ammonium in the lumen, a physiological constituent of the contents of rat distal colon in vivo, has a marked inhibitory effect upon the secretion of CO2 into the contents of the lumen of the colon.
Storage of ATP and 5‐hydroxytryptamine in blood platelets of guinea‐pigs
Authors: Da Prada M. , Pletscher A. , Tranzer J. P.
Published: December 2014

1. By density gradient centrifugation of homogenized blood platelets of guinea‐pigs, subcellular organelles have been isolated which exhibit much higher concentrations (μmole/μg protein) of ATP than the whole platelets.

2. The organelles also store endogenous 5‐HT whose concentration is, however, considerably inferior to that of ATP.

3. Investigated by electron microscopy most of the isolated organelles look empty and only very few show dense osmiophilic cores indicating the presence of 5‐HT. Accordingly the occurrence of dense osmiophilic organelles in the whole platelets is also very rare.

4. Exogenous 5‐HT taken up by the platelets markedly accumulates in the subcellular fraction containing the organelles storing ATP. Concomitantly, the platelets show a rise in the number of osmiophilic organelles and the frequency of osmiophilic cores in the isolated organelles is increased.

5. From these and previous in vitro experiments it is concluded that the so called 5‐HT storage organelles of blood platelets primarily store ATP and only subsequently accumulate 5‐HT.
Effect of microcirculation changes on brain tissue oxygenation
Authors: Bicher H. I. , Bruley D. , Knisely M. H. , Reneau D. D.
Published: December 2014

1. A new, 2 μ tip, oxygen micro‐electrode and a constantly circulated Beckman oxygen gas analyser were used to measure tissue and blood PO2 in anaesthetized, curarized cats under positive pressure breathing. As a parameter for the ability of the circulation to oxygenate tissue, the ‘reoxygenation time’ (defined as the time required to reach the previous PO2 level after a short period of anoxic anoxia) was determined on blood and cerebral cortex.

2. First, it was found that haemorrhage (from 15–25 c.c./kg) alone or haemorrhage combined with sludging of the blood (by the
I.V. administration of high molecular weight Dextran, 1 g/kg) markedly diminished PO2 levels in blood and tissue.

3. Further, the reoxygenation time was significantly affected by these procedures. Sludging markedly prolonged the reoxygenation time, an effect counteracted by the use of an anti‐adhesive drug breaking up the red cell aggregates.

4. Bleeding prolonged the reoxygenation time up to four times that found in the same animals previous to the bleeding.
Induction of the action potential mechanism in slow muscle fibres of the frog
Authors: Miledi R. , Stefani E. , Steinbach A. B.
Published: December 2014

1. The electrical and structural characteristics of ‘slow’ muscle fibres of the frog were studied in normal and denervated muscles, and in muscles undergoing re‐innervation by a mixed nerve containing large and small motor axons.

2. In agreement with previous studies, slow fibres in normally innervated muscles were incapable of producing action potentials.

3. Approximately 2 weeks after the sciatic nerve was transected or crushed, slow muscle fibres acquired the ability to generate action potentials. These fibres were positively identified as belonging to the slow type, because their passive‐electrical and ultrastructural characteristics remained essentially unchanged after the operations.

4. The action potential mechanism induced in slow fibres is sodium‐dependent, and is blocked by tetrodotoxin.

5. After long‐term re‐innervation by a mixed nerve, slow fibres lose their acquired ability to generate action potentials, presumably because small motor axons re‐establish connexion with the fibres.

6. It is concluded that the action potential mechanism of slow muscle fibres is under neural control, and is normally suppressed by small motor axons.
The effect of calcium on the force‐velocity relation of briefly glycerinated frog muscle fibres
Authors: Julian F. J.
Published: December 2014

1. Twitch fibres were isolated from the semitendinosus muscles of frogs. The sarcolemma was made more permeable by a 30 min soak in a solution containing 47·3% glycerine (v/v), 2 m
M‐EGTA and 10 m
M phosphate buffer, pH 7. This was followed by a 30–60 min soak in a solution containing the non‐ionic detergent Lubrol‐WX. The fibres were then placed in a relaxing medium containing (in m
M): KCl, 100; MgCl2, 1; ATP, 4; EGTA, 2; imidazole buffer, 10; pH 7·0.

2. A piece of fibre about 1‐2 mm long treated as described in (1) was attached to a servo apparatus. This apparatus made it possible either to hold fibre length constant giving isometric conditions, or alternatively to hold the force constant while measuring isotonic length changes. A special network made it possible to switch control from isometric to isotonic conditions so that afterloaded contractions with a shortening stop could be carried out.

3. Contractions were induced at about 4° C by lowering the pCa in the relaxing solution to various levels determined by the ratio of calcium and EGTA added. Contractions were never observed above pCa 7. The steady force generated reached a maximum over the range of pCa 6·09 to 5·49. The relationship between steady force generated and pCa is S‐shaped and very steep, implying that multiple interacting binding sites for calcium are involved in the force generating process.

4. The relative force—velocity relation is the same at pCa 6·09 and 5·49 where the steady force is at a maximum. The data points can be well fitted by a hyperbola in which the extrapolated value for Vmax is 2·39 muscle lengths/sec. The values obtained for the Hill parameters a/P0 and b are within the range of those reported for living electrically excited frog muscle.

5. The relative force—velocity points obtained at higher pCa values at which the steady force was on average 37% of that developed at pCa 5·49 can also be fitted by a hyperbola. However, the extrapolated value for Vmax is only 1·12 muscle lengths/sec. The value for a/P0 is increased slightly and the value for b is markedly decreased.

6. Evidence is presented against the possibility that an unrecognized fixed internal load is responsible for the change in the relative force—velocity relation obtained at high pCa.

7. The relative force—velocity relation does not change appreciably over at least part of the range of sarcomere lengths in which the force generated varies linearly with overlap provided the pCa is held constant.

8. The results support the view that lowering the pCa produces a mechanical state equivalent to that produced by tetanic electrical stimulation.

9. Some models for calcium activation are discussed. It is concluded that a model based on calcium binding to troponin on the thin filaments is difficult to reconcile with all of the experimental evidence. There is additional evidence for believing that activating calcium may directly influence the cross‐bridges.
Enhancement of the post‐occlusive oscillation in the splenic circulation by adenosine
Authors: Hashimoto Koroku , Satoh Susumu
Published: December 2014

1. The blood flow to the splenic artery of dogs anaesthetized with sodium pentobarbitone was measured under constant pressure perfusion with the animal's own blood led from the femoral artery.

2. Immediately after release of occlusion there was a rapid increase of inflow rate above the pre‐occlusion level which then oscillated up and down. In a majority of cases such oscillatory responses continued for a while but progressively diminished during a period of about 6 min.

3. This post‐occlusive oscillatory response was not modified by either neural or autonomic receptor blocking agents such as tetrodotoxin, guanethidine, phentolamine, propranolol, atropine and methysergide.

4. In the cases with a relatively short‐lasting response, the selective administration of adenosine into the splenic artery caused a distinct enhancement of the oscillation.

5. These results suggest that adenosine may play an important role in the post‐occlusive oscillatory response of the splenic circulation.
Thermoregulation around a new ‘set‐point’ established in the monkey by altering the ratio of sodium to calcium ions within the hypothalamus
Authors: Myers R. D. , Yaksh T. L.
Published: December 2014

1. The cerebral ventricles of the unanaesthetized monkey were perfused at a rate of 50–100 μl./min with artificial cerebrospinal fluid (c.s.f.) containing 11·0–34·0 m
M excess sodium or 23·9–47·9 m
M excess calcium ions. By repeated perfusions, a marked hyperthermia elicited by excess sodium or deep hypothermia by excess calcium was sustained for up to half a day.

2. During the sodium‐induced hyperthermia or calcium‐induced hypothermia, the monkey thermoregulated adequately around the new level of temperature in response to either 50 or 150 ml. water heated to 58° C or chilled to 0° C and given by the intragastric route. Cold water produced a transient hypothermia after which temperature returned to the pre‐load level; hot water given in the same way evoked a short‐lasting hyperthermia, and again the temperature returned just to the new setpoint level.

3. Perfusions at 50 μl./min of isolated areas of the diencephalon by means of push‐pull cannulae with a solution containing 11·0–34·0 m
M excess sodium ions or 11·3–47·9 m
M excess calcium ions altered the body temperature of the monkey only when the sites of perfusion were located in the mammillary region of the posterior hypothalamus. Following the prolonged hyperthermia produced by excess sodium ions or the deep hypothermia evoked by excess calcium ions in the push‐pull perfusion fluid, the monkey thermoregulated around the new temperature level again in response to 150 ml. of either hot or cold water given in the stomach.

4. Chelation of calcium ions within the ventricles by perfusing EGTA through the cerebral ventricles caused a long‐lasting elevation in temperature. When EGTA was perfused directly in the posterior hypothalamus by means of push‐pull cannulae, a profound hyper‐pyrexia ensued which could be abolished immediately by perfusing a solution of excess calcium at the same diencephalic site.

5. During the calcium‐induced hypothermia, the heart rate declined but the electrical activity of the cortex was relatively unchanged. Feeding was also elicited in the hypothermic monkey by noradrenaline microinjected at a site in the hypothalamus at which eating was evoked when the body temperature was normal.

6. The evidence supports the hypothesis that in the primate, the inborn mechanism which establishes the set‐point for body temperature at 37° C is the constancy in the intrinsic ratio between sodium and calcium ions within the posterior hypothalamus. If the set‐point is elevated or lowered by a disturbance of the balance between these two cations, the monkey nevertheless can thermoregulate normally around the new level of body temperature.
Effect of Na, metabolic inhibitors and ATP on Ca movements in L cells
Authors: Lamb J. F. , Lindsay R.
Published: December 2014

1. The Ca movements in normal and ‘ghost’ L cells have been examined; all measurements were made using 45Ca.

2. Normal cells have a Ca concentration of about 1 m‐mole/l. of cell volume, and exchange Ca in a complex way but with great rapidity; the time taken for the initial Ca* content to fall to half was less than 2 min.

3. Poisoning normal cells with DNP 10−3
M + IAA 10−4
M causes a marked reduction in the Ca efflux, no change in Ca influx and an increase in total Ca.

4. Variation in internal or external Na concentration does not alter the Ca fluxes or concentrations. Application of cyanide or ouabain and alteration of external K concentration had no effect on the Ca fluxes.

5. The sulphydryl reagents, ethacrynic acid and
N‐ethylmaleimide (NEM), have a rapid and marked effect on reducing the Ca efflux.

6. L cell ghosts previously poisoned with DNP+IAA have a low Ca efflux. When ATP or CTP is incorporated into such cells the Ca efflux becomes normal.

7. An extra amount of phosphate is produced by L cell ghosts when pumping Ca. This is equivalent to the splitting of 1·8 moles of ATP per mole of Ca pumped.

8. It is concluded that L cells have a Ca pump driven by ATP, and that Na has no effect on Ca movements in these cells.
Effects of calcium and magnesium on the frequency of miniature end‐plate potentials during prolonged tetanization
Authors: Hurlbut W. P. , Longenecker H. B. , Mauro Alexander
Published: December 2014

1. End‐plate potentials (e.p.p.s) and miniature end‐plate potentials (min.e.p.p.s) were recorded intracellularly from the cutaneous pectoris nerve‐muscle preparation of the frog during prolonged stimulation at low frequencies (5/sec—50/sec).

2. When Ca was present in the bathing solution, the quantum content of the e.p.p. and the frequency of occurrence of the min.e.p.p.s gradually increased during the period of stimulation. During the first few minutes of stimulation, the min.e.p.p. frequency increased linearly with time, and the rate of increase was dependent on the Ca concentration of the bathing solution. However, Mg had no effect on this Ca‐dependent increase in min.e.p.p. frequency.

3. A large maintained increase in min.e.p.p. frequency also occurred during prolonged stimulation in solutions that contained no added Ca and 1‐2 m
M‐EGTA. Under these conditions the increase in min.e.p.p. frequency was dependent on the Mg concentration of the bathing solution and was exponential in time.

4. It is suggested that the rise in min.e.p.p. frequency is caused by an accumulation of Ca or Mg ions in the nerve terminal, and it is suggested that these ions enter the terminal at relatively non‐specific sites distinct from the Ca‐specific sites that trigger the ‘phasic’ release of transmitter.
The effect of metal ions and antidiuretic hormone on oxygen consumption in toad bladder
Authors: Cuthbert A. W. , Wong P. Y. D.
Published: December 2014

1. The sodium‐dependent oxygen consumption of pieces of toad bladder (Bufo marinus) has been investigated using an oxygen electrode.

2. The effect of polyvalent cations (Ca2+, Sr2+, Mg2+, Eu3+, La3+ and Mn2+) on sodium‐dependent oxygen consumption has been measured. All cations inhibited oxygen consumption, the order of effectiveness being Ca2+ > Sr2+ > Mg2+ > Mn2+ > Eu3+ > La3+.

3. Treatment of bladder pieces with antidiuretic hormone (50 m‐u./ml.) decreased the effectiveness of Ca2+ and Sr2+ as inhibitors of sodium‐dependent oxygen consumption. Mn2+, Eu2+ and La2+ were more effective after hormonal treatment, while the effectiveness of Mg2+ was unaltered.

4. The results have been interpreted in terms of a model in which sodium entry to the transporting mechanisms of the epithelium is controlled by Ca2+, and in which antidiuretic hormone alters Ca2+ binding and so affects sodium transport.
Na and Ca components of action potentials in amphioxus muscle cells
Authors: Hagiwara S. , Kidokoro Y.
Published: December 2014

1. The ionic mechanism of the action potential produced in lamella‐like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques.

2. The resting potential and action potential overshoot in normal saline are −53±5 mV (
S.D.) and +29±10 mV (
S.D.) respectively.

3. The action potential is eliminated by tetrodotoxin (3 μ
M) and by replacing NaCl in the saline with Tris‐chloride but maintained by replacing Na with Li.

4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 m
M) to the external saline makes the membrane capable of producing a regenerative potential change.

5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal.

6. The Ca dependent response is reversibly suppressed by Co or La ions.

7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba.

8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca.
Sodium transport by perfused giant axons of Loligo
Authors: Baker P. F. , Foster Rachel F. , Gilbert D. S. , Shaw T. I.
Published: December 2014

The sodium efflux from perfused squid giant axons has been studied using radioactive sodium, and the sufficient conditions for the maintenance of a potassium‐ and ouabain‐sensitive sodium efflux have been established. The following were found.

1. Axons extruded and then perfused with their own axoplasm had a sodium efflux which was sensitive to cyanide, potassium and ouabain and was thus similar to the efflux from intact axons.

2. A method for replacing natural axoplasm into fibres previously perfused with artificial axoplasm was developed and used to establish an artificial perfusate that was not irreversibly toxic.

3. Short perfusion (5 min) with a variety of artificial perfusates was then found to give fibres which had potassium‐ and ouabain‐sensitive sodium effluxes when ATP was present in the perfusate.

4. In the absence of ATP the sodium efflux was small and relatively insensitive to both external potassium and to ouabain.

5. With ADP in the perfusate, fibres gave a sodium efflux which was ouabain‐sensitive but was little affected by the removal of external potassium from the sodium‐rich sea water bathing the fibres.

6. The perfused fibres differed from intact fibres in having large ouabain‐insensitive sodium effluxes.

7. After very long perfusions (40–90 min), with the simple media containing ATP, the rate constant for sodium efflux from the fibres tended to be large and was relatively insensitive to potassium or to ouabain.

8. Fibres refilled with natural axoplasm after long perfusion showed increased sensitivity to external potassium; refilled with dispersed axoplasm the sodium efflux tended to become very large.

9. After very long perfusions with artificial axoplasms containing ATP, a potassium‐ and ouabain‐sensitive sodium efflux was found to persist provided that dextran was present and the total osmotic pressure and the hydrostatic pressure of the perfusate were controlled. Under these conditions the sodium efflux resembled that from briefly perfused fibres.

The necessary and sufficient conditions for the maintenance of sodium transport by perfused giant axons are discussed.
Interaction effects of visual contours on the discharge frequency of simple striate neurones
Authors: Bishop P. O. , Coombs J. S. , Henry G. H.
Published: December 2014

1. The discharge frequency of simple neurones in the cat striate cortex responding to the two edges of a slit of light moving over their receptive fields was studied as a function of slit width. While one edge of the slit was discharging the cell, the other edge had a modifying influence on that discharge either by way of facilitation or of inhibition.

2. The most common form of the curve relating discharge frequency and slit width had a maximal discharge at narrow slit widths (< 0·5°) and relative inhibition at medium widths (between 0·5° and 2°). At greater slit widths there was usually a region of facilitation before the effects of the two edges became independent of one another. Three other response patterns to slits of different width are described.

3. The curve relating slit width and response amplitude for a particular cell provides an important clue to the various activity profiles for that cell. An activity profile plots the excitability of a cell along a line through the receptive field in the direction of stimulus movement. Each type of edge, light and dark, has its own set of activity profiles which differ depending upon stimulus parameters such as the direction of the movement of the edge.

4. Two other methods were used to provide further data concerning the activity profiles and as a check on the evidence provided by the responses to slits of different width. One of these two methods used the test stimulus against the background of an artificially produced maintained discharge and the other involved the interaction of the two receptive fields of binocularly activated cells.

5. A model is put forward to explain the receptive field organization of simple striate neurones which takes into account not only the main features of what is known concerning the synaptology of the visual cortex but also the new data provided by the present paper and the one which precedes it.
Amino acids and presynaptic inhibition in the rat cuneate nucleus
Authors: Davidson N. , Southwick C. A. P.
Published: December 2014

1. Presynaptic inhibition was evoked in the rat cuneate nucleus by a peripheral conditioning stimulus. The dicarboxylic amino acid salts glutamate and aspartate and the neutral amino acids glycine and γ‐aminobutyric acid (GABA) were topically applied to a restricted area of the cuneate nucleus and their effects on both resting primary afferent terminal excitability and the increase in excitability of afferent terminals during presynaptic inhibition determined.

2. Aspartate had no effect on either resting primary afferent terminal excitability or on the increase in excitability during presynaptic inhibition.

3. Glycine reduced both resting primary afferent terminal excitability and presynaptic inhibition.

4. Glutamate increased both resting primary afferent terminal excitability and presynaptic inhibition while GABA increased resting primary afferent terminal excitability but reduced the increase in excitability during presynaptic inhibition.

5. The convulsant alkaloids picrotoxin (given intravenously) and bicuculline (topically applied) blocked presynaptic inhibition. The blocking action of picrotoxin was overcome by topical application of GABA but not glutamate.

6. Simultaneous measurement of pre‐ and post‐synaptic excitability in the cuneate nucleus showed that while glutamate increased excitability at both sites, GABA increased primary afferent terminal excitability but depressed post‐synaptic excitability.

7. It is concluded that glycine and glutamate exert non‐specific actions on primary afferent terminals similar to their effects at post‐synaptic sites elsewhere in the
C.N.S. while GABA depolarizes primary afferent terminals by a specific action at the same receptor site as the presynaptic inhibitory transmitter. The possibility is discussed that the presynaptic inhibitory transmitter in the cuneate nucleus is GABA or a closely related substance.
Fatigue of maintained voluntary muscle contraction in man
Authors: Stephens J. A. , Taylor A.
Published: December 2014

1. The mechanism of fatigue has been studied in maintained maximal voluntary contractions of the first dorsal interosseous muscle of the hand.

2. Fatigue occurs in two phases. In the first, lasting 1 min, force falls to about 50%. The smoothed rectified e.m.g. (s.r.e.) falls with the same time course and the normal linear relation between s.r.e. and force of unfatigued muscle is preserved.

3. In the second phase, force falls relatively faster than s.r.e.

4. Arterial occlusion does not affect the first phase, but in the second phase causes force to fall to zero, whereas without occlusion it tends to stabilize at about 25%.

5. The size of the synchronous muscle action potential evoked by ulnar nerve stimulation falls to about 65% of normal, most of this fall occurring in the first phase.

6. During recovery after prolonged fatigue, the relation between force and s.r.e. is changed for weak voluntary contractions much more than for strong ones, such that force is less for a given s.r.e. than normal.

7. These results are interpreted as evidence that, in a maximal voluntary contraction, neuromuscular junction fatigue is most important at first, but later, contractile element fatigue increases, particularly when the blood supply is obstructed.

8. Neuromuscular junction fatigue is believed to be most marked in high threshold motor units, while contractile element fatigue more especially affects low threshold units.
Re‐investigation of the effect of adrenaline and noradrenaline on renal function in situ
Authors: Liang C. C. , Yang Mabel M. P.
Published: December 2014

1. Adrenaline or noradrenaline in single doses (0·01–0·10 μg/kg) or by continuous infusion (0·3–3·0 μg.kg−1 min−1) into anaesthetized dogs has been administered by different routes. The changes in femoral arterial
B.P., hepatic portal venous pressure, renal venous pressure, intrarenal venous pressure, kidney volume, renal plasma flow (RPF), glomerular filtration rate, urine flow and plasma protein concentration have been followed. The effects varied with route of administration, with dose and time.

2. Direct injection of single doses of these drugs (≤ 0·02 μg/kg) into the renal artery reduced RPF and urine flow without affecting the systemic
B.P. or hepatic portal venous pressure.

3. When the catecholamines were administered in single small doses (≤ 0·02 μg/kg),
I.M. or
S.C. or via the hepatic or common carotid arteries, only a slight effect on systemic
B.P. was observed. There was little effect on hepatic portal venous pressure, and no diuresis was observed.

4. Single injection of these drugs (≤ 0·02 μg/kg) into the mesenteric artery caused an immediate fall of hepatic portal venous pressure without a direct effect on the kidney. A subsequent rise in hepatic portal venous pressure was associated with an increase in urine flow.

5. Administration of these drugs (0·01–0·10 μg/kg) into the femoral vein, inferior vena cava or internal jugular vein caused a great rise in systemic
B.P., a decrease in hepatic portal venous pressure and an antidiuresis, but this was usually followed by a rise of hepatic portal venous pressure and by an associated diuresis, as systemic
B.P. returned to normal values.

6. The total and segmental renal vascular resistance were calculated from parameters measured during ureteral occlusion. The primary effect of the catecholamines was to increase the resistance in all renal vascular segments and produce antidiuresis; subsequently a drastic drop of all segmental resistances occurred and this was accompanied by a diuresis.

7. After block of the α‐adrenergic receptors by dibenzyline or ergotamine, manipulations which increased the hepatic portal venous pressure could still evoke an immediate reflex diuresis.

8. Since the primary renal effect of catecholamines is a vasoconstriction and antidiuresis, it seems that the subsequent reduction of the renal vascular resistance and the associated diuresis is caused by some other mechanism.

9. It is concluded that the complex effects of catecholamine on renal function represent the resultant of direct intrarenal together with indirect extrarenal actions and that the relative significance of these various actions depends on dose, time and the route of administration.
The influence of deep body temperatures and skin temperatures on respiratory frequency in the pig
Authors: Ingram D. L. , Legge K. F.
Published: December 2014

1. The influences on respiratory frequency of ambient temperature, the temperature of the skin, the temperature and humidity of the inspired air, hypothalamic temperature, the temperature of the spinal cord, rectal temperature and some temperatures in the abdomen have been studied in the pig.

2. At a constant ambient temperature the effect on respiratory frequency of heating a thermode in the hypothalamus was modified by the temperature of the skin of the trunk which was varied independently by means of a temperature‐controlled coat. A cold skin inhibited panting; a warm skin enhanced panting. The effect of heating a thermode over the spinal cord was similarly modified by skin temperatures.

3. Simultaneous heating of thermodes in the hypothalamus and spinal cord increased respiratory frequency more than heating either alone, and in a warm environment the rectal temperature influenced the extent to which respiratory frequency increased on heating the thermodes.

4. Cooling the thermodes decreased respiratory frequency in a warm environment and the cooling of one thermode enhanced the effect of cooling the other.

5. At a constant trunk skin temperature the effect on respiratory frequency of heating the thermode in the hypothalamus depended on ambient temperature.

6. Changing the temperature of thermodes in the abdomen did not affect respiration nor was there any evidence that the temperature and humidity of the inspired air had a direct effect on respiration.
The temperature dependence of activation by phosphatidylserine of the sodium pump adenosine triphosphatase
Authors: Priestland R. N. , Whittam R.
Published: December 2014

1. Treatment of rabbit brain homogenates with deoxycholate reduced ouabain‐insensitive ATPase sixfold and subsequently adding phosphatidylserine had no effect. Ouabain‐sensitive ATPase was made entirely latent but it was fully restored on adding phosphatidylserine.

2. Temperature and pH were varied to see if the reconstituted system resembled that in the original membranes. Linear Arrhenius plots were always obtained with the homogenate, and the activation energy was higher for the ouabain‐sensitive than for the ouabain‐resistant enzyme.

3. A break at about 15° C was found in the Arrhenius plot of the reconstituted enzyme, but there was no break without added phosphatidylserine or when ouabain was added. The break suggests that the conformation and catalytic activity of the enzyme protein depended on the physical state of phosphatidylserine.
Regional distribution of cardiac output in young lambs: effect of cold exposure and treatment with catecholamines
Authors: Alexander G. , Bell A. W. , Setchell B. P.
Published: December 2014

1. Lambs less than 3 days old, exposed to thermoneutral or intensely cold conditions in a respiration chamber, were infused with adrenaline or noradrenaline, 1 or 10 μg/kg.min; and the effects on oxygen consumption, cardiac output and its distribution to skin, skeletal and cardiac muscle, liver, spleen, kidney, gut, brown adipose tissue and brain were determined. Cardiac output was estimated by the Fick and dye dilution methods and the distribution of cardiac output by Sapirstein's method of fractional distribution of indicators.

2. Under thermoneutral conditions, metabolic rate was stimulated by both doses of noradrenaline and by the low, but not the high dose of adrenaline. Under cold conditions, the low dose of catecholamines had little effect on the already elevated metabolic rate, but the high doses depressed the metabolic response to cold.

3. The low dose of adrenaline increased cardiac output under thermoneutral conditions whereas the high dose decreased cardiac output; the effects of noradrenaline were less marked, in contrast to reported effects in new‐born rabbits. The low doses of catecholamine given under cold conditions had little effect on the already elevated cardiac output, but the high doses, particularly of adrenaline, decreased cardiac output.

4. Blood flow through the skin of the extremities was markedly reduced by cold exposure, while flow through the peri‐renal fat was doubled, flow through the skeletal muscle was quadrupled and flow through the cardiac muscle was trebled. These increases, particularly in skeletal muscle, were due to increased cardiac output and to vasodilation, as indicated by the reduced ratio of blood pressure to blood flow. Results are contrasted with published reports that blood flow through brown fat in new‐born rabbits was greatly increased by cold, but muscle flow was scarcely altered.

5. In almost all organs examined the high doses of adrenaline infused in either environment markedly reduced blood flow, presumably by generalized vasoconstriction. Changes due to noradrenaline were small under thermoneutral conditions and flow through brown fat was increased by only 60% during infusion of 10 μg/kg.min. Much greater increases have been reported in new‐born rabbits. Under cold conditions the high doses of noradrenaline tended to decrease flow in most organs including brown fat and muscle.

6. The results provide likely explanations for published reports that adrenaline failed to stimulate non‐shivering thermogenesis or suppressed the mobilization of metabolites and the metabolic response to cold.