bluuebunny/crossref_metadata_2025 huggingface dataset:
Follicle‐stimulating hormone induces hyperpolarization of immature rat Sertoli cells in monolayer culture.
Authors: Joffre M , Roche A
Published: December 2014

1. The effect of FSH on the membrane potential of Sertoli cells has been investigated by intracellular microelectrode recording from monolayer cultures of cells, isolated from immature rat testes by enzymatic treatment. 2. In standard Earle's solution, the membrane potential of unstimulated cells in a 3‐day‐old monolayer was ‐21.6 +/‐ 0.2 mV (n = 300). The recorded potentials were unchanged on varying the culture period from 3 to 7 days or by removal of chloride or calcium from the media. However, they were decreased in a low‐sodium or potassium‐rich medium. 3. Ovine FSH caused hyperpolarization of the cell in a dose‐dependent manner. Maximal values were obtained with concentrations ranging between 2.9 and 5.9 micrograms/ml (‐37.0 +/‐ 0.2 mV; n = 310). Dibutyryl cyclic AMP (1 mM) produced a similar effect to FSH. Under similar conditions human chorionic gonadotrophin (hCG) had no effect on the membrane potential. 4. The FSH‐induced hyperpolarization was unchanged by chloride or bicarbonate replacement. It was decreased by low‐sodium media (9 mM) (‐29.6 +/‐ 0.3 mV; n = 110), by removal of calcium (‐32.4 +/‐ 0.6 mV; n = 128) and by an increase in the potassium concentration of the bathing medium. A tenfold increase in potassium concentration depolarized the cell by 29.5 mV against 16 mV for unstimulated cells. 5. FSH‐induced hyperpolarization was decreased by application of ouabain (10(‐4) M), quinidine (1.4 x 10(‐4) M) and cobalt (10(‐3) M) (respectively: ‐28.7 +/‐ 0.3 mV, n = 124; ‐26.6 +/‐ 0.3 mV, n = 52 and ‐24.8 +/‐ 0.3 mV, n = 68) but was unchanged by amiloride (10(‐4) M) and TTX (3 x 10(‐6) M). None of these drugs modified the membrane potential of unstimulated cells. 6. All these results suggest that FSH stimulation of Sertoli cells in monolayer culture involves the modification of their membrane permeabilities.
Excitatory amino acids in synaptic excitation of rat striatal neurones in vitro.
Authors: Cherubini E , Herrling P L , Lanfumey L , Stanzione P
Published: December 2014

1. Intracellular recordings were made from rat striatal neurones in vitro. The cells had resting membrane potentials greater than ‐60 mV and action potentials greater than 70 mV with spike overshoot of 10‐30 mV. 2. In the presence of bicuculline intrastriatal stimulation evoked an excitatory postsynaptic potential (EPSP). The relationship between EPSP amplitude and membrane potential was not linear. The EPSP decreased in amplitude and duration for values of membrane potential more negative than ‐80 mV and increased in amplitude and duration for values of membrane potential more positive than ‐50 mV. 3. The mean reversal potential for the EPSP recorded with electrodes filled with potassium methyl‐sulphate was ‐9.2 +/‐ 1.7 mV (mean +/‐ S.E.M.) in presence of bicuculline (30 microM). A similar reversal potential was obtained with CsCl‐filled electrodes. 4. The endogenous broad‐spectrum excitatory amino acid antagonist, kynurenic acid (100‐500 microM), reduced the EPSP in a dose‐dependent way, maximally by 80% at 500 microM, but a residual depolarization remained even at high antagonist concentrations. This effect was associated sometimes with a membrane depolarization and an increase in input resistance. 5. In normal artificial cerebro‐spinal fluid solution and at resting membrane potential the specific N‐methyl‐D‐aspartate (NMDA) antagonist, (D,L)‐2‐amino‐7‐phosphonoheptanoic acid (([D,L)‐AP7), did not affect the EPSP amplitude. However, this antagonist partially reduced the EPSP amplitude when the membrane was depolarized beyond ‐50 mV by intracellular current injection. 6. The nicotinic cholinergic antagonist mecamylamine (10 microM) caused a partial (24 +/‐ 3%) reduction of EPSP amplitude at resting potential in normal medium. However, in the cells where a reduction of EPSP amplitude was observed it was always accompanied by membrane depolarization (7.1 +/‐ 2.1 mV). (+)‐Tubocurarine and hexamethonium were without effect at 10 microM. 7. When Mg2+ was removed from the bathing solution, the EPSP increased in amplitude (89 +/‐ 9.5%) and duration. In Mg2+‐free medium at resting membrane potential (D,L)‐AP7 (30 microM) partially reduced EPSP amplitudes (59 +/‐ 2.5%). 8. It is proposed that a major component of the EPSP evoked by intrastriatal stimulation is mediated by excitatory amino acids. At resting membrane potential and in normal medium only non‐NMDA receptors seem to contribute to the synaptic depolarization, but at depolarized potentials and in Mg2+‐free medium an NMDA receptor‐mediated component of the EPSP can be demonstrated.
Co‐ordinated variations in chloride‐dependent potassium transport and cell water in normal human erythrocytes.
Authors: Stewart G W
Published: December 2014

1.The capacity of the loop‐diuretic‐sensitive Na+‐K+‐Cl‐ system in normal human erythrocytes shows tenfold interindividual variation between different donors, although the transport rate is constant from month to month for any one donor. 2. The present work shows that this variation in Na+‐K+‐Cl‐ transport is inversely correlated with a low‐capacity loop‐diuretic‐insensitive K+ transport, which is chloride dependent and is stimulated by cell swelling in hypotonic media. 3. These variations in K+ transport from donor to donor are related to cell water. Those donors who show high loop‐diuretic‐sensitive Na+‐K+‐Cl‐ co‐transport have lower cell water and vice versa.
Potassium secretion by rat distal colon during acute potassium loading: effect of sodium, potassium intake and aldosterone.
Authors: Edmonds C J , Willis C L
Published: December 2014

1. Potassium secretion by the distal colon before and during intravenous infusion of a potassium load was measured in vivo in groups of rats treated in various ways: A, normal control; B, adrenalectomized; C, sodium depleted; D, on potassium‐rich diet for 7 days; E, after 72 h aldosterone (1 microgram/h); F, after 72 h aldosterone (10 micrograms/h). 2. Potassium infusion produced no increase of secretion in the adrenalectomized rats but in all the other groups it increased by 2‐ to 3‐fold. Secretion during infusion correlated well with the basal (pre‐infusion) rate and in groups C and D reached 140 +/‐ 15 and 173 +/‐ 17 nmol min‐1 cm‐1 respectively compared with 28 +/‐ 6 nmol min‐1 cm‐1 in the controls (A). The passive paracellular pathway for potassium was unaffected by the infusion. Amiloride (100 mumol/l) did not significantly affect potassium secretion rate either before or during the acute potassium infusion. The potassium channel blocker, tetraethylammonium chloride, reduced both basal and the secretion rate during infusion. 3. Transepithelial potential difference (PD), active sodium absorption and sodium fluxes were similar in normal controls and rats fed the potassium‐rich diet. However, the PD was partially amiloride sensitive in the latter group although amiloride insensitive in the normal group. In sodium‐depleted rats, the PD was elevated and totally amiloride insensitive. 4. In both aldosterone‐treated groups (E and F), basal potassium secretion rate was high and similar, and during potassium infusion rose 3‐fold to 114 +/‐ 24 (E) and 105 +/‐ 5 (F) nmol min‐1 cm‐1. However, the PD was not elevated significantly in group E and was only partially amiloride sensitive, whereas in those infused at the higher rate (F) the PD was increased and was totally amiloride sensitive. 5. The high potassium secretion rates developed by this epithelium in sodium‐restricted and potassium‐enriched dietary states appear to depend on the presence of an amiloride‐insensitive transcellular potassium pathway which is induced at a lower level of aldosterone stimulation than is the amiloride‐sensitive transcellular sodium pathway.
Role of the human fusimotor system in a motor adaptation task.
Authors: Al‐Falahe N A , Vallbo A B
Published: December 2014

1. Single‐unit activity was recorded with the microneurographic technique from the radial nerve of attending human subjects. During active finger movements, impulses in spindle afferents from the extensor digitorum muscle were analysed along with joint movements, size of imposed load and EMG activity of the receptor‐bearing muscle. 2. In a simple motor adaptation task the subjects were requested to perform ramp‐and‐hold movements of prescribed amplitudes and velocities at a single metacarpo‐phalangeal joint. A test run consisted of a series of movement cycles when the flexor muscle was continuously loaded with a constant torque, immediately followed by cycles when this load was abruptly decreased during the flexion movement, producing a fast stretch of the receptor‐bearing muscle. The subjects' task was to strive for movements of constant velocity and particularly to minimize the effect of the disturbance. In order to allow prediction on the basis of immediately preceding cycles, the disturbance was always injected at the same angular position in a number of successive cycles. 3. Motor adaptation was manifested as a successive decrease of the perturbation amplitude, usually associated with the development of a continuous and growing EMG activity in the parent muscle and a growing reflex response of long latency (60 ms). Short‐latency reflexes were not seen. 4. The main mechanism accounting for the improved performance was a co‐contraction of the agonist‐antagonist muscle pair during voluntary movements, producing an increased muscular stiffness. The reflex did not contribute to the motor adaptation because it was not fast enough to curtail the perturbation. 5. The development and the growth of the reflex were not due to a growing fusimotor drive during adaptation, because spindle discharge actually decreased when the reflex increased. The size of spindle response was related to the amplitude of perturbation rather than to the amplitude of the reflex. These findings suggest that reflex modifications were due to central excitability changes which paralleled the muscle contraction. 6. Spindle firing rate during active movements was generally higher in disturbed cycles compared to undisturbed cycles, indicating a higher fusimotor drive. Since muscle contraction was present mainly in the former, this finding may simply represent a case of fusimotor activation along with skeletomotor activation. No indication of an independence between the two was found. 7. The findings lend no support for the view that the size of the stretch reflex in a behavioural task is adjusted by selective changes of the fusimotor drive.
Gastroduodenal motor activity associated with gastric emptying rate in sheep.
Authors: Malbert C H , Ruckebusch Y
Published: December 2014

1. Gastric emptying rate was calculated from dye dilution and was measured as the net flow over periods of 5 days through an electromagnetic probe inserted into a T‐cannula, 5 cm beyond the pylorus in conscious hay‐fed sheep. The net aboral flow was related to the motor activity of the antrum and duodenal bulb which was recorded via chronically fixed strain‐gauge transducers. Nichrome wire electrodes were also implanted in order to quantify the electrical activity of the musculature associated with the abomasal outflow in sheep sustained on a liquid diet infused at fixed rates. 2. The abomasal outflow occurred as gushes of 2.1‐9.2 ml associated with antroduodenal contractions during 90‐95% of the recording time. In the sheep eating 0.7 kg/day hay, the daily outflow of chyme was 5.1 l which increased to 7.5 l of less viscous chyme when the sheep was fed 1 kg/day lucerne hay. During gastric infusion of 3.9 and 7.9 l of the liquid diet, the outflow was 5.7 and 8.3 l/day respectively of low‐viscosity chyme propelled as gushes of 5.9‐6.9 ml during 95% of the recording time. 3. Increasing the viscosity of the liquid diet with guar‐gum caused a reduction in both antroduodenal motility and flow. Dilution of the liquid diet with saline doubled the flow as a result of an increase in the amplitude of the antral contractions. Circadian variations in outflow were also related to concomitant variations in antral motility. 4. It is concluded that the minute‐to‐minute flow rate of chyme through the pylorus could be satisfactorily measured at the duodenal bulb level and related to the motor activity of the antrum and duodenum. The rate of abomasal outflow depended primarily upon the strength of antral contractions, while the viscosity of the chyme also appeared capable of exerting a major influence on the outflow rate.
Short‐ and long‐latency muscarinic inhibition of noradrenaline release from rabbit atria induced by vagal stimulation.
Authors: Habermeier‐Muth A , Muscholl E
Published: December 2014

1. The influence of the time interval between vagal and sympathetic nerve stimuli on the magnitude of muscarinic inhibition of noradrenaline release was studied in the isolated perfused rabbit atria preparation. The transmitter stores were labelled with [14C]choline and [3H]noradrenaline. 2. The right cardiac postganglionic sympathetic nerves were stimulated at 3 Hz for 3 min three times at intervals of 10 min. The [3H]noradrenaline outflow evoked by the second stimulation equalled the averaged means of the log values of amine outflows evoked by the first and third stimulations. 3. During the second sympathetic stimulation the right vagus nerve was stimulated (3 Hz, 3 min) in such a way that the impulses preceded the sympathetic stimuli by a fixed time interval varying within the range 0.3‐283 ms. Outflow of [3H]noradrenaline was then compared with the individual ‘expected value’ calculated from the first and the third nerve stimulations. 4. [3H]Noradrenaline outflow was significantly decreased when the sympathetic impulses were delayed for between 3 and 10 ms or between 200 and 283 ms with respect to the vagus impulses. No significant inhibition of [3H]noradrenaline outflow occurred with delay times between 0.3 and 1.7 or 30 and 167 ms. Acetylcholine release was unaffected by varying the impulse delay time. 5. Atropine (1‐300 nM) decreased and eventually abolished vagally mediated inhibition of [3H]noradrenaline outflow at both the 3 and 233 ms impulse delay periods and the evoked outflow of [14C]choline and [14C]acetylcholine was then approximately doubled. No enhancement of [3H]noradrenaline outflow was observed at an intermediate impulse delay time (100 ms) in the presence of atropine. 6. In the presence of (+)‐tubocurarine (10 microM) [3H]noradrenaline outflow was unaffected by vagal stimulation at either the short or the long impulse delay time whereas that of [14C]choline and [14C]acetylcholine dropped to 3.4% (short) and 4.6% (long) of the control values. 7. Allowing for estimated conduction times in the vagal and sympathetic nerve pathways, the initial peak of muscarinic inhibition of noradrenaline release corresponds with excitation of the terminal cholinergic fibres occurring 20 ms before their adrenergic counterparts. A 'silent period’ follows and then a second phase of muscarinic presynaptic inhibition occurs, peaking 250 ms after excitation of the cholinergic nerve terminals and levelling off completely within 100 ms. 8. It is concluded that both inhibitory peak responses are caused by a single volley of acetylcholine that affects two separate populations of muscarinic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Effect of training on maximal oxygen uptake and aerobic capacity of locomotory muscles in tufted ducks, Aythya fuligula.
Authors: Butler P J , Turner D L
Published: December 2014

1. The effects of artificial swim training on maximal oxygen consumption and heart rate, as well as on the capillarity and oxidative capacity of locomotory muscles, have been studied in the tufted duck, Aythya fuligula. 2. The artificial training programme resulted in a 27% increase in maximal oxygen consumption, mainly as a result of an increase in muscle capillarity (20% increase in capillary/fibre ratio). In addition, activity of an oxidative enzyme, citrate synthase, increased (by 42%) and there was a significant transformation of fibre types in the lateral gastrocnemius muscle. 3. Altering the duration and nature of the training stimulus, for example flying and diving, can bring about different degrees of muscular adaptation, particularly in oxidative capacity.
Step‐related discharges of Purkinje cells in the paravermal cortex of the cerebellar anterior lobe in the cat.
Authors: Edgley S A , Lidierth M
Published: December 2014

1. Extracellular recordings were made of the simple spike discharges of Purkinje cells in the lateral part of the paravermal cortex of lobule V in the cerebellum of awake cats. The cells were located within the c2 and c3 zones of Oscarsson (1979). 2. The peripheral receptive fields in which light mechanical stimuli could evoke simple spikes were examined in 252 Purkinje cells. Ninety‐two per cent were activated by stimulation of the ipsilateral forelimb and 52% of 113 tested cells also discharged simple spikes in response to stimulation of the contralateral forelimb. The receptive fields were concentrated on the distal parts of the limbs: 67% of the 139 cells which were examined in most detail responded to stimulation of the paw or wrist of the ipsilateral forelimb. 3. In 135 of the Purkinje cells, the discharges were recorded during locomotion. Simple spikes were discharged at a mean rate of 54.3 +/‐ 27.8 impulses/s (S.D., n = 135) during steady walking on a belt moving at 0.5‐0.7 m/s. The discharges of each cell were rhythmically modulated in time with the movements of stepping and although the timings of the discharges were highly variable between cells, activity in the population was greatest at the times of transition between the stance and swing phases in the ipsilateral forelimb and least during mid‐stance. 4. As a population Purkinje cells with simple spike receptive fields on the distal parts of the forelimb(s) exhibited two activity maxima. These occurred during early stance and during the transition from stance to swing in the ipsilateral forelimb. Cells with receptive fields on the proximal parts of the limb achieved an activity maximum during late swing, and their average discharge rate fell at the time of onset of the swing phase in the ipsilateral forelimb instead of rising as was the case for the distal group. 5. The present results are compared with those from cells located more medially in the paravermal cortex. It is shown that medially located cells tend to discharge earlier in stance (or in late flexion) than laterally located cells with similar receptive fields.
Evidence for interaction between the contributions to ventilation from the central and peripheral chemoreceptors in man.
Authors: Robbins P A
Published: December 2014

1. The question of whether there is any interaction between the peripheral and central chemoreceptor contributions to ventilation in man has been addressed. 2. Subjects were exposed to an end‐tidal PCO2 of ca. 10 Torr above resting for 8 min at an end‐tidal PO2 of 100 Torr. The end‐tidal PCO2 was then reduced to near eucapnia. This provided a period of time when the PCO2 at the peripheral chemoreceptors would be near eucapnia, but would still be raised at the central chemoreceptors. 3. Against the background above, the effect of an hypoxic end‐tidal step from a PO2 of 100 Torr to a PO2 of 50 Torr was studied, and compared with the effect of the same step when both sets of chemoreceptors were near eucapnia. 4. Three subjects were studied, each contributing twelve sets of data to each of the three protocols required for the comparisons. 5. In two of the three subjects, the ventilatory response to hypoxia was augmented when central PCO2 was high. 6. The results support the idea that there is an interaction between the central and peripheral chemoreceptors in man. The consequences of this and other possible interpretations of the results are discussed.
Effects of potassium, oxygen and carbon dioxide on the steady‐state discharge of cat carotid body chemoreceptors.
Authors: Burger R E , Estavillo J A , Kumar P , Nye P C , Paterson D J
Published: December 2014

1. We have studied the effects of intravenous infusions of 0.1 mmol/min KCl (raising arterial potassium from ca. 3.2 to 6.0 mM) on the steady‐state responses of carotid body chemoreceptors to end‐tidal PCO2 and PO2 in the pentobarbitone‐anaesthetized cat. 2. The excitatory effect of these KCl infusions was enhanced by hypoxia and reduced or abolished by hyperoxia. 3. Hypercapnia did not enhance, and usually reduced, excitation by KCl. 4. When similar control discharge frequencies were established by hypoxia or by hypercapnia, a KCl infusion excited the hypoxic discharge by about twice as much as it did the hypercapnic discharge. 5. These observations are not inconsistent with the idea that the mechanism underlying hypoxic excitation of arterial chemoreceptors is one that controls extracellular potassium concentration near the afferent nerve ending. 6. Insofar as potassium‐induced excitation of chemoreceptor discharge is abruptly reduced by hyperoxia it behaves like Asmussen and Nielsen's postulated ‘anaerobic work substance’ and it may therefore contribute to the increased importance of the arterial chemoreflex reported in exercise.
On the mechanism of a pH‐induced rise in membrane potassium conductance in hamster eggs.
Authors: Georgiou P , House C R , McNiven A I , Yoshida S
Published: December 2014

1. The effect of external pH (pHo) on the membrane potential and resistance of unfertilized zona‐free hamster eggs was investigated by intracellular recording techniques. 2. A hyperpolarization of the hamster egg membrane was induced by raising the extracellular pH above 8.0. This hyperpolarization was accompanied by a rise in membrane conductance and was reversible by washing the egg. 3. The estimated value of the reversal potential of the hyperpolarizing response to a solution with pHo 9.5 was about ‐85 mV. The membrane potential changed linearly with log [K+]o with a slope of 43 +/‐ 2 mV (mean +/‐ S.D.; n = 4) for a 10‐fold change in [K+]o, while it was unaltered by the removal of Cl‐ from the solution. 4. The amplitude of the pHo‐induced hyperpolarization decreased substantially as [Ca2+]o was lowered from 20 to 1 mM. Sr2+ could substitute for Ca2+ in sustaining the response to high pHo, whereas Ba2+ or Mg2+ could not. 5. Injection of the Ca2+ chelator EGTA into the egg prevented the pHo‐induced hyperpolarization suggesting that a rise in [Ca2+]i is required. 6. The rate of rise of Ca2+ action potentials was reversibly enhanced by raising pHo. However, influx through the voltage‐gated Ca2+ channels is not involved in initiation and maintenance of the pHo‐induced response, as responses were not affected by the Ca2+ channel blocker La3+. 7. The duration of the hyperpolarization evoked by intracellular Ca2+ injection in eggs bathed in normal solution or Na+‐free solution was greatly prolonged by raising pHo. 8. It is suggested that a rise in external pH produces an increase in [Ca2+]i, activating a Ca2+‐mediated K+ conductance which hyperpolarizes the egg membrane. 9. It is concluded that both a Na+‐Ca2+ exchange system and a Ca2+ pump are responsible for Ca2+ extrusion and that inhibition of the Ca2+ pump by high pHo is the chief mechanism underlying the pH‐induced hyperpolarization in hamster eggs. Although the Na+‐Ca2+ exchange system is facilitated at high pHo, the effect of this facilitation of efflux is outweighed by the inhibition of the Ca2+ pump.
Effect of alpha‐latrotoxin on the frog neuromuscular junction at low temperature.
Authors: Ceccarelli B , Hurlbut W P , Iezzi N
Published: December 2014

1. alpha‐Latrotoxin (alpha‐LTx) was applied to frog cutaneous pectoris muscles bathed at 1‐3 degrees C in either Ringer solution, Ca2+‐free Ringer solution with 1 mM‐EGTA and 4 mM‐Mg2+ or Ringer solution plus 4 mM‐Mg2+, and its effects on miniature end‐plate potential (MEPP) frequency, nerve terminal ultrastructure and uptake of horseradish peroxidase (HRP) were studied. 2. Large concentrations (2 micrograms/ml) of alpha‐LTx increased MEPP rates to levels above 100/s at all junctions, but the time course of the increases depended upon the divalent cation content of the bathing solution. However, similar numbers of MEPPs (0.3‐0.7 x 10(6] were recorded at all junctions during 2 h of secretion. 3. Nerve terminals exposed to alpha‐LTx for 2 h lost 60‐75% of their synaptic vesicles and were swollen; their presynaptic membranes were deeply infolded and they often contained many large vesicular structures. Terminals in Ringer solution retained the largest number of synaptic vesicles; terminals in Ringer solution plus Mg2+ swelled the least and contained the largest number of coated vesicles. The average number of synaptic vesicles lost was approximately equal to the average number of MEPPs recorded. 4. Few vesicles became loaded with HRP when this extracellular tracer was present in the bathing solution and the muscles were fixed near the peak of secretion. 5. When the terminals were warmed to 20 degrees C, those in the Ca2+‐free solution with Mg2+ secreted additional quanta and lost almost all their residual vesicles; those in Ringer solution without Mg2+ secreted few additional quanta and retained most of their residual vesicles. 6. These results suggest that recycling was blocked at these terminals and that for each quantum secreted a vesicle became permanently incorporated into the axolemma.
Lung C‐fibre receptor activation and defensive reflexes in anaesthetized cats.
Authors: Tatar M , Webber S E , Widdicombe J G
Published: December 2014

1. With pentobarbitone‐anaesthetized cats we have elicited cough reflexes from the tracheobronchial tree and the larynx, and the aspiration and sneeze reflexes from the nasopharynx and the nose respectively. The reflexes were induced by mechanical stimulation of the mucosa, before and during activation of pulmonary C‐fibre receptors by intravenous injections of capsaicin or phenylbiguanide. 2. During the 20‐30 s apnoea due to C‐fibre stimulation, the cough reflex from both sites and the sneeze reflex were completely abolished, whereas the aspiration reflex response was approximately halved. Reflex contractions of genioglossus muscle still occurred at this time, but were far weaker than in the control state. 3. During the rapid shallow breathing that immediately followed apnoea due to C‐fibre receptor stimulation, the defensive reflexes recovered: the aspiration and sneeze reflexes fully and the cough reflexes to about half of the control response. 4. Acute hypotension due to haemorrhage, of a size considerably greater than that due to stimulation of the pulmonary C‐fibre receptors, caused no significant inhibition of the cough reflex from the tracheobronchial tree. 5. We conclude that the pulmonary C‐fibre reflex powerfully inhibits airway defensive reflexes, and that its activation is unlikely to contribute positively to coughing induced by aerosols of capsaicin and similar agents.
Instability in human forearm movements studied with feed‐back‐controlled muscle vibration.
Authors: Prochazka A , Trend P S
Published: December 2014

1. Frequency‐modulated vibration was applied to the elbow flexor and extensor tendons to produce reflex movements of the forearm in normal subjects. The modulating (command) signal caused equal and opposite deviations from the 40 Hz carrier frequency so that when flexor vibratory frequency increased, extensor frequency decreased, and vice versa. 2. It is argued that the movements resulted largely from the reflex action of muscle spindle primary afferents whose firing frequency had been ‘taken over’ and modulated by the vibration. 3. Bode plots relating forearm movements to command signal (modulating) frequency showed the transfer function of the Ia afferent‐CNS‐muscle‐load system to have a low‐pass filter characteristic. The phase lag of movement on command increased progressively with command signal frequency, exceeding 180 deg at 3‐4 Hz. 4. The transduced forearm movements were fed back to provide the command signal to the vibrators (and thus indirectly to the spindle afferents) via a filter mimicking the dynamic responsiveness of muscle spindle primary endings. Our aim was to ‘break into’ the reflex arc, and re‐route it so that we could artificially vary the gain without significantly altering the dynamics of the pathway. 5. Nearly all subjects developed forearm oscillations (tremor) when the gain exceeded a threshold value. Subjects varied widely in their threshold, though for a given subject the threshold remained fairly constant from day to day. The results suggest that reflexly active individuals may not have a large safety margin with respect to forearm instability. 6. The frequency range of the oscillations observed in seven subjects was 3‐8 Hz. The frequencies depended upon the level of flexor‐extensor co‐contraction, and increased from 3 to 5 Hz at 10% co‐contraction to 5‐8 Hz at 100% co‐contraction. An analysis of the mechanical impedance of the arm provided estimates of tremor frequencies consistent with these results. 7. These unexpectedly low tremor frequencies led us to propose that it may be erroneous to expect stretch reflexes to contribute to forearm tremor in the range 8‐12 Hz (e.g. physiological and ‘enhanced’ physiological tremors). Rather, their contributions should be sought in the range 3‐8 Hz (e.g. pathological tremors such as those of Parkinson's and cerebellar disease).
Instability in human forearm movements studied with feed‐back‐controlled electrical stimulation of muscles.
Authors: Jacks A , Prochazka A , Trend P S
Published: December 2014

1. Amplitude‐modulated electrical stimulation was applied to the elbow flexors and extensors to produce movements of the forearm in normal subjects. The parameters of the modulating (command) signal were set in isometric trials so as to produce equal and opposite background torques, and equal and supportive torque modulations. 2. Bode plots relating forearm movement to command signal (modulating) frequency showed the muscle‐load to have a low‐pass characteristic similar to that previously described in the cat, and a slightly larger bandwidth than described previously in man. 3. The transduced forearm signals were fed back to provide the command signal to the stimulators via a filter which mimicked the transfer function of muscle spindle primary endings. In effect this replaced the neural part of the reflex arc with an accessible model, but left the muscle‐load effector intact. 4. All six subjects developed forearm oscillations (tremor) when the loop gain exceeded a threshold value. The mean tremor frequency at onset was 4.4 Hz, which was similar to that of the equivalent vibration‐evoked tremor (previous paper, Prochazka & Trend, 1988). 5. With the linear spindle model, oscillations tended to grow rapidly in amplitude, and the stimuli became painful. The inclusion of a logarithmic limiting element resulted in stable oscillations, without significant alterations in frequency. This allowed us to study the effect on tremor of including analog delays in the loop, mimicking those associated with peripheral nerve transmission and central reflexes. In one subject, loop delays of 0, 20, 40 and 100 ms resulted in tremor at 4.0, 3.6, 3.0 and 2.1 Hz respectively, as quantified by spectral analysis. 6. By considering separately the phase contributions of the different elements of the reflex arc, including delays, it became clear that muscle‐load properties were important in setting the upper limit of tremor frequencies which could conceivably be supported by reflexes. 7. The results support the conclusion of the related vibration study (Prochazka & Trend, 1988), that for moderate levels of background co‐contraction, the contribution of stretch reflexes to tremor at the elbow should be sought in the 3‐5 Hz range. Exaggerated long‐latency reflexes would be expected to reduce these baseline frequencies by 1 or 2 Hz.
A thermal surface phenomenon in the rabbit lung: possible basis for the conversion of heat into work.
Authors: Hills B A
Published: December 2014

1. Surfactant and fluid expressed from rabbit lungs has been used to form films on a simple Maxwell frame having a ratio of area‐to‐thermal capacity comparable to that existing in vivo. 2. When the area was increased by 2:1, the temperature fell by 5.6 degrees C and returned to 37 degrees C upon contraction as recorded by an infra‐red thermometer with no thermal capacity. 3. The experiment was repeated upon thin lung sections when the temperature fall was 2.4 degrees C and was again reversed upon contraction. 4. When surfactant was removed from the surface of those sections, the temperature changed in the opposite direction, indicating that surfactant was responsible for the changes described above. 5. This surface energy phenomenon is discussed in relation to the common assumption that the lung operates under isothermal conditions when it may explain some of the discrepancies between studies of lung mechanics over different time scales. 6. Since the results are compatible with the inversion of hysteresis loops for surface tension versus the area of surfactant monolayers cycled to steady state in previous studies, it is speculated that heat, e.g. waste metabolic heat, might be the energy source for this surface ‘engine’ if, indeed, it is contributing to the work available for breathing.
Transport of L‐phenylalanine and related amino acids at the ovine blood‐brain barrier.
Authors: Brenton D P , Gardiner R M
Published: December 2014

1. Unidirectional influx of amino acids at the blood‐brain barrier was studied in the lamb and sheep under barbiturate anaesthesia using the single‐pass indicator‐dilution technique. 2. In the lamb, influx of both L‐phenylalanine (14 +/‐ 1 nmol g‐1 min‐1) and L‐alanine (12 +/‐ 2 nmol g‐1 min‐1) was greater than in the sheep: L‐phenylalanine influx, 9 +/‐ 1 nmol g‐1 min‐1; L‐alanine influx, 5 +/‐ 1 nmol g‐1 min‐1 (P less than 0.01). This difference reflected higher blood concentrations of these amino acids in the younger animal. 3. The kinetic parameters of transport for L‐phenylalanine were determined in the lamb and sheep from measurements of influx over a range of blood concentrations. The concentration dependence of L‐phenylalanine influx was best described by a model with a saturable and non‐saturable component. Maximum influx (Jmax) was higher and apparent transport constant (km, app) lower in the lamb. Values obtained (mean +/‐ S.E.M.) were: lamb, Jmax, 138 +/‐ 6 nmol g‐1 min; km, app, 0.85 +/‐ 0.10 mmol l‐1; sheep, Jmax, 107 +/‐ 7 nmol g‐1 min‐1; km, app, 2.25 +/‐ 0.25 mmol l‐1. 4. L‐Phenylalanine inhibited influx of L‐leucine, L‐tyrosine, L‐valine and L‐glutamine but not L‐arginine and L‐lysine. Its influx was inhibited by L‐histidine, L‐valine and L‐leucine, but not by L‐glutamine or L‐alanine. In the lamb, L‐phenylalanine inhibited L‐histidine influx with an apparent inhibitor constant (kh) of 139 mumol l‐1, and a maximum inhibition of 92%. In the sheep, L‐phenylalanine inhibited L‐methionine influx with an apparent kh of 33 mumol l‐1 and a maximum inhibition of 82%. 5. Fractional extraction of phenylalanine and alanine was stereospecific with preference for the L‐enantiomer. In the lamb, fractional extraction values (mean +/‐ S.E.M.) were: L‐phenylalanine, 0.58 +/‐ 0.03; D‐phenylalanine, 0.20 +/‐ 0.02; L‐alanine, 0.16 +/‐ 0.03; D‐alanine, 0.05 +/‐ 0.02. Self‐inhibition of extraction was evident for L‐phenylalanine and L‐alanine in both lamb and sheep.
Burst‐patterned stimulation promotes nicotinic transmission in isolated perfused rat sympathetic ganglia.
Authors: Birks R I , Isacoff E Y
Published: December 2014

1. Intracellular recordings of small nicotinic excitatory postsynaptic potentials (EPSPs) were made from rostral cells in superior cervical ganglia (SCG) of rats during and after test stimulation of small preganglionic fibre bundles, while perfusing the isolated ganglia via their arterial vasculature. Perfusion, in contrast to superfusion of desheathed ganglia, (a) produced much more rapid and complete equilibration of drugs and ions at synaptic sites, (b) greatly reduced depression of EPSPs during high‐frequency stimulation, and (c) largely prevented slowing of conduction, presumably by minimizing accumulation of K+ in the intercellular spaces surrounding these sites. 2. Preganglionic inputs were found to fall into two major groups: those in which the EPSP amplitude during 200 pulse trains was facilitated and others in which it was depressed as stimulation frequency in the train was increased from 2 to 20 Hz or from 0.2 to 1.25 Hz. Both the facilitation and the depression were presynaptic, since they occurred without changes in miniature EPSP amplitude. 3. The maximum maintained facilitation was reached at 5‐10 Hz with a value 1.26 times the 1.0 Hz control. This was associated with an increase in the binomial parameter n. While long 20 Hz trains produced a similar facilitation to an early plateau, and an increase in n, EPSP amplitude declined as the train progressed. This was associated with a decrease in the binomial parameter p. 4. Unlike the 20 Hz trains, stimulation with 0.5 s long, 20 Hz bursts given every 8 s produced a marked potentiation in facilitating units and this was maintained for as long as the stimulation was continued (3‐11 min). Burst‐patterned potentiation was 1.66 times larger than the facilitation evoked by tonic stimulation at the same average frequency (1.25 Hz), and more than twice that achieved with long, 200 pulse trains. The potentiation was associated with increases in both n and p in the first EPSP of the burst and mainly with an increase in n at the end of the burst. Potentiation persisted unchanged for about 30 s following the return to control 0.2 Hz stimulation, before declining to control levels over the next 2‐3 min. Depressing units on average showed neither burst‐patterned potentiation nor post‐burst‐patterned potentiation. 5. All inputs tested in Locke solution in which Ca2+ was reduced to 0.5 mM with addition of 1.2 mM‐Mn2+ or 3.8 mM‐MgCl2 exhibited a pronounced facilitation within each burst but no extension of potentiation into ensuing bursts. Both burst‐patterned potentiation and the post‐burst‐patterned potentiation were abolished.(ABSTRACT TRUNCATED AT 400 WORDS)
Ion transfer characteristics of the calcium current in bull‐frog atrial myocytes.
Authors: Campbell D L , Giles W R , Shibata E F
Published: December 2014

1. Voltage clamp studies on single cells from bull‐frog atrium have been carried out to study the ion transfer characteristics of the calcium current, ICa. In agreement with the preliminary results of Hume & Giles (1983), a TTX‐resistant, 'second transient inward current’ was recorded consistently. Its average peak size at 0 mV in 2.5 mM [Ca2+]o Ringer solution was approximately ‐200 pA, and it was blocked by Cd2+ and La3+ but not by tetrodotoxin (TTX, 3 x 10(‐6) M). 2. The peak size of this current increases by approximately 4 times when [Ca2+]o is raised from 1.25 to 7.5 mM, indicating that Ca2+ is a major charge carrier. 3. A well‐defined reversal potential, Erev, for ICa can be recorded in normal Ringer solution and also when Ba2+ or Sr2+ serve as the charge carriers. When [Ca2+]o is changed the shifts in Erev follow the predictions of a Nernstian Ca2+ electrode. However, all Erev values are well below those predicted from the thermodynamic Nernstian ECa values (see Campbell, Giles, Hume, Noble & Shibata, 1988a). 4. The Ca2+ current exhibits voltage‐dependent inactivation, whether the direction of net current flow is inward or outward; however, the rate of inactivation is affected by the species of cation carrying the current. Inactivation is reduced substantially in Ba2+ Ringer solution. 5. Magnesium (5 mM) is not a significant carrier or blocker of ICa in normal [Ca2+]o Ringer solution; however, 5 mM [Mg2+]o can block the current carried by either Sr2+ or Ba2+. In the absence of Mg2+, equimolar substitutions of Sr2+ or Ba2+ for Ca2+ result in larger currents than those carried by Ca2+ in the normal Ringer solution. 6. Sodium appears not to be a significant charge carrier in the presence of normal [Ca2+]o. However, after free [Ca2+]o has been reduced to extremely low levels (less than 10(‐6) M) Na+ can carry a significant fraction of ‘ICa’. Thus, it appears that the high selectivity of ICa for Ca2+ ions depends upon the presence of Ca2+. 7. ‘Slow tails’ are frequently recorded after repolarizing clamp steps back to the holding potential. These 'slow tails’ are prominent in normal [Na+]o, [Ca2+]o and [Sr2+]o Ringer solution; however, they are markedly reduced in [Ba2+]o, in Na+‐free and Ca2+‐free Ringer solutions. Experimental and theoretical work suggests these slow tails may be generated by an electrogenic Na+‐Ca2+ exchanger (see Campbell, Giles, Robinson & Shibata, 1988b).(ABSTRACT TRUNCATED AT 400 WORDS)
Voltage dependence of sodium‐calcium exchange current in guinea‐pig atrial myocytes determined by means of an inhibitor.
Authors: Lipp P , Pott L
Published: December 2014

1. Spontaneous transient inward currents (Iti) caused by cyclic release of Ca2+ ions from the sarcoplasmic reticulum were studied in cultured atrial myocytes from hearts of adult guinea‐pigs. K+ channel currents were blocked by replacing K+ on both sides of the membrane by Cs+; the L‐type Ca2+ current was inhibited by D600. 2. The voltage dependence of peak Iti and the background current displayed distinct outward‐going rectification. The I‐V curves for both currents approach each other at strongly positive membrane potentials but do not intersect. 3. 3'‐4'Dichlorobenzamil (DCB) causes a concentration‐dependent inhibition of peak Iti and a shift of the holding current (at ‐60 to ‐40 mV) in the inward direction. Inhibition of Iti is half‐maximal at a concentration of 30 microM. 4. DCB reduces the outward‐rectifying component of both peak Iti and the background current. The I‐V curves of the control and DCB‐inhibited currents intersect at ca. +10 mV (peak Iti) and negative to ‐75 mV (background current), suggesting the reversal potential of the DCB‐inhibited current to be shifted by ca. 85 mV in the positive direction if Cai2+ rises following Ca2+ release. 5. The voltage dependence of the DCB‐inhibited currents is highly compatible with the concept of Na+‐Ca2+ exchange being the charge‐carrying mechanism of the outward‐rectifying background current. Ca2+ release from the SR alters the I‐V curve of this current according to the shift of the thermodynamic driving force.
Occlusion of cobalt ions within the phosphorylated forms of the Na+‐K+ pump isolated from dog kidney.
Authors: Richards D E
Published: December 2014

1. Co2+ ions can replace Mg2+ ions as co‐factors for the Na+‐K+ pump purified from dog kidney outer medulla. The evidence comes from (a) measurement of ouabain‐sensitive Na+,K+‐ATPase activity, (b) measurement of ATP‐dependent 22Na uptake catalysed by the Na+‐K+ pump reconstituted into phospholipid vesicles, (c) measurements of phosphorylation of the Na+‐K+ pump either in the presence of ATP and sodium ions or in the presence of inorganic phosphate, and (d) measurement of occlusion of rubidium ions through the route involving phosphorylation and dephosphorylation. 2. Purified Na+,K+‐ATPase incubated in the presence of ATP, Na+ ions and [60Co]CoCl2, can carry occluded Co2+ ions through a cation‐exchange resin. The enzyme fails to occlude the divalent cation (i) if ADP replaces ATP, (ii) if the enzyme is heat‐inactivated, (iii) if the enzyme is inactivated by treatment with fluorescein isothiocyanate, (iv) if K+ replaces Na+ in the incubation medium, (v) if Na+ ions are omitted, and (vi) if Mg2+ ions are added in a sufficient concentration. 3. The amount of occluded Co2+ ions is unaffected by pre‐treatment of the Na+,K+‐ATPase with oligomycin, which stabilizes the phosphoenzyme in the E1P form. 4. The addition of K+ ions to Na+,K+‐ATPase that has been phosphorylated in the presence of ATP, Na+ ions and [60Co]CoCl2 releases the occluded Co2+ ions from the enzyme. Under those conditions, K+ ions accelerate the hydrolysis of the phosphoenzyme, and become occluded in the resulting dephosphoenzyme. 5. The stoichiometry of Co2+ ion occlusion is about one occluded Co2+ ion per phosphorylation site. 6. These results support the hypothesis that, in the normal working of the Na+‐K+ pump, Mg2+ ions are trapped in the phosphorylated forms of the enzyme, and are released by a K+‐dependent dephosphorylation reaction.
p‐chloro‐mercuriphenyl sulphonate activates a quinine‐sensitive potassium conductance in frog lens.
Authors: Duncan G , Emptage N J , Hightower K R
Published: December 2014

1. The effects of the sulphydryl‐complexing reagent p‐chloro‐mercuriphenyl sulphonate (pCMPS) on membrane voltage and electrical conductance were studied on the isolated frog lens. 2. At low concentrations (0.1‐50 microM) pCMPS induced a rapid and graded hyperpolarization of the lens membrane potential which saturated at ‐97 mV. 3. The lens conductance also showed a graded increase, but the initial changes were apparent only at concentrations above 1 microM. 4. Decreasing the external potassium concentration from 2.5 to 0.5 mM had little effect on the membrane potential in the absence of pCMPS, but increased the voltage from ‐97 to ‐110 mV when pCMPS was present. 5. Quinine (300 microM) had no effect when added in control solution, but depolarized the membrane potential and decreased the conductance when added to a pCMPS‐treated preparation. 6. These data suggest that pCMPS activates voltage‐sensitive potassium channels that are quiescent at the frog resting potential in control solution. 7. At pCMPS concentrations greater than or equal to 100 microM, the initial hyperpolarization is followed by a marked but slow depolarization of the membrane potential and a further increase in lens conductance. These data suggest that non‐specific cation channels are activated in this case. 8. Cysteine (5 mM) added to a pCMPS‐treated lens leads to a rapid recovery of membrane potential and conductance to near their resting values whether the lens had previously been exposed to low or high concentrations of pCMPS. 9. All of these changes in lens voltage and conductance occurred without apparent alteration in the lens internal sulphydryl content.
Gastric relaxation and vasoactive intestinal peptide output in response to reflex vagal stimulation in the dog.
Authors: Ito S , Ohga A , Ohta T
Published: December 2014

1. Gastric relaxation, vasodilatation and vasoactive intestinal peptide (VIP) output from the stomach in response to stimulation of the central end of the cut vagus nerve were studied in anaesthetized dogs. 2. Central vagal stimulation (10 Hz, 40 V, 0.5 ms) normally produced a non‐adrenergic, non‐cholinergic (NANC) gastric relaxation via a vago‐vagal reflex. It also caused an increase followed by a decrease in gastric blood flow. 3. The increase in blood flow was attributable to a NANC gastric vasodilatation via a vago‐vagal reflex and the subsequent reduction in blood flow was decreased by splanchinicotomy. All these gastric and vascular responses were abolished by hexamethonium. 4. The gastric relaxation and vasodilatation induced by the vago‐vagal reflex had similar stimulation frequency‐response and pulse duration‐response relations. 5. Central vagal stimulation caused an increase in gastric venous VIP output which was abolished by vagotomy or hexamethonium but unaffected by splanchnicotomy. 6. VIP injected into the gastric artery mimicked the gastric relaxant and vasodilator responses to the vago‐vagal reflex. 7. We conclude that the intramural NANC inhibitory nerves activated by the vago‐vagal reflex release VIP which causes both gastric relaxation and vasodilatation.