bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of the sodium‐potassium pump by trypsin in low potassium type erythrocytes of goats.
Authors: Dunham P B , Ellory J C
Published: December 2014

1. Treatment of low K goat red cells with trypsin stimulated the Na‐K pump more than twofold. Dose dependence and time course experiments indicated a half‐maximal stimulation at 1.6 mg trypsin/ml. (37 degrees C, 3 hr), and a maximum effect after 5 hr (10 mg/ml). 2. Trypsin had only a small and variable effect on the ouabain‐insensitive component of K influx. 3. The Na‐K pump activity of high K goat red cells was not affected by trypsinization. 4. When intracellular K was varied by the PCMBS technique, it was found that the trypsin stimulation was greatest (2‐5‐fold) in cells with the highest K (40 m‐mole/1. cells) and lowest (1.1‐fold) in cells with low K (<1 m‐mole/1. cells). 5. The trypsin effect was reversed by nystatin treatment or hypotonic lysis. 6. Trypsin did not increase the number of ouabain‐binding sites. 7. It is concluded that trypsinization modifies the L antigen in low K goat red cells to decrease the apparent internal affinity for K of the Na‐K pump in these cells.
The respiratory frequency response to carbon dioxide inhalation in conscious rabbits
Authors: Maskrey M. , Nicol S. C.
Published: December 2014

1. The respiratory responses to CO2 inhalation were measured in New Zealand White rabbits. Prior to testing, the rabbits either received drinking water ad libitum (C), or were subjected to 72 hr water deprivation (WD). The rabbits were tested in a climatic chamber at either 20 °C, (C20, WD20) or 30 °C (C30, WD30).

2. CO2 exposure caused increases in both tidal volume (VT) and minute volume (VE). The direction and magnitude of changes in respiratory frequency (f), however, were dependent upon treatment.

3. Linear regressions were drawn for f vs.% CO2 in inhaled gas. Treatment C20 showed zero slope, treatment C30 a large negative slope, and treatments WD20 and WD30 a significant positive slope.

4. The slopes of the regression lines obtained from plotting f vs.% CO2 were plotted against their intercepts for each rabbit under each treatment condition. This yielded a highly significant linear regression from which it could be concluded that the frequency response to CO2 exposure is dependent upon the initial frequency when the rabbits are breathing air.

5. It is suggested that frequency is shifted during hypercapnia towards an optimal value which is dependent upon the existing% CO2 in the inspired gas.

6. Comparison of the results obtained for the rabbit with results reported for the conscious dog and sheep suggest that a similar relationship may hold for these species.
Membrane electrical properties of frog slow muscle fibres.
Authors: Gilly W F , Hui C S
Published: December 2014

1. Pyriformis slow (and sartorius twitch) fibres from Rana temporaria were studied with a three‐micro‐electrode voltage‐clamp technique to obtain an approximate measurement of membrane current density at a fibre end. In most experiments, a modified Ringer solution containing 2H20 and 230 mM‐sucrose was used to reduce movement. 2. Linear membrane properties of slow fibres obtained with this method are consistent with results from previous studies. Measured Cm (microF/cm2) increases with fibre diameter in a manner consistent with a tubular location of part of the fibre capacitance. 3. Voltage steps to ‐50mV and more positive potentials result in outward membrane currents in both slow and twitch fibres. These currents develop along similar sigmoid time courses and are blocked by tetraethylammonium (TEA+) ions. The reversal potential for delayed current channels in slow fibres varies with external K+ concentration, suggesting that the delayed current in slow fibres, as in twitch, is carried by K+ ions. 4. Maximum GK,GK, in slow fibres is an order of magnitude smaller than twitch fibres. The steady‐state GK‐V curve of slow fibres is very broad (e‐fold for approximately 15 mV), saturating at very positive voltages, whereas the GK of twitch fibres varies more steeply with voltage. 5. No evidence of inward currents was seen in slow fibres during pulses of duration up to 96 msec. 6. Slow outward currents, which do not inactivate appreciably, are seen in slow fibres during long (10 sec) pulses. Tail currents following such long pulses are very slow. The reversal potential shifts to more positive values with increasing pulse duration.
Binding of 125I‐physalaemin to rat parotid acinar cells.
Authors: Putney J W , Van de Walle C M , Wheeler C S
Published: December 2014

1. The binding of [125I]physalaemin to rat parotid acinar cells was investigated. 2. The [125I]physalaemin exhibited a small degree of specific binding that was rapid, reversible and saturable. 3. The EC50 values for inhibition of binding by four peptides were well correlated with their ability to activate Ca‐dependent K release from the rat parotid gland. 4. The number of binding sites, which may represent substance P receptors, was estimated to be in the range of 200/cell, a value quite different from those reported previously for muscarinin (840/cell) or alpha‐adrenergic (15,000/cell) receptors. 5. It is concluded that if, as previously suggested, these receptors regulate the same population of Ca channels, then the mechanism or perhaps efficiency by which this is achieved may differ for the three receptors.
Morphological aspects of the safety factor for action potential propagation at axon branch points in the crayfish
Authors: Smith Dean O.
Published: December 2014

1. In the crayfish, regions of axonal bifurcation where action potential propagation failed during repetitive activity were visualized using modulation‐contrast optics. To determine if a reduced safety factor for conduction at the branch sites has a morphological basis, the geometrical ratio (GR) of axon diameters, where GR = (d13/2+d23/2)/dp3/2, was calculated; d1, d2, and dp are the diameters of the two daughter branches and the parent axon, respectively.

2. Values of GR at sites of conduction block were usually slightly higher than 1, indicating a small drop in safety factor; however the values were well below the level at which failure might occur due to an impedance mismatch.

3. Calculated values of GR were generally higher in the most peripheral axon regions where propagation was observed to block most readily.

4. Short collaterals containing numerous synaptic vesicles and apparent release sites were observed to have relatively low values of GR (about 0.8); collaterals containing densely populated mitochondria were characterized by relatively high values of GR (about 1.3).

5. It is concluded that the morphological characteristics of the axon in the branching region are conducive to an inherent low safety factor for conduction, but that they cannot play a major role in block development.
Characteristics of histamine release evoked by acetylcholine in isolated rat mast cells.
Authors: Blandina P , Fantozzi R , Mannaioni P F , Masini E
Published: December 2014

1. Histamine secretion from rat mast cells occurs in the presence of nanomolar concentrations of acetylcholine. 2. Intact glycolytic and oxidative metabolism is required for the acetylcholine‐induced histamine secretion. Removal of extracellular glucose, hypoxia, cyanide and monoiodoacetate almost completely inhibit the secretion. 3. The secretion of histamine is dependent on the extracellular H ion concentration and is blocked when the cells are exposed to Na‐deficient media. 4. The order of potency of cholinrgic agonists in evoking the secretion of histamine is oxotremorine > acetylcholine > choline > carbamycholine > nicotine. 5. Atropine competitively blocks the acetylcholine‐induced histamine secretion, indicating the presence of cholinergic muscarinic receptors on mast cells. 6. Dibutyryl cyclic AMP and adrenaline inhibit the acetylcholine‐induced histamine secretion, indicating a regulatory function afforded by cyclic nucleotides in the cholinergic histamine release.
Mouse pancreatic acinar cells: effects of electrical field stimulation on membrane potential and resistance.
Authors: Davison J S , Pearson G T , Petersen O H
Published: December 2014

1. Intracellular micro‐elctrode recordings of acinar cell membrane potential and resistance were made from the mouse pancreas superfused in vitro. The acinar cells under investigation were stimulated by electrical field stimulation using two platinum wire electrodes and by micro‐ionophoretic acetylcholine (ACh) application from an extracellular AChCl‐filled micro‐electrode. 2. Field stimulation evoked membrane depolarization and reduction in input resistance. Maximal effects were observed at 20‐40 Hz frequency, 1‐2 msec pulse width and 8‐20 V amplitude. The mean latency for the field stimulation‐evoked depolarization was 900 msec. Field stimulation responses were seen at low frequency levels of stimulation, the majority of cells responding at 5 Hz and some at 2 Hz. The physiological significance of the low frequency stimulation is discussed. 3. The field stimulation effects resembled those induced by ACh ionophoresis and were abolished by atropine. The equilibrium potentials for both field stimulation and ACh ionophoresis were identical at about ‐15 mV. The field stimulation response was selectively abolished by tetrodotoxin and by superfusion with Na‐free or Ca‐free media, while the ACh ionophoretic response persisted. Field stimulation therefore initiated nerve action potentials and consequent ACh release. 4. Spontaneous miniature depolarizations observed in some preparations were not abolished by tetrodotoxin and woult therefore seem to be a result of quantal release of ACh from nerve terminals. 5. There is no indication from the present studies of the existence of neurotransmitters other than ACh. No inhibitory effects have been observed. 6. All preparations studied to date have responded to field stimulation and it is concluded that all acinar cells are potentially under cholinergic neural influence.
Chloride efflux in single barnacle muscle fibres.
Authors: Bittar E E , Schultz R , Tesar J
Published: December 2014

1. A study has been made of the behaviour of the radiochloride efflux in single muscle fibres from the barnacle, Balanus nubilus. 2. In the majority of the fibres studied, the fractional rate constant for 36Cl efflux is a constant and unaffected by the injection of distilled water (approximately 0 . 3 microliter. in volume). 3. Acidification of the HCO3(‐)‐containing medium causes stimulation of the Cl efflux, the threshold value being pH 7 . 0. The magnitude of the response is a logarithmic function of the external H+ and HCO3 concentration over a wide concentration range. 4. (i) Total replacement of the external Cl and NO3 fails to alter the course of the Cl efflux. However, the magnitude of the response to acidification is reduced to a marked degree. (ii) Replacement of the external Na by Li reduces not only the Cl efflux but also the size of the response to acidification. 5. Injection of HCl, HCO3 or KCl fails to alter the Cl efflux. Injection, however, of 4 M‐KCl or NaCl causes a fall in the efflux. 6. 10( 4)M‐ouabain is ineffective. It also fails to alter the response of the Cl efflux to acidification. 7. (i) Injection of cyclic AMP stimulates the Cl efflux in a dose‐dependent manner, but only transitorily. (ii) Preinjection of pure protein kinase inhibitor causes a marked reduction in the magnitude of the response to cyclic AMP. 8. Preinjection of pure protein kinase inhibitor fails to affect the response to external acidification. 9. (i) Pretreatment externally with ethacrynic acid reduces the response to external acidification. (ii) External application of 4‐acetoamineo‐4'‐isothiocyano‐2,2'‐stilbene disulphonate (SITS) reduces the resting Cl efflux. It also abolishes completely the response to acidification. (iii) The effect of 4,4'‐diisothiocyano‐2,2'‐stilbene disulphonate (DIDS) resembles that of SITS. (iv) Injection of H2DIDS fails to reduce the resting efflux but tends to reduce the magnitude of the response to acidification. 10. (i) 5 X 10(‐4) M‐benzolamide is without effect on the basal Cl efflux. (ii) Benzolamide in high concentration reduces the magnitude of the response to acidification. This occurs within a rather narrow concentration range. 11. (i) A sudden reduction in environmental temperature from 24 to 0 degrees C causes a marked fall in the Cl efflux. (ii) Acidification of the artificial sea water at 0 degrees C stimulates the efflux. 12. The present experiments have led to evidence which is consistent with the view that the Cl efflux is modulated by at least two distinct mechanisms: one is responsive to acidification when HCO3 as buffer is present and involves participation of a benzolamide‐sensitive component presumably lying in the fibre membrane. The other is responsive to injection of cyclic AMP, and, and probably involves cyclic AMP‐protein kinase.
Increased sodium appetite in the rat induced by intracranial administration of components of the renin‐angiotensin system.
Authors: Avrith D B , Fitzsimons J T
Published: December 2014

1. Intracranial injections of components of the renin‐angiotensin system in rats in normal water and Na balance caused an immediate thirst followed by a progressive increase in Na appetite during a test session which lasted 18 h. The effect on water and Na intake was dose‐dependent. 2. Long‐term (7 day) infusions of angiotensin II into the third cerebral ventricle at rates of 1 or 10 pmol h‐1 produced large and sustained increases in intake of water and 2 . 7% NaCl. Intakes sometimes exceeded 100 ml 2 . 7% NaCl per day but quickly fell to normal when the infusion was stopped. 3. Intracranial injection or infusion of carbachol caused a transient increase in water intake but had no effect on the intake of NaCl. 4. The Na appetite induced by intracranial injection of angiotensin was specific for Na since rats offered a choice of water and equimolar concentrations of NaCl and KCl took only water and NaCl. This resembles the pattern seen in Na‐depleted rats. 5. Increased Na appetite was not secondary to increased water intake since it occurred when only 2 . 7% NaCl was available to drink. 6. Increased Na appetite was not secondary to natriuresis since, first, the angiotensin‐stimulated rats went into positive Na balance, secondly, intracranial renin did not cause increased Na excretion in Na‐loaded rats and thirdly, anureic rats showed a significant Na appetite in response to renin. 7. These results suggest that angiotensin in the brain may play a role in the development of Na appetite.
The effect of feeding on cerebral blood flow and oxygen consumption in the new‐born calf
Authors: Gardiner R. M.
Published: December 2014

1. The effect of feeding on cerebral blood flow and oxygen consumption has been investigated in unrestrained calves between 7 and 28 days after birth.

2. Cerebral blood flow was determined using an inert gas clearance technique, and oxygen consumption by the simultaneous measurement of the arterio—cerebral venous oxygen content difference.

3. Cerebral blood flow increased during feeding from 74 ± 4 to 116 ± 9 ml. 100 g−1 min−1 and reverted afterwards to the pre‐feed level. No alteration in cerebral oxygen consumption occurred.

4. Feeding was associated with an increase in mean arterial blood pressure and heart rate, and mild asphyxia.

5. The sensitivity of the cerebral circulation to alterations in arterial PCO2 was investigated in seven calves under sodium pentobarbitone anaesthesia. In the range of arterial PCO2 15‐75 mm Hg the relationship was linear (r = 0.71; P < 0.001) with an average slope of 0.68 ml. 100 g−1 min−1 mmHg Pa,CO2−1.

6. Increases in mean arterial blood pressure comparable to those occurring during feeding (96 ± 6 to 159 ± 8 mmHg) were produced by compression of the thoracic aorta in three calves under sodium pentobarbitone anaesthesia and were associated with an increase in cerebral blood flow from 48 ± 4 to 76 ± 8 ml. 100 g−1 min−1. No significant change in calculated cerebral vascular resistance occurred during either feeding or aortic compression.

7. These results suggest that the rise in blood pressure which occurs during feeding in the calf exceeds the autoregulatory capacity of the cerebral circulation.
The effects of reserpine on motor activity and pallidal discharge in monkeys: implications for the genesis of akinesia
Authors: Iansek R.
Published: December 2014

1. A reversible disturbance of basal ganglia function was produced in monkeys by the intramuscular administration of reserpine.

2. Pallidal discharge was then compared with that recorded in the same animals during movement performance and following passive manipulation of the limbs.

3. Akinesia, loss of postural support of the trunk, head and neck and absent postural reflexes were the predominant motor abnormalities produced by reserpine administration.

4. Occasionally, postural tremor and catatonia were apparent. Rigidity and resting tremor were absent.

5. Recordings made in the pallidum during the presence of akinesia revealed a marked reduction in natural neuronal discharge.

6. Some pallidal neurones that remained active were driven in an uncharacteristic manner by peripherally generated afferent inputs from wide territories and by a variety of peripheral stimuli.

7. The findings suggest the hypothesis that the akinesia in these animals was due to the diminished pallidal activity, and that pallidal discharge is normally a prerequisite for the performance of spontaneous motor activity. Pallidal neuronal firing may provide a background excitability to motor regions involved in the maintenance and elaboration of natural motor activity.
Dark adaptation within the receptive field centre of rat retinal ganglion cells.
Authors: Cicerone C M , Green D G
Published: December 2014

1. Recordings from single axons of retinal ganglion cells in the rat's optic tract were used to determine whether bleaching a small area of the receptive field reduced sensitivity globally or locally, near the bleached photoreceptors. 2. When a suprathreshold test spot was alternated between two equally sensitive positions, the ganglion cell gave an approximately balanced response. The balance was upset if a small‐spot bleach was selectively applied to one position. Recovery of the balanced condition was rapid. 3. Varying the duration of a constant illuminance bleach varied the duration of the imbalance following the bleach. 4. The recovery of sensitivity after small‐spot bleaches was measured both at the location of the bleach and also at another location, initially equally sensitive. The recovery at the bleached location lagged recovery at the unbleached location; but even in the bleached location, the return of sensitivity was rapid. 5. Recovery of sensitivity after half‐field bleaches was measured in the bleached and unbleached halves of the receptive field. Recovery in the bleached half lagged that in the unbleached half. 6. A comparison between the effects of a small‐spot bleach and a half‐field bleach of the same strength show that the duration of dark adaptation depends on the area of the bleach.
Cyclic AMP in the sublingual glands of the mouse.
Authors: Amerongen A V , Roukema P A , Vreugdenhil A P
Published: December 2014

1. The cyclic AMP levels in the sublingual glands of the mouse has been determined in relation to mucin secretion under the influence of several agonists in vivo and in vitro. 2. Isoprenaline increased the cyclic AMP level in these glands only in the presence of a phosphodiesterase inhibitor, indicating the presence of an active cyclic AMP phosphodiesterase. 3. Inhibition of phosphodiesterase results in an increase of the cyclic AMP levels. EGTA prolonged the effect of the PDE‐inhibitors, indicating that Ca2+‐ions may be involved in the maintenance of the cyclic AMP concentration in the sublingual glands. 4. NaF is able to induce both a slight increase of the cyclic AMP level and a significant mucin secretion by the sublingual glands. However, other secretagogues do not significantly influence the cyclic AMP concentration in these glands, and compounds which do not elevate its level, do not significantly stimulate sublingual mucin secretion. 5. These data suggest that there is no direct relationship between cyclic AMP and sublingual mucin secretion.
Carbon dioxide, membrane potential and intracellular potassium activity in frog skeletal muscle.
Authors: Huguenin F , Reber W , Zeuthen T
Published: December 2014

1. The membrane potential of isolated frog muscle fibres has been measured in absence and in presence of CO2, at constant external pH. 2. At a normal external Cl concentration, CO2 (PCO2 = 97 mmHg; pH = 7.0) applied for 10 min caused a highly variable depolarization, the average potential change being 8 mV after 5 min. The effect was reversible 3. In Cl‐free solutions, CO2 (PCO2 = 97 mmHg; pH = 7.0) caused a biphasic depolarization of 20 mV after 5 min. The effect was fully reversible on CO2 removal. 4. The same effect appeared at a lower partial pressure (PCO2 = 38 mmHg; pH 7.3) in the presence of tetrodotoxin (10(‐7) M). 5. In order to investigate the cause of the CO2‐induced depolarization, membrane potential and intracellular K activity (ai/K,)( of surface muscle fibres were measured with voltage and ion‐sensitive micro‐electrodes. 6. At a normal external Cl concentration, CO2(PCO2 approximately equal to 97 mmHg; pH = 7.0) decreased ai/K by 5 mM after 5 min. 7. The same effect appeared at low external Cl concentration (11 mM). 8. At high partial pressure (PCO2 approximately equal to 588 mmHg; pH = 6.8), CO2 reduced ai/K by 19 mM in 10 min. 9. In long‐term experiments performed over 4 h with a normal external Cl concentration, CO2 (PCO2 approximately equal to 97 mmHg; pH 5.8 or 7) changed practically neither membrane potential, nor ai/K. 10. It is concluded that increasing the PCO2 when keeping the external pH constant causes an early depolarization of muscle. This effect is particularly marked in the absence of chloride. It can be explained partly, in surface muscle fibres, by a decrease of the intracellular K activity.
Control of junctional acetylcholinesterase by neural and muscular influences in the rat.
Authors: Lømo T , Slater C R
Published: December 2014

1. The development of AChE at ectopic neuromuscular junctions forming between a transplanted foreign nerve (the superficial fibular nerve) and the denervated soleus muscle has been studied in adult rats. 2. Junctional AChE activity began to appear in the vicinity of the fibular nerve sprouts 6‐7 days after section of the soleus nerve and 3‐4 days after the onset of transmission. 3. No histochemically detectable AChE appeared when the fibular nerve was cut 0‐4 days after the soleus nerve had been cut. 4. Direct electrical stimulation of the denervated soleus muscle caused plaques of true AChE, as determined by inhibitor studies, to appear in muscles where the fibular nerve had been cut 2‐4 days after the soleus nerve but not in muscles where the two nerves had been cut at the same time. The plaques appeared only in the vicinity of fibular nerve sprouts and coincided with newly formed but stable peaks of ACh sensitivity. Local application of Neostigmine prolonged and increased the depolarising response evoked by pulses of ACh at these sites. 5. In muscles where the fibular nerve was intact the AChE plaques changed gradually over a few weeks from an immature appearance to a mature appearance characteristic of normal end‐plates. In stimulated muscles where the fibular nerve had been cut the plaques stained intensely but remained morphologically immature. 6. We conclude (1) that muscle activity is important for the appearance of AChE at developing neuromuscular junctions and (2) that AChE accumulates only at sites on the muscle surface where the nerve fibres have left a ‘trace’ upon contact with the muscle fibres. These traces form quickly and persist after nerve‐muscle interaction of as little as 2 days. The muscle appears as a major source of junctional AChE since stimulation of the muscle induces intense AChE activity in muscles where the nerve has degenerated.
Effects of tetraethylammonium chloride on contractile, membrane and cable properties of rabbit artery muscle.
Authors: Haeusler G , Thorens S
Published: December 2014

1. Two types of effects of tetraethylammonium chloride (TEA) have been found in the smooth muscle cells of the rabbit main pulmonary artery. (a) With rapid onset of action TEA depolarizes the cell membrane, increases the membrane resistance, causes anomalous rectification and occasionally spike potentials in response to externally applied depolarizing current pulses and produces tonic contractions. (b) During prolonged (greater than 30 min) incubation in TEA phasic contractions develop progressively and the vascular strips respond to electrical stimulation with synchronized and powerful contractions. 2. There is a linear relationship between log concentration TEA and depolarization over the range of 10‐100 mM‐TEA. TEA (10 and 30 mM) raises the membrane resistance and decreases the core resistance. The latter effect appeared to develop more slowly than the former. 3. During short exposure to TEA part of the smooth muscle cells respond to depolarizing current pulses with spike potentials of variable amplitude and duration. These spikes are very sensitive to inhibition by verapamil or nickel chloride but are not affected by tetrodotoxin. The amplitude of electrotonic potentials, increased by TEA, is slightly further elevated by verapamil or nickle chloride. 4. TEA (10 mM) increases the mechanical response to low and intermediate potassium concentrations but has no effect on maximal contractions to high potassium. The slope of the line relating log potassium concentration to membrane potential is decreased by TEA. 5. TEA (10 mM) shifts the concentration response curve for the contractile effect of noradrenaline to the left and increases the maximum of noradrenaline‐induced contractions. In the presence of TEA, noradrenaline reduces the membrane potential to markedly lower values than under control conditions. 6. It is concluded that the rapidly occurring effects of TEA on the vascular smooth muscle cells of the rabbit main pulmonary artery are a decrease in potassium and an increase in calcium conductance. The latter effect may be related to a blockade of potassium channels; however, we cannot rule out the possibility that TEA affects calcium conductance independent of its presumed action on potassium channels. The slowly developing effects of TEA may be ascribed to the formation of gap junctions and/or (less likely) to an intracellular accumulation of TEA.
The reflex responses of single motor units in human first dorsal interosseous muscle following cutaneous afferent stimulation.
Authors: Garnett R , Stephens J A
Published: December 2014

1. Changes in the probability of firing of motor units active during voluntary muscle contraction have been studied in human first dorsal interosseous muscle in response to cutaneous afferent stimulation. 2. Electrical stimulation of the digital nerves of the index finger produces a reflex response consisting of three phases, early excitation followed by inhibition followed by late excitation. 3. Motor units recruited at low levels of voluntary contraction strength had larger early inhibitory and larger late excitatory responses than those recruited at higher levels of force. 4. Taking together the size of the short latency excitatory and inhibitory responses, units recruited at low levels of voluntary contraction strength and with slow twitch contraction times had predominantly inhibitory responses. In contrast, units in which the short latency excitatory responses predominated had fast twitch contraction times and were recruited at high levels of contraction strength. 5. It is concluded that for the cutaneous reflex pathway there are differences in the balance of excitatory and inhibitory sets of interneurones impinging on first dorsal interosseous motoneurones which are related to the kind of muscle unit innervated.
Contrasting roles of 5‐hydroxytryptamine and noradrenaline in fever in rats.
Authors: Ford D M , Klugman K P
Published: December 2014

1. We have investigated the effects of endogenous monoamine depletion on the development of fever in rats. 2. Fever was produced in rats by a single intraperitoneal injection of Salmonella typhosa endotoxin or leucocyte pyrogen manufactured from ox blood. 3. Depletion of brain 5‐hydroxytryptamine (5‐HT) by pretreatment with p‐chlorophenylalanine prevented the rise in rectal temperature produced both by bacterial endotoxin and by leucocyte pyrogen. 4. On the other hand depletion of noradrenaline (NA) by 6‐hydroxydopamine pretreatment resulted in a potentiation of the fever produced by bacterial endotoxin. 5. These results suggest that 5‐HT is involved in mechanisms responsible for the rise in temperature during fever and that NA is involved in mechanisms which serve to attenuate the rise.
Rapid effect of nerve injury upon axonal transport of phospholipids.
Authors: Dziegielewska K M , Evans C A , Saunders N R
Published: December 2014

1. Axonal transport of phospholipids labelled by lumbosacral spinal cord injection of [3H]choline has been studied in normal and injured sciatic nerves of the rat. 2. The appearance of labelled material in progressively increasing amounts in the sciatic nerve following spinal cord injection was consistent with a maximum velocity of axonal transport of about 20 mm/hr. There was also evidence of substantial amounts of labelled phospholipids being transported at much slower velocities. 3. In sciatic nerves injured by crushing there was an accumulation of labelled phospholipid immediately proximal to the crush. The accumulation was progressive with time. There was also an increase of labelled phospholipid in all the more proximal segments of the crushed nerves; this reached a maximum of about twice that in uncrushed nerves at 10 hr. after spinal cord injection. 4. The labelled phospholipid was shown to be about 80‐90% phosphatidylcholine both in uncrushed and crushed nerves. 5. The nature of the mechanism of this very rapid response of neurones to peripheral injury did not appear to be due to loss of ‘information’ from the periphery or action potentials initiated at the site of injury. The phenomenon has been further investigated by injection of drugs into the injured or control nerves. KCl injected at (but not proximal to) the site of injury was effective in blocking the injury response providing it was injected between a few minutes before or up to 30 min after the time of injury. Injection of either tetrodotoxin or local anaesthetic was as effective as injury in increasing the amount of labelled phospholipid transport. 6. These results suggest that the occurrence of an injury in a distant process of a neuron can be signalled retrogradely to the cell body by a mechanism involving a signal velocity of at least 140 mm/hr.
Inhibitory action of DIDS on chloride transport across the amphibian cornea.
Authors: Bentley P J , McGahan M C
Published: December 2014

1. DIDS (4,4'‐diisothiocyano‐2,2'‐stilbene disulphonic acid) reduced the CI Isc across the toad's (Bufo marinus) cornea. It acted on either the aqueous or tear side and these effects were additive. 2. The reduction in the Isc was equivalent to the decline in the undirectional flux of Cl from the aqueous to the tear side. The Cl flux from tear to aqueous was not changed. 3. DIDS did not change transmural Na transport. 4. The action of the diuretic bumetanide, which also inhibits Cl transport was additive to that of DIDS when both compounds were present on the aqueous though not when they were on the tear side of the cornea. 5. The results are consistent with the role of a Cl‐/anion exchange mechanism in active Cl transport across the cornea. 6. A hypothesis regarding the interactions and site of action of bumetanide in relation to that of DIDS, and the Cl transport process, is proposed.
Changes in permeability of sea urchin egg membrane to urea after fertilization or activation.
Authors: Christen R , Sardet C
Published: December 2014

1. Fertilization or artificial activation of the sea urchin egg, are known to increase the plasma membrane permeability to ions and small metabolites. We have examined the permeability properties of the egg membrane to urea. 2. Urea influx is not saturable and is slightly dependent on temperature. It is inhibited by phloretin. 3. Fertilization leads to a biphasic increase in urea flux kinetics. The first acceleration lasts about 10 min. The second acceleration is maintained at least up to the first cleavage. 4. The ionophore A 23187 mimics exactly fertilization. 5. Weak bases such as procaine lead to a gradual acceleration in urea flux kinetics. The response depends on the dose of procaine added. 6. The inhibitor of oxydative phosphorylation 2,4‐DNP fails to block the accelerations triggered by fertilization or activation by A 23187. 7. We discuss the results in light of the early and late events of egg activation.
Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.
Authors: Fernández‐Repollet E , Martínez‐Maldonado M , Opava‐Stitzer S
Published: December 2014

1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3‐day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long‐Evans rats. 3. During a 9‐day balance study urinary potassium excretion was higher than that of normal rats on days 1‐3, but not different on days 4‐9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1‐8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition.
Volume‐ and temperature‐dependent permeabilities in isolated rat liver cells.
Authors: Berthon B , Claret M , Mazet J L , Poggioli J
Published: December 2014

1. Water, K, Na and Cl contents and fluxes of K and Na were determined in isolated rat hepatocytes incubated at 1 degrees C (90 min) then at 38 degrees C (60 min). At 1 degrees C cells progressively gained Na and Cl, lost K and increased their volume by 17%. 2. Rewarming triggered a net loss of K and gain of Na. They were transitory (about 60 sec) being overcome rapidly by movements in the opposite direction until cells recovered their initial K and Na gradients. 3. Determination of time courses of the K rate constant (kappa' K) and net Na influx (phi Na) in cells incubated in ouabain K‐free media indicated that these paradoxical movements were due to a temporary shunting of the Na pump by sudden increases in K and Na permeabilities. 4. Increases in kappa' K and phi' Na were not sensitive to inhibitors of Ca‐activated K channels such as quinine (10(‐3) M) of apamin (10(‐8) M), suggesting they were not dependent on internal ionized Ca. 5. In control media containing 1.8 mM‐Ca divalent ionophore A23187, though stimulating the Ca pump (Ca efflux), presumably by increasing internal ionized Ca concentration, did not cause substantial and rapid changes in K permeability. This supports the hypothesis that Ca‐sensitive K channels are lacking in rat hepatocytes. 6. A 10% increase in cell volume provoked by a hypo‐osmotic shock triggered increases in both kappa' K and phi' Na with time courses very similar to those brought about by rewarming. 7. It is proposed that transient changes in K and Na permeabilities are the consequence of the cell swelling, induced by cooling. These volume‐dependent permeabilities are blocked at 1 degrees C and revealed by rewarming.
Two different responses of hippocampal pyramidal cells to application of gamma‐amino butyric acid.
Authors: Andersen P , Dingledine R , Gjerstad L , Langmoen I A , Laursen A M
Published: December 2014

1. Extra‐ and intracellular recordings were made from CA1 cells in hippocampal slices in vitro. The effects of ionophoretically applied GABA on somatic and dendritic regions were studied. 2. Ionophoresis of GABA at dendritic sites gave a reciprocal effect by inhibiting the effect of excitatory synapses close to the dendritic application, while facilitating those lying further away. For example, GABA delivered to the mid‐radiatum dendritic region reduced the population spike generated by a radiatum volley, while facilitating the population spike evoked by oriens fibre stimulation. Similarly, when single cells were recorded from, mid‐apical dendritic delivery of GABA abolished the synaptically driven discharges evoked by fibres terminating at this part of the dendritic tree, but facilitated the responses to input from fibres terminating on the basal dendrites of the same cell. 3. With intracellular recording two effects were observed. Applied near the soma, GABA induced a hyperpolarization associated with an increased membrane conductance. When applied to dendrites, GABA caused a depolarization also associated with an increased membrane conductance. Both types of GABA applications could inhibit cell discharges, although in some cases the depolarizing response could facilitate other excitatory influences or cause cell firing by itself. 4. Both the hyperpolarizing and depolarizing GABA responses persisted after blockade of synaptic transmission by applying a low calcium high magnesium solution, indicating mediation via a direct effect upon the cell membrane. 5. The reversal potential for the hyperpolarizing GABA effect was similar to the equilibrium potential for the i.p.s.p. evoked from alveus or orthodromically, and was 10‐12 mV more negative than the resting potential. The size of the depolarizing response was also dependent upon the membrane potential. By extrapolation an estimated equilibrium potential was calculated as about ‐40 mV. 6. Our results support the idea that the hyperpolarizing basket cell inhibition at the soma is mediated by the release of GABA. This hyperpolarizing response causes a general inhibition of firing. The dendritic effects of GABA, however, seem to represent another type of inhibition, which by shunting synaptic currents makes possible a selective inhibitory influence on afferents synapsing locally while facilitating more remotely placed excitatory synapses. We propose the term discriminative inhibition for this postulated new type of control of pyramidal cell discharges.
Properties of toxin‐resistant sodium channels produced by chemical modification in frog skeletal muscle.
Authors: Spalding B C
Published: December 2014

1. Single skeletal muscle fibres from the frog Rana pipiens were treated with the carboxyl group modifying reagent trimethyloxonium ion (TMO) and voltage clamped by the method of Hille & Campbell (1976). 2. TMO treatment reduced current through sodium channels to 0.33 +/‐ 0.03 that before treatment, but only 45 +/‐ 3% of this remaining current was blocked by 1 microM‐tetrodotoxin (TTX) and only 37 +/‐ 5% by 100 nM‐saxitoxin (STX). 3. This toxin resistance persisted in 90 microM‐TTX, was not due to inactivation of toxin nor to components of the reaction solution other than TMO, but was prevented by the presence of 100 nM‐STX during treatment with TMO. TMO‐modified sodium channels can be blocked by the local anaesthetic lidocaine. 4. The permeabilities of TMO‐modified channels to hydroxylammonium, ammonium, guanidinium, aminoguanidinium, methylammonium and tetramethylammonium ions relative to sodium were not significantly different from the permeabilities of untreated sodium channels. 5. Hydrogen ions blocked TMO‐modified sodium channels, but the apparent pKa for block at +38 mV of 5.07 was significantly less than the corresponding value of 5.32 in untreated sodium channels. 6. It is suggested that TMO produces toxin resistance by esterifying an ionized carboxyl group which is an essential part of the toxin binding site. Such esterification would electrostatically reduce the local cation concentration, thus reducing the apparent pKa of hydrogen ion block and the single‐channel conductance (Sigworth & Spalding, 1980). 7. It is concluded that the sodium channel contains a second acid group, near but distinct from an acid group previously hypothesized to be part of the selectivity filter and hydrogen ion binding site (Hille, 1971, 1972, 1975a).
Electrical responses of muscle fibres in a small foot muscle of Xenopus laevis
Authors: Ridge R. M. A. P. , Thomson Alex M.
Published: December 2014

1. Extensor digitorum longus IV (EDL IV) of Xenopus laevis was isolated together with its nerve and the 8th and 9th spinal roots. Motor units were functionally isolated.

2. Glass micro‐electrodes were used to penetrate the muscle fibres and to record their electrical responses to stimulation of single motor axons, or the total motor supply to the muscle.

3. Three types of electrical response were recorded from muscle fibres: an action potential in response to a single nerve stimulus (type 1), an action potential following repetitive nerve stimulation but not in response to single shocks (type 2) and end‐plate potentials which summed to a plateau of depolarization during repetitive nerve stimulation without producing action potentials (type 3).

4. In general muscle fibres giving type 1 responses belonged to fast motor units with high twitch: tetanus ratios; those giving type 3 responses, to small units with low twitch: tetanus ratios; and those giving type 2 responses, to units with intermediate properties.

5. In many cases the several muscle fibres innervated by a single axon gave different responses to stimulation of that axon and a single muscle fibre might give different responses to stimulation of two single axons. Thus it was not possible to classify motor units or muscle fibres by electrical responses.

6. Stimulation of the total motor supply to the muscle favoured the production of type 1 responses so that the proportion of muscle fibres giving type 1 responses was higher when the muscle nerve was stimulated than when single motor axons were stimulated. The proportion of fibres giving type 2 responses was lower, and the proportion of fibres giving type 3 responses was similar, in both cases. The implications of this are discussed.

7. Low neuromuscular junctional efficacy is suggested as an explanation for fluctuating twitch tensions and low twitch: tetanus ratios in many motor units in this muscle, and may also affect the activity patterns imposed on the muscle fibres by the motor axons which supply them.
Effects of some heavy metal ions on the ionic currents of myelinated fibres from Xenopus laevis.
Authors: Arhem P
Published: December 2014

1. The effect of the heavy metal ions Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Hg2+ on permeability parameters of the nerve membrane was investigated. The ions were applied externally to single myelinated fibres of Xenopus laevis. The ionic currents, associated with potential steps were measured and analysed. 2. Zn2+ reversibly slowed down the kinetics of the K system. The effect at large potential steps was described as an increase of tau n. 3.4 mM‐Zn2+ increased tau n about three times. 3. Ni2+ and Cu2+ also reversibly increased tau n in a similar way. The effect was larger than that of Zn2+. The other period 4 ions tested did not affect tau n markedly. Nor did the group 2b ion Cd2+. 4. The relative efficiency of the different ions agreed well with their tendency to form complexes with certain ligands. The effect was not a simple function of affinity for sulphydryl groups. 5. All the studied ions decreased PNa. The decrease was reversible except for that caused by Hg2+. Cu2+ caused the largest reversible effect. Hg2+ irreversibly decreased PNa at low concentrations (1‐10 microM). 6. All ions studied shifted the Na activation curve in a positive direction along the potential axis. The effect was reversible except for that caused by Hg2+. The largest reversible shift was caused by Cu2+. 7. The relative efficiency of the different ions on the parameters studied in Xenopus axons showed great similarity to the corresponding efficiency on axons from other species, although some differences were noted.
The effect of sodium removal on the contractile response of the guinea‐pig taenia coli to carbachol.
Authors: Brading A F , Burnett M , Sneddon P
Published: December 2014

1. The effects of Na‐free solutions (using Li, Tris, sucrose or Mg as Na substitutes) on the contractile responses, membrane depolarization and 42K efflux produced by carbachol in the smooth muscle of the guinea‐pig taenia coli have been investigated. The effect of these Na‐free solutions on intracellular ion content of the muscle has also been studied. 2. Na removal induced a pattern of changes in the tone of the muscle characteristic of the substitute used, probably reflecting changes in transmembrane Ca fluxes involving Na. 3. Contractile responses to 10 sec application of 5 x 10(‐5) M‐carbachol were greatly reduced in Na‐free solutions with all the Na substitutes used. This did not correlate with reduction in membrane depolarization or 42K efflux produced by the drug in the various Na‐free medial used. 4. Intracellular Na seems important for maintaining the contractile response, since in Na‐free solutions cellular Na levels and contractile responses were better maintained at 13 degrees than 34 degrees C and in tissues stimulated with carbachol every 10 min the final magnitude of the response was related to cellular Na content. If, however, the tissues was left unstimulated in Na‐free Mg or sucrose solution a large response could still be obtained when cellular Na content was very low. A model is described which could account for these results in terms of an intracellular Ca store released by carbachol and requiring intracellular Na. 5. In tissues continuously exposed to 10(‐4) M‐carbachol Na removal, even for only 10 sec, produced rapid relaxation, probably secondary to changes in electrical properties of the membrane caused by removal of external Na.