bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of carbon dioxide on heat production of frog skeletal muscles.
Authors: Kitano T
Published: December 2014

1. Maintenance heat produced in tetani of frogs' sartorius muscles (Rana japonica) was measured under various values of intracellular pH (pHi) brought about by increasing the CO2 concentration in Ringer solution. The pHi values were measured using 31P nuclear magnetic resonance from the chemical shifts of the inorganic phosphate resonance. The pHi was 7.10 +/‐ 0.009 (mean +/‐ S.E. of the mean, n = 10) in the gas mixture of 5% CO2/95% O2 at 4 degrees C and it was reduced to 6.44 +/‐ 0.001 (n = 23) in 45% CO2. 2. As CO2 was increased, the maximum force was decreased and relaxation was prolonged. This is in accordance with the results of Edman & Mattiazzi (1981) and Curtin (1986). 3. An increase in CO2 induced a reduction of the maintenance heat production, which can be divided into stable and labile heats (Aubert, 1956). The stable heat, which is produced with a steady rate during contraction, was decreased as CO2 was increased. The labile heat, which is produced with an exponentially declining rate, was not significantly altered by increasing CO2 within the range studied. 4. The effect of previous contractile activity on the labile heat production, i.e. the time course of repriming of the labile heat, could be described by an equation with two exponential terms in 5% CO2 in accordance with the result of Peckham & Woledge (1986). The time course of repriming of the labile heat was not affected by increasing CO2 to 20%.
The effect of neuropeptide Y and peptide YY on electrogenic ion transport in rat intestinal epithelia.
Authors: Cox H M , Cuthbert A W , Håkanson R , Wahlestedt C
Published: December 2014

1. Neuropeptide Y (NPY), peptide YY (PYY) and, to a lesser extent, human pancreatic polypeptide (HPP) reduced short‐circuit current (SCC) in a concentration‐dependent manner in epithelial preparations of rat jejunum and descending colon. 2. From concentration‐response curves in the jejunum EC50 values of 3 nM for PYY and 10 nM for NPY were obtained. HPP was much less potent, the threshold concentration being around 100 nM, and NPY 13‐36 was inactive. 3. Repeated exposure of jejunal preparations to either NPY or PYY led to a rapid desensitization. Cross‐desensitization to the actions of these two peptides was also observed. Neither tetrodotoxin (TTX) nor phentolamine affected responses to either NPY or PYY on the jejunum. 4. Responses to both peptides were inhibited by the presence of transport inhibitors, particularly diphenylamine‐2‐carboxylate (DPC, a chloride channel blocker) and piretanide (Na+‐K+‐2Cl‐ co‐transport inhibitor). These results may indicate that the reduction in SCC caused by the neuropeptides is due to a net increase in chloride movement in the apical to basolateral direction. 5. 36Cl‐flux studies identified an inhibition of chloride secretion as the predominant mechanism of action of NPY and PYY, together with a smaller stimulation of chloride absorption. No significant changes in the movement of 22Na were seen in either direction. 6. The cyclo‐oxygenase inhibitors piroxicam (5 microM) and indomethacin (5 microM) significantly reduced the responses to both NPY and PYY in rat jejunum. From this and other evidence it was concluded that the peptides depended for their effect on the endogenous formation of eicosanoids, the prevention of which attenuated the SCC reduction due to the peptides.
Synapse‐specific protein kinase C activation enhances maintenance of long‐term potentiation in rat hippocampus.
Authors: Lovinger D M , Routtenberg A
Published: December 2014

1. Protein kinase C (PKC) stimulators, 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) or cis‐unsaturated fatty acid (UFA), have been shown to prolong synaptic enhancement induced by long‐term potentiation (LTP). This observation suggests a role for PKC in the biochemical mechanisms underlying maintained enhancement. 2. To determine if PKC stimulators prolong LTP by acting selectively at synapses given high‐frequency stimulation or by actions that are not synapse‐specific (e.g. increased postsynaptic excitability) we examined the effect of TPA or UFA on input‐selective enhancement. Population EPSPs, evoked in the same granule cell population by either the medial (MPP) or lateral (LPP) perforant path, can be selectively enhanced leaving the other perforant path input which receives only low‐frequency stimulation as an internal control for PKC stimulator effects not specific to enhanced synapses. 3. Synapse‐specific effects were in fact observed, as UFA or TPA selectively prolonged MPP enhancement following two trains of high‐frequency MPP stimulation, without affecting responses evoked by the LPP. A similar synapse selectivity of PKC stimulator action was seen following high‐frequency LPP stimulation. 4. These findings suggest that PKC stimulators prolong enhancement by acting specifically at high‐frequency‐stimulated synapses. PKC stimulators do not appear to affect either postsynaptic neurone excitability or synapses given only low‐frequency stimulation. This provides further evidence that PKC acts synergistically with the consequences of repetitive synaptic activation to maintain enhancement.
Analysis of quantal acetylcholine noise at end‐plates of frog muscle during rapid transmitter secretion.
Authors: Molenaar P C , Oen B S
Published: December 2014

1. Using the theory of noise analysis an attempt was made to measure frequency and amplitude of miniature end‐plate potentials (MEPPs) under conditions of vigorous transmitter release. Frog sartorius muscles were incubated in a depolarizing (32 mM‐K+) medium which lacked Ca2+ to prevent transmitter release. Subsequently, when the membrane potential had become stable at about ‐40 mV, end‐plates were superfused with 4 mM‐Ca2+‐containing medium for 1 min periods with 5 min intervals between the superfusions. 2. Most junctions ('fast' type) responded to Ca2+ with a relatively large, noisy depolarization (5.8‐14.5 mV) which subsided rapidly during subsequent challenges with Ca2+. Other junctions ('slow' type) responded with only 1‐1.6 mV depolarizations which were rather well sustained during the consecutive Ca2+ applications. 3. From the variance, E2, and the depolarization, V, caused by Ca2+ the frequency n and amplitude factor q of the MEPPs were calculated. Values of n were 3‐4 x 10(4) and 0.1‐1 x 10(4) s‐1 in the fast‐ and slow‐type junctions, respectively. The mean value of q was 0.16 mV; it remained more or less constant in the fast‐type junctions, but tended to decline in the slow‐type junctions. 4. As expected, cholinesterase inhibitors potentiated V and E2 as well as individual MEPPs. However, no advantage could be taken from this finding, since these drugs caused burst‐like peaks superimposed on the voltage signal, precluding application of noise analysis. 5. The results strongly suggest that, at least in the fast‐type junctions, K+ caused an extremely rapid depletion of the store of transmitter quanta, whose mean size did not change appreciably in the course of the experiment. However, in the slow‐type junctions during prolonged incubation, it cannot be excluded that the gradual decline of q was due to the release of newly formed, unripe quanta.
Complex spikes in Purkinje cells of the paravermal part of the anterior lobe of the cat cerebellum during locomotion.
Authors: Armstrong D M , Edgley S A , Lidierth M
Published: December 2014

1. The temporal pattern of the discharge of complex spikes by Purkinje cells in the paravermal cortex of the cerebellar lobule V b/c has been examined during locomotion in awake cats. 2. The peripheral receptive fields of 138 Purkinje cells were examined using light tactile stimulation. In 91% of these cells, complex spikes were evoked by stimuli applied to the ipsilateral forelimb and of eighty‐eight cells examined in most detail, 76% had receptive fields including the paw or wrist. Sixty‐six per cent had receptive fields restricted to the paw and/or wrist. 3. Complex spikes were not discharged at rigidly fixed times during the step cycle in any of sixty‐nine Purkinje cells which were recorded during locomotion on a moving belt. 4. When the discharges were averaged over many steps the probability of occurrence of complex spikes showed small fluctuations during the course of the step cycle, but these fluctuations were shown not to be statistically significantly different from those which could arise by chance. 5. These findings are inconsistent with previous suggestions (e.g. Armstrong, 1974; Rushmer, Roberts & Augter, 1976) that, during locomotion, the climbing fibres act to signal the occurrence of specific peripheral events, such as foot touch‐down or lift‐off.
Effects of pulse frequency on single‐unit baroreceptor activity during sine‐wave and natural pulses in dogs.
Authors: Abboud F M , Chapleau M W
Published: December 2014

1. Previous studies using sine‐wave pulses have shown that changes in pulse frequency do not alter single‐unit activity per unit time. Since baroreceptor activity is phasic with most of the activity occurring in systole, we reasoned that the lack of effect of pulse frequency is due to the associated reciprocal change in duration of systole with sine‐wave pulses. Therefore, we tested the hypothesis that change in frequency using natural arterial pulses alters baroreceptor unit activity per unit time. 2. In chloralose‐anaesthetized dogs the isolated carotid sinus was connected to an electromagnetic pressure converter driven by a voltage generator that controlled pulse pressure and sine‐wave pulse rate. To generate a natural pulse the converter was driven by the output from the pressure channel used to record arterial pressure. Systolic and diastolic pressures were maintained constant by a pressurized air source and an adjustable control on the voltage generator. The rate of natural pulses was decreased by electrical stimulation of the peripheral right vagus nerve which slowed the heart rate of the dog. 3. Decreases in sine‐wave rate by approximately 73 pulses/min (from 156 +/‐ 2 to 83 +/‐ 1 pulses/min) at a mean pressure of 114 +/‐ 8 mmHg (n = 13) did not alter activity per unit time (28 +/‐ 3 vs. 29 +/‐ 3 spikes/s). 4. In contrast, decreases in natural pulse rate by an average of 78 pulses/min (from 182 +/‐ 7 to 104 +/‐ 15 pulses/min) at a comparable mean pressure (104 +/‐ 7 mmHg) (n = 9) decreased activity per unit time by 28% from 32 +/‐ 4 to 23 +/‐ 4 spikes/s (P less than 0.05). Similar findings were observed in five of six single units using an intact (normally perfused) carotid sinus preparation in dogs with heart block and cardiac pacing. 5. The results indicate that a change in natural pulse rate is an important determinant of single‐unit baroreceptor activity.
Effects of 2‐(4‐phenylpiperidino)cyclohexanol (AH5183) and barium ions on frog neuromuscular transmission.
Authors: Maeno T , Shibuya Y
Published: December 2014

1. By applying electrophysiological techniques such as frequency facilitation, tetanic run‐down and depression, recovery from depression and post‐tetanic potentiation (PTP) of the end‐plate potential (EPP), the effects on frog neuromuscular transmission of 2‐(4‐phenylpiperidino)cyclohexanol (AH5183), a compound known to inhibit specifically the loading of newly synthesized acetylcholine (ACh) molecules into synaptic vesicles, and Ba2+, a selective activator of the augmentation phase of PTP, were investigated to elucidate whether these were related to ACh turnover. 2. Effects of AH5183 and Ba2+ ions were frequency dependent. At low frequency of stimulation, both agents showed essentially no effects on the EPPs recorded from Mg2+‐blocked preparations. 3. AH5183 pivoted the log‐linear frequency facilitation relation clockwise without altering the intercept on the ordinate, whereas Ba2+ ions did so counter‐clockwise. As is the case with Ca2+ ions, Sr2+ ions shifted the relation upwards leaving its slope unaffected. 4. AH5183 selectively depressed the component of potentiation in PTP while the effect of Ba2+ ions was a specific increase in the augmentation phase of PTP. 5. Ba2+ ions increased the amplitude of EPPs in the late depressed phase during the tetanic run‐down and depression experiment, but 4‐aminopyridine and Ca2+ ions failed to do so. 6. AH5183 increased, Ba2+ ions reduced but Ca2+ ions did not change the constant of recovery from depression of the EPP measured on curarized preparations. 7. The present results suggested that mobilization of the ACh quanta readily available for release might be a common mechanism underlying both frequency facilitation and two components of PTP (augmentation and potentiation). The term ‘frequency facilitation’ would be more comprehensive if it were re‐termed ‘frequency augmentation’ or ‘frequency potentiation’.
Changes in spontaneous firing patterns of rat hippocampal neurones induced by volatile anaesthetics.
Authors: Fujiwara N , Higashi H , Nishi S , Shimoji K , Sugita S , Yoshimura M
Published: December 2014

1. The effects of the volatile anaesthetics, halothane, isoflurane and enflurane, on rat hippocampal CA1 and CA3 neurones in in vitro preparations were studied by intracellular recording methods. 2. The three anaesthetics, at concentrations similar to those used clinically (0.2‐1.2 mM), initially increased and then subsequently decreased the spontaneous firing of CA1 neurones without affecting the resting membrane properties or the EPSPs evoked by focal stimuli. 3. The anaesthetics at these concentrations depressed both the fast after‐hyperpolarization of the soma spike and the post‐tetanic hyperpolarization induced by repetitive stimulation. They also decreased the IPSPs evoked by focal stimuli. 4. The threshold for spike generation was gradually elevated by as much as 4‐6 mV during application of the anaesthetics at these concentrations. The subthreshold potential oscillations (which are likely to be associated with periodic alterations in non‐inactivating Ca2+ and Na+ currents) were enhanced in the low concentrations (0.2‐0.5 mM), but were depressed in the high concentrations (0.8‐1.2 mM). 5. The results suggest that the transient increase in the firing frequency was caused by a depression of both the spike after‐hyperpolarization and the post‐tetanic hyperpolarization, and that the reduction of spontaneous firing was mainly due to an elevated threshold for spike generation. 6. The three anaesthetics altered the pattern of spontaneous spike‐firing in CA3 neurones from solitary spiking to burst firing without affecting the resting membrane properties. 7. The effects of the anaesthetics on the active membrane properties and the postsynaptic potentials in CA3 neurones were similar to the effects in CA1 neurones. 8. In the majority of CA3 neurones, soma spikes elicited by depolarizing current pulses were followed by a Ca2+‐dependent after‐depolarization, which was in turn followed by a prolonged after‐hyperpolarization (post‐burst hyperpolarization). The anaesthetics facilitated the after‐depolarizing potential, while they depressed the post‐burst hyperpolarization. Combination of the two effects would give rise to the highly stereotyped burst (about 1 Hz in frequency) in the presence of the volatile anaesthetics.
Responses to passive movement of receptors in joint, skin and muscle of the human hand.
Authors: Burke D , Gandevia S C , Macefield G
Published: December 2014

1. Microneurographic techniques were employed to record unitary activity from afferents associated with digital joints of six conscious human subjects. Of 120 single afferents sampled from the median and ulnar nerves at the wrist, eighteen (15%) were classified as joint afferents; the majority of the sample (72.5%) were of cutaneous origin, and 12.5% were from muscle spindles and tendon organs. 2. Of the eighteen joint afferents six were tonically active in the rest position of the hand. All except two were recruited or accelerated their background discharge during passive joint movement. Three tonically active afferents were responsive to passive movement throughout the physiological range. The majority of the afferents, including the other three tonically active units, responded only towards the limits of joint rotation. 3. As a group, the sample of joint afferents had a limited capacity to signal the direction of joint movement. Nine of the sixteen joint afferents sensitive to movement responded in two axes of angular displacement, and two responded in all three axes. In any one axis of rotation eight afferents were activated in both directions of movement. However, one afferent, associated with the interphalangeal joint of the thumb, responded uni‐directionally throughout the physiological range of joint movement and was thereby capable of adequately encoding joint position and movement. 4. Twenty‐one of twenty‐nine slowly adapting and eleven of eighteen rapidly adapting cutaneous afferents tested were activated by joint movement, but only towards the limits of joint rotation; half of the thirty‐two movement‐sensitive afferents were bi‐directionally responsive. Muscle spindle afferents responded to stresses applied to the joint only if the resulting passive movement stretched the parent muscle. 5. It is concluded that human joint afferents possess a very limited capacity to provide kinaesthetic information, and that this is likely to be of significance only when muscle spindle afferents cannot contribute to kinaesthesia.
Intracellular pH regulation in resting and contracting segments of rat mesenteric resistance vessels.
Authors: Aalkjaer C , Cragoe E J
Published: December 2014

1. The pH‐sensitive dye 2',7'‐bis‐(2‐carboxyethyl)‐5 (and ‐6)‐carboxyfluorescein (BCECF) was used to measure intracellular pH (pHi) in segments of rat resistance vessels (internal diameter about 200 microns) with the vessels mounted in a myograph for simultaneous measurements of isometric contraction. 2. BCECF loaded slowly into the vessels over 1 h and did not affect the maximal contractility of the vessels. There was a loss of dye with time which, however, was very slow when the segments were only excited for 2 s/min, suggesting that the loss was mainly due to dye bleaching with only a very slow leak. 3. The ratio of the emissions (at 540 nm) with excitation at 495 and 450 nm was calibrated in terms of pH using the K+‐H+ ionophore nigericin. This calibration gave a pHi value of 7.15 +/‐ 0.02 (n = 20), suggesting that hydrogen ions are not in electrochemical equilibrium in these vascular smooth muscles which have a membrane potential of about ‐60 mV. 4. Addition of 10 mM‐NH4Cl caused a transient alkalinization and wash‐out of 10 mM‐NH4Cl a transient acidification. Increasing CO2 with maintained bicarbonate caused a rapid acidification followed by an incomplete recovery. Removal of CO2 and bicarbonate (HEPES‐buffered solution) with constant extracellular pH caused a transient alkalinization but steady‐state pHi was not significantly altered. 5. In bicarbonate‐free buffer the Na+‐H+ exchange blocker 5‐(N‐ethyl‐N‐isopropyl) amiloride (EIPA) and sodium‐free conditions caused a slow acidification. In bicarbonate buffer (PSS) EIPA had no detectable effect after 10 min but the anion exchange blocker diisothio‐cyanatostilbenedisulphonic acid (DIDS) caused a small acidification over that time course. 6. The rate of recovery after an acid load was about 50% lower in HEPES buffer compared to PSS and it was inhibited by EIPA. In PSS amiloride and EIPA each had a small inhibitory effect on the pH recovery after an acid load. DIDS also inhibited the recovery from an acid load in PSS and this effect was additive to that of EIPA. DIDS and EIPA also had additive inhibitory effects on the 22Na+ influx stimulated by the acid loading, while in HEPES buffer DIDS had no effect on either pH recovery or 22Na+ influx. These results suggest that a Na+‐H+ exchange and an influx of bicarbonate coupled to sodium influx are of importance for pHi control in these vessels.(ABSTRACT TRUNCATED AT 400 WORDS)
Circulatory effects of a depilatory dose of mouse epidermal growth factor in sheep.
Authors: Carter N B , Fawcett A A , Hales J R , Moore G P , Panaretto B A
Published: December 2014

1. Haemodynamic parameters and tissue blood flow rates were measured in two groups of five sheep infused I.V. for 24 h with either saline or 128.6 micrograms mouse epidermal growth factor (mEGF) kg‐1 body weight. Measurements were made preinfusion and at +3, +12, +24, +27 and +48 h. We wished to assess relationships between blood flow rates and known functional changes in various organs during EGF treatment, especially any relationship between skin blood flow rate and the known depilatory effects of the protein in sheep. 2. Cardiac output increased and total peripheral resistance and mean arterial pressure decreased during and after infusion in the mEGF‐treated group relative to the control group. 3. The greatest increase in blood flow rates occurred in woolled skin (+500%) during mEGF infusion, a result which in itself may have been disparate with the known depilatory effects of EGF. The mucosas of the alimentary tract (except abomasum) and the submaxillary and sublingual salivary glands also showed vasodilatation. 4. There were short‐term increases in pituitary and adrenal gland blood flow that may have been associated with the corticotrophin‐releasing factor properties of EGF. Flow in the thyroids showed the greatest increase post‐infusion when thyroid hormone metabolism may have been reverting to normal. Blood flow rates decreased in the pancreas and perirenal fat. 5. Our general conclusion was that mEGF had specific vasodilator effects in the skin, the thyroid, submaxillary and sublingual glands and the mucosas of most of the alimentary tract.
Bilateral inputs and supraspinal control of viscerosomatic neurones in the lower thoracic spinal cord of the cat.
Authors: Cervero F , Lumb B M
Published: December 2014

1. Single‐unit activity has been recorded from eighty‐three viscero‐somatic neurones in the lower thoracic spinal cord (T9‐T11) of chloralose‐anaesthetized cats. These neurones were driven by natural and/or electrical stimulation in their somatic receptive fields and gave excitatory responses to electrical stimulation of the ipsilateral splanchnic nerve. Contralateral visceral inputs were tested by electrical stimulation of the contralateral splanchnic nerve. Tonic and phasic descending influences were tested by reversible spinalization with cold block at T7 and by electrical stimulation in nucleus raphe magnus and the immediately adjacent reticular formation. 2. Most viscero‐somatic neurones (89%) gave an excitatory response to stimulation of the contralateral splanchnic nerve and were therefore considered to have bilateral visceral inputs. In this group of neurones three categories of cells were identified depending on whether their responses to ipsilateral splanchnic nerve stimulation were decreased (50%), increased (42%) or unchanged (8%) in the spinal state. Only one cell with an exclusively ipsilateral visceral input was tested for the effects of reversible spinalization. Stimulation of contralateral splanchnic nerve failed to evoke activity in this cell in the spinal state. 3. Sixty‐four viscero‐somatic neurones with bilateral visceral inputs and four neurones with exclusively ipsilateral visceral inputs were tested with electrical stimulation in nucleus raphe magnus and the adjacent reticular formation. Seventy‐eight per cent gave an initial excitatory response which was followed by a period of reduced responsiveness to stimulation of visceral and somatic afferents. Three of the four neurones with an exclusively ipsilateral visceral input had no excitatory drive from the brain stem but their responses to stimulation of visceral and somatic afferents were depressed. 4. The majority (77%) of neurones with bilateral inputs were located in laminae VII and VIII with the remainder in the dorsal horn, predominantly laminae I and V, whereas all but one of the neurones with an exclusively ipsilateral visceral input were located in the superficial dorsal horn, predominantly lamina I, and none in laminae VII and VIII. 5. These results show that the majority of viscero‐somatic neurones in the cat's lower thoracic spinal cord receive bilateral visceral inputs and that the transfer of this information is subjected to descending control which includes excitation as well as inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
Blood‐brain, blood‐cerebrospinal fluid and cerebrospinal fluid‐brain barriers in a marsupial (Macropus eugenii) during development.
Authors: Dziegielewska K M , Hinds L A , Møllgård K , Reynolds M L , Saunders N R
Published: December 2014

1. The blood‐brain, blood‐CSF and CSF‐brain barriers to protein have been studied in post‐natal tammar wallabies (newborn to 70 days) using morphological and physiological techniques. 2. Endogenous and exogenous plasma proteins, and in some experiments horseradish peroxidase, were used as indicators of barrier integrity or permeability. 3. Immunocytochemical studies of endogenous tammar proteins showed that these (e.g. albumin) were present in the lumen of vessels in the brain, in cerebrospinal fluid (CSF) and within some cells in the choroid plexus and brain. No staining of the brain extracellular space was obtained; in particular there was no perivascular staining. Possible artifacts that could account for this lack of staining are discussed. 4. Ultrastructural studies showed the presence of well‐formed tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells, even as early as the day of birth. A membrane specialization between adjacent neuropendymal cells that had the same ultrastructural appearance as the 'strap junction' previously described in human and sheep fetuses was observed. These junctions may act as a barrier (CSF‐brain barrier) to the passage of protein from CSF into brain in these immature animals, as has previously been described in eutherian fetuses. 5. In experiments in which exogenous plasma proteins or horseradish peroxidase were injected intravenously, care was taken to limit both the volume and protein load injected. These proteins penetrated into CSF. The naturally occurring steady‐state CSF/plasma ratio for several proteins was approached by several of the injected (human) proteins within a few hours of I.V. injection, suggesting that much of the protein in CSF, at least when sampled from the hindbrain, originates from plasma in this species. No penetration across cerebral vessels was observed. Uptake of some proteins (e.g. albumin), occurred into neuroependymal cells at some ages. 6. These results suggest that the very immature brain of the newborn tammar is protected from protein present in the circulating plasma even at an embryonic stage of development by a combination of a well‐formed blood‐brain barrier to protein in the cerebral vessels and a CSF‐brain barrier to protein at the level of the neuroependyma. The adult‐type blood‐CSF barrier to protein (tight junctions between adjacent choroid plexus epithelial cells) is present but appears to be bypassed in the immature brain, probably by a transcellular route across the choroid plexus.
Inward rectification in rat cerebral arterioles; involvement of potassium ions in autoregulation.
Authors: Edwards F R , Hirst G D , Silverberg G D
Published: December 2014

1. The resting membrane potentials of proximal and distal segments of the arterioles which arise from the rat middle cerebral artery were determined. Proximal segments had stable membrane potentials with a mean value of ‐69 mV. The membrane potentials of distal segments were less negative and often unstable. 2. When the extracellular concentration of potassium ions [( K+]o) was increased proximal segments of arteriole were depolarized whereas distal ones were hyperpolarized. When [K+]o was decreased both proximal and distal segments were depolarized, the changes being more marked in proximal arterioles. 3. The membranes of proximal segments of arteriole displayed inward rectification at potentials near rest; inward rectification in distal segments of arteriole, when detected, was less pronounced. 4. The activation curve for inward rectification in proximal segments of arteriole was changed by changing the extracellular concentration of K+. A reduction in [K+]o caused the activation curve to move to such negative potentials that the inward rectifier no longer contributed to the resting conductance. 5. Increasing [K+]o changed the activation curve for inward rectification in distal segments of arteriole so that more K+ current flowed at potentials near resting. At the same time the membrane potential hyperpolarized. 6. The results are discussed in relation to autoregulatory changes which occur following changes in the K+ concentration of cerebrospinal fluid.
Left ventricular oxygen extraction during submaximal and maximal exertion in ponies.
Authors: Manohar M
Published: December 2014

1. Left ventricular (LV) myocardial O2 extraction was studied in five healthy ponies which had catheters implanted in the great cardiac vein and main pulmonary artery 15‐30 days before the study. The abdominal aorta was percutaneously catheterized to sample arterial blood. 2. In addition, phasic LV and aortic pressures, LV dP/dtmax and rate‐pressure product were also studied; dP/dtmax is the maximal rate of rise of the left ventricular pressure during the isovolumic phase, and is considered an index of myocardial contractility. Measurements were made at rest (control) and during adenosine infusion (3 mumol kg‐1 min‐1) at rest, moderate exercise (heart rate 169 +/‐ 10 beats min‐1), heavy exercise (heart rate 198 +/‐ 7 beats min‐1), maximal exercise (heart rate 232 +/‐ 7 beats min‐1), and adenosine infusion (3 mumol kg‐1 min‐1) during maximal exercise (heart rate 230 +/‐ 6 beats min‐1). 3. In resting ponies, LV arterial to coronary venous O2 content difference (delta LVa‐v O2) was 8.9 +/‐ 0.5 ml dl‐1 and O2 extraction was 59.9 +/‐ 2.2%. Adenosine infusion at rest decreased delta LVa‐v O2 and O2 extraction precipitously (2.6 ml dl‐1 and 14.3 +/‐ 1.7%, respectively), thereby indicating superfluous LV myocardial perfusion. 4. Moderate, heavy and maximal exercise increased delta LVa‐v O2 to 185, 194 and 218% of its control value and O2 extraction rose to 71 +/‐ 2, 75 +/‐ 1.5 and 78 +/‐ 0.9%, respectively. The widening of the delta LVa‐v O2 gradient was due to the increased arterial O2 content during exercise. 5. Combining these observations with equine myocardial perfusion, the LV O2 consumption was calculated to be 7.8, 47.9 and 103.6 ml min‐1 100 g‐1 at rest, moderate and maximal exercise. In order to achieve the 13.4‐fold increase in LV O2 consumption, the LV perfusion rose only 6‐fold; the rest being met by widening the delta LVa‐v O2. 6. Adenosine infusion during maximal exercise decreased delta LVa‐v O2 and O2 extraction (10.7 +/‐ 1 ml dl‐1 and 45%, respectively; P less than 0.0001). This indicated that coronary vasodilator capacity was not being completely expended in maximally exercising ponies. It is concluded that coronary circulation is unlikely to be a limiting factor to further exertion in ponies. Organ/tissue perfusion studies in exercising ponies have demonstrated that of all working muscles, the left ventricular (LV) myocardium received the highest level of blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)
Activation of feline spinal neurones by potentiated ventricular contractions and other mechanical cardiac stimuli.
Authors: Blair R W , Foreman R D
Published: December 2014

1. Neurones in the spinal cord were tested for responses to premature ventricular contractions (PVCs), produced by controlled electrical extra stimuli, and other mechanical stimuli applied to the heart. Thirty‐eight neurones were antidromically activated from the medial medullary reticular formation and/or the caudal thalamus, and twenty‐four neurones did not project to these sites. 2. Only those neurones excited by electrical stimulation of the left stellate ganglion were tested for responses to PVCs. A total of twenty neurones (32%) responded to electrically induced PVCs. Three major patterns of responses occurred. Three neurones exhibited an early burst and a late burst (or bursts) during the arrhythmia, one neurone fired only an early burst, and sixteen neurones responded with only a late burst. The early bursts occurred shortly after the onset of the compensatory pause accompanying the PVC; the late bursts were usually associated with the subsequent potentiated contraction, although the stimulus eliciting the burst must often have occurred late in the compensatory pause. 3. Responses to PVCs were only seen in neurones receiving C fibre and A delta fibre input. However, there were some neurones with both A delta and C input that did not respond to PVCs. No neurones with only A delta input responded to PVCs. 4. Neurones projecting to thalamus were less likely to respond to PVCs than either spinoreticular neurones or neurones with unidentified projections. 5. Neurones responsive to PVCs were likely to exhibit a cardiac rhythmicity in their spontaneous or evoked activity. 6. A total of 42% of tested neurones responded to a rapid infusion of saline into the heart, 52% had a cardiac receptive field, and 74% responded to aortic occlusion. A given neurone might respond to one or more of these stimuli, without responding to every mechanical stimulus tested. 7. Cervical vagotomy never abolished a response to PVCs, although either the spontaneous discharge rate or magnitude of response was sometimes altered. 8. Neurones responsive to PVCs were also responsive to intracardiac bradykinin. In addition, 95% of the neurones received convergent somatic input. 9. We conclude that about a third of spinal neurones excited by electrical stimulation of the left stellate ganglion receive information regarding mechanical, presumably innocuous, events in the heart. Most responsive neurones also receive somatic input and noxious cardiac input, and this information is transmitted to the thalamus, reticular formation, and probably to other spinal segments.
Changes in intracellular pH and pH regulating mechanisms in somitic cells of the early chick embryo: a study using fluorescent pH‐sensitive dye.
Authors: Gillespie J I , Greenwell J R
Published: December 2014

1. Measurements of intracellular pH (pHi) have been made using the fluorescent dye dicyano‐hydroquinone (DCH) in somites isolated from 2‐day‐old chick embryos. Measurements of pHi, from freshly dissected somites, gave values of 7.18 +/‐ 0.02 (mean +/‐ S.D., n = 12) while in somites kept in media containing 10% fetal calf serum for 2‐5 h pHi was 7.36 +/‐ 0.02 (n = 11). 2. In freshly dissected control tissue recovery from an acid load (NH4Cl pre‐pulse), in the nominal absence of HCO3‐, was 0.007 +/‐ 0.003 pH units/min (n = 11). In the presence of 5 mM‐HCO3‐ the rate of recovery was increased to 0.132 +/‐ 0.003 pH units/min (n = 11). This HCO3(‐)‐dependent recovery was inhibited by pre‐treatment with DIDS (5 X 10(‐4) M) and stopped when Na+ was replaced in the bathing medium with K+ or N‐methylglucamine. Amiloride (10(‐3) M) had no effect. 3. Replacement of Cl‐ with gluconate had little effect on pHi in control somites suggesting that absence of Cl(‐)‐HCO3‐ exchange. 4. These observations are consistent with the presence of a coupled Na+‐HCO3‐ entry and the absence of Na+‐H+ exchange. 5. In serum‐treated cells recovery from an acid load was 0.101 +/‐ 0.01 pH units/min (n = 11) in the nominal absence of HCO3‐. Increasing the HCO3‐ concentration (5‐10 mM) or pre‐treatment with DIDS had no effect on the rate of acid extrusion. Recovery is Na+ dependent and inhibitable with amiloride, indicating the presence of Na+‐H+ exchange. 6. These results suggest that during somitic development the mechanisms regulating pHi and recovery from acid loading are modified from a Na+‐HCO3‐ influx to a Na+‐H+ exchanger. This transition allows the cells to increase pHi by up to 0.2 pH units and may have a role in somitic cell development.
Transport and metabolism of adenosine in the perfused guinea‐pig placenta.
Authors: Wheeler C P , Yudilevich D L
Published: December 2014

1. Uptake and metabolism of adenosine were investigated from both maternal (M) and fetal (F) circulations of the isolated, dually perfused guinea‐pig placenta by using a single‐circulation paired‐tracer [( 14C]sucrose as extracellular reference, and [3H]adenosine) dilution technique. 2. Maximal [3H]adenosine uptakes (percentage of dose) from adenosine‐free perfusates were 75 +/‐ 1 and 87 +/‐ 2% (mean +/‐ S.E. of mean) at maternal and fetal blood‐tissue interfaces respectively. Rapid backflux (percentage of influx) of tritium (labelled adenosine and/or adenosine derivatives) from the placental tissue into the ipsilateral circulation was higher at the fetal (24 +/‐ 2%) than at the maternal side (11 +/‐ 2%). 3. Tritium uptakes were reduced to 50 +/‐ 4 (M) and 60 +/‐ 6% (F) when the perfusion medium contained 100 microM‐unlabelled adenosine; backflux was highly stimulated (44% M and 84% F). Neither uptake nor backflux were affected by inosine, uridine, adenine or hypoxanthine present in the perfusion medium (1 mM). 4. Tissue sequestration of tritium (5‐6 min) was approximately 60% of the injected dose when perfusates were adenosine‐free and 20% or less in the presence of 100 microM‐adenosine. 5. Cellular uptake of [3H]adenosine at both sides of the placenta was markedly reduced by the nucleoside transport inhibitors dipyridamole (DIP, 10 microM) and nitrobenzylthioinosine (NBMPR, 5 microM). 6. Thin‐layer chromatographic separation of [3H]inosine, [3H]hypoxanthine and [3H]phosphorylated derivatives in venous effluents following a bolus arterial injection of [3H]adenosine showed a greater fraction of metabolites at the fetal side (about 0.75) than at the maternal side (about 0.50). The percentage of [3H]inosine increased when perfusates contained 100 microM‐adenosine and the effect was more marked in the fetal circulation. In the presence of DIP and NBMPR the fractional recovery of 3H‐labelled metabolites was greatly reduced. 7. During steady‐state perfusion of [3H]adenosine (100 microM) a maintained (5‐60 min) tritium uptake of about 55% was observed and all the effluent activity was 3H‐labelled metabolites [( 3H]adenosine was only 2.8 +/‐ 0.2%). Under these conditions high‐performance liquid chromatography (HPLC) showed that effluents contained xanthine and urate at 16 +/‐ 1 and 23 +/‐ 2 microM respectively. 8. Transplacental transfer (6 min) of tritiated compounds (of which only 10‐20% was [3H]adenosine) was often less than that of the extracellular marker [14C]sucrose in both maternal‐to‐fetal and fetal‐to‐maternal directions.(ABSTRACT TRUNCATED AT 400 WORDS)
The voltage‐dependent block of ATP‐sensitive potassium channels of frog skeletal muscle by caesium and barium ions.
Authors: Quayle J M , Standen N B , Stanfield P R
Published: December 2014

1. Patch clamp techniques were used to study the action of external Cs+ and Ba2+ on adenosine 5'‐triphosphate (ATP)‐dependent K+ channels in sarcolemmal vesicles from frog skeletal muscle. Both ions block channels in a voltage‐dependent fashion, block increasing with hyperpolarization. 2. The Cs+ block is flickery, mean unitary current being reduced and open‐level noise increased. The concentration dependence is consistent with 1:1 binding, with a dissociation constant (Kd) of 4.1 mM at ‐62 mV. The Kd increases e‐fold for a 20 mV depolarization. 3. The kinetics of Cs+ block were analysed by amplitude distribution analysis, and by measurement of the excess open‐level variance. Both methods gave similar rate constants for blocking and unblocking; about 20 mM‐1 ms‐1 and 75 ms‐1 at ‐62 mV. 4. All the voltage dependence of the Cs+ block appears to lie in the blocking reaction; unblocking is independent of voltage. 5. Ba2+ blocks with slower kinetics, so that blocking events can be resolved in single‐channel records. Ba2+ reduces mean open time and causes long closings. 6. The blocking rate constant for Ba2+ was measured from the open times. It was about 1.7 mM‐1 ms‐1 at ‐62 mV and increased e‐fold for a 40 mV hyperpolarization. The unblocking rate, measured from closed times, yielded a Kd of about 0.1 mM at ‐62 mV, in agreement with that measured from the reduction in open‐state probability. 7. Our results suggest that Cs+ and Ba2+ block at sites within the channel, and provide evidence that the channel is a multi‐ion pore.
Evidence for non‐monosynaptic Ia excitation of human wrist flexor motoneurones, possibly via propriospinal neurones.
Authors: Malmgren K , Pierrot‐Deseilligny E
Published: December 2014

1. The possibility that activation of low‐threshold afferents in the median and ulnar nerves in man evokes an interneuronally mediated excitation of wrist flexor motoneurones was investigated. Two independent techniques were used: (i) the indirect technique of spatial and temporal facilitation of the flexor carpi radialis H reflex; (ii) the post‐stimulus time histogram (PSTH) method for measurement of the firing probability of voluntarily activated motor units following different stimuli. 2. Conditioning volleys were evoked by weak electrical stimuli (to the median nerve, the ulnar nerve, the skin and cutaneous nerve branches) and by a tap to the tendon of the flexor carpi radialis muscle. 3. In the H reflex experiments the comparison was drawn between the effects of two conditioning stimuli applied separately or together. In some experimental conditions the facilitation of the reflex evoked when combining two conditioning stimuli was larger than the algebraic sum of the effects from separate stimuli. The central latency of this additional facilitation, which is denoted ‘extra facilitation’, was 3 ms. It is argued that the extra facilitation reflects summation at a premotoneuronal level. 4. PSTHs of voluntarily activated flexor carpi radialis and flexor carpi ulnaris motor units were computed following stimulation of the median or the ulnar nerve. In 60% of the recordings the afferent volley evoked a peak of increased firing probability with a latency which was 3‐6 ms longer than the monosynaptic Ia latency. 5. Both the extra facilitation of the reflex and the late peak in the PSTH were evoked from very low‐threshold afferents. A contribution from Ia afferents was demonstrated in reflex experiments. Group I afferents alone are responsible for the onset of the non‐monosynaptic excitation but it is probable that cutaneous afferents give a later contribution. 6. On the basis of the characteristics of the non‐monosynaptic excitation studied with the two methods (same very low‐threshold, comparable central latencies), it is argued that both the extra facilitation of the H reflex on combined stimulation and the late peak in the PSTHs from individual motor units are mediated through the same pre‐motoneuronal pathway. 7. The possibility that the non‐monosynaptic excitation may be mediated through propriospinal neurones is discussed.
The deformation matrix theory of basement membrane: a study of water flow through elastic and rigid filaments in the rat.
Authors: Fisher R F
Published: December 2014

1. When the volume of water per unit time which flows through natural elastic basement membrane is divided by the applied pressure, the value‐the hydraulic conductivity‐is not constant but decreases as pressure increases. In contrast when the same membrane is tanned with glutaraldehyde and rendered inelastic, the hydraulic conductivity is constant at all pressures. 2. Over a pressure range of 0‐6.7 kPa equivalent to a membrane stress of 0‐195 kPa in natural elastic membrane the hydraulic conductivity (Lp) can be related by the linear equation Lp = Lp.0 + apP where P is the hydraulic pressure, Lp.0 is the initial hydraulic conductivity and ap is a constant which is the decreased hydraulic conductivity per unit pressure (correlation coefficient 0.764. P less than 0.001). 3. The initial conductivity of the basement membrane of the crystalline lens of the adult rat (lens capsule) was 47.6 +/‐ 7.3 x 10(‐12) m s‐1 Pa‐1 while the decrease in hydraulic conductivity per unit increase in pressure was ‐3.38 x 10(‐15) m s‐1 Pa‐2. 4. Following tanning with glutaraldehyde the hydraulic conductivity was constant at 27.4 +/‐ 4.0 x 10(‐12) m s‐1 Pa‐1. 5. A change in the configuration of the superhelices of the filaments of type IV collagen which form the framework of basement membrane is termed. ‘The deformation matrix theory’ and can satisfactorily account for the changes in hydraulic conductivity of both natural and tanned membrane. 6. In natural membrane the filaments deform easily and the pitch of the filament superhelices is increased by axial stress induced by pressure. The filaments straighten and become compacted together and the hydraulic permeability is thereby decreased. 7. In tanned membrane the filaments become more rigid and axial stress barely deforms them: moreover the pitch of the filament superhelices is decreased so that the filaments become more closely coiled and compacted together. Because of these changes the hydraulic conductivity is reduced as compared with unstressed natural membrane and remains unaltered by increasing pressure.
Localization by kainic acid lesions of neurones transmitting the carotid chemoreceptor stimulus for respiration in rat.
Authors: Housley G D , Sinclair J D
Published: December 2014

1. An attempt has been made to test the hypothesis that in the nucleus of the tractus solitarius (NTS) in the rat, the most caudal region of synaptic terminals of the carotid sinus nerve, just caudal to the obex, represents mainly the site of synapse of chemoreceptor fibres from the carotid body. 2. Under halothane anaesthesia, the neurotoxin kainic acid was used to lesion this region and a second region, immediately rostral to obex, where terminals are thought to arise mainly from baroreceptor fibres of the carotid sinus nerve. 3. Measurements based on the distribution of fluorescent dye co‐injected with the kainic acid showed that the two groups of 100 nl microinjections were centered 0.82 mm apart and that the injectate spread through mean distances of 0.57 mm (caudal microinjections) and 0.52 mm (rostral microinjections). Nissl staining was used to determine cellular degeneration. The caudal lesions mostly involved ventrolateral and commissural subnuclei of NTS and the rostral lesions involved lateral and dorsolateral subnuclei. 4. Ventilatory sensitivity to hypoxia was tested under light halothane anaesthesia, 1 day after lesioning. To enhance the responses, the contralateral carotid sinus nerve was sectioned prior to experiments. Caudal lesions reduced the ventilatory response to inspired oxygen (20.9‐9.6% O2) by a mean of 67% and rostral lesions by 18% of the effect produced by carotid sinus nerve section on that side. Subsequent section of the carotid sinus nerve on the side of the NTS lesion confirmed that caudal lesions produced effects comparable to those of carotid body denervation; rostral lesions did not. 5. These results strongly support the hypothesis that chemoreceptor and baroreceptor afferent fibres in the carotid sinus nerve synapse at substantially separable sites in the nucleus of the tractus solitarius. The identification of the site in NTS caudal to the obex as the principal site of carotid chemoreceptor synapses places them close to but not upon respiratory premotor neurones of the same nucleus.