bluuebunny/crossref_metadata_2025 huggingface dataset:
Inotropic and arrhythmogenic effects of potassium‐depleted solutions on mammalian cardiac muscle.
Authors: Eisner D A , Lederer W J
Published: December 2014

1. We have investigated the electrical and mechanical effects of reducing the bathing K concentration, K0, over the range from 4‐0 mM in guinea‐pig papillary muscle and in sheep Purkinje fibres. 2. In papillary muscle, reducing K0 to zero produces a negative shift in the resting potential and an initial increase in action potential duration. An increase of twitch tension ensues, followed by a reduction in actin potential duration and, eventually, an increase in tonic tension. This increase in tonic tension is often accompanied by a decrease of twitch tension. Finally, transient depolarizations and after contractions are produced. 3. In voltage clamped Purkinje fibres, K0 reduction decreases the slope conductance at the more negative potentials and reduces the pace‐maker current, iK2. Twitch tension increases rapidly and voltage dependent tonic tension develops. After even very short exposures to very low K0 (1 mM and below), an oscillatory transient inward current and accompanying aftercontraction can be seen. The oscillatory transient inward current and aftercontraction are similar to those described for cardiotonic steroid intoxication by Kass, Lederer, Tsien & Weingart (1978). 4. Prolonged exposure to 0 K0 leads to the development of a slow current ‘creep'. This current is activated by depolarization and has a reversal potential of ‐6.7 +/‐ 3.5 mV. The development of this creep current is accompanied by an increasing ‘creep’ in tonic tension with the same time course. On repolarization both the current creep and creep in tension recover with time courses still similar to each other. 5. Fluctuations appear in both the tension and current records during exposure to low K0. The tension and current fluctuations have similar principal frequencies (about 1 Hz). 6. Ca0 removal, substituting Ba0 for Ca0 or adding Mn0 (2 mM) can each remove the transient inward current, aftercontraction, fluctuations of current and tension, and creep current as well as the increase of twitch and tonic tension. 7. Replacing Ca0 by Sr0 leads to an increased inotropic effect of low K0 with altered kinetics and appears to abolish the transient inward current, aftercontraction and fluctuations of current and tension. 8. It is concluded that Ca1 plays a central role in the inotropic and arrhythmogenic effects of low K0. Possible mechanisms of Ca1 control are discussed in light of the results that have been presented.
Neural mechanisms of reflex facilitation and inhibition of gastric motility to stimulation of various skin areas in rats.
Authors: Kametani H , Sato A , Sato Y , Simpson A
Published: December 2014

1. Experiments were performed on chloralose‐urethane anaesthetized rats to determine the involvement of extrinsic gastric autonomic nerves in reflex facilitation and inhibition of gastric motility when mechanical nociceptive stimulation was delivered to either hind paw or abdominal skin, respectively. 2. After bilaterally sectioning the splanchnic nerves in vagal intact animals, the reflex facilitation of gastric motility produced by hind paw stimulation persisted, but the reflex inhibition previously produced by abdominal skin stimulation disappeared. 3. Hind paw stimulation increased efferent activity of the gastric branch of the vagus nerve, but stimulation of abdominal skin had little influence. 4. Bilateral vagotomy in splanchnic nerve intact animals did not influence the gastric reflex inhibition by abdominal skin stimulation, but either abolished gastric reflex facilitation produced by hind paw stimulation or reversed the reflex facilitation response to slight reflex inhibition. 5. Efferent activity of the gastric sympathetic nerve was greatly increased by abdominal skin stimulation, and was either slightly increased or not influenced by hind paw stimulation. 6. It was concluded that reflex increase of efferent activity of the gastric vagi was responsible for the gastric motility facilitation produced by hind paw stimulation, and also that reflexly increased efferent activity of the gastric sympathetic nerves resulted in gastric motility inhibition produced by abdominal skin stimulation. It is suggested efferents are inhibitory. 7. After spinal transection at the cervical level, the reflex facilitation of gastric motility previously produced by stimulation of a hind paw was completely abolished, or reversed to slight reflex inhibition, while reflex inhibition of gastric motility produced by stimulation of abdominal skin remained. It was concluded that the gastric reflex inhibition was a spinal reflex. 8. Interaction between reflex facilitation and inhibition of gastric motility during simultaneous stimulation of both hind paws and abdominal skin was observed as partial cancellation of each effect by the other. However, sympathetic reflex inhibition of gastric motility seemed to be much stronger than the vagal reflex facilitatory effect.
Hypothalamic thermo‐responsive neurones in the new‐born rat.
Authors: Hori T , Shinohara K
Published: December 2014

1. Single unit activities were recorded from the neurones in the preoptic area and anterior hypothalamus of developing new‐born rats (aged 1‐24 days old) during thermal stimulation of the brain. During the first 2 weeks of life, about 80% of these neurones had low spontaneous firing rates between 0.1 and 5 impulses/sec at 38 degrees C hypothalamic temperature (Thyp). 2. Out of 640 units studied, 118 units increased the firing rate upon elevation of Thyp (warm‐units) and fourteen showed the opposite type of response to temperature changes (cold‐units). Warm‐units were found in the rats of all the age span studied and cold‐units were recorded in the rats more than 8 days old. 3. Thermal coefficients of warm‐units and cold‐units varied between +0.11 and +2.47 and between ‐0.10 and ‐0.49 impulses/sec, degrees C, respectively. Number of warm‐units with higher rates of firing and greater thermal coefficients, comparable to those of warm‐units in the adult, gradually increased with growth. The thermal responsiveness of warm‐units, when expressed by Q10, are already high even in the immediate neonatal period. Their Q10 values were in the range between 2 and 38.5 (mean 6.4). 4. Units responding to extrahypothalamic temperatures were only found in the rats more than 14 days old. 5. All the six warm‐units tested increased the firing rates following subcutaneous injections of capsaicin, while the majority of thermo‐unresponsive units were not affected by this drug. 6. It is suggested that thermo‐responsive neurones in the preoptic area and anterior hypothalamus in the new‐born rat have attained some degree of electrophysiological maturity, despite their slowly firing characteristics.
Development of spinal reflexes in the rat fetus studied in vitro.
Authors: Saito K
Published: December 2014

1. The onset and development of spinal reflex activity was investigated using the isolated spinal cord of the rat fetus. The potential changes generated in motoneurones were recorded extracellularly from L3 ventral roots. 2. A spike potential was recorded from the ventral root at embryonic day 13.5 in response to stimulation of the cord surface close to the ventral root. The discharge persisted in Ca2+‐free solution but was blocked by tetrodotoxin. 3. At embryonic day 14.5, trans‐synaptically evoked discharges were detected in motoneurones. 4. Stimulation of the dorsal root was first effective in eliciting reflex discharges at embryonic day 15.5. The reflex response then consisted of a prolonged depolarization upon which were superimposed small spikes, and was probably polysynaptic. 5. A spike potential, presumably a monosynaptic reflex, was generated at the end of fetal life. This discharge appeared first at embryonic day 17.5 in a primitive form. 6. Between embryonic day 16.5 and 17.5, stimulation of the dorsal root of diffferent segments (L1‐L6) elicited responses similar to those induced by the corresponding (i.e. L3) dorsal root stimulation. These inter‐segmentally induced responses were then reduced in size toward the birth. However, in the presence of strychnine, a train of spike discharges of similar shape to the segmentally induced response was also evoked by stimulation of the dorsal root at L4 or L5. These spikes disappeared during further post‐natal development. 7. It is concluded that synapses in the segmental polysynaptic pathway become functional in a retrograde sequence with respect to the direction of normal reflex impulse flow. The reflex responses, elicited by stimulation of the dorsal roots of different segments, are suggested to be suppressed first by the development of inhibitory mechanisms and then by neuronal cell death or by elimination of the synapses responsible for generating the inter‐segmental reflexes.
Intercellular spaces in chemically fixed corneal endothelia are related to solute pump activity not to solvent coupling.
Authors: Hodson S , Mayes K R
Published: December 2014

1. Stereological analyses of the lateral intercellular spaces in the endothelium of rabbit corneas after chemical fixation were undertaken. 2. Immediately preceding chemical fixation the endothelia were in one of four transport modes: (a) bicarbonate pump activated and no coupled solvent flux, (b) bicarbonate pump activated and, coupled to it, a solvent flux, (c) no fluxes across the endothelia and (d) passive fluid fluxes across the endothelia. 3. In each transport mode, the intercellular spaces were measured after immersion in a series of fixatives in which the concentration of buffer (sodium cacodylate) was increased. 4. Lateral intercellular spaces were a function of buffer concentration in the fixative and activity of the bicarbonate pump. They were not a function of either solvent coupling or passive solvent flow. 5. It is concluded that the characteristic changes of lateral intercellular spaces, when transport is inhibited, do not indicate the site of local osmotic coupling.
Activation by sanguinarine of active sodium efflux from frog skeletal muscle in the presence of ouabain.
Authors: Moore R D , Rabovsky J L
Published: December 2014

1. Applied to intact Na‐rich muscle cells, sanguinarine causes an increased 22Na efflux in the presence or absence of extracellular K+ or of ouabain. 2. The increased 22Na efflux does not represent Na:Na exchange as indicated by the fact that it is not associated with an increase in one‐way isotopic Na influx nor is it abolished by the absence of external Na+. 3. In both K‐free Ringer and K‐free Ringer containing ouabain, sanguinarine not only increases one‐way efflux of 22Na, it also induces net efflux of Na+ in the face of both an electrical and a concentration gradient. Moreover, the induction of net Na+ efflux occurs in the face of an approximately fourfold increase in PNa. These surprising results lead to the conclusion that, contrary to all experiments, sanguinarine induces active Na+ efflux even in K‐free Ringer containing 10(‐3) M‐ouabain. 4. Sanguinarine depolarizes the Na‐loaded muscle to approximately the same value, ‐54 mV, regardless of the presence or absence of extracellular K+. This depolarization is most likely secondary to the increase in PNa. 5. Sanguinarine causes a net loss of K+, presumably secondary to the depolarization. 6. The stimulation of net Na+ efflux is not correlated with the depolarization. The stimulation in K‐free conditions (with or without ouabain), which is associated with the largest depolarization, produces an increment in net Na+ efflux which is not significantly different from the increment in net Na+ efflux in 10 mM‐K+ Ringer where the depolarization is smallest. 7. Although sanguinarine increases active Na+ efflux in intact cells, it inhibits the isolated (Na+ + K+)‐ATPase, presumably due to interaction with a site on the inner face of the membrane fragment. 8. The surprising stimulation of active Na+ efflux in the presence of 10(‐3) M‐ouabain must be due to interaction of sanguinarine with a site on the outer face of the membrane, perhaps the K+ activation site. It seems probable that the component of active Na+ efflux induced by sanguinarine is mediated by the Na pump. Sanguinarine may produce a K+‐like effect upon the Na pump with consequent unbinding of ouabain.
Recovery of cat retinal ganglion cell sensitivity following pigment bleaching.
Authors: Bonds A B , Enroth‐Cugell C
Published: December 2014

1. The threshold illuminance for small spot stimulation of on‐centre cat retinal ganglion cells was plotted vs. time after exposure to adapting light sufficiently strong to bleach significant amounts of rhodopsin. 2. When the entire receptive field of an X‐ or Y‐type ganglion cell is bleached by at most 40%, recovery of the cell's rod‐system proceeds in two phases: an early relatively fast one during which the response appears transient, and a late, slower one during which responses become more sustained. Log threshold during the later phase is well fit by an exponential in time (tau = 11.5‐38 min). 3. After bleaches of 90% of the underlying pigment, threshold is cone‐determined for as long as 40 min. Rod threshold continues to decrease for at least 85 min after the bleach. 4. The rate of recovery is slower after strong than after weak bleaches; 10 and 90% bleaches yield time constants for the later phase of 11.5 and 38 min, respectively. This contrasts with an approximate time constant of 11 min for rhodopsin regeneration following any bleach. 5. The relationship between the initial elevation of log rod threshold extrapolated from the fitted exponential curves and the initial amount of pigment bleached is monotonic, but nonlinear. 6. After a bleaching exposure, the maintained discharge is initially very regular. The firing rate first rises, then falls to the pre‐bleach level, with more extended time courses of change in firing rate after stronger exposures. The discharge rate is restored before threshold has recovered fully. 7. The change in the response vs. log stimulus relationship after bleaching is described as a shift of the curve to the right, paired with a decrease in slope of the linear segment of the curve.
Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells.
Authors: Ascher P , Large W A , Rang H P
Published: December 2014

The mode of action of ACh antagonists on the parasympathetic neurones of the submandibular ganglion of the rat was studied by means of a two‐micro‐electrode voltage‐clamp technique. The currents produced by various agonists (carbachol, ACh, suberylcholine) were studied in steady state and after voltage steps, before and after perfusion of various antagonists. 2. For three antagonists (tubocurarine, hexamethonium, decamethonium) the blocking action increases with hyperpolarization. For three other antagonists (surugatoxin, trimetaphan, mecamylamine) the effects observed at low concentrations appear to be independent of membrane potential, although in some cases voltage dependence of the block was observed for mecamylamine. 3. The blocks the ‘open’ channel‐reception complex. The block produced by tubocurarine, hexamethonium and decamethonium increases with the agonist concentration, an observation which supports a ‘sequential’ scheme in which the antagonist blocks the ‘open’ channel‐receptor complex. The block produced by trimetaphan and mecamylamine decreases slightly with increased agonist concentration, which in turn suggests that these two compounds are competitive antagonists, preventing binding of the agonists to the closed channel‐receptor complex. 4. In the cases where the block is voltage dependent, voltage jumps trigger slow relaxations which are not present in control conditions. In the case of tubocurarine and hexamethonium, the relaxation following a hyperpolarizing voltage jump corresponds to a decrease in conductance. In the case of decamethonium, the slow relaxation is in the opposite direction. 5. The slow relaxations observed with tubocurarine and hexamethonium are speeded by an increase of the antagonist concentration; the slow relaxations observed with decamethonium are slowed by an increase of the decamethonium concentration. 6. The steady‐state observations and the relaxations can be interpreted in terms of a scheme in which tubocurarine, hexamethonium and decamethonium act mainly by blocking the channels opened by the cholinergic agonists. 7. The two types of slow relaxation are those predicted if tubocurarine and hexamethonium dissociate slowly from the channel, and decamethonium rapidly. 8. An additional effect of tubocurarine is described, which consists of a potentiation of the rising phase of the response to an ionophoretic pulse. Possible mechanisms of this effect are discussed.
Microvascular filling pattern in rat liver sinusoids during vagal stimulation.
Authors: Koo A , Liang I Y
Published: December 2014

1. The terminal microcirculation in the transilluminated ventral margin of the rat liver was observed and recorded by a video‐microscope system. The volumetric flow rate in a liver sinusoid was calculated from the observed diameter of the sinusoid and the intra‐sinusoid erythrocyte flow velocity. 2. The topographic distribution of liver sinusoids within an arbitrary boundary of a microscopic field of terminal liver microcirculation was observed and the total inflow and outflow in the field were determined. 3. Both vagus nerves at the lower end of the oesophagus were stimulated at supramaximal voltage. Vagal stimulation dilated the calibre of liver sinusoids and paradoxically diminished the erythrocyte flow velocity in each individual liver sinusoid, but the total volumetric flows in a microscopic field remained unchanged. 4. Vagal stimulation also increased the number of liver sinusoids in a microscopic field by opening previously closed liver sinusoids. This recruitment contributed two‐thirds of the total increase of the sinusoidal capacity while the other one third was the result of distension of existing liver sinusoids.
The effect of stimulation by meat on gastrins in pyloric antral mucosa of anaesthetized cats.
Authors: Blair E L , Hamill A , Jackson B , Lund P K , Nicholson E , Sanders D J
Published: December 2014

Chloralose anaesthetized cats were prepared with fundic and antral pouches. After stimulation with meat extract suspension in the antral pouches, the antral mucosae were collected, homogenized and subjected to subcellular fractionation to produce whole homogenates, debris, mitochondrial, granule and microsomal fractions and the cell supernatant. Total gastrin concentration and the quantities of gastrin components were measured in these cell fractions and compared with values obtained from a group of control animals which were not stimulated. Stimulation significantly increased the concentration of total gastrin in whole homogenates and in the cell supernatant. In whole homogenates the concentrations of gastrin components I, II, III and void volume gastrin all increased significantly after stimulation. In granules the concentration of Component III significantly increased. In microsomes the concentration of Componenet IV increased significantly. In cell supernatant the total amounts of Components III and IV increased significantly. It is concluded there was synthesis of gastrin under the experimental conditions used. The concentrations of those gastrin components which are larger than the predominant storage form (Component III) are increased and these larger components may be biosynthetic precursors. The significant increase in Component IV concentration in the cell supernatant and microsomes may suggest that Component IV is formed at least in part by antral tissue as well as by the known conversion process which occurs in cat blood.
A critical assessment of the Wilhelmy method in studying lung surfactants.
Authors: Barrow R E , Hills B A
Published: December 2014

1. The surface properties of over 250 films of diplamitoyl lecithin (DPL) and Tween 20 on distilled water have been investigated using two different surface balances simultaneously, the Wilhelmy balance, popular in physiological studies, and the Du Nuoy ring method whose readings are independent of contact angle. 2. Using concentrations of DPL ranging from 0.08 to 1.90 microgram cm‐2 on a Langmuir trough where the pool area was cycled from 100 to 27.5% of maximum, the Wilhelmy balance registered virtually the same force per wetted perimeter as the ring method for both pure water and Tween 20, but appreciably lower values for DPL over the whole cycle. 3. The above differences can be explained on the basis of a significant (45‐70 degrees) contact angle, a surface property also demonstrated photographically and by direct measurement. 4. Contact angle was shown to vary with pool area, a relationship exhibiting hysteresis. 5. This study indicates that the Wilhelmy balance has been an unfortunate choice of instrument for studying DPL films whose surface tensions are appreciably higher than previously estimated.
Lateral interactions in human cone dark adaptation.
Authors: Hayhoe M M
Published: December 2014

1. The course of cone dark adaptation after exposure to a strong bleaching light depends on the size of the bleached region. Threshold for brief, tiny test flash centred in the bleached region is elevated more, and recovery is retarded by a small bleach. This effect has its parallel in the sensitization effect observed with steady backgrounds. 2. Previous results, that a similar sensitization effect is not observed in rod dark adaptation, are confirmed. 3. This sensitization effect in cone dark adaptation does not transfer binocularly, and is unaffected by pressure blinding during the bleaching exposure. 4. Threshold following a small bleach may be lowered by adding a steady annular background to the region surrounding the bleached patch. Conversely, bleaching the area surrounding a small, steady background can lower threshold for a test flash centred on the background. 5. These interactions between backgrounds and bleaches may be explained if bleaches produce long‐lasting signals from neurones in the bleached area, which then lead into a spatially opponent stage of processing. 6. It is likely that the persisting signals come from the cone receptors, since the Bunsen‐Roscoe Law (intensity‐time reciprocity) holds for small bleaches as well as large, for durations up to about 3 sec.
After‐effects of small adapting fields.
Authors: Hayhoe M M
Published: December 2014

1. Sensitivity to a small test probe in the centre of a small, steady background is less than when the background is large (sensitization). When an equiluminous steady annulus is added to the region surrounding a small background, rod threshold takes several minutes to stabilize at its new, lower level. The after‐effects of the small background follow a time course characteristic of cortical adaptation. 2. The sensitivity loss and time course of recovery after intense bleaching lights in the cone system depend markedly on the size of the retinal region bleached, although no such effect is observed in the rod system. If a steady annular surround is added to the region surrounding the bleached patch, threshold falls rapidly to the value it would have after a large‐area bleach of the same intensity. 3. The interaction between bleaches and steady surrounds suggests that bleaches produce long‐lasting signals in the cone receptors. 4. The different temporal properties of sensitization on rod backgrounds and sensitization after cone bleaches suggest that different mechanisms underlie the two phenomena. 5. In cone vision, if light is added to the area surrounding a small, steady background, the subsequent readjustment takes minutes to complete, as it does in rod vision. But in addition, for cones, a large proportion of the sensitivity loss caused by the small background can be rapidly restored, as it is with cone bleaches. 6. The above results, together with the known absence of sensitization in rod dark adaptation, are consistent with the hypothesis that sensitization occurs at least partly at the retinal level in the cone system, but not (or only weakly) in the rod system, and that there is an additional, probably cortical elevation, common to rod and cone systems, for small backgrounds, but not for small, brief bleaches.
Hypothalamic sensitivity to leukocytic pyrogen of adult and new‐born guinea‐pigs.
Authors: Blatteis C M , Smith K A
Published: December 2014

1. Experiments were conducted to localize the hypothalamic site of action of microinjected leucocytic pyrogen and to compare the pyrogenic sensitivity of this locus in adult and new‐born guinea‐pigs.2. To identify the site reactive to leucocytic pyrogen, bilateral (0.8‐1.0 mm from the mid line) injections of 1 microliter were made into conscious adult guinea‐pigs via cannulas stereotaxically palced at 0.5 mm intervals and varying depths from the olfactory tegmentum to the mammillary bodies. Injections into the preoptic area produced sharp monophasic fevers with short latencies, whereas injections into circumjacent sites evoked smaller fevers with longer latencies. 3. To assess the ontogeny of the pyrogenic sensitivity of this locus, the febrile response to 1.00, 0.50, and 0.25 microliter leucocytic pyrogen injected bilaterally was compared to 0 to 5‐, 6 to 12‐, and 13 to 16‐day old and in adult guinea‐pigs. The minimum pyrogenic dose in both new‐born and adult guinea‐pigs was 0.25 microliter, but the 0 to 5‐day old animals which responded with a fever to this dose were few in number and large in weight; ‘small‐for age’ neonates became hypothermic. 4. The number of febrile animals increased with age; it also could be increased by increasing the dose of leucocytic pyrogen at any age. 5. These results suggest that febrile responsiveness may depend on the stage of development of, presumably, the pyrogen‐receptive mechanism. They further imply that the preoptic sites where leucocytic pyrogen acts and thermoafferents are integrated may not be the same, since thermoregulatory capability is fully competent from birth.
Drinking behaviour in rats treated with isoprenaline, angiotensin II or angiotensin antagonists
Authors: Chiaraviglio Emma
Published: December 2014

1. Isoprenaline hydrochloride injected subcutaneously in rats given a choice test of 1·8% NaCl and water, first induced saline intake which started immediately and was almost concluded in 15 min, followed by a copious water intake. When either saline or water were given in a separate test, saline intake surpassed the water intake in the first 15 min.

2. The delay of 15, 30 or 60 min after injection of isoprenaline, 100 μg/kg, before drinking was allowed, significantly reduced saline intake but did not modify the amount of water subsequently drunk.

3. Isoprenaline caused a sudden drop in arterial blood pressure, the extent and duration depending on the dose. The time of maximum drop 3‐4 min after injection coincided with the time the rat drank salt.

4. Isoprenaline‐induced saline drinking was significantly reduced after bilateral nephrectomy but water intake was unaffected.

5. The beta‐adrenoceptor blocking agent, propranolol, inhibited isoprenaline‐induced NaCl and water intake, while the alpha‐adrenoceptor antagonist phenoxybenzamine abolished isoprenaline‐induced NaCl intake and enhanced water intake.

6. Saralasin acetate (P‐113), a competitive inhibitor of angiotensin II, given into the third brain ventricle, prevented the isoprenaline‐induced NaCl and water intake as well as angiotensin II‐induced drinking. The angiotensin converting enzyme inhibitor SQ‐20881 reduced the isoprenaline‐induced NaCl and water intake.

7. In conclusion, hypotension might be a component of salt drinking evoked by isoprenaline although the dipsogenic action of beta‐stimulation is mainly due to endogenous renin‐angiotensin activation.
The effects of sudden airway hypercapnia on the initiation of exercise hyperpnoea in man.
Authors: Ward S A
Published: December 2014

1. In three healthy individuals, the first breath of cycle ergometer exercise was characterized by increases of minute ventilation (VE) and pulmonary capillary CO2 output (VCO2), with little change of end‐tidal PCO2, suggesting a concomitant increase of pulmonary blood flow (Q) and preservation of V/Q status. Functional residual capacity fell, depleting lung gas stores of O2 and CO2. 2. The following hypothesis purporting to account for the initiation of exercise hyperpnoea was examined (Filley, 1976): (a) assuming pulmonary capillary plasma to remain unexposed to carbonic anhydrase, its slow alkalinization consequent upon CO2 exchange causes a more acid plasma to enter the pulmonary veins if Q increases abruptly, as at exercise onset; (b) the fall of pulmonary venous plasma pH stimulates an intrapulmonary chemoreflux to elicit a proportionate hyperpnoea, so preserving arterial isocapnia; (c) the initial hyperpnoea should therefore be abolished if pulmonary capillary VCO2 is suppressed at exercise onset, as the absence of pulmonary capillary plasma alkalinization should sever the postulated intrapulmonary humoral link between Q and VE. 3. In the present study, while abrupt CO2 inhalation (approximately 6% in air) at exercise onset abolished pulmonary capillary VCO2 during the first breath of exercise, the initial hyperpnoea was unaffected. This observation argues against the hypothesis that exercise hyperpnoea is initiated by an intrapulmonary chemoreflex which detects perfusion‐related changes in pulmonary venous plasma pH.
The relationship between end‐plate size and transmitter release in normal and dystrophic muscles of the mouse.
Authors: Harris J B , Ribchester R R
Published: December 2014

1. The morphology of nerve terminals and sub‐neural apparatuses was examined in the muscles of normal and dystrophic adult mice of the Bar Harbor 129 ReJ strain. Nerve terminals were larger in dystrophic muscles than in normal muscles and nerve terminal sprouting was evident in about 50% of the dystrophic muscles fibres. End‐plate area was positively correlated with muscle fibre diameter in both normal and dystrophic muscles. 2. Polynueronal innervation was found in only 1% of dystrophic muscle fibres impaled with micro‐electrodes. 3. Miniature end‐plate potential amplitude was positively correlated with muscle fibre input resistance in both normal and dystrophic muscles. There was however, a greater than normal variation in the amplitudes of m.e.p.p.s recorded from individual dystrophic muscle fibres. 4. Quantum contents of end‐plate potentials were estimated in normal and dystrophic mouse nerve‐muscle preparations partially blocked with D‐tubocurarine. The quantum content of e.p.p.s seemed to be related to muscle fibre diameter, and in dystrophic muscles the characteristics of evoked release were indistinguishable from normal. 5. It was concluded that the nerve terminal sprouting and the expansion of end‐plate area which were observed in dystrophic muscles are not a consequence of any form of denervation, but represent an attempt by the axon to expand the area of synaptic contact in hypertrophied muscle fibres.
The role of vasopressin in blood pressure regulation immediately following acute haemorrhage in the rat
Authors: Laycock J. F. , Penn W. , Shirley D. G. , Walter S. J.
Published: December 2014

1. The possible pressor effect of vasopressin immediately after acute haemorrhage has been studied using anaesthetized Brattleboro rats with diabetes insipidus and rats of the Long Evans parent strain.

2. A blood loss of 0·5% of the body weight caused a significant decrease in mean arterial blood pressure, measured 10 min later, in Brattleboro rats, whereas this degree of haemorrhage was non‐hypotensive in the control Long Evans rats. Following subsequent blood losses (each of 0·5% of the body weight), mean arterial blood pressure in Brattleboro rats was always significantly lower than in Long Evans rats.

3. While no antidiuretic activity was at any time found in the plasma of Brattleboro rats, haemorrhages greater than 1% of the body weight were associated with marked increases in plasma arginine vasopressin (AVP) of Long Evans rats.

4. When Brattleboro and Long Evans rats were subjected to a single haemorrhage of 2% of the body weight, the immediate decrease in arterial blood pressure was similar in the two groups. However, 5 and 10 min after the haemorrhage the arterial blood pressure was significantly higher in the Long Evans rats. When vasopressin was infused into Brattleboro rats so that plasma levels of the hormone approached those found in Long Evans rats, the mean arterial blood pressure 0, 5 and 10 min after haemorrhage was similar to that in the Long Evans animals.

5. It is concluded that in the anaesthetized rat, vasopressin plays an important role in the regulation of arterial blood pressure during the period immediately following acute haemorrhage.
Epithelial transport pathways of rat colon determined in vivo by impulse response analysis.
Authors: Edmonds C J , Smith T
Published: December 2014

1. A method is described for studying transepithelial pathways for the movement of different solutes and water. Using the blood and the secretory curves of changing tracer activity following an intravenous bolus, the rate of transit of molecules together with their impulse response functions, which reflect the transfer processes can be examined. 2. Movements of Na, Cl, I, urea and water from blood to lumen across rat colonic epithelium were all consistent with simple diffusion through a paracellular route. Most of the secreted K, however, passed through a K selective route associated with a significant K epithelial pool. 3. Adding cyanide to the luminal solution caused a reversible fall of transepithelial potential difference associated with changes in the impulse response functions of water, urea and K indicating reduction of the restriction on diffusion. Cellular K content was unaffected. 4. K entered the bulk of the epithelial cellular K almost exclusively from the blood side. A small epithelial K pool, identified by studies with a miniature GM counter, had kinetic characteristics like those of the K selective pathway observed in the studies of impulse response functions.
The effects of post‐ganglionic axotomy on selective synaptic connexions in the superior cervical ganglion of the guinea‐pig.
Authors: Purves D , Thompson W
Published: December 2014

Stimulation of preganglionic axons arising from different levels of the thoracic spinal cord causes different effects on end‐organs supplied by the superior cervical ganglion (Langley, 1892; Nja & Purves, 1977a; Lichtman, Purves & Yip, 1979). For example, stimulation of the first thoracic ventral root (T1) causes pupillary dilatation and widening of the palpebral fissure; stimulation of T4, on the other hand, has little effect on the eye, even though axons arising from this level innervate about as many superior cervical ganglion cells as those from T1. Thus ganglion cell innervation is selective. (1) Three months after crushing the major post‐ganglionic branches of the superior cervical ganglion this differential effectiveness is lost: T1 and T4 stimulation have approximately equal effects on the end‐organs of the eye. (2) In normal animals, the cellular counterpart of selective end‐organ effects is the innervation of each ganglion cell by a contiguous subset of the spinal segments that innervate the ganglion as a whole. One of these segments is usually dominant, the strength of innervation from adjacent segments falling off as a function of distance from the dominant one (Nja & Purves, 1977a). Intracellular recordings from ganglion cells 3 months after post‐ganglionic axotomy showed that this selective pattern is re‐established. (3) Since the innervation of ganglion cells appears normal, the abnormal end‐organ responses after post‐ganglionic axotomy suggest that ganglion cell axons are not limited to their original targets during peripheral re‐innervation. This suggestion is supported by the finding that ganglion cells sending axons to different peripheral destinations via the second and third cervical spinal nerves were no longer distinguishable on the basis of their segmented inputs 3 months after post‐ganglionic axotomy. (4) Similar results were obtained when the preganglionic cervical trunk was cut at the same time as the post‐ganglionic axons were crushed; the pattern of end‐organ responses was abnormal, whereas individual ganglion cells were re‐innervated according to the rules of contiguity and segmental dominance. (5) These results indicate that ganglion cells do not undergo a compensatory change in the segmental innervation they receive when their axons regenerate to targets different from, or in addition to those they originally innervated, even when an entirely new set of ganglionic connexions is formed. This suggests that ganglion cells, or some aspect of their immediate environment, possess a permanent label that determines the segmental innervation they receive.
The choice of models relating tritiated water absorption to subepithelial blood flow in the rumen of sheep.
Authors: Dobson A
Published: December 2014

1. The blood flow to the ruminoreticulum of anaesthetized sheep was varied by changing the proportion of CO2 in the gas stirring solutions confined to this organ. 2. Clearance of tritiated water was thereby varied fourfold, from 10 to 44ml./min.100 g epithelium, with negligible net water movement. 4. Subepithelial blood flow, observed with radioactive microspheres using the reference organ technique, varied tenfold, from 20 to 200 ml./min.100 g epithelium. 4. The relation between tritiated water absorption and blood water flow was approximated by a hyperbolic model, but was appreciably better described using a higher order term in blood flow consistent with a countercurrent exchange of tritiated water between arterioles and venules. 5. The distribution of blood flow between different regions of the organ and between epithelium and muscle is described.
The interaction of ouabain and salicylate on sheep cardiac muscle.
Authors: Cohen I , Noble D , Ohba M , Ojeda C
Published: December 2014

1. The action potential duration in sheep ventricular fibres is rapidly diminished on exposure to 10(‐6) M‐ouabain. However, if 10‐‐20 mM‐sodium salicylate is added to the ouabain solution, glycoside‐induced shortening is prevented, and a substantial increase in duration then occurs. Sodium salicylate also reverses the shortening effect of ouabain if applied after the glycoside has been allowed to act alone. 2. Sodium salicylate alone produces a much smaller prolongation than in the presence of ouabain. Alone and in the presence of ouabain it eventually increases the threshold and produces inexcitability. 3. Three other surface charge agents have been compared with salicylate: aminonaphthalene sulphonate, sodium dodecylsulphate and salicylamide, were unable to counter the actions of ouabain at the concentrations used. Since they also produced no changes in excitability it is likely that they did not bind significantly to the cell membrane. 4. In Purkinje fibres the reversal potential for the pacemaker current, iK2, is initially shifted in a negative direction in the presence of 10(‐6) M‐ouabain and 10 mM‐salicylate instead of the positive shift expected with ouabain alone at this concentration. 5. In guinea‐pig ventricle, salicylate alone reduces the duration of the action potential. This effect is rapidly reversible. Toxic levels of ouabain also reduce the action potential duration but this effect takes several hours to reverse. By contrast, the effects of salicylate and ouabain applied together are readily reversible. 6. It is suggested that the mechanism of these effects may depend on the ability of a surface negative charge agent like salicylate to increase the surface K+ concentration at the membrane and so protect the sodium‐potassium pump from inhibition by large doses of ouabain.
Differential effect of perhydrohistrionicotoxin on ‘intrinsic’ and ‘extrinsic’ end‐plate responses.
Authors: Albuquerque E X , Gage P W , Oliveira A C
Published: December 2014

1. At rat and frog neuromuscular junctions, perhydrohistrionicotoxin (H12‐HTX), at concentrations below 10(‐6) M, blocked end‐plate currents and potentials generated by ionophoretic application of ACh (extrinsic responses) more effectively than end‐plate currents and potentials generated by neurotransmitter secreted from the motor nerve (intrinsic responses). 2. In contrast, (+)‐tubocurarine affected both extrinsic and intrinsic responses in a parallel manner. 3. There was no change in the time course and little or no change in the amplitude of intrinsic end‐plate currents when extrinsic currents were depressed by H12‐HTX nor was there any change in the conductance or lifetime of channels activated by applied ACh. 4. The depressant effect of H12‐HTX on extrinsic responses persisted both when carbachol was used as the agonist and when acetylcholinesterase was inhibited with diisopropylfluorophosphate. 5. Large end‐plate currents elicited by nerve stimulation that presumably activate the whole end‐plate area were not depressed by H12‐HTX to the same degree as extrinsic end‐plate currents generated by ionophoresis of ACh at the same end‐plate. 6. Brief (50 microsec) pulses of ACh produced brief end‐plate potentials which were depressed by concentrations of H12‐HTX that had little or no effect on miniature end‐plate potentials. 7. Extrinsic responses to ACh at extrajunctional regions of denervated fibres were also depressed by low concentrations of H12‐HTX. 8. It was concluded that the differential effects of H12‐HTX on intrinsic and extrinsic end‐plate responses could be due to the existence of two populations of receptor‐channel complexes or to protection of local receptor‐channel complexes from the toxin by a substance secreted from motor nerve terminals.
The size of motor units during post‐natal development of rat lumbrical muscle.
Authors: Betz W J , Caldwell J H , Ribchester R R
Published: December 2014

1. The number of muscle fibres innervated by individual motor neurones (motor unit size) was measured in lumbrical muscles of rats aged 0‐‐28 days, during the period of elimination of polyneuronal innervation. Motor unit sizes were determined from twitch tension measurements combined with muscle fibre counts made from histological sections of the muscles. 2. The relative tensions contributed by individual motor units declined from about 25% of the total tension at birth, to about 9% at 28 days of age. Intracellular recordings showed that part of this decrease reflected the elimination of synapses from polyneuronally innervated muscle fibres. 3. During the same period, however, new muscle fibres were produced. The total number of muscle fibres present increased from about 500 at birth to about 950 fibres in mature muscles. 4. These two processes were offsetting: some synapses were eliminated (from polyneuronally innervated fibres) while simultaneously others were formed de novo (on newly produced muscle fibres). Quantitative measurements showed that for the first 10 days after birth, there was little change in motor unit size. Thereafter production of new muscle fibres ceased, and motor unit size decreased to the adult level. 5. It is concluded that during early post‐natal development, a lumbrical motor neurone maintains a nearly constant number of synapses, but extensively reorganizes its synaptic field, retracting synapses from some muscle fibres, while forming new synapses with other fibres.
Light adaptation in toad rods: requirement for an internal messenger which is not calcium.
Authors: Bastian B L , Fain G L
Published: December 2014

1. The mechanism of light adaptation was investigated by recording intracellularly from single rods in the isolated, superfused retina of the toad, Bufo marinus. Steady background lights produce decreases in rod sensitivity and changes in response wave form similar to those previously observed in the toad eyecup. 2. The sensitivity of a dark‐adapted rod is halved by a background light which bleaches about 4 rhodopsins per rod per second. Since a toad rod contains over 2000 disks, a rhodopsin bleached in one disk must alter the effectiveness of rhodopsins bleached in others. This could occur if the state of adaptation in the rod were regulated by the concentration of some diffusable substance. 3. This diffusable substance cannot be Ca2+. Increases in intracellular Ca2+, produced experimentally either by increasing extracellular Ca2+ or by facilitating Ca2+ permeability into the rod with the ionophore X537A, cause a hyperpolarization of membrane potential and a decrease in response amplitude; but they do not produce changes in sensitivity and response wave form like those produced by background light. 4. Either Ca2+ is not the internal transmitter released from the disks during excitation, or the disks release or otherwise alter the concentration of a second diffusable substance, in addition to Ca2+, which regulates the state of adaptation.
An electrophysiological analysis of the actions of prostaglandin on neuromuscular transmission in the guinea‐pig vas deferens.
Authors: Ito Y , Tajima K
Published: December 2014

Effects of prostaglandins (PGs) on the neuromuscular junction of the guinea‐pig vas deferens were investigated by the micro‐electrode and double sucrose gap methods. 1. PGE1, PGE2 or PGF2 alpha (10(‐10) to 10(‐7) g/ml.) did not change the membrane potential, membrane resistance and electrical threshold required to produce the action potential. 2. PGs markedly suppressed the amplitude of excitatory junction potential (e.j.p.) but the facilitation phenomena seen with repetitive stimulation were not affected. PGs did not change the amplitude and frequency of the miniature e.j.p. 3. The action potential recorded from the small nerve bundle with the aid of an extracellular micro‐electrode method was not affected by PGS. 4. The amplitude of the e.j.p. was dependent on the external concentration of Ca. When plotted against [Ca]o on a double log scale, the above relation yielded a straight line with a slope of 1.0. Application of PGs resulted in a parallel shift of this relation to the right. 5. From the concentrations of [Ca]o to produce a given e.j.p. in the absence and presence of various concentrations of PGE1, the linear relation was observed from double logarithmic plot between [[Ca]o ratio ‐1] and [PGE1]o. However the slope of the line was too small (‐0.37) to indicate a simple competition between [PGE1]o and [Ca]o. 6. Indomethacin (10(‐6) g/ml.) had no effect on the amplitudes of e.j.p. produced by repetitive stimulation. 7. These results indicate that a low concentration of PGs interact with [Ca]o at the activated nerve terminals, but that there is no modification of the actions of Ca in the nerve terminals required for release of chemical transmitter.