bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional relationships between the hippocampus and the cerebellum: an electrophysiological study of the cat.
Authors: Newman P P , Reza H
Published: December 2014

1. Functional interrelationships between the hippocampus and the cerebellum have been investigated in the anaesthetized cat. Plots of the stimulating and recording sites as well as the latency range of the responses indicated the extent of ascending and descending lines of operation between these two structures. 2. Stimulation of the fastigial nucleus evoked the discharge of single hippocampal units on both sides of the brain. Early responses had a mean latency of 12 msec and late responses had a mean latency of 21 msec. Increasing the intensity of the stimulus had little effect on the patterns of discharge. 3. There was no topographical organization within the hippocampus. On the other hand, the activity evoked by a cutaneous stimulus was shown to be greatly depressed by a preceding cerebellar stimulus, particularly at intervals 30‐‐40 msec between the two stimuli. 4. Cerebellar responses evoked by stimulating the hippocampus were found mainly in lobule VI of the posterior lobe. Early and late responses were frequently recorded in the same trace, ipsilateral stimulation yielding the shortest latencies. Increasing the intensity of the stimulus increased the likelihood of there being a response and increased the number of spikes in each discharge. Hippocampal stimulation also had a profound influence on resting cerebellar discharges. 5. Symmetrical points in the two hippocampi were chosen for conditioning and testing sequences. The conditioning stimulus had a long‐lasting inhibitory effect on the test response followed by a slow recovery. 6. The location and extent of hippocampal influences on the cerebellum were determined by plotting the presence or absence of a response at each stimulated site. The results indicated the existence of bilateral descending projections containing fast and slow components in conformity with the known conduction properties of mossy fibre and climbing fibre inputs. 7. The physiological significance of interrelationship between the hippocampus and the cerebellum is discussed. It seems that there are many similarities as well as fundamental differences in the cerebellar control of movement under normal circumstances and in conditions of stress.
Effects of central administation of probenecid on fevers produced by leukocytic pyrogen and PGE2 in the rabbit.
Authors: Crawford I L , Kennedy J I , Lipton J M , Ojeda S R
Published: December 2014

1. Single intracerebroventricular (I.C.V.) injections of probenecid (PBCD, 0.125‐‐0.5 mg) enhanced and prolonged fever caused by I.V. administration of leukocytic pyrogen (LP) in rabbits resting in neutral (23 degrees C), cold (10 degrees C) and hot (30 degrees C) environments. Similar effects were produced by single I.C.V. injections of PBCD given before PGE2 (0.5 microgram) was injected I.C.V. in the three ambient temperatures. 2. Fever produced by IV. LP was also prolonged by infusion and by multiple injections of PBCD. 3. PBCD given I.P. (100 mg/kg) enhanced and prolonged fever caused by I.V. injection of Salmonella typhosa endotoxin. 4. Hyperthermia produced by I.C.V. PGE2 was not augmented by subsequent PBCD infusion. However, pre‐treatment with PBCD followed by PGE2 injection and PBCD infusion caused hyperthermia that was very high and prolonged, and, in some cases, lethal. 5. Acetaminophen (2 mg, I.C.V.) and indomethacin (10 mg/kg, I.V.) lowered body temperature when given during fever induced by LP and prolonged by PBCD infusion. 6. The concentration of PGE in cerebrospinal fluid (c.s.f.) samples taken from the third or lateral ventricles rose or stabilized during PBCD infusions made during LP fever. However, similar changes in PGE concentration also occurred during control infusions when body temperature was low. 7. We conclude that termination of the actions of both central endogenous pyrogen and centrally administered PGE2, and the subsequent reduction of fevers produced by them, require a PBCD‐sensitive facilitated transport system. The reduction of PBCD‐prolonged PL fevers by antipyretics which block PGE synthesis suggests that prolongation by PBCD of LP fever is not due to blockade of PGE transport in a subsequent step in fever mediation per se, but is due to inhibition of transport of LP itself, or of other mediators associated with it.
The effects of tenotomy upon the contraction characteristics of motor units in rabbit soleus muscle
Authors: Bagust J.
Published: December 2014

1. Isometric contractions of tenotomized rabbit solei have been compared with a group of unoperated control muscles. A large decrease in the tension developed by the tenotomized muscle was accompanied by a slight shortening of the twitch contraction time, and a larger, progressive, reduction in the time to half relaxation.

2. A comparison of motor units obtained from muscles which had been tenotomized for six weeks with those of the control muscles showed a large reduction in the range of contraction and half relaxation times of the units from the tenotomized muscles.

3. The mean motor unit tension (expressed as a percentage of the whole muscle tension) was similar for both those units from the control muscles and those from muscles which had been tenotomized for six weeks, indicating a uniform atrophy of motor units within the tenotomized muscles.

4. It was concluded that the change in the pattern of motor unit contraction times was not the result of a process of differential atrophy favouring the preservation of the faster contracting motor units.

5. A correlation between axon conduction velocity and both the speed of contraction and the size (tension) of the motor units was demonstrated in the control muscles. Following tenotomy the relationship between axon conduction velocity and motor unit tension was lost.
The response characteristics of an inhibitory binocular interaction in human vision.
Authors: Ruddock K H , Waterfield V A , Wigley E
Published: December 2014

1. The contrast threshold level for visual detection of a linear grating consisting of parallel light and dark bars is increased by adaptation to a high contrast grating of spatial characteristics similar to those of the test grating (e.g. Blakemore & Campbell, 1969). This so‐called contrast threshold elevation effect is significantly reduced if two adaptation gratings, with appropriate different spatial characteristics, are presented one to either eye (Ruddock & Wigley, 1976). We have studied the contrast threshold elevation effect obtained with a test and an adaptation grating presented to one eye and a second adaptation grating, referred to as the conditioning grating, presented to the other. 2. Preliminary data are presented for three subjects with normal stereoscopic vision. In each case, the contrast threshold elevation effect for a pair of spatially identical test and adaptation gratings is significantly reduced by a conditioning grating of spatial frequency in the range 1‐5 c/deg. 3. Reduction in the contrast elevation effect is observed whether the conditioning and adaptation gratings are of the same or of different wave‐lengths and the effect of the conditioning grating increases to a steady‐state level over a period of some 30 sec following onset of its presentation. 4. Measurements were made with a 5 deg diameter circular test grating presented at retinal locations up to 8 deg in the horizontal and vertical meridians from a foveal fixation point. It was found that in the horizontal meridian, the amplitude of the suppression effect associated with the conditioning grating falls as the displacement angle of the test field from the fixation point increases. For displacements in the vertical meridian, however, the amplitude of the suppression effect is virtually independent of the retinal location of the test field. 5. Under experimental conditions which yield suppression of the contrast threshold elevation effect for subjects with normal stereoscopic vision, no suppression was found for three subjects who possessed neither global nor fine stereoscopic vision. Results for a subject who possessed fine, but not global stereoscopy, did, however, show the suppression effect.
Disuse enhances synaptic efficacy in spinal mononeurones.
Authors: Gallego R , Kuno M , Núñez R , Snider W D
Published: December 2014

1. Monosynaptic excitatory post‐synaptic potentials (e.p.s.p.s) were recorded from triceps surae motoneurones in the cat following section or chronic conduction block of the medial gastrocnemius (m.g.) nerve with tetrodotoxin (TTX) or after daily stimulation of the sciatic nerve. 2. The mean maximum amplitudes of homonymous and heteronymous monosynaptic e.p.s.p.s evoked by stimulation of the mg. nerve were reduced significantly between 1 and 2 weeks after section of the muscle nerve. The mean amplitudes of monosynaptic e.p.s.p.s produced in the same motoneurones by afferent volleys from the intact synergists showed no significant alterations. 3. Reduction of the amplitude of monosynaptic e.p.s.p.s. evoked by the sectioned m.g. afferent volleys was not prevented by daily stimulation of the sciatic nerve. The chronic stimulation of the sciatic nerve did not increase the amplitude of monosynaptic e.p.s.p.s evoked by stimulation of the intact, lateral gastrocnemius (l.g.) or soleus nerve. 4. Chronic conduction block of the intact m.g. nerve with TTX cuffs for 2 weeks resulted in a significant increase in the homonymous e.p.s.p. amplitude. The amplitude of the heteronymous e.p.s.p.s evoked in the same m.g. motoneurones by stimulation of the intact l.g. or soleus nerve showed no significant changes. 5. It is concluded that decreased central synaptic transmission following section of the peripheral nerve is not due to elimination of impulse activity (disuse) of the sensory input and that prolonged disuse of the sensory fibres causes an increase, rather than a decrease, in central synaptic efficacy.
The heat produced by frog muscle in a series of contractions with shortening.
Authors: Irving M , Woledge R C , Yamada K
Published: December 2014

1. Heat production has been measured in muscles undergoing rapid shortening 1 sec after the start of stimulation in a 2 sec tetanus. In a series of three such tetani where the periods of shortening were separated by 5 sec the shortening heats in the second and third tetani were 111 (+/‐ 4)% and 116 (+/‐ 6)% respectively of that in the first tetanus (mean +/‐ S.E. of mean, nine experiments). 2. When a similar series was carried out after an interval of 3 min the shortening heat in the first tetanus of the second series was 127 (+/‐ 3)% of that in the first tetanus of the first series (mean +/‐ S.E. of mean, three experiments). 3. The results are not in agreement with those of Dickinson & Woledge (1974). The discrepancy is explained by an artifact which, with certain arrangements of the apparatus, affects the measurements of shortening heat in a series of contractions. We have measured this artifact by two independent methods; the shortening heat values quoted above have been corrected accordingly. 4. The increase in the shortening heat in repeated contractions is not a specific consequence of previous shortening; an increase of the same magnitude is observed following isometric tetani. 5. During the time when the muscle is shortening, the total rate of heat production, which is initially high, falls to a steady value. This value is not significantly different in the three tetani of the series.
Stimulation by cyclic GMP of sodium efflux in barnacle muscle fibres.
Authors: Bittar E E , Sharp D M
Published: December 2014

1. The ouabain‐insensitive Na efflux in barnacle muscle fibres is promptly stimulated by injection of cyclic GMP. The minimal effective injected concentration is found to be about 10(‐7) M. This effect of cyclic GMP could not be mimicked by injecting 5'‐GMP. 2. External application of ouabain (10(‐4) M) to fibres not pretreated with ouabain during the stimulatory response to cyclic GMP causes some inhibition of the Na efflux indicating that cyclic GMP does not cause appreciable inhibition of the Na:K pump. 3. The magnitude of the stimulatory response to injected cyclic GMP depends on the external Ca2+ concentration, as well as pHe but not on the Na+, K+ or Mg2+ concentration. It also depends on pHi, since acidification of HCO3‐containing ASW leads to a greater enhancement of the response to cyclic GMP than is observed with acidified HERPES‐ASW. 4. Stabilization of myoplasmic pCa by injecting 100 mM‐EGTA before or after cyclic GMP fails to alter the magnitude of the response to the nucleotide. Enrichment of the fibre with Mg2+ at the time of injection of cyclic GMP leads to a reduced response. No change in response, however, is seen when the internal free Mg concentration is suddenly reduced by injecting 0.05 M‐pyrophosphate with cyclic GMP. 5. Injection of cyclic GMP‐dependent protein kinase stimulatory modulator before cyclic GMP fails to enhance the response to the nucleotide. The same is true of the phosphodiesterase inhibitor protein. However pre‐injection of 10(‐2) M‐papaverine enhances the response to a subsequent injection of 10(‐3) M‐cyclic GMP. 6. Injection of pure protein kinase inhibitor (1.6 x 10(‐4) M) before 10(‐3) M‐cyclic GMP reduces the response to the nucleotide. 7. The argument is put forward that injected cyclic GMP stimulates the ouabain‐insensitive Na efflux mainly by activating cyclic AMP‐protein kinase rather than cyclic GMP‐proton kinase.
The electrogenic potential in rat C nerve fibres: some effects of lithium and thallium
Authors: Smith I. C. H.
Published: December 2014

1. Subsequent to bathing a desheathed vagus nerve in a K‐free medium Li (5‐50 m
M) generates a hyperpolarizing response in the same manner as does K except that Li is 23 times less potent than K. Preincubation with small concentrations of either Li or K inhibits a subsequent K response.

2. The Li response is less phasic than the K response. In the presence of a cardiac glycoside Li has no effect whereas K depolarizes the preparation. Thus Li is presumed to generate a relatively pure ouabain‐sensitive electrogenic response.

3. If a Li response is always terminated with 50 m
M‐Li, but various concentrations are used during the first half, the total response has a constant area despite the wide range of activation during the first half. This implies that the electrogenic pump ratio is constant over this range of activation.

4. Thallium (1 m
M) also generates a ouabain‐sensitive response, but even short exposures (5 min) produces a strong and lasting inhibition of subsequent potassium responses. On a slower time scale Tl also inhibits the electrogenic post‐tetanic hyperpolarization. After exposure to Tl a test action potential shows that the afterpotential is also decreased.

5. If action potentials are produced during an electrogenic response the hyperpolarizing afterpotential reverses polarity. It is supposed that this is due to a short‐circuiting of the electrogenic potential during this time.
Effect of intraventricular injection of transmitter substances and temperature on autonomic functions of conscious sheep.
Authors: Beal A M , Bligh J
Published: December 2014

1. Changes in cardiovascular and renal functions following injection of noradrenaline, 5‐hydroxytryptamine and carbachol into one lateral cerebral ventricle were investigated in conscious sheep at ambient air temperatures of 0 and 40 degrees C. The dose rates used were known to produce predictable changes in thermoregulation in sheep. 2. The changes in body temperature, respiratory frequency and shivering caused by the intracerebroventricular (I.C.V.) injections of noradrenaline, 5‐hydroxytryptamine and carbachol were as reported previously. 3. The cardiovascular and renal responses of the sheep at both high and low ambient temperatures were consistent for each transmitter indicating that these activities had no major dependence on the type of thermoregulatory response. 4. I.C.V. injection of noradrenaline increased heart rate and decreased pulse pressure but caused no change in mean arterial blood pressure (B.P.). Urine flow rate, sodium clearance, potassium clearance and osmolal clearance were decreased whereas solute‐free water reabsorption was unaltered. 5. I.C.V. injection of 5‐hydroxytryptamine caused no significant alterations in either cardiovascular or renal function. 6. I.C.V. injection of carbachol increased systolic and diastolic B.P., heart rate and haematocrit. Sodium, potassium and osmolal clearances were increased after administration of carbachol. 7. The changes in renal function after noradrenaline and carbachol injection could be explained by the concurrent changes in cardiovascular function.
Effect of adenosine triphosphate and some derivatives on cerebral blood flow and metabolism.
Authors: Forrester T , Harper A M , MacKenzie E T , Thomson E M
Published: December 2014

1. Responses of cerebral blood vessels to peri‐ and intravascular doses of ATP (adenosine triphosphate) and some derivatives were studied in cat and baboon. 2. Perivascular application of ATP to cat pial arterioles gave a threshold dilatory effect at a concentration of 10(‐11) M. This figure is comparable to the amount of ATP calculated to be released from electrically stimulated brain slices. 3. It is concluded that adenine nucleotides have a major role to play in the local control of cerebral blood flow. 4. Intracarotid injection of ATP showed a calculated threshold effect at 4 x 10(8) M in the cat and 4 x 10(‐9) M in the baboon. 5. The threshold response of the vasculature to intracarotid adenosine lay between 4 x 10(‐7) M and 4 x 10(‐6) M in the baboon. Little effect was produced with AMP, pyrophosphate and inorganic phosphate. 6. Intracarotid ATP increased the oxygen consumption of the baboon brain parenchyma. This effect was attributed in part to an elevation of the cellular cyclic AMP levels. 7. Osmotic disruption of the blood‐brain barrier in baboon did not affect the vasodilatory or metabolic effect of intracarotid ATP. 8. It is postulated that circulating purine compounds mediate a form of metabolic communication inthe body. Also, release of purine compounds from active local nerves might influence cerebral blood flow.
Isopotentiality and an optical determination of series resistance in Limulus ventral photoreceptors.
Authors: Brown J E , Harary H H , Waggoner A
Published: December 2014

1. Photoreceptor somas in the ventral rudimentary eye of Limulus polyphemus were impaled with three micropipettes. Two micropipettes were connected in a voltage‐clamp circuit and the cells were stimulated by brief flashes. The third micropipette did not measure any significant deviations from the ‘clamped’ voltage during responses to the flashes, in several geometries of electrode placement, even for very bright flashes. Therefore using the described techniques there is no evidence for spatial non‐uniformity of intracellular voltage in the soma of these photoreceptors. 2. A voltage‐sensitive dye was used to monitor light‐induced changes in membrane voltage while intracellular voltage was held clamped by a feed‐back circuit. With a known series resistance connected between the bath and ground the dye recorded a light‐induced change in membrane voltage. When there was no added series resistance, the light‐induced change was smaller and often undetectable. From these data the naturally occurring series resistance was calculated to be less than or equal to 30 k omega. 3. From these measurements, as well as from calculations for a model spherical cell, we conclude that membrane potential can be controlled to within 2 mV using our micropipette ‘point clamp’ methods, for all but the brightest stimuli.
A comparison of duodenal osmolality and energy content as controlling factors of gastric emptying in the calf.
Authors: Bell F R , Webber D E
Published: December 2014

1. The relative importance of energy content and osmolality of the duodenal chyme in the feed‐back control of gastric emptying was investigated in the milk‐fed calf fitted with gastric (abomasal) and duodenal re‐entrant cannulae. 2. Duodenal infusion of isosmolal solutions, containing glucose, fructose or galactose, with a range of combustible energy content (0‐‐1.46 MJ/l.) resulted in the same high rate of emptying of test meals from the stomach (abomasum). Abomasal emptying was, therefore, not affected by the energy content of the duodenal infusate. 3. Gastric secretion of acid and pepsinogen, and the volume of gastric secretions produced were also unaffected by the energy content of isosomolal duodenal infusates. 4. The results of the study show that the combustible energy content of the intestinal chyme is not a direct determinant of gastric function and that total osmolality of the lumenal contents is the only parameter influencing duodenal receptors under the conditions of our experiments.
Voltage clamp analysis of acetylcholine receptor desensitization in isolated mollusc neurones.
Authors: Bregestovksi P D , Bukharaeva E A , Iljin V I
Published: December 2014

1. Desensitization produced by acetylcholine (ACh) in completely isolated Limnaea stagnalis neurones with chloride‐selective membrane channels was studied using a voltage‐clamp technique. 2. A difference in the time course of the neurone responses to ACh, depending on whether the measured parameter was voltage or current, was observed and explained on the basis of an equivalent electric scheme of the neurone soma membrane. 3. Desensitization onset was shown not to depend on membrane potential in the range of ‐30 to ‐120 mV. 4. Variation of external Ca2+, Na+ and Cl‐ concentrations over a wide range had little influence on the onset of desensitization and recovery from it. 5. An obvious difference is shown to exist between features of desensitization in mollusc neurone and frog muscle end‐plate ACh receptors.
Rod and cone signals in the horizontal cells of the tiger salamander retina.
Authors: Hanani M , Vallerga S
Published: December 2014

1. Intracellular recordings of horizontal cell responses to monochromatic lights of various wave‐lengths and intensities were made in the retina of the larval tiger salamander in order to determine the contributions of rod and cone activities to horizontal cell responses. 2. Under conditions of extensive dark adaptation, and with dim light stimulation, the horizontal cell responses reflected mainly rod activity. In the light‐adapted state or at high light intensities the cone contribution was dominant. 3. Bright adapting flashes selectively suppressed the rod component of horizontal cell responses. 4. Intracellular recordings from rods and cones showed that interactions between the two receptor types are very small and cannot account for the large rod‐‐cone mixed input observed in horizontal cells. It is concluded that this input is mediated by direct connexions between receptors and horizontal cells.
Segregation of leech neurones by the effect of sparteine on action potential duration.
Authors: Kleinhaus A L
Published: December 2014

1. Sparteine (SPT) and 3‐ or 4‐aminopyridine, were applied to leech segmental ganglia and the electrophysiological responses of the Retzius (R) and sensory neurones responding to pressure (P), touch (T), and noxious (N) stimuli analysed. 2. SPT 0.05‐0.5 mM when presented via the bath to the whole ganglion prolonged the action potentials of these neurones to characteristically different degrees; the cells were clearly segregated in the order R greater than N greater than P greater than T at 0.5 mM, regardless of exposure time. 3. The plateau of the prolonged action potentials in the R and N cells was sustained by either Ca or Sr and was blocked by Mn, in normal or Na‐free Ringer. These responses were similar to those seen in the same cell types with TEA under the same condition. 4. The SPT prolongation of action potentials was favoured by alkalinization of the Ringer solution. This implies that the drug acted in its uncharged form. SPT was ineffective when applied by pressure into the somata of these four neurones. This may be because SPT was charged at the intracellular pH or because it acted at some external membrane site. 5. The aminopyridines when applied in the bath had no effect on the repolarization of these four neurones. 6. These results suggest that TEA and SPT probably act on repolarization by similar mechanisms. The parameter of membrane function principally affected is probably a K current which contributes to repolarization to different degrees in the four cells and which may be activated by Ca.
Increased sensitivity of ADH bio‐assay in rats by change in diet.
Authors: Kappagoda C T , Linden R J , Pashley M
Published: December 2014

1. Water‐loaded rats anaesthetized with ethanol were used for the detection of antidiuretic hormone (ADH). 2. Litter‐mates were divided into groups and placed on different diets during the fourth week of life directly after weaning, and maintained on their respective diets for approximately 1 month and their sensitivity to vasopressin was determined. 3. The rats maintained on a diet of only vegetable or vegetable plus casein supplement showed a greater sensitivity to exogenous vasopressin than rats maintained on a standard laboratory diet (pellets). 4. It is proposed that the quantitative relationship between ADH and urine flow is dependent upon the previous history of water consumption.
Further evidence for a physiological role for hypothalamic dopamine in thermoregulation in the rat
Authors: Cox B. , Lee T. F.
Published: December 2014

1. Intrahypothalamic injection of either dopamine or noradrenaline in a dose volume of 1 μl. caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 ± 1 °C.

2. The hypothermic effects of dopamine (10 μg) and noradrenaline (2 μg) were selectively antagonized by systemic pre‐treatment with pimozide (0·5 mg/kg) and phentolamine (1 mg/kg) respectively.

3. The location of the dopamine‐ and noradrenaline‐sensitive sites were defined more accurately by reducing the dose volume to 0·5 μl. and making injections at different points throughout the preoptic region.

4. Both the dopamine‐ and the noradrenaline‐sensitive sites were located within the preoptic region, but they did not have identical locations being separated by a distance of 0·4 mm.

5. Unilateral intrahypothalamic injection of 6‐hydroxydopamine (10 μg in 2 μl.) caused a significant fall in core temperature, which was antagonized by systemic injection of either pimozide or phentolamine.

6. Rats placed 0·65 m below a 250 W infra‐red lamp responded to the imposed heat load by vasodilation of tail skin blood vessels, indicated by an increased tail skin temperature.

7. Rats were tested two weeks after bilateral intrahypothalamic injection of 6‐hydroxydopamine (10 μg in 2 μl.). This pre‐treatment significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. Rats receiving similar 6‐hydroxydopamine pre‐treatment following injection of desipramine (25 mg/kg,
I.P.) were also less able to cope with a heat load.

8. Three serial sections (0·8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the dopamine‐sensitive site.

9. Pre‐treatment with 6‐hydroxydopamine reduced both the dopamine and the noradrenaline concentration in the dopamine‐sensitive site. Pre‐treatment with desipramine and 6‐hydroxydopamine selectively reduced dopamine.

10. These results indicate that there are receptors for both dopamine and noradrenaline in the preoptic anterior hypothalamus, which mediate a fall in core temperature in rats, but the evidence suggests that it is endogenous dopamine which is more likely to play an important physiological role.
Mechanisms of action potential propagation failure at sites of axon branching in the crayfish.
Authors: Smith D O
Published: December 2014

1. The phenomena leading to action potential conduction block during repetitive stimulation of the excitor axon of the opener muscle in the crayfish walking leg were studied. 2. Action potentials, recorded extracellularly with micro‐electrodes, failed to propagate past sites of axonal bifurcation following at least 3000 impulses; reduction of the rate or brief cessation of stimulation resulted in restored conduction. 3. Failure occurred initially at branch points located most peripherally and then more centrally as stimulation continued; this centripetal progression of the site of block resulted in a stepwise reduction of the number of synaptic terminals from which transmitter was released. 4. Prior to conduction failure, the conduction velocity and the sodium inward current of the action potentials decreased. 5. Local application of hyperpolarizing current or of physiological saline with low [K+] in the vicinity of a block can restore propagation; thus depolarization of the membrane most probably causes failure. 6. Soaking the preparation for as long as 2 hr in the metabolic inhibitor 2,4‐dinitrophenol had no effect on the number of stimulus impulses before initial conduction block; however, the time required for recovery from the failure was prolonged. 7. The number of impulses prior to block was related directly to the temperature of the preparation; this had a Q10 calculated to be about 1 . 3. 8. It is suggested that during repetitive activity, the K+ gradient across the membrane is reduced, resulting in depolarization and eventually in conduction failure.
Light adaptation within the receptive field centre of rat retinal ganglion cells.
Authors: Cicerone C M , Green D G
Published: December 2014

1. Responses from axons of single retinal ganglion cells in the rat's optic tract were used to measure the pooling of adaptive signals within the cells' receptive field. Computer‐aided analyses of response measurements were used to evaluate sensitivity at a number of field locations. 2. A small adapting spot caused a localized decrease in sensitivity within the receptive field centre of ON‐ and OFF‐centre ganglion cells. 2. The functions describing response versus test luminance were similar in shape for all test and adaptation configurations. This assured that, using a fixed criterion response, sensitivity determinations could be made just as well in any receptive field location and under any of the experimental conditions. 4. A concentric surround, antagonistic to the receptive field centre, was readily apparent only under conditions of light adaptation. Experiments on the local effects of small adapting spots, conducted with selective surround adaptation, showed that the non‐uniform spread of adaptation within the receptive field centre was not linked to surround intrusion. 5. The possibility that the photopic mechanism intruded to contaminate these results was considered and rejected. 6. When a suprathreshold spot was alternated between two equally sensitive positions, the ganglion cell gave an approximately balanced response. An upset of this balance was produced by placing a small adapting spot at either position, thus demonstrating, in another way, the non‐uniform spread of adaptation within the receptive field centre. 7. It is concluded that significant pooling of adaptation effects occurs prior to the combination of influences which contribute to the centre response of a ganglion cell.
Voltage clamp of cat motoneurone somata: properties of the fast inward current.
Authors: Barrett J N , Crill W E
Published: December 2014

1. The soma membrane of cat spinal motoneurones was voltage clamped using separate intracellular voltage and current electrodes directed into the same motoneurone with a new guide system. 2. Antidromic stimulation of the motoneurone's axon or small depolarizing voltage clamp steps (10‐20 mV from the resting potential) evoked a small (30‐80 nA) all‐or‐none action potential current, which was shown by occlusion experiments to originate from the initial segment of the axon. Except for this axonal current spike, there was no indication of active (voltage‐dependent) conductance changes in membrane regions not under good voltage clamp control. Calculations based on motoneuronal geometry, and electrophysiological recordings from spinal cord neurones in tissue culture, indicate that the proximal portions of dendritic membranes were also under good voltage clamp control. 3. Clamp depolarizations greater than 20 mV activated a fast, transient inward current, which increased in a smoothly graded manner with depolarization between 20 and 40 mV from the resting potential, reaching a peak magnitude of up to 450 nA, and then decreased smoothly for larger depolarizations. Extrapolation of the current‐voltage relationship for this current indicated a reversal potential about 80‐116 mV positive to the resting potential. 4. This transient inward current is blocked by tetrodotoxin. After a depolarizing voltage clamp step the conductance system controlling this current first activates with fast, non‐linear kinetics, and then inactivates with first‐order kinetics. These properties are similar to those of the Na conductance system in squid and frog axons. 5. Conditioning‐testing experiments showed that the time constant of inactivation ranges from 1.0‐1.3 msec at potentials slightly negative to the resting potential to 0.1‐0.3 msec for depolarizations 60 mV from the resting potential. The degree of steady‐state inactivation also varied with membrane potential, ranging from total inactivation at depolarizations greater than 30 mV from the resting potential, to minimal inactivation at potentials more than 10 mV negative to the resting potential.
Interactions between the regulation of the intracellular pH and sodium activity of sheep cardiac Purkinje fibres.
Authors: Deitmer J W , Ellis D
Published: December 2014

1. We have investigated the influence of the H+ and Na+ gradients across the cell membrane on the regulation of the intracellular pH (pHi) and of the intracellular Na activity (aNai) in sheep heart Purkinje fibres, using Na+‐ and pH‐sensitive microelectrodes. 2. In oxygenated, nominally bicarbonate‐free solutions (buffered with HEPES) the steady‐state pHi changed linearly with the extracellular pH (pHo) by 0.23 pH units/pHo unit change over the pHo range of 5.4‐8.4. The H+ equilibrium potential changed by about 47 mV/pHo unit change. 3. Both the steady‐state pHi and the pHi recovery from acidification induced by lowering the pHo to 6.4 were affected only to a small extent by reducing the extracellular Na concentration [Na]o, to one half or to one tenth normal. 4. The steady‐state aNai decreased by 5 to 20% when the pHo was reduced to 6.4 and increased by 3 to 8% when the pHo was raised to 8.4. These changes in aNai were still present when the Na‐K pump had been inhibited by the cardioactive steroid strophanthidin (10(‐5) M). 5. Exposure to K‐free solutions caused an increase in aNai. Following addition of 6 mM‐K (to re‐activate the Na‐K pump) the rate of decrease of aNai was not affected by pHo changes from 6.4 to 8.4. 6. Inhibition of the Na+‐K+ pump by strophanthidin (10(‐5) M) caused aNai to rise rapidly within 2‐3 min. The pHi remained unchanged for the first 1‐30 min after the pump inhibition, but then decreased by several tenths of a pH unit. 7. Amiloride (10(‐3) M) caused a small decrease in a Nai and an intracellular acidification of up to 0.2 pH units. 8. Under conditions, where aNai was high due to inhibition of the Na‐K pump by strophanthidin, lowering the [Na]o to one tenth normal produced a very large intracellular acidification, while aNai decreased. Amiloride increased this intracellular acidification even more, while the decrease in aNai remained unaffected. 9. Application of NH4Cl (20 mM) produced a decrease of aNai and a rapid intracellular alkalinization, followed by a slower acidification. Upon removal of NH4Cl the pHi dropped by several tenths of a pH unit but rapidly recovered. During this pH recovery there was a small transient increase in aNai above the control level before returning to normal. 10. The pHi recovery after the removal of NH4Cl was slowed by lowering the [Na]o to one tenth normal, and it was greatly inhibited in the presence of amiloride. The transient overshoot of aNai after NH4Cl removal was suppressed by amiloride. 11. We conclude that under some conditions there appears to be an exchange of intracellular H+ for extracellular Na+ across the cell membrane and that this exchange can help regulate the intracellular pH.
Contributions of the lymphatic and microvascular systems to fluid absorption from the synovial cavity of the rabbit knee.
Authors: Levick J R
Published: December 2014

1. The trans‐synovial flow (Qs) of Ringer solution from the cavity of immobile knee (stifle) joints was determined in anaesthetized rabbits when intra‐articular hydrostatic pressure (PJ) was elevated in steps from 2 to 25 cm H2O. 2. It has been demonstrated previously (Levick, 1978) that slope DQs/dPJ shows an abrupt sixfold increase at a ‘breaking point’ (PB) around 9 . 5 cm H2O, rising from a mean of 0 . 49 microliter.min‐1 cm H2O‐1 (PJ less than PB) to 2 . 81 microliter.min‐1 cm H2O‐1 (PJ greater than PB). 3. Perforation of the synovial intima by an intra‐articular cannula increased dQs/dPJ below breaking pressure and thus largely abolished the breaking point phenomenon, indicating that the phenomenon might be simulated by a break‐down in synovial resistance to flow. 4. Ligation of the femoral lymph trunks draining the joint did not significantly alter the relationship between Qs and PJ. The slope dQs/dPJ was 0 . 60 +/‐ 0 . 17 microliter.min‐1 cm H2O‐1 (mean +/‐ S.E.) below a breaking pressure of 8 . 8‐‐10.5 cm H2O, and 2 . 90 +/‐ 0 . 64 microliter.min‐1 cm H2O‐1 above breaking pressure. Thus changes in synovial lymph flow did not explain the breaking point phenomenon. 5. Interruption of synovial blood flow by vascular clamps or by killing the animal reduced, but did not abolish fluid absorption; nor was the breaking point phenomenon abolished. Slope dQs/dPJ increased from 0 . 37 +/‐ 0 . 06 microliter.min‐1 cm H2O‐1 below breaking point (10 . 5 +/‐ 1 . 0 cm H2O) to between 1 . 82 and 0 . 96 +/‐ 0 . 15 microliter.min‐1 cm H2O‐1 above breaking pressure. Fluid accumulated in extra‐synovial interstitial spaces. 6. When the synovial intima was divested of its surrounding tissues, lymphatic and vascular supplies by extensive dissection, the denuded synovium still showed a marked increase in hydraulic conductivity at normal breaking pressures. The breaking point phenomenon was therefore not caused by changes in extra‐synovial interstitial pressure or compliance. 7. It is concluded that fluid absorption from the joint cavity occurs by two parallel pathways viz. the synovial capillary bed and the extra‐synovial interstitial spaces. A simple analysis of the system indicates that the breaking point phenomenon cannot be explained by an abrupt increase in synovial conductivity (cf. Edlund, 1949) but is explicable if synovial conductivity (and possibly interstitial conductivity) becomes a continuous function of PJ above breaking pressure. This hypothesis reconciles the non‐linear pressure‐flow relationship with Starling's hypothesis for fluid absorption from connective tissue spaces (1896).
Sodium channel permeation in squid axons. II: Non‐independence and current‐voltage relations.
Authors: Begenisich T B , Cahalan M D
Published: December 2014

1. The concentration and voltage dependence of current through the Na channels of squid giant axons was studied. The permeant cations Na, K and ammonium were used. 2. The Na channel current at a fixed voltage saturates as the internal permeant ion concentration is increased. The half‐saturation activities at 50 mV were found to be 623, 268, 161 mM for Na, NH4, and K, respectively. These Km values for Na and K appear to be voltage‐dependent. 3. Instantaneous current‐voltage relations were determined with two different internal Na concentrations and with Na outside and K inside. 4. A three‐barrier, two‐site ion permeation model previously used in describing Na channel reversal potentials is shown here to account for the Na channel currents as well.
A micropuncture investigation of electrolyte transport in the parotid glands of sodium‐replete and sodium‐depleted sheep.
Authors: Compton J S , Nelson J , Wright R D , Young J A
Published: December 2014

1. Parotid secretion has been studied by micropuncture in sodium‐replete and sodium‐deficient sheep. 2. The osmolality of unstimulated primary saliva was slightly higher than in plasma and fell following cholinergic nerve stimulation. In sodium‐depleted animals the osmolality of final saliva was hypotonic and exhibited flow dependency, where as in sodium‐replete animals it was always isotonic. 3. In sodium‐replete sheep, the primary fluid sodium concentration was about 120‐130 mmol l‐1 but in final saliva it was about 167 mmol l‐1 and showed little or no flow‐dependency. In sodium‐depleted sheep, the primary sodium concentration averaged only 82.2 mmol l‐1 and it was concluded that sodium‐depleted primary fluid contained some other unidentified solute that allowed it to remain approximately isotonic; in final saliva the unstimulated sodium concentration was about 40 mmol l‐1 and it rose with increasing flow rate to a maximum of 114.9 mmol l‐1. 4. The primary fluid potassium concentration in sodium‐replete animals did not differ significantly from that seen in sodium‐depleted animals and the values were uninfluenced by stimulation; the over‐all mean value was 11.2 mmol l‐1. In final saliva, in sodium‐replete sheep, the potassium concentrations averaged 7.8 mmol l‐1 but in sodium‐depleted sheep the concentrations were between 5 and 10 times greater than in primary fluid. 5. It was calculated from the equilibrium pH that the primary bicarbonate concentration would have been about 35 mmol l‐1. In final saliva, where bicarbonate was measured directly, the concentrations were much greater and increased with stimulation to about 115 mmol l‐1. 6. The primary fluid phosphate and chloride concentrations were the same in both sodium‐replete and sodium‐depleted animals and were unchanged by stimulation; the mean concentration of phosphate was 1.30 mmol l‐1 and of chloride, 53.0 mmol l‐1. In final saliva the phosphate concentrations were little changed but the chloride concentrations fell to an average value of 20.0 mmol l‐1. In final saliva it was found that the summed sodium and potassium concentrations exceeded the summed chloride, bicarbonate and phosphate (in mequiv l‐1) concentrations, on average by 13.9 mequiv l‐1, regardless of sodium status or flow rate. 7. The results indicate that secretion by the sheep parotid can be accounted for in terms of the standard two‐state model. Phosphate seems to enter the saliva only in the primary fluid and potassium and bicarbonate appear to enter at both primary and secondary sites; sodium and chloride enter at the primary level and can be reabsorbed in the ducts. Salt depletion causes the primary fluid concentrations of sodium and chloride to fall and the content of an unidentified solute to rise markedly while, at the ductal level, it causes normally quiescent sodium and potassium transport processes to become activated.
The kinetics of slow muscle acetylcholine‐operated channels in the garter snake.
Authors: Dionne V E
Published: December 2014

1. Slow muscle synaptic responses were modelled kinetically in an attempt to define the mechanism by which slow fibre acetylcholine‐operated channels differ from those in twitch fibres. 2. Three kinetically distinguishable states were necessary. 3. All applicable three‐state kinetic schemes were considered in an attempt to identify the simplest description of the data. Experimental tets eliminated several models. Two models were not tested because they contained an excessive number of adjustable parameters. 4. The data were not fitted by kinetic schemes which postulated (i) channels which opened with one as well as two bound agonist molecules, (ii) channels which became blocked after opening, or (iii) separate populations of synaptic and extrasynaptic channels. 5. The three‐state kinetic model of del Castillo & Katz (1957) accurately described all the data. This sequential model relates a closed channel state with no agonist bound to its receptors, an intermediate state (also closed) with agonist bound, and an open channel state. It is the same model which has been used to describe synaptic responses in twitch fibres. 6. The variation which allows this model to describe both twitch and slow fibre synaptic responses is the lifetime of the intermediate state. In twitch fibres the intermediate state lifetime is undetectably brief by electrophysiological methods. However, in slow fibres this lifetime appears to be 1‐2 msec, varying with voltage. 7. Three of the four transition rates in this three‐state kinetic scheme may be estimated by fitting the model to the data. These are the channel opening rate, the channel closing rate and the rate at which closed channels lose their bound agonist molecules. The latter two rates appear to depend exponentially on voltage. The channel opening rate was not detectably voltage‐sensitive.
An energy‐dependent, sodium‐independent component of active p‐aminohippurate transport in rabbit renal cortex.
Authors: Maxild J , Møller J V , Sheikh M I
Published: December 2014

1. The relation between the coupling of metabolic energy to renalp‐aminohippurate (PAH) accumulation and Na+‐K+ transport was studiedin rabbit cortical slices. 2. Cyanide (CN‐), 2,4‐dinitrophenol (DNP)and fluoride (F‐( at low‐medium concentrations, giving rise to aslight decline of tissue ATP concentration, caused a reduction o PAHaccumulation without significantly affecting intracellular Na+ and K+concentrations. However, higher levels of the metabolic inhibitorsalso resulted in considerable inhibition of active Na+‐K+transport. 3. The rate of carrier‐mediated PAH uptake was slow underanaerobic conditions, relative to that measured under aerobicconditions in Na+‐depleted slices. In the latter case the maximalaccumulation achieved was only 1.55 +/‐ 0.16. 4. The uptake rate ofPAH under anaerobic conditions was not inhibited by the absence of Na+or addition of metabolic inhibitors in the concentrations used underaerobic conditions. 5. It is concluded that although Na+ is requiredfor the attainment of high accumulation ratios of PAH, oxidativemetabolism stimulates PAH flux by a Na+‐independentmechanism.
Interaction between pre‐activity and stretch reflex in human triceps brachii during landing from forward falls.
Authors: Dietz V , Noth J , Schmidtbleicher D
Published: December 2014

1. Electromyographic (e.m.g.) profiles of proximal arm muscles were studied in human subjects falling forward onto a platform. 2. The stretching of the triceps lasted 200‐300 msec for deep falls, and immediately after impact angular velocities of the elbow joint up to 1000 degrees sec‐1 were reached. 3. For angles of fall between 50 and 90 degrees, more than half of the subjects exhibited marked short‐latency e.m.g. responses of the triceps brachii. Such responses began 20‐30 msec after touchdown, arising from a more or less plateau‐like activity which started about 130 msec before impact. In some cases distinct later responses were found, the second peak having a latency of 60‐80 msec after touchdown. 4. The early e.m.g. response even appeared when the subject was blindfolded and when the depth of the fall was randomly varied. 5. It is concluded that both the pre‐existing activity and the spinal stretch reflex contribute significantly to the over‐all activity of the triceps during stretch after impact.