bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative study of the effects of cholinergic drugs on carotid chemoreceptors in the cat.
Authors: McQueen D S
Published: December 2014

1. Conflicting qualitative evidence exists concerning the effects on chemoreceptor activity of some drugs which influence the cholinergic system. Quantitative evidence has been obtained in the present study which should resolve the conflict. 2. Experiments were performed in pentobarbitone‐anaesthetized cats in which the activity of chemoreceptor units in the sinus nerve was used to assess chemoreceptor responses. The effects of drugs on responses to I.A. ACH and NaCN were determined from dose‐response data obtained from several animals and expressed as mean dose ratios 3. The chemoreceptor response to ACh was slightly inhibited by atropine, alpha‐ and beta‐bungarotoxin and HC‐3, almost completely suppressed by mecamylamine, and markedly potentiated by physostigmine. 4. Concomitant responses to NaCN were unaffected by atropine, beta‐bungarotoxin, mecamylamine or physostigmine. There was a slight inhibition following alpha‐bungarotoxin and a potentiation after HC‐3. 5. The results do not support the theory that ACh is an excitatory sensory transmitter in the carotid body.
Interaction between longitudinal and circular muscle in intestine of cat
Authors: Connor J. A. , Kreulen David , Prosser C. L. , Weigel R.
Published: December 2014

1. Slow waves recorded from isolated longitudinal muscle averaged 13 mV and had slow rate of rise (0.04 V/sec) whereas when recorded from intact segments the amplitude averaged 27 mV and the rate of rise was more rapid (0.09 V/sec), often with a notch between the initial peak and the plateau. Membrane potentials of longitudinal muscle were similar in isolated and intact preparations (‐ 66 mV). Resting potentials of circular muscle averaged ‐ 67 mV.

2. Small bundles of circular muscle tested in the double sucrose gap produced activity, either spontaneously or in response to stimulation, which fell into three categories: fast spikes (50‐200 msec duration), slow spikes (1‐5 sec duration), and small graded responses. The duration of fast spikes could be increased severalfold by the addition of TEA; the graded responses were converted to full‐sized spikes by TEA.

3. Treatment of circular muscle with Ca‐free Krebs solution eliminated spikes, and in intact preparations reduced the amplitude and rate of rise of slow waves and eliminated the notch on slow waves.

4. Current—voltage curves of longitudinal muscle show delayed rectification in the depolarizing quadrant; similar curves of circular muscle show anomalous rectification, i.e. a region where a very small current causes a large voltage change.

5. Non‐polarized electrotonic coupling between longitudinal and circular layers indicates low‐resistance pathways. Apparent space constants of longitudinal muscle are greater when attached to circular muscle than when isolated.

6. It is concluded that small slow potentials originate rhythmically in longitudinal muscle, that these spread passively to circular muscle where a regenerative amplification occurs which depends on Ca conductance and the amplified slow waves spread back to the longitudinal layer. In the intact intestine pacemaking is, therefore, separate from propagation and the circular muscle provides the bulk of depolarizing current for propagation.
Inhibition of hydrochloric acid and pepsin secretion from gastric pouches by antral pouch acidification in sheep.
Authors: McLeay L M , Titchen D A
Published: December 2014

1. Secretion of acid and pepsin from separated pouches of the body of the abomasum was studied in sheep during perfusion of antral pouches with acid solutions. 2. Resting secretion of acid and pepsin was reduced by acidification of antral pouches to pH 2.7 or less. 3. Increases in the secretion of HCl and pepsin normally obtained on feeding were reduced or abolished by perfusion of antral pouches with solutions at pH 1.3‐‐2.0. 4. Perfusion of antral pouches with acetylcholine at pH 2.5 failed to stimulate acid secretion as it did at a higher pH. 5. Pentagastrin stimulated acid and pepsin secretion during the inhibition of secretion produced by antral pouch acidification. 6. Increases in reticular motility occurred on antral pouch acidification with solutions of pH 1.1‐‐1.3. 7. The contribution of antral pH in regulating abomasal acid secretion is discussed.
The contribution of excitatory and inhibitory inputs to the length preference of hypercomplex cells in layers II and III of the cat's striate cortex
Authors: Sillito A. M. , Versiani Vera
Published: December 2014

1. The GABA antagonist bicuculline has been applied to hypercomplex cells in layers II and III of the cat's striate cortex in an attempt to test the hypothesis that their length preference derives from the action of a GABA mediated post‐synaptic inhibitory input.

2. Iontophoretic application of bicuculline to these cells resulted in a reduction but not an elimination of the length preference. The reduction in length preference was only observed in the case of slits extended to one side of the receptive field or to slits only partially covering what appeared to be inhibitory flanking regions either side of the field centre. In cells normally showing a clear and stable length preference it was never possible to produce by the application of bicuculline a significant response to a slit fully extended to cover both flanking regions.

3. The orientation tuning was basically eliminated by the application of bicuculline. In contrast the directional specificity was relatively unaffected.

4. The action of bicuculline on hypercomplex cell orientation tuning supports the view that GABA mediated inhibitory inputs were effectively blocked and suggests that the partial effect on length preference and lack of effect on directional specificity reflect the varying degree of involvement of a GABA mediated inhibitory input to these receptive field properties.

5. These observations introduce the possibility that the excitatory input to the superficial layer hypercomplex cells exhibits directional specificity, length preference with respect to a slit extended to both sides of the field and a low degree of orientation selectivity. Evidence is presented indicating that certain layer V cells with hypercomplex type receptive field properties exhibit some of the characteristics required of this input.
Secretion of a potassium‐rich fluid by the secretory coil of the rat paw eccrine sweat gland
Authors: Sato Fusako , Sato Kenzo
Published: December 2014

1. It is already known that the rat paw eccrine sweat contains high K+ (greater than 150 m
M) and low Na+ concentrations (less than 70 m
M). The present study was intended to clarify the site of K+ secretion within the sweat gland, namely, the duct or the secretory coil. In vivo paw sweat was first induced by systemic pilocarpine injection or nerve stimulation. Both K+ and Na+ concentrations were studied in relation to the sweat rate to determine indirectly whether there is ductal secretion or reabsorption.

2. Both Na+ and K+ concentrations in paw sweat agreed with the previous studies but did not show any saturation‐type flow dependence at the high sweat rate range.

3. A method has been developed to isolate a single segment of the secretory coil and induce sweat secretion directly from it in an in vitro condition.

4. In the presence of fresh serum (30%, preincubated for 30 min at 56 °C) in the incubation medium, stable secretory activity due to 10−6
M‐Mecholyl could be maintained for 40 min or longer. The primary sweat thus induced contained low Na+ (30 m
M) and high K+ (160 m
M) concentrations.

5. In the secretory coil sweat in vitro, K+ concentration decreased and Na+ concentration increased as the secretory rate fell either spontaneously or after addition of atropine or cyanide.

6. It remains to be studied whether auxiliary ductal secretion or reabsorption is present at low rates of sweating in the rat sweat gland.

7. It was concluded that the secretory coil of the rat paw sweat gland is the major, if not the sole, site of K+ secretion.
The renin‐angiotensin system and sodium appetite
Authors: Fitzsimons J. T. , Wirth J. B.
Published: December 2014

1. Bilateral nephrectomy or bilateral ureteric ligation greatly reduced the intake and retention of sodium in sodium‐depleted adrenalectomized rats which were experienced at drinking aversive concentrations of saline and which otherwise would have drunk and retained substantial quantities of sodium.

2. Pharmacological activation of the renin—angiotensin system with isoprenaline or phentolamine caused increased intake of water but did not stimulate sodium appetite in sodium‐replete adrenalectomized rats, and decreased sodium appetite in sodium‐depleted adrenalectomized animals.

3. Neither
I.P. injections of renin nor intravenous infusions of angiotensin II stimulated sodium appetite in normal rats or sodium‐replete adrenalectomized rats.

4. No differences were found in the saline preference—aversion curves of normal rats not maintained on saline given intracranial injections of angiotensin II or carbachol.

5. Preoptic injections of renin, renin substrate or angiotensin II into sodium‐replete adrenalectomized rats which were maintained on water and 2·7% saline induced immediate thirst followed by some saline intake. The saline intake was markedly less than the spontaneous saline intake of the same rats when sodium depleted.

6. Similar preoptic injections in sodium‐depleted adrenalectomized rats caused increased water intake but did not increase the saline intake any further.

7. Intracranial injections of carbachol had little effect on saline intake in either sodium‐replete or sodium‐depleted adrenalectomized rats but caused increased water intake.

8. In conclusion, peripheral activation of the renin—angiotensin system stimulates water intake but has no direct effect on sodium appetite. Secondly, central administration of components of the renin—angiotensin system causes thirst and does not inhibit sodium appetite whereas centrally administered carbachol causes thirst and inhibits sodium appetite. Therefore the renin—angiotensin system has only a minor role in sodium appetite.
On the role of barium in supporting the asynchronous release of acetylcholine quanta by motor nerve impulses.
Authors: Silinsky E M
Published: December 2014

1. The effect of Ba2+ on the evoked secretion of individual acetylcholine (ACh) quanta was studied on frog neuromuscular junctions using conventional electro‐physiological techniques. 2. In solutions containing 1.8 mM‐Ba2+ and no added Ca2+, 1 Hz stimulation for less than 1 min elevated miniature end‐plate potential (m.e.p.p.) frequencies to 5‐20 times the control level (seven experiments). Similar results were obtained when a Ca2+‐chelating agent was added to the Ba2+ solution. 3. Repetitive nerve stimulation at frequencies greater than 1 Hz in concentrations of Ba2+ greater than or equal to 1.8 mM elevated m.e.p.p. frequencies to unmeasurable levels (greater than 100/sec). Such high m.e.p.p. frequencies were accompanied by a steady depolarization of the post‐synaptic membrane, which was used to estimate the number of ACh quanta released. 4. The number of ACh quanta released asynchronously by nerve impulses was directly related to the external concentration of Ba2+ in a non‐linear fashion. 5. Ba2+ was two orders of magnitude more effective than Ca2+ in supporting the evoked discharge of m.e.p.p.s. Ca2+ was a potent antagonist of asynchronous release in Ba2+ solutions. 6. Mg2+ and Co2+ both competitively antagonized evoked release in Ba2+ solutions. The equilibrium dissociation constant for each ion as an antagonist of asynchronous, Ba2+‐dependent release was similar to its corresponding value as an antagonist of synchronous, Ca2+‐mediated release. 7. It is suggested that Ba2+ supports dispersed, quantal ACh release directly by acting through the same conductance pathway normally traversed by Ca2+.
Membrane currents in cat myocardium: separation of inward and outward components
Authors: McDonald T. F. , Trautwein W.
Published: December 2014

1. The single sucrose gap method was used to control the membrane potential of cat ventricular fibres.

2. Following the early rapid events (capacitive, Na and slow inward (si) current spikes) the membrane current on depolarization contained three time‐dependent components which appeared attributable to the inactivation of Isi and the activation of two outward currents labelled IK and Ix.

3. Tail currents were analysed with a view to confirming these conductance changes. At ‐60 mV the tail progressed from being predominantly inward in direction after short (30‐50 msec) depolarizations to being predominantly outward after long (> 300 msec) depolarizations. Inward and outward components decayed exponentially with time constants independent of previous membrane history. The Q10s were about 3.

4. Experiments with D600 and variations of the driving force identified the inward tail component (τ ≈ 55 msec at ‐60 mV) as Isi. The major outward tail component (τ ≈ 300 msec) appears to be carried primarily by potassium. A second outward tail component (τ ≈ 3 sec) of much smaller amplitude than IK was observed after long depolarizations and is tentatively labelled Ix.

5. Membrane currents at 0 mV can be described as the sum of three exponential processes: Isi inactivation (τ ≈ 90 msec), IK activation (τ ≈ 370 msec) and Ix activation (τ ≈ 3 sec). Conductance measurements (envelops of Isi and IK tails) supported these time courses. Isi time constants increased from 50 msec at ‐40 mV to 120 msec at +40 mV. IK time constants increased from 400 msec at ‐40 to about 520 msec at ‐25 mV before declining to 300 msec at +40 mV.

6. Isi amplitudes measured visually (difference between peak Isi and current level after 200‐500 msec) were compared with those measured graphically (semilog plots, subtraction of IK and Ix). As a consequence of the relative amplitudes and time courses of Isi and IK, the shapes of the Isi voltage relations were not markedly different: visual estimates at 200 msec were in agreement with graphic estimates, visual estimates at 300 or 500 msec exceeded these by 15‐30% between ‐20 and +20 mV.
The visual pigments of rods and cones in the rhesus monkey, Macaca mulatta.
Authors: Bowmaker J K , Dartnall H J , Lythgoe J N , Mollon J D
Published: December 2014

1. New microspectrophotometric measurements have been made of the photo‐pigments of individual rods and cones from the retina of the rhesus monkey (Macaca mulatta). The measuring beam was passed transversely through isolated outer segments. 2. The transverse absorbance for rods ranged from 0.02 to 0.04 and that for cones from 0.01 to 0.03. 3. The mean absorbance spectrum for rods (n = 25) had a peak of 502 +/‐ 2.7 nm. A digitonin extract from the same group of eyes gave a lambda‐max. of 499 +/‐ 1 nm. 4. Of a sample of 82 cones, 40 were 'red' (P565 nm) and 42 were 'green' (P536 nm). The mean absorbance spectrum for the green cones is very similar to the Dartnall nomogram, but that for the red cones is narrower. 5. No bleachable, blue‐sensitive outer segments were recorded, although structures were found that absorbed at short wave‐lengths and were neither photosensitive nor dichroic. 6. If the long wave‐length and middle wave‐length cone pigments of the rhesus monkey are assumed to be identical to those of man and if additional assumptions are made about the lengths of human outer segments and about prereceptoral absorption, it is possible to derive psychophysical sensitivities that closely resemble the pi5 and pi4 mechanisms of W. S. Stiles.
Calcium‐induced increase in membrane permeability in the guinea‐pig taenia coli: evidence for involvement of a sodium‐calcium exchange mechanism.
Authors: Brading A F
Published: December 2014

1. High‐Na tissues exposed to a Na‐free solution with dimethyldiethanol ammonium chloride (DDA) or sucrose replacing Na, develop an increase in membrane permeability to small ions and molecules such as Na, K, sucrose and CoEDTA. 2. The increase in permeability only occurs when the Na gradient across the cell membrane is reversed, and is not due to damaging effects of the Na‐free solution. It does not occur in normal or high‐K tissues, and 15 mM‐[Na]0 is enough to prevent the permeability change in high‐Na tissues. 3. Tissues with increased permeability maintain high levels of Ca and the increased permeability does not occur in Ca‐free solutions, or in solutions containing 5 mM‐La3+. The rate of development of membrane leakiness depends on the level of extracellular Ca. 4. Tissues exposed to iodoacetic acid (IAA) and dinitrophenol (DNP) also develop a membrane leakiness, dependent on extracellular Ca and blocked by La3+. 5. The time taken for development of the increase in membrane permeability in metabolically inhibited tissues can be affected by the Na gradient. With no gradient, or a slightly reversed gradient the membrane break‐down occurs more rapidly. 6. It is concluded that the increase in permeability is caused by an increase in internal Ca ions, and that the Na gradient as well as the levels of ATP are important in controlling Ca movements. 7. Tension recordings also support the some form of Na‐‐Ca exchange mechanism operating in the taenia, and this mechanism is not completely blocked by La3+ ions, although they suppress the break‐down in membrane permeability.
Mechanical properties of smooth muscle cells in the walls of arterial resistance vessels.
Authors: Halpern W , Mulvany M J , Warshaw D M
Published: December 2014

1. Methods have been developed for measuring the dynamic mechanical response of arterial resistance vessels (i.d. 83‐‐235 micrometer) with a time resolution of about 4 msec. 2. Observations of the microscope image of the smooth muscle cells in the walls of these vessels indicate that there is little intercellular compliance in this preparation, and that the mechanical properties of the activated preparation are a reflexion of the mechanical properties of the individual smooth muscle cells. 3. Under isometric conditions the force developed per unit cell area was about 350 mN/mm2. Under isotonic conditions the cells had a maximum velocity for shortening at 37 degrees C of about 0.17 lengths/sec. 4. Quick releases of activated vessels indicate that the instantaneous elastic characteristic of smooth muscle cells is approximately exponential. 5. The wall tension response to small (0.3%) square wave changes in circumference was proportional to the logarithm of the time following the start of each circumference change. 6. Active wall tension, deltaT, was varied by varying the Ca2+ concentration of the activating solution. Under these conditions the active dynamic stiffness, k, was proportional to deltaT, and was not temperature dependent. The active half response time, tau (the time, taken to recover half the tension change caused by a small change in circumference) was also proportional to deltaT, but here the constant of proportionality had a Q10 of about 1.8. 7. It is concluded that the quick release response and the square wave response are in part a function of the mechanical properties of the crossbridges between the contractile filaments. Calculations show that both these responses can be explained if it is assumed that there is a relatively compliant passive component in series with the crossbridges.
Characterization and ionic basis of GABA‐induced depolarizations recorded in vitro from cat primary afferent neurones.
Authors: Gallagher J P , Higashi H , Nishi S
Published: December 2014

1. Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or by iontophoresis were recorded using intracellular micro‐electrodes. 2. Of the twelve structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. 3. Studies determining concentration‐response relationships indicate that two to three molecules of GABA are required to combine with the GABA receptor for activation. 4. Bicuculline and picrotoxin, each act in a non‐competitive manner to antagonize the GABA‐induced membrane current. 5. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was found to be ‐23.5 plus or minys 6.1 mV. EGABA was independent upon [cl‐]o, but independent of [Na+]o, [K+], or [Ca2+]o. 6. Intracellular injection of twenty antions (Br‐, I‐, NO2‐, NO3‐, ClO4‐, SCN‐, Bf4‐, HS‐, OCN‐, ClO3‐, BrO3‐, F‐, HCO2‐, HSO3‐, HCO3‐, CH3CO2‐, SO42‐, C6H5O73‐) indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no larger than that of ClO‐3. 7. Restoration of the GABA depolarization to its control level after augmentation by Cl‐ injection had a mean time constant of 27.8 plus or minus 2.6 min. Picrotoxin did not alter this value. 8. When foreign anions were exchanged for Cl‐ in the perfusion solution, the ten anaions smaller or equal to ClO3‐, decreased the GABA depolarization by 50‐90% and increased its time course 1.5‐2.0 x control. The only exception having a small radius was Br‐ which augmented the amplitude 10‐30%. 9. The ten anions larger than ClO3‐ produced a biphasic effect, i.e. an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO‐, CH3SO4‐, or HOCH2CH2SO3‐, indicated that this depression was non‐competitive.
Firing behaviour of dorsal spinocerebellar tract neurones.
Authors: Gustafsson B , Linström S , Zangger P
Published: December 2014

1. The repetitive discharge evoked by constant current injection from an intracellular micropipette has been studied in dorsal spinocerebellar tract cells of the cat. 2. The discharge frequency decreased with time, the decrease being more pronounced at high current intensities. Most of the frequency change occurred during the first ten intervals but the decrease continued slowly for several seconds. In some cells the frequency rose initially, the first interspike interval being larger than immediately succeeding ones. 3. The frequency‐current (f/I) curves for the first interspike intervals were S‐shaped, as found in spinal motoneurones. With successive intervals the lower leg of the f/I curve extended to higher frequencies, giving a progressive linearization of the f/I curves. In almost all cells this linearization was completed at 200 msec after current onset. 4. The experimental f/I curves were compared with the f/I curves obtained with a simple neurone model based on the properties of the postspike afterhyperpolarization. For the first interspike interval there was a good agreement between the experimental and calculated f/I curves of individual neurones up to frequencies of several hundred impulses per second. In the high frequency range, it was necessary to compensate for changes in initial postspike voltage trajectories caused by the injected current. Other aspects of the firing of real neurones, such as the progressive linearization of the f/I curves, the negative adaptation and the changes in the interspike voltage trajectories with increasing current were also reproduced by the neurone model. 5. It is concluded that the conductance process underlying the postspike afterhyperpolarization is a major factor in the regulation of repetitive firing in dorsal spinocerebellar tract neurones.
Changes in the intracellular concentration of free calcium ions in a pace‐maker neurone, measured with the metallochromic indicator dye arsenazo III.
Authors: Gorman A L , Thomas M V
Published: December 2014

1. The bursting pace‐maker R‐15 cell of Aplysia was injected with the Ca2+ sensitive dye arsenazo III. Changes in absorbance were measured with a differential spectrophotometer to monitor changes in free intracellular Ca2+, [Ca‐a], during activity. 2. Dye absorbance increased during each pace‐maker‐induced burst of action potentials and decreased during the hyperpolarizing phase of the pace‐maker cycle. 3. The increase in dye absorbance was, at least in part, dependent upon action potential discharge and was greater when action potential duration was prolonged by treatment with tetraethylammonium chloride. 4. Changes in dye absorbance occurred under voltage clamp conditions when the membrance was depolarized 5‐15 mV from a holding potential near the resting potential and were larger with greater step depolarizations. 5. These changes were completely blocked by the addition of 3mM‐La3+ to normal ASW. 6. The ratio of the absorbance change between two pairs of wave‐lengths during the pace‐maker cycle was compared with the ratio observed following injection of Ca2+, Mg2+ and H+ ions. The ratio for the pace‐maker cycle was well matched by that for Ca2+ injection, but not by that for injection of Mg2+ or H+. 7. Intracellular Ca2+ injections which increased [Ca]1 to the same amount as occurred during the pace‐maker cycle also produced an outward current of sufficient magnitude to account for the post‐burst hyperpolarization. 8. Depolarization of the cell membrane by extrinsic current during the burst increased and prolonged the change in dye absorbance as well as the post‐burst hyperpolarization. 9 It is suggested that Ca2+ enters during the pace‐maker cycle, thereby increasing [Ca]i, and that this increase is sufficient to activate an outward current carried by K+ ions which causes or contributes to the post‐burst hyperpolarization.
Control of acetylcholine sensitivity and synapse formation by muscle activity.
Authors: Lømo T , Slater C R
Published: December 2014

1. The formation of ectopic junctions between the 'foreign' superficial fibular nerve and the soleus muscle of adult rats, and its relation to changes in extrajunctional sensitivity to acetylcholine (ACh), has been studied by denervating the muscle 3‐6 weeks after implanting the foreign nerve. 2. The earliest signs of nerve‐muscle transmission were seen 2.5‐3 days after denervation, in those fibres where the extrajunctional ACh sensitivity first reached its full post‐denervation level. The number of innervated fibres continued to increase throughout the first week after denervation until 70‐100% of fibres underlying the foreign nerve growth were innervated. 3. Direct stimulation of muscles with chronically implanted electrodes from the time of denervation prevents the formation of functional neuromuscular junctions (n.m.j.s). If stimulation begins 2 or 4 days after denervation, some functional n.m.j.s are formed which can be detected 7‐9 days after denervation, though not as many as in the absence of stimulation. 4. Direct stimulation of muscles from the time of denervation prevents the development of detectable extrajunctional ACh sensitivity. If stimulation begins 2 days after denervation nearly maximal sensitivity develops during the third day and then rapidly declines to undetectable levels by the beginning of the eight day after denervation.
Electrical coupling and dye transfer between acinar cells in rat salivary glands.
Authors: Hammer M G , Sheridan J D
Published: December 2014

1. Adjacent acinar cells in isolated rat parotid and submaxillary glands were found to be electrically coupled in greater than 90% of the pairs tested. 2. Cells injected with fluorescein or procion yellow showed transfer of the dyes to their coupled neighbours. While not all coupled cells exchanged dye, exchange occurred only between coupled cells. 3. In experiments using three micro‐electrodes, coupled acinar cells from parotid gland were found to have a mean coupling coefficient of 0.69 +/‐ 0.04. This value is higher than those reported for most other vertebrate epithelial systems. 4. Membrane damage sufficient to reduce the occurrence of coupling between cells by 97% lowered the transmembrane potential by only 13%. This would indicate that in this system membrane potential may not be the most sensitive indicator of cell damage. 5. The significance of the presence of electrical coupling and cell‐to‐cell transfer of small tracer molecules is discussed in relation to salivary gland structure and possible functional consequences.
Effect of cortisol on liver glycogen concentrations in hypophysectomized, adrenalectomized and normal foetal lambs during late or prolonged gestation.
Authors: Barnes R J , Comline R S , Silver M
Published: December 2014

1. The changes in liver glycogen concentration in normal, adrenalectomized and hypophysectomized foetal lambs have been examined during the last third of gestation using a biopsy technique to remove one or more samples of liver from the same foetus at different gestational ages. 2. The rate of glycogen deposition increased sharply from about 130 days' gestation in normal lamb foetuses whereas after hypophysectomy or adrenalectomy liver glycogen concentrations remained low even when gestation was prolonged. 3. I.V. infusions of cortisol (4‐10 mg/day) for 52 hr resulted in four‐ to fivefold increases in liver glycogen in all three groups of foetuses. The level of glycogen in the liver appeared to be related to log plasma corticosteroid concentration in all foetuses whether they had received cortisol infusions or not. 4. Little or no change occurred in glycogen concentration in other foetal tissues apart from a decrease in the glycogen levels in peri‐renal fat of adrenalectomized and hypophysectomized foetuses after cortisol infusion. There were also no detectable changes in foetal plasma lactate, urea or alpha amino nitrogen following the cortisol infusions. Foetal plasma glucose values rose slightly but this change was significant only in the adrenalectomized group. 5. The 52 hr cortisol infusions to the foetus resulted in a slight but significant fall in maternal plasma progesterone in the last few hours of the infusion period.
Autogenetic reflex action on to gamma motoneurones by stretch of triceps surae in the decerebrated cat.
Authors: Ellaway P H , Trott J R
Published: December 2014

1. Tonically firing gamma motoneurones of known conduction velocity (total eighty‐seven, range 15‐43 m/sec) have been isolated in peripheral muscular nerves to triceps surae. Their responses to stretch of triceps surae have been studied in decerebrated cats. A small amplitude, quick stretch and release was used to provide a selective stimulus for primary endings of muscle spindles. 2. To check the selectivity, recordings were made from 135 afferents from triceps surae under conditions closely similar to the reflex experiments. The threshold of all but a few primary endings of muscle spindles law below 50 micrometer whereas threshold was above 50 micrometer for the majority of secondary endings and tendon organs. A 20 micrometer stretch excited approximately half the primary endings but only one of thirty‐six secondaries and no tendon organs responded to such a small stretch. Nine group III afferents were also studied but none responded to stretch. 3. Stretch of up to 50 micrometer excited twenty‐three and inhibited eleven gamma motoneurones while thirty‐three remained unaffected. A further twenty showed mixed responses, being inhibited initially before being excited at longer latency. Thresholds for reflex responses of gamma motoneurones frequently occurred below 20 mum and responses were close to maximal for stretch of 50 micrometer. 4. Excitation always had a lower threshold to stretch than did inhibition for those gamma motoneurones showing mixed responses and was the more potent of the two effects. 5. Excitation to stretch had central delays, to the incoming group Ia volley, ranging from 5 to 14 msec while similarly calculated delays for excitation of alpha motoneurones ranged from 0.6 to 3.0 msec. Central delays of the gamma inhibitory responses lay in an intermediate range of 1.7‐7.0 msec. 6. The long central delays of excitation of gamma motoneurones in response to stretch do not reflect transmission in supraspinal pathways since the reflex persisted following spinal section. 7. Excitation of gamma motoneurones was weak in comparison with that of tonically firing alpha motoneurones recorded in the same preparations and it was always necessary to sum a number of responses in order to reveal an effect...
The influence of extracellular calcium binding on the calcium efflux from squid axons.
Authors: Baker P F , McNaughton P A
Published: December 2014

1. The Ca efflux from unpoisoned squid axons seems to consist of three components: Cao‐dependent Ca efflux and a 'residual' flux that persists in the nominal absence of external Ca and Na and is little affected by the further removal of external Mg. 2. Evidence is presented to show that much of the apparent dependence on Cao of the Ca efflux from unpoisoned axons probably does not reflect a membrane process but results instead from the existence of a Ca‐binding matrix external to the plasma membrane. Removal of external Ca produces a fall in efflux which is not maintained but returns to its original level over 20‐60 min. Readmission of Ca produces only a transient increase in Ca efflux. Addition of EGTA to nominally Ca‐free media also produces only a transient rise in Ca efflux. 3. Direct measurement of Ca binding to the surface of highly cleaned axons reveals appreciable binding over a wide range of Ca concentrations. A high affinity component of superficial binding can be recognized which has a capacity of about 60 p‐mole/cm2 axon membrane and is half‐maximal about 0.3 micrometer‐Ca in Na‐ASW. This component of binding is unaltered in cyanide‐poisoned axons and in media in which Na is replaced isosmotically by Tris; but is reduced in the presence of 1 mM‐La or after brief exposure of the axon to pronase. There is also a component of large capacity and lower affinity which was not saturated by 100 mM‐Cao. 4. After brief pronase treatment the sensitivity of the Ca efflux to external Ca is markedly reduced although the Na‐dependent Ca efflux persists apparently unaltered. 5. Addition of La produces a transient increase in Ca efflux followed by a maintained fall. 300 micrometer‐La largely inhibits the component of the Ca efflux that persists in the nominal absence of external Na and Ca. Higher concentrations of La also inhibit Nao‐dependent Ca efflux. 6. The Cao‐dependent Ca efflux and Nao‐dependent Ca efflux seen in poisoned axons persist in the presence of EGTA or after pronase treatment, suggesting that both are genuine membrane processes. 7. We conclude that in unpoisoned axons 50‐90% of the Ca efflux can continue in the absence of external Ca, Na and Mg and may reflect an uncoupled extrusion of Ca. Most of the remaining efflux from these axons is Nao‐dependent although a small Cao‐dependent component can be distinguished in the absence of Na. Poisoning results in the loss of uncoupled Ca efflux, the appearance of appreciable Cao‐dependent Ca efflux and alteration in the kinetics of Nao‐dependent Ca efflux.
Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles.
Authors: Fabiato A , Fabiato F
Published: December 2014

1. The effects of decreasing pH from 7.40 to 6.20 on the tension developed by direct activation of the myofilaments and by Ca2+ release from the sarcoplasmic reticulum were studied comparatively in segments of single cells of skeletal muscle (frog semitendinosus) and cardiac muscle (rat ventricle) from which the sarcolemma had been removed by micro‐dissection (skinned muscle cells). 2. The concentration of free Ca2+ in the solutions was buffered with ethylene glycol‐bis (beta‐aminoethylether N,N'‐tetraacetic acid (EGTA). The change of the buffer capacity of a given [total EGTA] caused by varying pH and the uncertainty about the value of the equilibrium constant for Ca‐EGTA have been taken into account in the interpretation of the results. 3. Decreasing pH from 7.40 to 6.20 produced an increase in the [free Ca2+] required for the myofilaments to develop 50% of the maximum tension by a factor of about 5 in skinned cardiac cells but of only 3 in skeletal muscle fibres. In addition, acidosis depressed the maximum tension developed in the presence of a saturating [free Ca2+] by approximately the same amount in the two tissues. 4. The pH optimum for loading the sarcoplasmic reticulum of skinned fibres from skeletal muscle decreased when the pCa (‐log [free Ca2+]) in the loading solution decreased. The optimum was pH 7.40‐7.00 for a loading at pCa 7.75, pH 7.00‐6.60 at pCa 7.00 and pH 6.60‐6.20 at pCa 6.00. 5. The pH optimum for loading the sarcoplasmic reticulum of skinned cardiac cells with a solution at pCa 7.75 was about pH 7.40 as in skeletal muscle fibres. But the cardiac sarcoplasmic reticulum could not be loaded with a [free Ca2+] much higher than pCa 7.75 because a higher [free Ca2+] triggered a Ca2+‐induced release of Ca2+ from the sarcoplasmic reticulum. 6. The pH optimum of about 7.40 for the loading of the cardiac sarcoplasmic reticulum was also optimum for the Ca2+‐induced release of Ca2+ from it. 7. It was concluded that the effects of acidosis on the cardiac sarcoplasmic reticulum accentuate the depressive action of decreasing pH on the myofilaments. This may explain the pronounced depression of contractility observed during acidosis in cardiac muscle. In contrast, a moderate acidosis causes an effect on skeletal muscle sarcoplasmic reticulum that could compensate for the depressive action on the myofilaments, which is, in addition, less pronounced than in cardiac muscle.
Long‐term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency.
Authors: Dunwiddie T , Lynch G
Published: December 2014

1. The consequences of repetitive activation of excitatory synaptic inputs to the CA1 pyramidal cells of rat hippocampus have been studied using in vitro techniques. 2. Single stimulation trains of 100 pulses at rates of 5‐100/sec resulted in potentiation of population spike amplitudes lasting the duration of a 5 min test period in thirty‐four out of thirty‐five cases. Trains of 100 pulses delivered at 1/sec resulted in depression of the stimulated pathway in ten out of twelve experiments. 3. Responses to test stimulation of other excitatory inputs to the same cell population were depressed following conditioning trains at frequencies in the range 1‐100/sec. Depression was seen both in the population spike amplitude (reflecting synchronous cell discharge) as well as the extracellularly recorded population e.p.s.p., and appeared to be maximal at lower frequencies. 4. Trains of antidromic stimulation of the CA1 cell population produced subsequent decreases in synaptically evoked responses, indicating that repetitive firing of pyramidal neurones or interneurones do not cause potentiation, but may be involved in heterosynaptic depression. 5. The results suggest that potentiation and heterosynaptic depression arise from different mechanisms, and that potentiation is confined to the set of terminals activated by a conditioning train, whereas the depression is generalized to the whole neurone.
Renin substrate in plasma of unanaesthetized pregnant ewes and their foetal lambs.
Authors: Carver J G , Mott J C
Published: December 2014

1. In unanaesthetized preparations 6‐14 days after catheterization, the concentration of renin substrate (AI 212 +/‐ 20 ng/ml. S.E. of mean) in the plasma of foetal lambs during the last third of gestation was significantly less than that of paired samples of maternal plasma (AI 350 +/‐ 27 ng/ml.). 2. During the first 5 days following catheterization the concentration of renin substrate in maternal plasma was lower than subsequently but was raised if the uterus contained a nephrectomized foetus. 3. The concentration of renin substrate in the plasma of intact foetal lambs without nephrectomized twins varied little in the post‐catheterization period and later; the concentration of substrate in nephrectomized foetal lambs averaged threefold that of intact lambs and a similar concentration of substrate was found in intact twins of such lambs in the immediate post‐catheterization period. 4. It is suggested that the ratio of foetal/maternal plasma renin activity understates their relative enzyme activity since foetal substrate concentration is so considerably less than maternal.
Cross‐bridge detachment and sarcomere 'give' during stretch of active frog's muscle.
Authors: Flitney F W , Hirst D G
Published: December 2014

1. A study has been made of the tension responses and sarcomere length changes produced by servo‐controlled stretches applied to isometrically contracting frog muscle. Sarcomere lengths were monitored by cine‐photography of diffiraction spectra obtained by illuminating a small area of muscle with a laser. 2. The tension increment produced by a ramp‐and‐hold stretch of approximately 1 mm (ca. 4% of the muscle length) comprises three phases whose limits are defined by two points, S1 and S2, where the slope of the response decreases abruptly. S1 and S2 correspond to extensions of 0.13 and 1.2% of the muscle length. 3. Movements of the first order spectra relative to the zero order recorded during stretch reveal that S2 coincides with an abrupt elongation of the sarcomeres. This is termed sarcomere 'give' and it occurs when the filaments are displaced by 11‐12 nm from their steady‐state (isometric) position. 4. The stiffness of the sarcomeres, Es, up to S2 decreases with increasing sarcomere length. The maximum force sustained by the muscle at S2, PS2, also shows an inverse dependence on sarcomere length. Both Es and PS2 fall to zero at an extrapolated sarcomere spacing of 3.6‐3.7 micrometer, coinciding with the length at which the actin and myosin filaments no longer overlap. 5. The ratio PS2/P0 (where P0 = maximum isometric tension) varies with temperature and speed of stretch. It increases with increasing speeds of stretch until a certain critical velocity, Vc, is reached, beyond which it is almost independent of any further increase. Vc has a positive temperature coefficient, increasing 5‐6 in the range 0‐30 degrees C (Q10 = 1.8). There is a positive correlation between the maximum speed of isotonic shortening (Vmax.) and Vc in different muscles. 6. Sarcomere 'give' during stretch is considered to be due to forcible detachment of cross‐bridges between the actin and myosin filaments. This results in recoil of the extended series elastic elements in the muscle at the expense of the sarcomers. The amount of filament displacement required to induce sarcomere 'give' (11‐12 nm) is thought to represent the range of movement over which a cross‐bridge can remain attached to actin during a stretch.
Activation of the electrogenic sodium pump in guinea‐pig atria by external potassium ions
Authors: Glitsch H. G. , Grabowski W. , Thielen J.
Published: December 2014

1. When cardiac preparations are rewarmed following prolonged hypothermia a transient hyperpolarization occurs in K‐containing media. This hyperpolarization is correlated with the active Na efflux. It might be due to electrogenic Na pumping or to extracellular K depletion brought about by the activity of an electroneutral Na—K exchange pump. In order to distinguish between these mechanisms the effect of various extracellular K concentrations ([K]o) on the membrane potential of guineapig atria was studied before and after hypothermia.

2. The membrane potential increased with decreasing [K]o before cooling. It reached values of ‐64 and ‐92 mV at 10·8 and 0 m
M‐K, respectively.

3. The membrane hyperpolarized transiently after hypothermia beyong the potential observed before cooling. Maximal values of about ‐94 mV were obtained during rewarming in solutions containing 0·4‐2·7 m
M‐K. The membrane potential was significantly lower (‐88 mV) in K‐free media. It was also diminished at [K]o higher than 2·7 m
M and was measured to be ‐74 mV at 10·8 m
M‐K.

4. The hyperpolarization of the cell membrane during the first 20 min of rewarming was maximal at 2·7 m
M‐K and yielded 15·5 mV. The hyperpolarization amounted to 7·2 and 10 mV at 0·4 and 10·8 m
M‐K, respectively. No hyperpolarization occurred in K‐free solutions.

5. The rate of decline of the transient hyperpolarization increased with [K]o.

6. Variations of membrane input resistance after changes in [K]o were measured in rewarmed atrial trabecula. The measurements revealed an increase in membrane resistance in lower [K]o.

7. It is concluded that the transient hyperpolarization of the cardiac cell membrane during rewarming is due to the activation of an electrogenic Na pump.

8. The (relative) strength of the pump current at various [K]o was derived from the observed dependence of the hyperpolarization and of the membrane input resistance on [K]o. The current is estimated to be half‐maximal at about 1·5 m
M‐K.
The effect of ouabain on noradrenaline output from peripheral adrenergic neurones of isolated guinea‐pig vas deferens
Authors: Nakazato Y. , Ohga A. , Onoda Y.
Published: December 2014

1. The effect of ouabain on the noradrenaline output from peripheral adrenergic neurones has been studied using isolated guinea‐pig vasa deferentia.

2. Exposure to ouabain (10−4
M) causes a gradual increase in the noradrenaline output. The effect occurs after a delay of 20 min and reaches a maximum during the period from 40‐60 min.

3. In the absence of external Ca, exposure to ouabain fails to produce an increase in the noradrenaline output. However, the reintroduction of Ca (2·5 m
M) after a 1 hr exposure to ouabain in Ca‐free media causes a rapid rise in noradrenaline output which reaches a maximum within the first 20 min.

4. After a 1 hr exposure to a low concentration of ouabain (10−5
M) the reintroduction of Ca is almost ineffective in increasing the noradrenaline output. When the concentration of ouabain is increased, the reintroduction of Ca becomes effective and causes a maximum effect with 10−4
M ouabain. In the presence of a constant amount of ouabain (10−4
M) the noradrenaline output induced by the reintroduction of Ca increases over the range 0·2‐2·5 m
M.

5. In the presence of ouabain (10−4
M) the Ca‐induced noradrenaline output increases in a linear fashion with increasing Na concentrations from 25 to 143 m
M, as long as NaCl is replaced with equimolar choline chloride or isotonic sucrose.

6. In the presence of the lowest effective concentration of sodium (25 m
M) the noradrenaline output induced by the reintroduction of Ca after a 1 hr exposure to ouabain is potentiated by LiCl. However, in the complete absence of Na+ ions, there is no Li‐dependent increase in the Ca‐induced noradrenaline output.

7. It is suggested that ouabain may cause an increase in noradrenaline output by an effect on the Na‐dependent Ca influx system.