bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of frequency‐dependent broadening of molluscan neurone soma spikes.
Authors: Aldrich R W , Getting P A , Thompson S H
Published: December 2014

1. Action potentials recorded from isolated dorid neurone somata increase in duration, i.e. broaden, during low frequency repetitive firing. Spike broadening is substantially reduced by external Co ions and implicates an inward Ca current. 2. During repetitive voltage clamp steps at frequencies slower than 1 Hz, in 100 mM‐tetraethyl ammonium ions (TEA) inward Ca currents do not increase in amplitude. 3. Repetitive action potentials result in inactivation of delayed outward current. Likewise, repetitive voltage clamp steps which cause inactivation of delayed outward current also result in longer duration action potentials. 4. The frequency dependence of spike broadening and inactivation of the voltage dependent component (IK) of delayed outward current are similar. 5. Inactivation of IK is observed in all cells, however, only cells with relative large inward Ca currents show significant spike broadening. Spike broadening apparently results from the frequency dependent inactivation of IK which increases the expression of inward Ca current as a prominent shoulder on the repolarizing phase of the action potential. In addition, the presence of a prolonged Ca current increases the duration of the first action potential thereby allowing sufficient time for inactivation of IK.
Catecholaminergic alpha‐receptors and shivering in the rat.
Authors: Marshall H W , Stoner H B
Published: December 2014

1. A rise or a fall in systemic blood pressure brought about by the I.V. infusion of peripherally acting drugs (adenosine, noradrenaline or methoxamine) inhibited shivering in the cold‐exposed rat. 2. Since the injection of commonly used doses of noradrenaline (0.05‐0.10 mumole) into a lateral cerebral ventricle of a rat was usually accompanied by a rise in blood pressure special precautious were required to determine whether noradrenaline had a specific central effect on shivering. 3. Small doses of noradrenaline (0.02‐0.03 mumole) or clonidine (0.01 mumole) which had no effect on blood pressure when injected into a lateral cerebral ventricle still inhibited shivering in the cold‐exposed rat and this effect was prevented by phentolamine. 4. It is concluded that noradrenaline can inhibit the cold sensor‐shivering pathway in its central course by an action on alpha‐receptors.
A comparison between the discharges of human nociceptive nerve fibres and the subject's ratings of his sensations.
Authors: Gybels J , Handwerker H O , Van Hees J
Published: December 2014

1. Impulses in cutaneous nerve fibres were recorded percutaneously with tungsten micro‐electrodes from the superficial radial nerve of adult human subjects. 2. Eight units studied had conduction velocities below 1.5 m/sec, and thus belong to the class of C fibres. On the basis of their responsiveness to mechanical and to thermal stimuli the units were classified as ‘polymodal nociceptors'. 3. Units were tested with 12 sec heat pulses starting from a base line temperature of 43.0‐43.5 degrees C. Heat stimuli reaching three different maximal levels were applied in randomized order, the subjects being blind with respect to stimulus size. Each of the eight units studied was tested with more tha 20 stimuli and with four of them were 80‐125 stimulus repetitions. 4. After each stimulus the subjects had to rate his sensations on a six‐point rating scale extending from ‘just noticeable’ to ‘very hot, painful'. 5. Discrimination between the three stimulus levels by the integtated spike discharges and by the ratings of the subject was compared using the P(A) measure of the Signal Detection Theory. It was found that both the neurophysiological and the psychophysical measurements provided about equal discrimination. 6. In addition it has been found that spike discharges and ratings share a common variance beyond their common dependence on the stimulus level. Among the factors contributing to this interdependence a ‘temporal position effect’ was the most significant. 7. In spite of this interdependence between discharge rates and subjective ratings, the latter gave a better estimation of the stimulus size than of the discharge rates of the individual C fibre under study. 8. It was concluded that the polymodal C‐nociceptors might be instrumental for the quantitative aspects of heat pain sensation. The hypothesis was derived from the present results that, under the conditions of cour experiments, the loss of information in the course of central processing might be about equal to the gain by the parallel processing in a population of nociceptors excited by a stimulus.
The calcium current and the activation of a slow potassium conductance in voltage‐clamped mouse neuroblastoma cells.
Authors: Moolenaar W H , Spector I
Published: December 2014

1. The Ca2+ inward current (ICa) and a slow outward current in differentiated cells of mouse neuroblastoma clone N1E‐115 have been studied under voltage‐clamp conditions. 2. ICa shows voltage‐ and time‐dependent inactivation when evoked by step‐wise depolarizations in Na+‐free solution containing high [Ca2+] (20 nM) and tetraethylammonium (TEA, 25 mM). Ba2+ and Sr2+ can substitute for Ca2+. 3. Holding potentials below ‐70 mV maximal activate ICa. Half inactivation occurs at ‐56 mV and ICa is completely inactivated beyond holding levels of ‐30 mV. Maximum peak currents are of the order of 10(‐4) A/cm2 and the reversal potential ranges from +40 to +60 mV. The ICa inactivation time course follows first‐order kinetics with a voltage‐depedent time constant ranging from 25 to 100 msec. 4. The striking resemblance between ICa and the Ca2+ current in the unfertilized mouse oocyte (Okamoto, Takahashi & Yamashita, 1977) is discussed. 5. A slow outward current with a rise time of several seconds is recorded on voltage steps beyond ‐20 mV in high [Ca2+] solutions. It is carried primarily by K+ on account of the value of the reversal potential and its dependence on [K]0. This K+ current is TEA‐insensitive and is blocked by Ca2+ antagonists. 6. The slow K+ current (IK(Ca)) is suggested to be mediated by Ca2+ influx, but the voltage‐dependence of the underlying conductance (GK(Ca)) differs significantly from the ICa voltage‐dependence. 7. The results are consistent with the hypothesis that IK(Ca) depends both on ICa and on membrane potential. An alternative hypothesis is briefly discussed.
Influence of potassium, sodium, calcium, perfusion pressure, and isoprenaline on renin release induced by high concentrations of magnesium.
Authors: Ettienne E M , Fray J C
Published: December 2014

1. These studies were conducted on isolated, perfused rat kidneys to determine the mechanism through which high concentrations of extracellular Mg (20mM) stimulated renin release. 2. Raising K concentrations in the perfusion fluid from 5 to 50 mM, and raising renal perfusion pressure from 100 to 150 mmHg inhibited the renin release induced by 20 mM‐Mg. The response was reversible. 3. Renin release induced by low renal perfusion pressure (50 mmHg) or isoprenaline (2.43 microM) was unaffected by 20 mM‐Mg. However, this release was augmented when 5 mM‐Ca was added in conjunction with 20 mM‐Mg. 4. In medium containing 20 mM‐Mg, lowering Na concentration from 145 to 100 mM augmented the renin release induced by low perfusion pressure and isoprenaline. Further lowering Na to 25 mM had no additional effect. 5. It is concluded that 20 mM‐Mg activates renin release by a mechanism which involves hyperpolarization of the juxtaglomerular cell membrane and an associated decrease in cytoplasmic Ca. Such a mechanism might be coupled to a Mg‐Na exchange pump.
Diaphragmatic and oesophageal activity in regurgitation in sheep: an electromyographic study.
Authors: Titchen D A
Published: December 2014

1. Electromyographic (e.m.g.) recordings of reactions of the oesophagus, vertebral and costal fibres of the diaphragm and from the reticulum‐one of the cranial divisions of the stomach were made during the regurgitation of rumination in sheep. 2. E.m.g.s indicated that a contraction of the caudal thoracic oesophagus developed over a period of about 2 sec before, and ceased at the time of, the more forceful inspiratory effort associated with regurgitation. 3. This contraction was confined to the caudal region of the thoracic oesophagus in which it was characteristically more prolonged and intense in its most caudal part within 15‐25 mm of the hiatus oesophageus. It is interpreted to contribute to development or intensification of a caudal thoracic oesophageal sphincter. 4. The more forceful inspiratory effort at the time of regurgitation was due to costal fibres of the diaphragm. Although active normally during inspiration the vertebral fibres of the hiatus oesophageus do not contribute to this more forceful inspiration. This may facilitate regurgitation of digesta. Similarly, inactivity of vertebral but not costal fibres detected during primary oesophageal contractions (of swallowing) may make for easier passage of digesta into the stomach.
Receptive fields of fibres in the central ends of divided dorsal roots.
Authors: Millar J
Published: December 2014

1. Action potentials were recorded from single fibres in the central ends of divided lumbar dorsal root filaments in anaesthetized cats. 2. Six classes of receptive field could be identified in such fibres, which corresponded very closely to the receptive fields of single primary afferent fibres. 3. For fibres with superficial receptive fileds (cutaneous or hair), a percutaneous electrical stimulation was used to drive the afferents at sustained high frequencies (100, 200 or 300 Hz), and the ability of the recorded fibre to follow the stimulation monitored. About one half of fibres with superficial receptive fields could be driven at sustained high frequencies. 4. The shape of the action potential from the fibre was analysed at different distances from the spinal cord. Close to the spinal cord a clear action potential could be recorded, but further out along the filament the action potential was often attenuated or absent. 5. It is suggested that some at least of these fibres are recurrent collaterals of primary afferent fibres, that taper in size after leaving the spinal cord. The function of such fibres is discussed.
Aldosterone induced changes in colonic sodium transport occurring naturally during development in the neonatal pig.
Authors: Ferguson D R , James P S , Paterson J Y , Saunders J C , Smith M W
Published: December 2014

1. Serum concentrations of aldosterone in later fetal, 3‐6 week old and adult pigs are of the order of 300 pg ml.‐1. This increases to about 2000 pg ml.‐1 in the period immediately after birth. 2. Canrenoate injected into pigs from birth onwards stops the increase in colonic short‐circuit current, seen to take place normally during early postnatal development. Amiloride has little or no effect on the short‐circuit current of colons taken from canrenoate injected pigs. 3. Canrenoate stops the post‐natal increase in colonic Na influx (and therefore net transport) seen to occur under normal conditions. 4. There is in the neonatal pig distal colon a portion of Na transport which appears to be resistant to inhibition by amiloride or canrenoate. 5. There is a second portion of Na transport, increasing in importance as the piglets become older, which is electrogenic and which is electrogenic and which is inhibited by prior injection of canrenoate. It is assumed that this fraction of Na transport is influenced by aldosterone. 6. There is a third part of Na transport, maximal in colons taken from one day old animals, which appears to be non‐electrogenic. This is also blocked by prior injection of canrenoate. 7. The physiological relevance of these findings is discussed.
The effect of hyperosmolarity and insulin on resting tension and calcium fluxes in rat soleus muscle.
Authors: Clausen T , Dahl‐Hansen A B , Elbrink J
Published: December 2014

1. The effect of hyperosmolarity on resting tension and on the fluxes of Na and Ca has been characterized in isolated soleus muscles of the rat. 2. When the osmolarity of the incubation medium was increased by the addition of non‐permeant solutes (100‐400 m‐osmole), the tension showed a rapid dos‐dependent rise which could be maintained for up to 60 min. 3. Tension development was unaffected by tubocurarine (2 X 10(‐5) M), considerably diminished by the omission of Na or Ca from the incubation medium, and inhibited by tetracaine (10(‐4) M). 4. The addition of mannitol or sucrose (200 mM) induced a prompt stimulation of the influx of 22Na and 45Ca. Both in the absence and the presence of extracellular Ca hyperosmolarity stimulated the washout of 45Ca from preloaded muscles. Tetracaine (5 X 10(‐4 M) suppressed the effects of hyperosmolarity on both the influx and the efflux of 45Ca, but only gave a modest reduction in the stimulation of 22Na influx. 5. Insulin (5‐100 mu./ml.) induced a considerable further rise in the resting tension of muscles exposed to mannitol or sucrose (200 mM). This effect was seen in a glucose‐free medium and could be abolished by the addition of insulin antibody. 6. It is concluded that hyperosmolarity leads to a rise in the concentration of free Ca2+ ions in the sarcoplasm, partly due to a mobilization of Ca from intracellular pools, but to a considerable extent supplemented from extracelluar sources. Under these conditions, insulin further augments the Ca2+ ion level in the cytoplasm.
Effects of dopaminergic antagonist and agonist on thermoregulation in rabbits.
Authors: Lin M T
Published: December 2014

1. The effects of dopaminergic antagonist haloperidol and agonist apomorphine on the thermoregulatory responses of unanaesthetized rabbits to different ambient temperatures (Ta) of 2, 22 and 32 degrees C were assessed. 2. I.V. administration of haloperidol produced dose‐dependent hypothermia at 2 and 22 degrees C Ta. At 2 degrees C Ta the hypothermia was due to a decrease in metabolic heat production. At 22 degrees C Ta the hypothermia was brought about by a decrease in metabolism and an increase in ear blood flow. However at 32 degrees C Ta, there was an increase in rectal temperature in response to haloperidol application; this hyperthermia was due to a decrease in both the ear blood flow and respiratory evaporative heat loss (Eres). 3. I.V. administration of apomorphine produced dose‐dependent hyperthermia at all the ambient temperatures studied. At 2 degrees C Ta the hyperthermia was due to an increase in metabolism. At both 22 and 32 degrees C, the hyperthermia was brought about by an increase in metabolic heat production and a decrease in ear blood flow. Also, there was an increase in Eres in response to apomorphine at 22 degrees C Ta. 4. The data, in general, indicate that dopamine agonist activates all effector pathways which modulate the autonomic processes of thermoregulation (i.e. respiratory heat loss, peripheral vasomotor tone and metabolism), and that the dopamine antagonist inhibits the activity in all three effector pathways. Such a clear pattern of results is readily expressible in terms of the ‘Bligh’ model dealing with the aminergic mechanisms of temperature regulation.
The influence of chloride ions on renal outer medullary cell volume.
Authors: Law R O
Published: December 2014

1. Slices of rat renal outer medulla have been incubated in media made hyperosmotic (540 and 1055 m‐osmole/kg H2O) by the addition of urea, and containing variable concentrations of Cl (90, 144, 189 and 215 mM) and constant concentrations of Na (180 mM) and K (5.9 mM). A small number of incubations have been conducted in the presence of 100 mM‐Na. 2. Changes in cell volume during incubation have been calculated on the basis of initial and final slice weight and inulin space. 3. The capacity of cells to shrink in response to extracellular osmotic stress was related principally to the external Cl concentration rather than to osmolality, increases in concentration being associated with enhanced shrinkage. Shrinkage was accompanied by net loss of cellular Cl. The ratio between intra‐ and extracellular Cl concentration (ca. 0.41) remained constant in all media. 4. In media containing low Cl concentration (90 mM), reduction of media Na concentration to 100 mM enhanced shrinkage. This effect was not observed when medium Cl concentration was greater than 90 mM. 5. Ethacrynic acid‐cysteine (1 mM) significantly impaired the shrinkage response to extracellular osmotic stress, and caused cell swelling in media of relatively low Cl concentration and osmolality. It did not abolish the dependency of cell volume upon Cl concentration. There was marked reduction in the net amount of Cl lost from cells. 6. Ethacrynic acid‐cysteine caused an increase in cellular Na content only in media containing 540 m‐osmole/kg H2O and Cl concentrations less than 215 mM. 7. Ouabain (1 mM) inhibited cell shrinkage to a lesser extent than ethacrynic acid‐cysteine in all media except that causing the greatest shrinkage under control conditions (215 mM‐Cl/1055 m‐osmole/kg H2O). It is suggested that a ouabain‐sensitive process may play an increasingly important role in Cl‐related cell shrinkage as this becomes more pronounced. 8. The findings are consistent with the view that Cl ions influence cell volume both through their effective external osmotic pressure and by means of Cl‐specific process; the latter is associated with net loss of cellular Cl. A dependence of this loss upon Na/k exchange‐linked metabolism is inferred, but the present findings do not permit the active or passive nature of the extrusion to be defined.
The relative importance of thermal, osmotic and hypovolaemic factors in the control of drinking in the pig.
Authors: Ingram D L , Stephens D B
Published: December 2014

1. The influence of thermogenic, osmotic or hypovolaemic stimuli on drinking has been measured in young pigs. Temperature changes in the hypothalamus and spinal cord were induced by means of implanted thermodes, while peripheral changes in skin and scrotal temperature were induced by circulating water through a coat. Osmotic stimuli were applied by I.V. injections of NaCl and hypovolaemia was induced by withdrawal of blood. 2. At an ambient temperature of 21‐‐24 degrees C warming the hypothalamus for 10 min increased the water intake approximately 40%, while cooling the hypothalamus for a similar period reduced it by about 70%. 3. At an ambient temperature of 21‐‐24 degrees C warming the scrotum caused the pigs to drink more than controls, and at the higher ambient temperature of 32 degrees C the effect was even greater. 4. Warming or cooling the spinal cord produced effects that were not consistent either within or between animals, thus temperature changes in this region play, at most, a minimal physiological role in the control of drinking in the pig. Warming the skin to 40 degrees C produced a slight increase in water intake, as also did cooling of the skin. 5. Drinking induced by an osmotic stimulus was proportional to the concentration of NaCl ranging from 5 to 30%. 6. Withdrawal of 500 ml. blood did not produce a statistically significant increase in water intake compared with controls.
Ballistic flexion movements of the human thumb.
Authors: Hallett M , Marsden C D
Published: December 2014

1. In response to an auditory stimulus normal subjects made ballistic flexion movements of the top joint of the thumb against a lever attached to the spindle of a low‐inertia electric motor. 2. Electromyographic (e.m.g.) activity was recorded from pairs of fine wire electrodes inserted into flexor pollicis longus and extensor pollicis longus, respectively the sole flexor and extensor of the joint. 3. Movements of 5 degrees, 10 degrees and 20 degrees were made from initial angles of 10 degrees, 20 degrees and 30 degrees flexion against torques of 0.04, 0.08 and 0.16 Nm. 4. The e.m.g. activity initiating such movements was characterized by a ‘triphasic’ pattern of sequential bursts of activity in the agonist (flexor pollicis longus), then in the antagonist (extensor pollicis longus), and then in the agonist again. 5. The duration of the first agonist and first antagonist bursts ranged from about 50 to 90 ms and there was no significant change of burst length in the different mechanical conditions. 6. In movements of differing angular distance, the rectified and integrated e.m.g. activity of the first agonist burst could be correlated with the distance moved. The rectified and integrated e.m.g. activity of the first antagonist burst could not be correlated with the distance moved. 7. Responses of the muscles to perturbations either before or during the ballistic movements were studied. Current in the motor could be altered so to extend the thumb ('stretch'), to allow it to accelerate ('release'), or to prevent further movement ('halt'). 8. Suitably timed stretch increased the e.m.g. activity of the first agonist burst while release decreased it. 9. There was a small response of the agonist to stretch or halt timed to act during the interval between the first two agonist bursts; the major response was an augmentation of the second agonist burst. 10. Stretch, timed to act between the first two agonist bursts which released the antagonist, diminished the activity of the first antagonist burst while halt virtually eradicated it in all but one subject. Release, at this time, which stretched the antagonist, increased the activity of the first antagonist burst. 11. It is concluded that the individual components of a ballistic movement are relatively fixed in duration and the amount of e.m.g. activity is altered within this time interval to produce the different forces required for fast movements of different amplitude. 12. Both agonist and antagonist muscles remain under some feed‐back control during the entire course of a ballistic movement, but the amount of influence of fedd‐back depends on the supraspinal command signal and the changes in the spindle during the course of the movement.
Inhibition by angiotensin II of baroreceptor‐evoked activity in cardiac vagal efferent nerves in the dog.
Authors: Lumbers E R , McCloskey D I , Potter E K
Published: December 2014

1. Action potentials were recorded in single baroreceptor fibres dissected from the carotid sinus nerves in dogs during increases in blood pressure caused by I.V. injection of angiotensin II, and by I.V. injection of phenylephrine or inflation of an aortic balloon. Action potentials were recorded in single cardiac efferent fibres dissected from the right cervical vagus nerve in other dogs during increases in blood pressure caused by angiotensin II, and by phenylephrine or by inflation of an aortic balloon. 2. There was no difference in the discharge frequency of single carotid sinus baroreceptor fibres at any blood pressure when phenylephrine, balloon inflation, or angiotensin II were used to raise the pressure. 3. Activity in single cardiac vagal efferent fibres was increased when blood pressure was increased by phenylephrine or by inflation of an aortic balloon. However, when blood pressure rose by a comparable amount in response to angiotensin II, vagal firing decreased (three fibres), was little changed from control levels (four fibres), or increased less than it did in response to phenylephrine (one fibre). 4. It is concluded that while angiotensin II has no effect on baroreceptor sensitivity, it does inhibit vagal discharge which is evoked by stimulation of arterial baroreceptors.
The role of the flocculus of the monkey in fixation and smooth pursuit eye movements.
Authors: Noda H , Suzuki D A
Published: December 2014

1. Purkinje cell discharges were recorded from the flocculus of monkeys trained to fixate a small visual target and to track the target when moved slowly. 2. A striking feature of Purkinje cell activity during the steady fixation was a high rate of tonic discharges with regular interspike intervals. The average discharge rate in the whole population of Purkinje cells ranged from 37 to 145 spikes/sec. The coefficient of variation of the interspike intervals was typically smaller than 0.5 in most units. 3. In 43.9% of the Purkinje cells, tonic levels of activity changed by more than 20% of the average background activity with shifts of gaze. 4. In some Purkinje cells, especially in most burst‐pause units, discharge rates during steady fixation were proportional to eye positions in one plane, implicating these cells as sources of eye position information to their target cells. 5. When the monkey tracked a sinusoidally oscillating target, the activity of some Purkinje cells was clearly modulated in phase with the eye velocity. 6. In the other Purkinje cells exhibiting smooth pursuit modulation, the activity curve appeared with a phase shift. When these cells were tested with sinusoidal target movements at different frequencies, but with a constant magnitude, the peak firing rates were proportional to the frequencies of the excursions, i.e. the velocities. 7. The flocculus thus provides the oculomotor system with eye position information during fixation and with velocity information during smooth pursuit and participates in the control of oculomotor functions stabilizing retinal images.
The kinetics of tubocurarine action and restricted diffusion within the synaptic cleft.
Authors: Armstrong D L , Lester H A
Published: December 2014

1. The kinetics of tubocurarine inhibition were studied at the post‐synaptic membrane of frog skeletal muscle fibres. Acetylcholine (ACh) and (+)‐tubocurarine were ionophoresed from twin‐barrel micropipettes, and the membrane potential of the muscle fibre was recorded intracellularly. Tubocurarine‐receptor binding was measured by decreases in the response to identical pulses of ACh. 2. The responses to both ACh and tubocurarine had brief latencies and reached their maxima rapidly. It is suggested that under these conditions the kinetics of tubocurarine action are not slowed by diffusion in the space outside the synaptic cleft. 3. After a pulse of tubocurarine, recovery from inhibition proceeds along a roughly exponential time course with a rate constant, 1/tau off approximately equal to 0.5 sec‐1. This rate constant does not depend on the maximal level of inhibition and varies only slightly with temperature (Q10 = 1.25). 4. After a sudden maintained increase in tubocurarine release, the ACh responses decrease and eventually reach a new steady‐state level. Inhibition develops exponentially with time and the apparent rate constant, 1/tau on, is greater than 1/tau off. When the steady‐state inhibition reduces the ACh response to 1/n of its original level, the data are summarized by the relation, 1/tau on = n(1/tau off). 5. When the ACh sensitivity is reduced with cobra toxin, both 1/tau on and 1/tau off increase. Thus, the kinetics of tubocurarine inhibition depend on the density of ACh receptors in the synaptic cleft. 6. After treatment with collagenase, part of the nerve terminal is displaced and the post‐synaptic membrane is exposed directly to the external solution. Under these circumstances, 1/tau off increases more than tenfold. 7. Bath‐applied tubocurarine competitively inhibits the responses to brief ionophoretic ACh pulses with an apparent equilibrium dissociation constant, K = 0.5 microM. 8. In denervated frog muscle fibres, extrasynaptic receptors have a lower apparent affinity for tubocurarine. After a pulse of tubocurarine, inhibition decays tenfold more rapidly at these extrasynaptic sites than at the synapse. 9. It is suggested that each tubocurarine molecule binds repeatedly to several ACh receptors before escaping from the synaptic from the synaptic cleft and that the probability of this repetitive binding is enhanced because the nerve terminal presents a physical barrier to diffusion out of the cleft. Consequently, the receptor transiently buffer the concentration of tubocurarine in the cleft, and the macroscopic kinetics of inhibition are much slower than the molecular binding rates for tubocurarine.
Characteristics of the anion channel in the sino‐atrial node cell of the rabbit.
Authors: Seyama I
Published: December 2014

1. The anion permeability of the sino‐atrial node cell membranes was determined by substituting various anions for Cl and observing the resultant transient changes in membrane potential. The permeability sequence was found to be in the following order: thiocyanate greater than NO3 greater than I Br greater than Cl greater than acetate. 2. The membrane resistance in Cl solution was compared with that in various anion solutions by the voltage‐clamp method. The conductance sequence for the sino‐atrial node cell membrane was observed to be the same as the permeability sequence. 3 The potential generated by the Na‐K pump was partly short‐circuited in normal bathing solution, and thus the pump could be responsible in part for the generation of the sin‐atrial node resting membrane potential. 4 When Cl was replaced by acetate, a less permeable ion, the inward‐going rectification disappeared. Thus, the inward‐going rectification might be due partly to a time‐ and voltage‐dependent Cl current.
Regulation of chloride in quiescent sheep‐heart Purkinje fibres studied using intracellular chloride and pH‐sensitive micro‐electrodes.
Authors: Vaughan‐Jones R D
Published: December 2014

1. The intracellular Cl activity, alpha iCl was measured inside quiescent sheep cardiac Purkinje fibres, bathed in normal Tyrode at pH 7.40, buffered with approximately 22 mM‐bicarbonate/approximately 5% CO2 + 95% O2. The measurements were made using liquid ion‐exchanger Cl‐sensitive micro‐electrodes. 2. After internal Cl levels had been depleted by prolonged exposure to Cl‐free media (glururonate‐substituted) when external Cl was restored, there was a rapid re‐accumulation of Cl inside the fibres to levels that were much higher than those expected for a passive Cl distribution. Such a process can be conveniently defined as an active inward Cl pump. 3. The inward‐pumping was noticeably temperature‐sensitive (Q10 approximately 2.6), its rate was reduced about eighteenfold in the nominal absence of external bicarbonate/CO2 and it was substantially inhibited by the drug SITS (4‐acetamido‐4'‐isothiocyanato‐stilbene‐2,2'‐disulphonic acid). 4. The fall of alpha iCl in Cl‐free solution was slow and was also equally temperature‐sensitive and substantially inhibited by SITS, but was only slightly impaired in the nominal absence of external bicarbonate/CO2. 5. pHi was measured using recessed‐tip pH‐sensitive micro‐electrodes, and in some experiments both pHi and alpha iCl were monitored simultaneously. When alpha iCl slowly declined in Cl‐free solution then pHi slowly became alkaline. Upon restoring external Cl, then there was, as usual, a rapid recovery of a high alpha iCl and this was accompanied by a rapid re‐acidification of pHi. Both the recovery of alpha iCl and pHi were exponential with virtually the same time constant. 6. Both the slow alkalinization of pHi in Cl‐free solution and the rapid re‐acidification upon restoring external Cl were substantially inhibited by the drug SITS. 7. When [k]O was raised to 45 mM or more (by removing equivalent amounts of [Na]O), there was a large depolarization of Em and a slow rise of alpha iCl, which was not accompanied by a large change of pHi. The rise of alpha iCl appeared to be unaffected by SITS. 8. It is suggested that a Cl/CHO‐3 exchange mechanism can operate reversibly across the membrane of quiescent Purkinje fibres, and that it can account, at least in part, for the high levels of alpha iCl measured in the resting state. It is also concluded that Cl can cross the membrane in other ways, especially in high‐K solution possibly by moving passively through conductance channels that are open under these conditions.
Cyclic GMP and the permeability of the disks of the frog photoreceptors.
Authors: Caretta A , Cavaggioni A , Sorbi R T
Published: December 2014

1. The diffusion of sodium, potassium and rubidium (not chloride) ions across the disk membrane is increased by cyclic guanosine monophosphate (cyclic GMP). 2. The increase is greater for sodium than for rubidium in the 0.01‐0.1 mM concentration range. 3. Cyclic adenosine monophosphate (cyclic AMP) is less efficient than cyclic GMP; GMP and guanosine triphosphate are without effect. 4. The effect is present with either 1.8 mM calcium ions or 4 mM‐EGTA in the perfusion fluid. 5. The presence of the cyclic GMP phosphodiesterase on the disk membranes is not needed for this effect. 6. The effect is present in both unbleached and fully bleached membranes.
Role of gastric antrum in gastric and intestinal phases of gastric secretion in dogs.
Authors: Fokina A , Konturek S J , Kwiecien N , Radecki T
Published: December 2014

1. The gastric and intestinal phases of gastric secretions were selectively evoked before and after the removal of the antral mucosa in four dogs provided with a special cannula that allowed complete separation of the stomach and duodenum without interrupting neural connexions between them. 2. The gastric phase induced by 5% liver extract meal administered into the stomach at various distension pressures (ranging from 0 to 15cm H2O) resulted in an increase in acid output to about 56% of the histamine maximum and in a marked rise in serum gastrin. 3. Following resection of the antral mucosa, the gastric acid response to meal of liver extract was reduced by about 50% and serum gastrin response was completely eliminated. Exogenous gastrin (G‐17) given during the gastric phase induced by such a meal in dogs with antral mucosectomy failed to restore acid output to pre‐resection level. 4. Intestinal perfusion of meal of liver extract in graded amounts stimulated gastric acid secretion to about 30% of histamine maximum acid output and raised significantly serum gastrin level. 5. Antral mucosectomy abolished almost completely both gastric acid and serum gastrin response to intestinal meal of liver extract. 6. Exogenous gastrin given during the intestinal meal of liver extract failed to restore acid output to the pre‐resection level, suggesting that this procedure greatly reduced the secretory capacity of the oxyntic glands. 7. We conclude that the antral gland area plays an important role in the gastric phase and that it is a prerequisite for the intestinal phase of gastric secretion.
Influence of sex and age on febrile responses to peripheral and central administration of pyrogens in the rabbit
Authors: Lipton J. M. , Ticknor C. B.
Published: December 2014

1. Intravenous injections of leucocytic pyrogen in doses of 15, 30 and 60 μl./kg caused febrile reactions in male rabbits that were related to age of the animal: rabbits under 2 yr of age developed fevers that were related to dose of pyrogen, while rabbits 2‐3 yr old showed large febrile responses which were not dose‐related.

2. Female rabbits of comparable ages generally showed smaller febrile reactions to
I.V. leucocytic pyrogen, and still older females (3‐5 yr) developed fever only after the largest dose.

3. Dose‐related febrile responses to 2·5, 5 and 10 μl. leucocytic pyrogen given intracerebroventricularly (
I.C.V.) were greater in male rabbits 1‐3 yr old than in females of comparable age. Female rabbits 3‐5 yr old showed dose‐related fevers that were smaller than those of younger animals of both sexes.

4. There were no major differences in response to 125, 250 and 500 ng PGE2, given
I.C.V., between male and female rabbits under 2 yr of age. Females 2‐3 yr of age had greater responses to PGE2 than males of comparable age whilst the oldest females showed smaller responses.

5. It is concluded that the febrile response of the rabbit to peripheral and central leucocytic pyrogen varies with both age and sex. Differences in sensitivity of central fever controls to endogenous pyrogen in animals of different ages and sexes may account for the different responses to peripheral pyrogen.
Inter‐relationship of sodium, chloride, bicarbonate and acetate transport by the colon of the pig.
Authors: Argenzio R A , Whipp S C
Published: December 2014

1. Net transport of Na, Cl, HCO3 and acetate was examined in the temporarily isolated colon of conscious pigs weighing 46 +/‐ 8 kg. 2. The entire colon absorbs 4.1 ml. H2O, 0.8 m‐equiv Na, 1.3 m‐equiv acetate and secretes 0.5 m‐equiv HCO3/min with a solution comparable to the normal contents. The absorptive capacity of the proximal and distal halves of the colon was comparable per unit dry weight of mucosa when each segment was presented with the same solution. 3. A series of studies using ion replacement solutions showed that net Na absorption and net HCO3 accumulation in the lumen solution were both increased in the presence of acetate. Cl absorption was independent of Na absorption and was accompanied by an equivalent net secretion of HCO3 in the absence of Na. When NaCl in the perfusion solution was replaced with Na2SO4, Na and HCO3 were absorbed at equal rates. 4. Final pCO2 values observed in NaCl and Na2SO4 solutions were greater than those observed in plasma while the pCO2 of the Na acetate solution after perfusion was reduced to values below plasma concentrations. 5. Results are consistent with the hypothesis that hydration of CO2 in the lumen solution or mucosal cell provides a continuous source of H ions for absorption of the more permeable undissociated acid. The evidence also suggests an additional source of H ions may be provided by a Na‐H exchange process located in one of the limiting cell membranes.
Protein deprivation: its effects on fever and plasma iron during bacterial infection in rabbits.
Authors: Hoffman‐Goetz L , Kluger M J
Published: December 2014

1. The effects of chronic dietary protein deprivation on fever and host plasma iron reduction in bacterially infected rabbits (Oryctolagus cuniculus) were investigated. 2. Injection with Pasteurella multocida, a Gram‐negative bacterium pathogenic to rabbits, led to an attenuated 24 hr fever in the protein‐deprived rabbits (0.26 degrees C) compared with the 24 hr fever in the control rabbits (1.43 degrees C). 3. Plasma iron concentration remained relatively high in the protein‐deprived rabbits as measured 24 hr after injection with bacteria. Total iron binding capacity did not change in the protein‐deprived rabbits as measured 24 hr after injection with bacteria. 4. Inoculation of the rabbits with endogenous pyrogen from donor rabbits resulted in fever and reduction in plasma iron concentration that was of equal magnitude in the protein‐deprived and control rabbits. 5. There were no differences in the concentration of total circulating leukocytes or in the differential count between the protein‐deprived and control rabbits before and 24 hr after injection with bacteria. 6. These data support the hypothesis that chronic protein deprivation in rabbits results in a diminished synthesis or release, or both, of endogenous pyrogen from circulating leukocytic phagocytes, resulting in an attenuated fever and a relative hyperferremia during infection.
Estimation of the density of sodium entry sites in frog skin epithelium from the uptake of [3H]benzamil.
Authors: Aceves J , Cuthbert A W , Edwardson J M
Published: December 2014

1. The inhibition of short circuit current in frog skin by benzamil (N‐benzyl‐amidino‐3,5‐diamino‐6‐chloropyrazine carboxamide) was investigated. When skins were bathed on both sides by Ringer solution (pH 7.6) the affinity was 5 x 10(7) M‐1. When the sodium concentration was reduced to 1.1 mM and the pH adjusted to 6.5 the affinity increased to 8.5 x 10(8) M‐1. 2. A method is described for measuring uptake of [3H]benzamil into the mucosal (outer) surface of pieces of isolated epithelium, 0.95 cm2 in area, under open circuit conditions. 3. The relation of [3H]benzamil uptake at the mucosal surface to its concentration was measured in solutions containing 1.1 mM‐sodium and adjusted to pH 6.5. Uptake could be resolved into a linear component (10.2 f‐mole nM‐1) and a saturable component (21.5 f‐mole cm‐2) with a half saturating concentration of 1 nM. 4. In the presence of amiloride (1 microM) or unlabelled benzamil (1 microM) uptake was linear with concentration, and was, respectively, 9.2 f‐mole nM‐1 and 8.8 f‐mole nM‐1. When the pH was reduced to 3.5 uptake was again linear but reduced to 3.3 f‐mole nM‐1. 5. The identity of the saturable component of [3H]benzamil uptake to sodium entry sites is discussed. The results suggest a sodium entry site density of around 130 micron‐2 of mucosal surface.
Membrane potential, chloride exchange, and chloride conductance in Ehrlich mouse ascites tumour cells.
Authors: Hoffmann E K , Simonsen L O , Sjøholm C
Published: December 2014

1. The steady‐state tracer exchange flux of chloride was measured at 10‐150 mM external chloride concentration, substituting either lactate or sucrose for chloride. The chloride flux saturates in both cases with a K 1/2 about 50 and 15 mM, respectively. 2. The inhibitory effect of other monovalent anions on the chloride transport was investigated by measuring the 36Cl‐ efflux into media where either bromide, nitrate, or thiocyanate had been substituted for part of the chloride. The sequence of increasing affinity for the chloride transport system was found to be: Br‐ less than Cl‐ less than SCN‐ = NO3‐. 3. The chloride steady‐state exchange flux in the presence of nitrate can be described by Michaelis‐Menten kinetics with nitrate as a competitive inhibitor of the chloride flux. 4. The apparent activation energy (EA) was determined to be 67 +/‐ 6.2 kJ/mole, and was constant between 7 and 38 degrees C. 5. The membrane potential (Vm) was measured as a function of the concentration of external K+, substituting K+ for Na+. The transference number of K+ (tK) was estimated from the slope of Vm vs. log10 (K+)e, and tCl and tNa were calculated, neglecting current carried by ions other than Cl‐, K+, and Na+. The diffusional net flux of K+ was calculated from the steady‐state exchange flux of 42K+, assuming the flux ratio equation to be valid. From this value the K+ conductance and the Na+ and Cl‐ conductances were calculated. The experiments showed that GCl, GNa, and GK are all about 14 muS/cm2. 6. The net (conductive) chloride permeability derived from the chloride conductance was 4 x 10(‐8) cm/sec compared with the apparent permeability of 6 x 10(‐7) cm/sec as calculated from the chloride tracer exchange flux. These data suggest that about 95% of the chloride transport is mediated by an electrically silent exchange diffusion. 7. Comparable effects of phloretin (0.25 mM) on the net (conductive) permeability and the apparent permeability to chloride (about 80% inhibition) may indicate that the chloride exchange and conductance pathways are not completely separate and distinct modes of transport, but may involve common elements. The reduced chloride permeability in the presence of phloretin is estimated to be two orders of magnitude larger than the ground permeability of the cell membrane.
Calcium and cyclic nucleotide interaction in secretion of amylase from rat pancreas in vitro.
Authors: Singh M
Published: December 2014

1. Interaction of Ca2+ and cyclic nucleotides in stimulus‐secretion coupling in rat pancreas in vitro was studied utilizing the divalent cation inophore A23187. phosphodiesterase inhibitors, cyclic nucleotides and cholera toxin. 2. Amylase secretion was increased by the ionophore in the presence of extracellular Ca2+ in a dose‐dependent fashion. Activation of CCK‐PZ receptors simultaneously with induction of amylase secretion by A23187 did not alter amylase secretion whereas theophylline or caffeine had effects additive to A23187. Dibutyryl cyclic AMP potentiated the effect of ionophore whereas dibutyryl cyclic GMP had no effect on basal or ionophore‐induced amylase secretion. Cholera toxin by itself did not effect amylase secretion whereas it potentiated the effect of ionophore. 3. A23187 increased bidirectional fluxes of 45Ca and increased efflux of 45Ca in a fashion similar to CCK‐PZ. Theophylline did not alter basal efflux of 45Ca. Dibutyryl cyclic AMP increased the basal efflux of 45Ca whereas, cholera toxin, dibutyryl cyclic GMP and sodium butyrate had no effect. 4. Theophylline increased basal cyclic AMP levels with a peak effect observed at 5 min. Combination of theophylline and ionophore did not lead to an increase in levels of cyclic AMP greater than that observed with theophylline alone. Cholera toxin increased cyclic AMP levels at 30 and 60 min of incubation. 5. Ionophore and CCK‐PZ increased tissue cyclic GMP levels significantly greater than that obtained with theophylline alone. This effect was dependent on extracellular Ca2+. The effect of ionophore on tissue levels of cyclic GMP could be dissociated from its effect on 45Ca efflux and amylase secretion. 6. It is concluded from these studies that Ca2+ plays a predominant role in regulating amylase secretion with interactions occurring between Ca2+ and cyclic AMP and Ca2+ and cyclic GMP. It appears that by themselves cyclic AMP and cyclic GMP do not play a significant role in regulating enzyme secretion.
Activation and inhibition of calcium‐dependent histamine secretion by ATP ions applied to rat mast cells.
Authors: Cockcroft S , Gomperts B D
Published: December 2014

1. The concentration dependence on ATP of mast cell histamine secretion in the presence of various concentrations of Mg2+ and Ca2+ confirms that the agonist form of ATP is the free form of ATP (ATP(free) not bound to divalent cations, i.e. ATP4‐. It induces 50% activation at about 1.2 microM, maximal secretion at about 2.7 microM and 50% self‐inhibition at about 4.4 microM. 2. The divalent cations Mg2+ and Ca2+ were used to buffer ATP(tree) in the range 1‐8 microM in the presence of much higher concentrations of ATP(total). In addition to its effect as a buffer for ATP, Ca2+ is required for secretion. 3. With ATP(free) at 1 microM, the time‐course of histamine secretion is characterized by a delay of about 10 min before secretion commences. With increasing concentration of ATP(free) the delay becomes shorter (less than 5 min with ATP(free) at 2 microM). 4. Secretion commences promptly on addition of Ca2+ to cells which have been pretreated with low concentrations of ATP(free) (less than 2 microM). This observation suggests that the delay normally observed represents the time taken for Ca2+ sensitivity to develop (i.e. probably the time taken for Ca2+ channels to open). 5. Late addition of Ca2+ to cells pretreated with higher concentrations of ATP(free) (greater than 2 microM) results in a reduced amount of histamine secretion compared with that which normally occurs. This reduction (which increases with time of exposure to ATP) and the self‐inhibition due to higher concentrations of ATP(free) may be two facets of a common inhibitory mechanism. 6. These results are discussed in the light of other experiments which show that mast cells treated with ATP(free) at self‐inhibitory concentrations become permeable to phosphorylated metabolites and nucleotides.