bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of age, potassium depletion and denervation on specific displaceable [3H]ouabain binding in rat skeletal muscle in vivo
Authors: Clausen Torben , Hansen Otto , Kjeldsen Keld , Nørgaard Aage
Published: December 2014

1. Following intraperitoneal injection of [3H]ouabain in rats, the isotope is rapidly distributed in blood plasma available for binding to the Na‐K‐ATPase in the plasma membranes of most tissues. In skeletal muscle tissue excised and washed 4 × 30 min in ice‐cold buffer, 95% of the 3H activity retained was shown to be [3H]ouabain using a specific binding assay.

2. The [3H]ouabain bound to soleus and extensor digitorum longus (e.d.l.) muscles in vivo and retained following wash‐out in the cold showed the same saturation characteristics as those determined when binding took place in vitro.

3. In soleus and e.d.l. muscles obtained from 28‐day‐old rats, the number of [3H]ouabain binding sites measured in vivo was 583±19 and 720±22 pmol/g wet wt., respectively, i.e. in good agreement with previous and present results obtained in vitro.

4. In vivo measurements showed that 7 days after denervation, the number of [3H]ouabain binding sites in soleus and e.d.l. muscles was reduced by 22 and 13%, respectively.

5. In the age interval from 28 to 85 days, the number of [3H]ouabain binding sites in soleus was found to decrease by 58%. Following I.P. injection of [3H]ouabain, the 85‐day‐old rats showed a more pronounced and sustained rise in plasma 3H activity, which in part can be due to the reduced capacity for [3H]ouabain binding in skeletal muscle.

6. K depletion induced by the administration of K‐deficient diet for 3 weeks reduced [3H]ouabain binding by 63% in soleus muscles. In the K‐depleted animals, the plasma 3H activity measured 15 min after I.P. injection of [3H]ouabain was 77% higher than in controls receiving the same dose per kg body weight.

7. The present in vivo results provide further support for the idea that increased digitalis toxicity due to increasing age or K depletion is related to reduced binding capacity for digitalis glycosides in skeletal muscle.
Evidence for the identification of synaptic transmitters released by photoreceptors of the toad retina.
Authors: Miller A M , Schwartz E A
Published: December 2014

1. When toad retinae were incubated with veratrine, kainic acid, and L‐alpha‐aminoadipic acid, photoreceptor cells survived and most other neurones died. This preparation of ‘isolated’ photoreceptor cells accumulated radioactive molecules from the incubation medium and metabolized these into labelled compounds. When a preparation was placed on a filter and superfused, radioactive molecules which were released into the superfusion fluid could be collected and later analysed. Several procedures were used for inducing the release of possible transmitter compounds. Each released compound was chemically identified. 2. Three compounds, aspartic acid, glutamic acid, and N‐acetyl histidine, were released when the potassium concentration was increased in media that lacked calcium and contained cobalt. 3. The release of these compounds was further increased when cobalt was removed and calcium returned to the extracellular medium. 4. Two additional compounds, putrescine and cadavarine, were also released during depolarization when calcium was present. 5. The efflux of each of the compounds listed in Section 2 was also increased by homo‐ and hetero‐exchange. For at least aspartate, exchange was sodium‐dependent. 6. The post‐synaptic effect of released compounds was tested by their ability to increase the efflux of [3H]GABA from ‘isolated’ horizontal cells. 0 . 1 mM‐L‐aspartate, or L‐glutamate produced an increase in GABA efflux. N‐acetyl histidine, putrescine, and cadavarine were ineffective. 7. Isolated photoreceptors and intact retinae were incubated with [3H]aspartate, or [3H]putrescine. Subsequent histology and autoradiography demonstrated that both compounds were selectively accumulated by cones.
Glomerular filtration rate and salt and water reabsorption during pregnancy in the conscious rat.
Authors: Atherton J C
Published: December 2014

1. Glomerular filtration rate (g.f.r.) and salt and water reabsorption were measured in age‐matched conscious virgin rats and rats at different stages of pregnancy that were infused with saline at 40 and 200 microliters min‐1. 2. G.f.r. and salt and water reabsorption were significantly higher at all stages of pregnancy irrespective of the the rate of infusion. 3. The similarity in both time course and magnitude, of changes in renal function between conscious and anaesthetized rats at the two infusion rates suggests that the detection of differences in the anaesthetized rat during pregnancy is not dependent on either the anaesthetic/surgery employed or the rate of expansion of the extracellular fluid volume. 4. During the induction of the diuresis in 20‐day pregnant rats infused at 40 microliters min‐1 urine flow was higher and osmolality lower than in virgin rats and rats at earlier stages of pregnancy, suggesting that late‐pregnant rats have an altered ability for elaborating concentrated or dilute urine.
Difference in kinetics between the distal and proximal parts of the canine parietal cell mass in response to histamine.
Authors: Larsson J O
Published: December 2014

Dogs provided with one denervated gastric pouch in the distal part of the corpus fundus and another of equal size in the proximal part, were studied during histamine stimulation. Dose‐response curves were determined for acid output and mucosal blood flow, which was measured with the Neutral Red technique. Maximum acid output was significantly higher for the distal (mean 234.0 mumol min‐1) than for the proximal pouch (120.0 mumol min‐1). ED50 for acid output was significantly higher for the distal (105.0 micrograms kg‐1 h‐1 of histamine) than for the proximal pouch (57.0 micrograms kg‐1 h‐1). ED50 for blood flow did not differ significantly between the distal (40.5 micrograms kg‐1 h‐1) and the proximal pouch (29.0 micrograms kg‐1 h‐1). For both pouches ED50 for blood flow was significantly lower than that for simultaneous acid output. This indicated that the rise in blood flow precedes that in acid output. Regression analysis showed a significantly higher ratio between maximum mucosal blood flow and maximum acid output for the distal (0.30 ml mumol‐1) than for the proximal pouch (0.15 ml mumol‐1). The finding that ED50 for acid output in response to histamine was lower for the proximal pouch is contrary to earlier results obtained with pentagastrin, which showed that ED50 was lower for the distal pouch. There is no valid explanation for these differences in ED50 between the pouches, but a difference at receptor level could be hypothesized. The difference in maximum acid output between the two pouches is explained by the known difference between distal and proximal parts in volume fraction of the parietal cells. The possibility that these differences in acid production depend on dissimilarities in mucosal blood flow can be excluded.
Actions on gamma‐motoneurones elicited by electrical stimulation of group III muscle afferent fibres in the hind limb of the cat.
Authors: Appelberg B , Hulliger M , Johansson H , Sojka P
Published: December 2014

The reflex actions evoked by electrical stimulation of group III muscle afferent fibres were investigated with micro‐electrode recordings from ninety‐three gamma‐motoneurones projecting to hind‐limb muscles of cats anaesthetized with chloralose. For seventy‐eight of the ninety‐three gamma‐cells the frequency of occurrence and types of effects mediated via group II and group III muscle fibres were compared. Seventy‐seven of the cells tested at intensities which excited group III and seventy‐five of the cells tested at intensities which excited both group II and group III afferent fibres were classified as either static or dynamic, using the method of mesencephalic stimulation (Appelberg, 1981). The responsiveness of the whole sample of gamma‐motoneurones to inputs from group III muscle fibres was high and comparable to that found with group II fibres. It was found that group III muscle fibres acted preferentially on static gamma‐motoneurones. In contrast, group II fibres acted preferentially on dynamic gamma‐motoneurones. Both excitatory and inhibitory effects were provoked by stimulation of group III fibres. Generally excitation was more frequent than inhibition. A strong dominance of excitation over inhibition was found in flexor muscles, and a weaker prevalence of excitation was also encountered in extensor muscles. This prevalence of excitation in extensor gamma‐motoneurones is in contrast to the striking predominance of group III‐evoked inhibition of extensor alpha‐motoneurones as described by the flexion reflex afferents concept. A comparative survey is also given of the patterns of responses elicited in individual posterior biceps‐semitendinosus and gastrocnemius‐soleus gamma‐cells by stimulation of group II and group III fibres. These data further corroborate the view that reflexes from high‐threshold muscle afferent fibres to gamma‐motoneurones are organized differently from those to alpha‐motoneurones. The functional implications of these findings are discussed. It is proposed that the pools of gamma‐motoneurones should be considered as integrative systems intercalated between descending and reflex pathways on the one hand and the skeletomotor neurones on the other. The descending messages and the multisensory peripheral information, integrated in the fusimotor neurones, undergo final adjustment in the muscle spindle. The link to the skeletomotor neurones is formed by the primary spindle afferents. These constitute a final common input, conveying integrated detailed polymodal feed‐back, to the central nervous system. This new concept is referred to as the ‘final common input’ hypothesis.
Modulation of noradrenergic transmission in the guinea‐pig mesenteric artery: an electrophysiological study.
Authors: Kuriyama H , Makita Y
Published: December 2014

We carried out electrophysiological experiments on guinea‐pig mesenteric arteries in an attempt to clarify the modification of noradrenaline (NA) release from noradrenergic nerve terminals by the action of prejunctional adrenoceptors. NA (10(‐7)‐10(‐5) M) suppressed the amplitude of the first excitatory junction potential (e.j.p.(f], the facilitation process, and the e.j.p. after facilitation was completed (e.j.p.(s]with no change in the post‐junctional membrane properties of smooth muscles. These actions of NA on e.j.p.s were antagonized by high concentrations of extracellular Ca, [Ca]o, but not in a simple competitive manner. NA (10(‐7) M) suppressed the appearance but not the amplitude of the miniature e.j.p.s. These effects of NA on transmission indicate that NA acts on prejunctional nerve terminals and suppresses the release of NA from nerve terminals rather than producing a desensitization of post‐junctional adrenoceptors. Prazosin and phentolamine (10(‐6) M) did suppress the NA‐induced contraction (greater than 10(‐6) M) but did not suppress the contraction evoked by perivascular nerve stimulation, below a frequency of 1.0 Hz. At a dose of 10(‐7) M, yohimbine, clonidine, prazosin and phentolamine had no effect on the muscle membrane potential and resistance. Yet on the e.j.p.(f), yohimbine and clonidine caused suppression, phentolamine enhancement and prazosin had no effect. On the e.j.p.(s), yohimbine and phentolamine caused enhancement, clonidine suppression and prazosin had no effect. These results indicate that at least three different adrenoceptors are distributed on the neuromuscular junction in this tissue, i.e. alpha 1‐extrajunctional, alpha 2‐prejunctional, and an unknown subtype of intrajunctional adrenoceptors. Furthermore, the feedback mechanism on NA release is mediated by suppression of the influx of Ca. Nonselective and non‐specific actions of alpha‐adrenoceptor agonists and antagonists were also elucidated.
Inhibition of the vagal component of the baroreceptor‐cardioinhibitory reflex by angiotensin III in dogs and sheep.
Authors: Lumbers E R , Potter E K
Published: December 2014

Angiotensin II inhibits baroreceptor‐evoked activity in cardiac vagal motoneurones. Because angiotensin III [( des‐1‐Asp ]angiotensin II) is a less potent pressor agent than angiotensin II, and has been reported not to share some of the actions of angiotensin II within the central nervous system, its influence on central vagal pathways was examined here. In unanaesthetized sheep equipressor doses of angiotensins II and III similarly inhibited the baroreceptor‐cardioinhibitory reflex, a reflex which is almost wholly dependent on cardiac vagal activity. In anaesthetized dogs, equipressor doses of angiotensin II and III were equally effective in inhibiting the cardiac vagal activity usually evoked by rises in arterial pressure. This was established by direct recordings of activity in single cardiac vagal efferent nerve fibres. Direct recordings from single baroreceptor nerves in anaesthetized dogs showed that the angiotensins do not depress the receptor responses to elevations in blood pressure. It is concluded that equipressor doses of angiotensin III and angiotensin II inhibit central vagal pathways to the same extent.
Extracellular potassium levels and axon excitability during repetitive action potentials in crayfish.
Authors: Smith D O
Published: December 2014

Changes in extracellular K+ levels were measured during repetitive stimulation of the excitor axon of the opener muscle of the crayfish walking leg. Mesaxon channels, through which K+ might diffuse away from the periaxonal ('Frankenhaeuser‐Hodgkin') space, were examined in electron micrographs; they were seen every 2‐10 micron along the axon, and their average (+/‐ S.D.) length and width were 3.0 (+/‐ 1.6) micron and 19.8 (+/‐ 8.9) nm, respectively. Intracellular recordings revealed a 40 ms after‐depolarization following an action potential; this was attributed to elevated levels of extracellular K+. During stimulation at 50 Hz, this resulted in a depolarizing shift of the membrane potential between impulses; the average depolarization was 9.3 mV, which corresponds to a 4.3 mM increase in extracellular K+. Using K+‐selective micro‐electrodes, changes in extracellular K+ activity, delta aK, were measured at distances ranging from 10 to 50 micron from the axon; during 50 Hz stimulation, delta aK rose within 15 s to a maximum value of 1.1 mM which was maintained at a steady level in most preparations. Conduction failure occurred in several preparations after at least 90 s of stimulation; levels of delta aK were not abnormally high in these cases. Soaking the axon for at least 15 min in saline with extracellular K+ levels at least 18 mM above normal values was necessary to cause blockage in unstimulated nerves. Soaking the preparation for 30 min in 10(‐3) M‐ouabain resulted in a 48% increase in the maximum values of delta aK during 50 Hz stimulation. It is concluded that K+ accumulates extracellularly during axon stimulation and that the extent of this accumulation is reduced by active uptake mechanisms; however, this accumulation probably cannot directly block action potential conduction, for neither the magnitude nor the kinetics of K+ build‐up approach values shown to reduce excitability.
Inhibition of thiamine transport across the blood‐brain barrier in the rat by a chemical analogue of the vitamin.
Authors: Greenwood J , Pratt O E
Published: December 2014

The flux of thiamine from the blood into the brain has been measured using a specially devised technique by which a steady raised level of the vitamin, with or without radioactive labelling, can be achieved rapidly and maintained in the bloodstream. This is done by a continuous injection, given at a rate which is adjusted by a pre‐determined programme so as to replace the tracer at the rate at which it has been found to leave the circulation in previous experiments. A further programme was worked out to maintain, in a similar manner by a separate injection, a steady raised level in the bloodstream of a chemical analogue of thiamine, 1‐[(4‐amino‐2‐propyl‐5‐pyrimidinyl)methyl]‐2‐picolinium chloride HCl (amprolium). In the presence of a high concentration of amprolium the flux of thiamine across the blood‐brain barrier was greatly reduced and no longer saturable by raising the blood thiamine concentration up to at least 10 microM. It was concluded that this analogue of thiamine inhibited the saturable component of thiamine transport across the barrier but not the non‐saturable component. In a further series of experiments, progressively higher levels of thiamine were maintained in the bloodstream and the influx of the vitamin across the blood‐brain barrier was measured. From kinetic analysis of the results, it was clear that the affinity of amprolium for the transport carrier was of a similar magnitude to that of thiamine itself. That the inhibition was competitive was shown by the way in which it could be overcome if the level of thiamine in the blood plasma was raised sufficiently above the normal.
Insensitivity of activation delays in potassium and sodium channels to heavy water in Myxicola giant axons.
Authors: Schauf C L
Published: December 2014

Substitution of heavy water (D2O) for H2O slows the Na+ and K+ currents in Myxicola giant axons by 40‐50% at 5 degrees C. In contrast, the delays in Na+ K+ activation which can be produced by hyperpolarizing pre‐pulses are not affected by solvent substitution. We suggest that in the cascade of transitions leading to the opening of Na+ and K+ channels, D2O affects only the final step that establishes the aqueous pore across the membrane.
Activation and desensitization of acetylcholine receptors in fish muscle with a photoisomerizable agonist.
Authors: Weinstock M M
Published: December 2014

Voltage‐clamped muscle fibres of the fish Xenomystus nigris were bathed in a solution containing 3,3‐bis[alpha‐(trimethylammonium)methyl]azobenzene (cis‐Bis‐Q; 100 nM). A flash of light photoisomerized some of the cis‐Bis‐Q (non‐agonist form) to trans‐Bis‐Q (agonist form). This resulted in agonist‐induced current. Current noise of channels activated by both trans‐Bis‐Q and ACh was analysed to find the channel conductances and open times associated with these two agonists. Channels activated by trans‐Bis‐Q and ACh had similar conductances (20‐30 pS) and open times (3‐4 msec) despite the photolabile azobenzene group of Bis‐Q. Light flashes subsequent to the first flash caused further increases in the ratio of trans‐Bis‐Q to cis‐Bis‐Q and accompanying increases in agonist‐induced current. Eventually, agonist‐induced currents levelled off as a photo‐equilibrium state was reached with a constant trans:cis ratio. After the photo‐equilibrium current level was reached, light flashes caused temporary increases in agonist‐induced current which decayed back to equilibrium in seconds. This result is interpreted according to a model in which trans‐Bis‐Q molecules are bound to a subpopulation of desensitized receptors, preventing recovery to native receptor. A flash of light then converts some trans‐Bis‐Q molecules bound to the desensitized receptor to the cis isomer. The newly formed cis‐Bis‐Q molecule may then unbind, allowing the desensitized receptor to recover. When light was flashed on muscle exposed to 300‐600 nM‐cis‐Bis‐Q, large (100‐200 nA) agonist‐induced currents were produced. These currents decayed exponentially over several seconds as the fibre desensitized. This result confirms that a first‐order process underlies the onset of desensitization.
Modulation of membrane conductance in rods of Bufo marinus by intracellular calcium ion.
Authors: Oakley B , Pinto L H
Published: December 2014

Double‐barrel micropipettes were used to pressure‐inject EGTA into the outer segments of rods in the isolated retina of Bufo marinus. We used these pipettes to point voltage clamp the cell to its resting membrane voltage during the injection of EGTA in order to prevent changes in membrane voltage from occurring. The input conductance of the rod was assessed by measuring the incremental membrane current required to hyperpolarize the membrane by less than or equal to 10 mV. When the retina was bathed in normal Ringer solution, the injection of EGTA during point voltage clamp evoked an inward membrane current and in increase in input conductance. This observation is consistent with an EGTA‐evoked increase in conductance for an ion with an equilibrium potential more depolarized than the resting membrane potential. Injections of control solutions that did not contain EGTA had no effect. The effects of injected EGTA were not altered by variations in the pH or buffering capacity of the injection solution, or by the addition of equimolar Mg2+. Furthermore, injections of a solution containing equimolar Ca2+ and EGTA were without effect. Thus, the observed effects of injected EGTA were due to the lowering of the [Ca2+]i. Replacement of extracellular Na+ with choline+ abolished both the response to light and the EGTA‐evoked increase in input conductance. A low [Na+]o solution containing 10(‐8) M‐Ca2+ reduced the response to injected EGTA by approximately the same amount as it reduced the response to light. Replacement of extracellular Cl‐ by methanesulphonate was without significant effect on either the response to light or to injected EGTA. These results are consistent with the interpretation that a lowered [Ca2+]i increases primarily the sodium conductance, gNa, of the plasma membrane of the rod outer segment. The conductance that is affected by a lowered [Ca2+]i appears to have the same specificity as the light‐dependent conductance. This conclusion is consistent with a hypothesis for visual transduction involving modulation of gNa by light‐evoked changes in the [Ca2+]i.
The influence of pH on the healing‐over of mammalian cardiac muscle.
Authors: De Mello W C
Published: December 2014

The process of healing‐over was followed in trabeculae from the right ventricle of guinea‐pigs and in Purkinje fibres from dogs by measuring resting potential and input resistance close to a site of damage. In Ca2+‐free bathing solution at pH 6.5 no signs of healing‐over were found; at pH 5.5 healing‐over was incomplete; at pH 5.0 and 4.0 healing‐over occurred promptly. It is concluded that transformation of low‐resistance nexus membranes into high‐resistance membranes separating the intracellular from the extracellular compartment normally is due to Ca2+, while protons can bring about the same effect under extreme conditions.
Passive biaxial mechanical properties of isolated canine myocardium.
Authors: Demer L L , Yin F C
Published: December 2014

Excised sheets of canine myocardium were subjected to cyclic loading and unloading in the predominant fibre and cross‐fibre directions to determine passive mechanical properties. Myocardium under biaxial loading exhibits both non‐linear elasticity and viscoelasticity with some strain‐rate dependence in the position of the stress‐strain relations, but very little rate dependence in the area enclosed by the loading and unloading portions of the stress‐strain loops. Fibre and cross‐fibre directions demonstrate anisotropic behaviour, with both the degree and direction of the anisotropy being dependent upon the region of the heart from which specimens are obtained. In the same specimen biaxial as compared with uniaxial loading yields different interpretations as to the material properties.
Non‐cholinergic fast and slow post‐stimulus depolarization in the guinea‐pig ileum.
Authors: Bywater R A , Taylor G S
Published: December 2014

Intracellular membrane potential recordings were made from circular muscle cells in the guinea‐pig ileum in vitro at 30 degrees C in the presence of atropine (1.4 microM). Following transmural nerve stimulation the inhibitory junction potential (i.j.p.) was followed by a post‐stimulus depolarization (p.s.d.). Both were abolished by tetrodotoxin. P.s.d. consisted of two phases; (i) an early fast phase (f.p.s.d.) which peaked about 1 s following the stimulus and (ii) a late slow phase (s.p.s.d.) which had a latency of 1‐2 s and peaked approximately 4 s following the stimulus. Both f.p.s.d. and s.p.s.d. were observed when the membrane was hyperpolarized by anodal current to the reversal potential of the i.j.p. F.p.s.d. and s.p.s.d. were therefore unlikely to result solely from a decrease in membrane conductance to potassium ions. During f.p.s.d., hyperpolarizing electronic potentials were reduced in amplitude suggesting that f.p.s.d. was associated with an increase in membrane conductance. There were no consistent changes in the amplitude of the electronic potentials during s.p.s.d. When the membrane potential was hyperpolarized by prolonged anodal current, an additional relatively rapid depolarizing potential could be induced by either transmural stimulation or depolarizing electrotonic current pulses.
The same interneurones mediate inhibition of dorsal spinocerebellar tract cells and lumbar motoneurones in the cat.
Authors: Hongo T , Jankowska E , Ohno T , Sasaki S , Yamashita M , Yoshida K
Published: December 2014

The aim of the study was to investigate whether inhibition of dorsal spinocerebellar tract (d.s.c.t.) cells evoked from group I afferents is mediated by the same interneurones which mediate the non‐reciprocal inhibition of hind‐limb motoneurones. The origin of inhibition of d.s.c.t. cells from group I afferents was compared in intact preparations, after lesions of the dorsal funiculi (when it could only be mediated by lower lumbar interneurones) and after lesions of the lateral and ventral funiculi (when it would be expected to be evoked by upper lumbar interneurones). In all three preparations extensors were the most common source of inhibition, as in motoneurones. Lower lumbar interneurones inhibiting d.s.c.t. cells were found to be co‐excited by group I (Ia and/or Ib) and cutaneous and joint afferents, and by rubrospinal tract fibres, as are interneurones mediating inhibition of motoneurones. Co‐excitation by group I and rubrospinal fibres was also found for upper lumbar interneurones. I.p.s.p.s were evoked in hind‐limb motoneurones from within Clarke's column in cats with the dorsal funiculi cut between L4 and L5 segments; they were evoked at thresholds as low as 2 microA, i.e. by stimuli with very local actions. The latencies of these i.p.s.p.s were short enough to allow them to be evoked monosynaptically via axonal branches of the same interneurones which projected to Clarke's column. Correspondingly, i.p.s.p.s were evoked in d.s.c.t. cells from within motor nuclei in L7 segments; they were evoked at similarly low thresholds and with similar latencies. In confirmation of previous reports i.p.s.p.s of Ia origin evoked in d.s.c.t. cells were not found to be depressed by Renshaw cells, which excludes their mediation by interneurones responsible for Ia reciprocal inhibition. The study leads to the conclusion that the inhibition of d.s.c.t. cells from group I afferents is, at least in part, collateral to the non‐reciprocal inhibition of lumbar motoneurones.
The effect of alterations in placental blood flow on the growth of and nutrient supply to the fetal guinea‐pig.
Authors: Jones C T , Parer J T
Published: December 2014

The distribution of the cardiac output and the maternal placental blood flow has been measured in guinea‐pigs at days 49‐51 of pregnancy using radioactively labelled microspheres. In some instances uterine blood flow was reduced chronically by ligating one uterine artery at day 30 of pregnancy. Between 3 and 4% of the cardiac output passed normally to placenta, and this could be reduced to less than 2% after uterine artery ligation. The result of the ligation was to reduce fetal and placental weight by up to 70%. Fetal and placental weight showed a close linear correlation in controls and in pregnancies with uterine artery ligation. However, when placental size was reduced below 60% of control, fetal weight was less affected by a reduction in placental weights than normal. Placental blood flow and placental size exhibited a close linear relationship over the whole range of values, but there was limiting placental weight which approached 1.3 g as placental blood flow approached zero. Thus a reduced placental size, particularly below about 50%, was associated with a proportionately greater reduction in maternal placental blood flow. Maternal placental blood flow or the percentage of maternal cardiac output to the placenta and fetal weight also showed a well‐correlated linear relationship. However, when placental blood flow was below about 50% of control values further reduction had a less than normal effect upon fetal growth. Small fetuses were hypoglycaemic and hypoinsulinaemic and the degree of each was dependent upon the extent of the reduction in fetal weight and in maternal placental blood flow. In fetuses that were below about 40% of normal size, and in which placental blood was below about 30% of control, fetal weight was less sensitive to falls in blood glucose, which in turn was more sensitive than normal to a fall in maternal placental blood flow. The results indicate that over the range of 50‐100% of normal fetal growth, maternal placental blood flow and probably nutrient supply to the fetus vary in parallel. Hence over this range fetal and placental growth rates are determined in part by placental blood flow. At placental blood flow rates and fetal growth rates below 40% of normal fetal growth is less dependent upon placental blood flow than usual, presumably because of a reduced dependence upon glucose metabolism for growth. This would appear to be essential, since as maternal placental blood flow is reduced to low values the placenta has to utilize an increasing proportion of the available glucose.
Intestinal fluid absorption in spontaneously hypertensive rats.
Authors: Dorey P G , King J , Munday K A , Parsons B J , Poat J A
Published: December 2014

A comparison has been made of intestinal fluid absorption between male Okamoto spontaneously hypertensive rats (s.h.r.) and normotensive male Wistar controls. S.h.r. show enhanced fluid absorption both in hypertensive adults and in young s.h.r. before hypertension has developed. Several potential causes for increased fluid transport in s.h.r. were tested using pharmacological antagonists. It is unlikely that enhanced fluid absorption is due to high sympathetic nervous activity, the renin‐angiotensin system or is secondary to hypertension. Intestine from s.h.r. have a high short‐circuit current indicating a change in ion pump activity. These results are discussed in relation to the possible causes of increased fluid (ion) transport by the intestine of s.h.r.
The visuotectal projection following translocation of grafts within an optic tectum in the goldfish.
Authors: Gaze R M , Hope R A
Published: December 2014

Rectangular grafts were translocated between the rostral and caudal tectum in adult goldfish. In some animals the optic nerve was also cut. After periods ranging from 161 to 378 days the retinotectal projections were mapped. The results showed that translocation of tectal grafts is followed by translocation of the corresponding part of the visuotectal map. In many cases the visual field positions projecting to points in the region between the grafts were abnormal and in some cases intercalated field positions were found across the borders between grafted and normal tissue. The results are taken as strong evidence for the existence of affinity labels on the tectum and their importance in the restoration of the retinotectal projection.
Cardiac action potential duration and contractility in the intact dog heart.
Authors: Drake‐Holland A J , Noble M I , Pieterse M , Schouten V J , Seed W A , ter Keurs H E , Wohlfart B
Published: December 2014

The maximum rate of rise of left ventricular pressure (DP) and action potential duration (a.p.d.) were measured in closed‐chest anaesthetized dogs with atrioventricular dissociation and beta‐adrenergic blockade. Right ventricular stimulation was carried out with protocols consisting of a conditioning ‘priming’ period and a test period. When a single test stimulus was introduced at varying intervals after the priming period, DP was found to be maximal at 800‐1000 ms. With this single test stimulus fixed at the optimum, DP was found to be a variable inverse function of the a.p.d. of the same beat; no positive correlation could be found between DP and a.p.d. When a second test stimulus at the optimum interval was introduced after the first, the DP (DP2) was found to be strongly dependent on that elicited by the first test stimulus (DP1); the relationship was positive, linear, independent of the method used to vary DP, and independent of whether DP1 was depressed or potentiated. The slope of the relationship was less than 1.0 and the line passed through the point where DP2 = DP1; this is the point of continuous stimulation at the optimum interval in a steady state. This result is consistent with the hypothesis that the coefficient relating DP1 to DP2, at constant a.p.d. of the first test pulse (AP1), is an index of the proportion of the activator of contraction stored during relaxation of test beat 1 which is released again on beat 2. In order to test the hypothesis that the remaining contractility depended on the action potential of test beat 1, AP1 was varied by changing the intervals between the priming stimuli. In order to determine the relationship between DP2 and AP1 it was necessary to carry out multiple regression analysis because DP2 was already known to be strongly dependent on DP1 (point 3 above), i.e. DP2 = BDP(DP1) + BAP(AP1 ‐ D). This analysis yielded highly significant positive values for the coefficients BDP and BAP. This result is compatible with the postulate that a.p.d. influences the amount of the activator of contraction entering the intracellular store, but that this activator is not available for release to the contractile proteins until the next depolarization.
Frequency selectivity of hair cells and nerve fibres in the alligator lizard cochlea.
Authors: Holton T , Weiss T F
Published: December 2014

Receptor potentials of hair cells and spike discharges of cochlear nerve fibres were recorded with micropipettes from the free‐standing region of the basilar papilla of anaesthetized alligator lizards in response to tones. In this region the hair‐cell stereocilia are free‐standing, i.e. they protrude directly into endolymph and are not in contact with a tectorial membrane. The frequency selectivity of hair‐cell responses was measured by means of isovoltage contours of the d.c. (V0) and fundamental‐a.c. (V1) component of the receptor potential, i.e. iso‐V0 and iso‐V1 contours. The frequency selectivity of the nerve‐fibre discharge was measured by iso‐rate (iso‐V0) contours. Iso‐V0, iso‐V1 and iso‐V0 contours are basically V‐shaped with a characteristic frequency (c.f.) defined as the frequency at which minimum sound pressure (Pmin) is required to evoke the criterion value of the response. Receptor potential iso‐V0 contours and neural iso‐V0 contours have similar slopes: the mean slopes of the low‐frequency sides (dB/decade) are ‐43.0 and ‐44.3; the slopes of the high‐frequency sides are 85.0 and 80.2. The band widths of iso‐V0 and iso‐V0 contours away from c.f. are similar (mean values of Q30dB are 0.40 and 0.53, respectively). The band widths of iso‐V0 contours near c.f. are narrower than those of iso‐V0 contours (mean values of Q10dB are 2.34 and 1.20, respectively). However, the shapes of the contours near c.f. depend on the iso‐response criteria, and we have not determined whether or not iso‐V0 and iso‐V0 contours are similar near c.f. The shapes of iso‐V1 contours differ from those of iso‐V0 and iso‐V0 contours. Nerve fibre c.f.s are tonotopically organized in the nerve, with lowest c.f.s recorded from fibres innervating the border of free‐standing and tectorial regions, a region in which hair‐cell stereocilia are longest, and the highest c.f.s recorded from fibres innervating the end of the free‐standing region in which hair‐cell stereocilia are shortest. The c.f. of nerve‐fibre response (and by implication hair‐cell response) is, therefore, correlated with the height of the stereociliary tuft. The shapes of iso‐V0 contours vary systematically with c.f. and, therefore, tonotopically with nerve position.(ABSTRACT TRUNCATED AT 400 WORDS)
Noradrenaline‐mediated synaptic inhibition in rat locus coeruleus neurones.
Authors: Egan T M , Henderson G , North R A , Williams J T
Published: December 2014

Intracellular recordings were made from neurones in the nucleus locus coeruleus (l.c.) in slices of rat pons maintained in vitro. Focal electrical stimulation to the slice surface within the region of the l.c. evoked a synaptic depolarization followed by a hyperpolarization. These potentials were graded with stimulus intensity and were abolished in calcium‐free and/or high‐magnesium solutions. The nature of the hyperpolarizing synaptic potential (i.p.s.p.) was investigated. The i.p.s.p. amplitude decreased as the membrane was artificially made more negative and reversed at ‐114 mV. This reversal potential shifted to less negative potentials in solutions of elevated potassium ion content as predicted by the Nernst equation. The i.p.s.p. was potentiated in amplitude and its time course was prolonged by desmethylimipramine (DMI). Yohimbine (100 nM) and phentolamine (100 nM) reversibly abolished the i.p.s.p. and did not change the synaptic depolarization. Noradrenaline hyperpolarized all l.c. neurones tested, whether applied by perfusion (1‐30 microM) or by pressure ejection from a micropipette placed in the solution near the recording site. The noradrenaline‐induced hyperpolarization was accompanied by an increase in conductance and it reversed in polarity at ‐104 mV. The reversal potential of the noradrenaline hyperpolarization became less negative when the potassium ion content was increased. The noradrenaline‐induced hyperpolarization was potentiated by DMI and was antagonized by yohimbine and phentolamine in the same concentrations which blocked the i.p.s.p. The results support the notion that l.c. neurones can release noradrenaline onto the somadendritic membrane of other l.c. neurones and thereby provide local feed‐back inhibition.
Inactivation of calcium conductance characterized by tail current measurements in neurones of Aplysia californica.
Authors: Eckert R , Ewald D
Published: December 2014

Calcium tail currents, recorded at ‐40 mV after repolarization from 7 or 10 ms voltage‐clamp depolarizations in axotomized Aplysia neurones in the presence of tetrodotoxin and tetraethylammonium, were used to investigate the inactivation of the calcium conductance without interference from contaminating potassium currents. Prior depolarization with a prepulse (V1) resulted in a reduction in size of the tail currents recorded following the test pulse (V2). The reduction occurred in both the fast (tau 1 less than 0.4 ms) and slow (tau 2 approximately equal to 2.0 ms) components of the tail current. The degree of inactivation remained constant when tail currents were measured at potentials ranging up to 30 mV on either side of the potassium equilibrium potential. Thus, any changes in potassium current must have contributed virtually nothing to the changes in tail current amplitude seen following presentation of the prepulse. Inactivation was greatest following prepulses to potentials (+10 to +40 mV) that produce maximal entry of calcium ions, and declined to about zero as the prepulse approached the calcium equilibrium potential. For V1 potentials above +50 mV, the prepulse caused an apparent short‐term facilitation of V2 tail currents in EGTA‐injected neurones. This effect, detected up to 50 ms following the pulse, is of uncertain origin. Pressure injection of calcium ions caused reduction in the size of the tail current, which was restored by subsequent injection of EGTA. Tail current amplitude was reduced by presentation of the prepulse for all test pulse voltages, but the measured inactivation declined exponentially towards a minimum with test pulses of increasingly positive potential. Removal of inactivation following a 200 ms prepulse was greatly accelerated by injection of EGTA. The EGTA‐resistant inactivation remaining at short times decayed with a time constant of about 0.12 s. The relation of tail current reduction to prepulse voltage is consistent with the interpretation that the EGTA‐resistant inactivation remaining at short times depends on entry of calcium ions during the prepulse, as does the EGTA‐sensitive inactivation remaining at later times. It is proposed that the ‘EGTA‐resistant’ phase of inactivation results from loading of EGTA with calcium ions near the inner surface of the membrane during sustained calcium entry, allowing the intracellular calcium concentration to rise. The results provide further evidence for a calcium‐mediated inactivation of the calcium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)
Locomotor‐related neuronal discharges in cat motor cortex compared with peripheral receptive fields and evoked movements.
Authors: Armstrong D M , Drew T
Published: December 2014

Discharge patterns of motor cortical neurones in cats walking steadily on a moving belt have been compared with other functional characteristics of the neurones. In forelimb motor cortex rhythmic discharges occurred in cells with peripheral receptive fields in all parts of the contralateral forelimb and also in cells with no discernible receptive field. Cells discharging at similar times during the step cycle often had very different receptive fields and cells with similar receptive fields (including neighbouring cells) could discharge at similar or at quite different times. In cells with a cutaneous receptive field including the forefoot the discharges during locomotion remained rhythmic (and their phasing relative to the step cycle was unchanged) when the response to mechanical stimulation in the receptive field was temporarily much reduced or abolished by local anaesthesia of the skin. The proportion of neurones showing accelerated firing during different parts of the step cycle fluctuated more for antidromically identified pyramidal tract neurones (p.t.n.s) than for non‐p.t.n.s and was highest during the second half of stance in the contralateral forelimb and lowest during swing. When the neurones were subdivided according to the movement evoked by threshold electrical stimulation through the micro‐electrode, p.t.n.s and non‐p.t.n.s recorded by electrodes evoking elbow flexion showed a wide variety of discharge patterns. For p.t.n.s the discharge rate reached an average of 69 impulses/s during late stance and declined to an average of 26 impulses/s during swing.
Post‐synaptic inhibition of bulbar inspiratory neurones in the cat.
Authors: Ballantyne D , Richter D W
Published: December 2014

Stable intracellular recordings from thirty‐six bulbar inspiratory neurones revealed three centrally originating, rhythmic patterns of synaptic inhibition (i.p.s.p.s). (i) A declining pattern of i.p.s.p.s accompanying the early stages of inspiration (early inspiratory inhibition) was identified in a total of twenty neurones representing examples of each of the functional classes of bulbar neurones examined, i.e. six R alpha‐ and two R beta‐neurones of the dorsal respiratory group and twelve R alpha‐neurones of the ventral respiratory group. (ii) A transient pattern of i.p.s.p.s just preceding or coinciding with the cessation of inspiration (late inspiratory inhibition) was present in the remaining sixteen neurones which were tested, representing six R alpha‐neurones and three R beta‐neurones of the dorsal respiratory group and seven R alpha‐neurones of the ventral respiratory group. (iii) An augmenting pattern of expiratory i.p.s.p.s was present in all thirty‐six neurones. Late inspiratory and expiratory i.p.s.p.s in the same neurones showed a similar time course of reversal when chloride was injected or allowed to diffuse into the cells and were associated with similar increases in input conductance. Both patterns of i.p.s.p.s appear to arise at or close to the cell soma. Early inspiratory i.p.s.p.s required a relatively longer period of chloride injection for reversal to be accomplished. Input conductance changes were either absent or smaller than those associated with late inspiratory or expiratory inhibition. These i.p.s.p.s appear to arise at more distal dendritic sites. These patterns of i.p.s.p.s are discussed in relation to the mechanisms shaping the growth of central inspiratory activity, bringing this activity to an end, and suppressing its redevelopment during expiration.
Thoracoabdominal motion during progressive isocapnic hypoxia in conscious man.
Authors: Chapman K R , Rebuck A S
Published: December 2014

Respiratory frequency and separate rib‐cage and abdomen‐diaphragm compartmental tidal volume (VT) responses to progressive isocapnic hypoxia to a level of 75% O2 saturation (PO2 approximately 40 torr) were measured in eight healthy subjects in both seated and supine postures. Hypoxia was induced by a rebreathing technique and compartmental contributions to VT were measured by inductive plethysmography. The ventilatory, frequency and spirometric VT responses to hypoxia did not differ significantly between sitting and supine trials. The range of VT responsiveness to hypoxia among sitting individuals (0.71 +/‐ S.D. = 0.56% VC X % fall in Sa,O2(‐1), where VC is vital capacity and Sa,O2 is arterial O2 saturation) was determined by both rib‐cage (0.507 +/‐ S.D. = 0.378% VC X % fall in Sa,O2(‐1) ) and abdomen‐diaphragm (0.194 +/‐ S.D. = 0.178% VC X % fall fall in Sa,O2(‐1) ) compartments. Among supine individuals the range of VT responsiveness to hypoxia (0.49 +/‐ S.D. = 0.45% VC X % fall in Sa,O2(‐1) was determined equally by both rib‐cage (0.27 +/‐ S.D. = 0.31% VC X % fall in SA,O2(‐1) ) and abdomen‐diaphragm (0.23 +/‐ S.D. = 0.29% VC X % fall in Sa,O2(‐1) ) compartments. Thus, the VT response to progressive isocapnic hypoxia in conscious man is determined by both rib‐cage and abdomen‐diaphragm compartments regardless of posture.
Nature of the anticholinesterase‐induced repetitive response of rat and mouse striated muscle to single nerve stimuli.
Authors: Clark A L , Hobbiger F , Terrar D A
Published: December 2014

The action of the anticholinesterase Paraoxon on neuromuscular transmission in rat diaphragm and mouse omohyoideus preparations was investigated. In both preparations, when Paraoxon potentiated the twitch in response to a single nerve stimulus, repetitive muscle action potentials were recorded with an intracellular electrode placed at the motor end‐plate region. At end‐plates of Paraoxon‐treated rat diaphragm preparations where the membrane potential was not sufficiently negative to support muscle action potentials, repetitive end‐plate potentials were recorded in response to a single nerve stimulus. No repetitive end‐plate potentials could be recorded under such conditions in preparations which had been exposed to dithiothreitol before being treated with Paraoxon, although twitch potentiation and repetitive muscle action potentials were still observed in these preparations. In Paraoxon‐treated mouse omohyoideus preparations only single end‐plate potentials were recorded from end‐plates where the membrane potential was not sufficiently negative to support muscle action potentials. This applied whether or not the preparation had been treated with dithiothreitol before being exposed to Paraoxon. In voltage‐clamped rat diaphragm preparations which had been treated with Paraoxon, repetitive end‐plate currents were frequently recorded in response to a single nerve stimulus. Under the same conditions mouse omohyoideus preparations responded with a single end‐plate current. It is concluded that Paraoxon‐induced twitch potentiation in rat diaphragm and mouse omohyoideus preparations is caused by repetitive muscle action potentials being triggered by a single nerve stimulus. Under the conditions stated, the repetitive muscle action potentials in rat diaphragm preparations arose from a prolonged end‐plate potential or repetitive end‐plate potentials or a combination of both. In mouse omohyoideus preparations the repetitive muscle potentials were the consequence of a single prolonged end‐plate potential.