bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma prolactin levels and body fluid deficits in the rat: causal interactions and control of water intake.
Authors: Kaufman S , Mackay B J
Published: December 2014

A study was made of the responses of chronically hyperprolactinaemic rats to selected dipsogenic stimuli. Measurements were also made of the correlation between the state of hydration of the animal and the plasma prolactin levels. After 24 h water deprivation. S.C. isoprenaline (10 micrograms/kg body wt.) or I.P. injection (5 ml/kg body wt.) of a hypertonic solution (50% w/w) of polyethylene glycol (mol. wt 20000) there was no difference between the hyperprolactinaemic and control rats with respect to the total water intake, the time course of drinking or the urine output. After I.V. injection of 2 M‐NaCl (5 ml/kg body wt.) there was no difference between the hyperprolactinaemic and control rats with respect to the total water intake or urine output. However, the hyperprolactinaemic rats drank more slowly than the controls. When angiotensin II was infused I.V. at a rate of 0.2 micrograms/min, the water intake was greater and the threshold to drinking lower in the hyperprolactinaemic than control rats. After 24 h water deprivation, plasma prolactin levels rose significantly in both the control and hyperprolactinaemic rats. When the rats were injected I.V. with hypertonic saline (5 ml, 2 M‐NaCl/kg body wt.) and denied access to water, plasma prolactin levels had not changed 1 h later in either the control or hyperprolactinaemic animals. It is concluded that there is no interaction either between the plasma osmolality and prolactin secretion or between the plasma prolactin levels and the amount of water drunk in response to intracellular fluid deficits. However, prolactin secretion is stimulated by the combined intra‐ and extracellular deficits resulting from water deprivation and there is a clearly demonstrated interaction between prolactin and the extracellularly mediated stimulus of angiotensin II.
Action potential propagation and threshold parameters in inhomogeneous regions of squid axons.
Authors: Moore J W , Westerfield M
Published: December 2014

The squid giant axon was used as a model system in which to determine the independent contributions of membrane excitability and diameter changes to threshold parameters and propagation of action potentials in inhomogeneous regions. The membrane excitability of a segment of an axon was altered by changes in the bathing solution, while its effective electrical diameter was increased by the insertion of a low‐resistance axial wire. In computer simulations of these experiments, similar alterations were made in the membrane's conductance and axon's diameter. The inflexions in the shapes of action potentials propagating into a region with abrupt decreases in axial resistance become more pronounced when the interval between impulses was shortened. At short intervals, propagation of the second impulse failed. In contrast, reduction of membrane excitability produced inflexion‐free changes in action potential shape and allowed a close‐following second impulse to pass through the inhomogeneity. A combined decrease in membrane excitability and increase in diameter of the same region exaggerated the changes in action potential shape characteristic of the diameter increase alone. Threshold parameters were obtained from ‘strength‐duration’ excitability relationships measured by injection of current at different points along the axon. When only the membrane excitability was reduced, threshold characteristics changed smoothly from one region of the nerve to another. In contrast, lowering the internal resistance or increasing the diameter in one region of a nerve lowered the time constant of excitation and the threshold for brief (relative to rheobasic) current stimuli in the small‐diameter region near the transition while raising them in the larger‐diameter region.
Spatial‐frequency‐specific inhibition in cat striate cortex cells.
Authors: De Valois K K , Tootell R B
Published: December 2014

Responses to single and multiple spatial frequency gratings were recorded from eighty‐eight cat striate cortex cells. A cell's response to a grating of its optimum spatial frequency (f) was examined both alone and in the presence of gratings of 1/4, 1/3, 1/2, 2, 3 and 4f, respectively. Some 97% (thirty‐seven of thirty‐eight) of all simple cells showed significant inhibition of f by one or more of the other frequencies. This inhibition was usually fairly narrowly tuned, with only one or two spatial frequencies producing significant inhibition. Thirty‐four simple cells were maximally inhibited by a higher frequency, three by a lower spatial frequency. By far the most common interaction was a considerable inhibition of f by 2f and/or 3f. Of the thirty‐seven simple cells showing inhibition to a complex grating, seventeen responded in a manner dependent on the relative phases of the two components. Some showed only inhibition of f; in others, the response to f was either increased or decreased, depending on the relative phase of the two frequencies. The other twenty simple cells showed phase‐independent inhibition: the inhibition was of approximately equal amplitude regardless of the relative phase angle of the two grating components. Such phase‐independent inhibition cannot be accounted for by linear summation within classical cortical receptive fields. Only eighteen of forty‐eight (38%) of the complex cells showed significant inhibition of f by one or more other spatial frequencies. Fourteen of these (29%) were maximally inhibited by a higher spatial frequency, four (8%) by a lower spatial frequency. Inhibitory interactions in complex cells were never dependent on the relative phase of the two component gratings. Six simple cells (16%) and fourteen complex cells (29%) showed significant facilitation of the response to f by one or more (most often lower) spatial frequencies. This enhanced response was greater than the sum of the responses to each component alone, was usually broadly tuned for spatial frequency, and did not depend on the relative phase of the two components. It thus differs from the increased response sometimes seen in a phase‐dependent interaction. Some of the observed spatial‐frequency‐specific interactions are incompatible with either a strictly hierarchical model of cortical architecture or a simple linear filter model of visual cortical processing. The asymmetry of inhibition suggests that it subserves some function other than (or in addition to) the narrowing of spatial frequency tuning functions.
Kinetics of activation of the sodium conductance in the squid giant axon.
Authors: Keynes R D , Kimura J E
Published: December 2014

The time course of the rise in sodium conductance during positive voltage‐clamp pulses was measured in squid giant axons perfused with CsF and immersed in low‐sodium solutions. The initial transients were eliminated by subtraction of records made after blocking the sodium channels with tetrodotoxin. The value of tau m as defined by Hodgkin & Huxley (1952) passed through a well defined maximum at a membrane potential of about ‐35 mV. On fitting the initial inflexion in the rise of INa to the expression mXh instead of m3h, the value of X was found to vary from axon to axon between 2.9 and 4.4, with an average of 3.5. For any given axon, X did not vary significantly with pulse potential. Measurements of tau m were made on approaching each value of the membrane potential both from the negative and from the positive side. The cube law kinetics of the Hodgkin‐Huxley equations were closely obeyed. Application of a negative prepulse to ‐180 mV delayed the rise of conductance by 20 musec at 7 degrees C without obviously changing tau m. Comparisons of the voltage dependence of tau m with that of the time constant tau 1 of the fast relaxation of the asymmetry current measured in the same axon, showed that tau 1 was smaller than tau m except at positive potentials, was less steeply voltage‐dependent, and reached its maximum at a more positive potential.
Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides.
Authors: Saito Y , Wright E M
Published: December 2014

We have studied the effects of ions, hormones, diuretics and cyclic nucleotides on the short‐circuit current (Isc) across the frog choroid plexus. In normal HCO3 Ringer solution, the trans‐epithelial potential difference (p.d.), Isc and resistance (Rt) were ‐0.8 mV (ventricular side negative with respect to to the blood (serosal) side), 6 microA/cm2 and 170 omega cm2, respectively. Removal of Na, Cl or HCO3 from the solution decreased the Isc to 1.9, 2.3 or ‐4.6 microA/cm2, respectively. Theophylline, dibutyryl cyclic AMP, isoproterenol, prostaglandin E1, ACTH, cholera toxin and forskolin all significantly increased the Isc. The theophylline‐induced change in Isc (delta Itheosc) was reduced by 50% upon Cl substitution with gluconate, and was abolished to less than 12% by Na‐free and HCO3‐free solutions. pH monitoring of the bathing solutions showed that acidification of the serosal bathing fluid was enhanced by theophylline while that of the ventricular solution was retarded. Ouabain, acetazolamide, SITS, DIDS and furosemide inhibited both Isc and delta Itheosc. We conclude that HCO3 secretion by the choroid plexus into the c.s.f. is controlled by hormones which stimulate the adenylate cyclase system, and propose a model of ion transport across the choroidal epithelium.
Changes in the bronchial reactivity of dogs caused by exposure to sulphur dioxide.
Authors: Dixon M , Jackson D M , Richards I M
Published: December 2014

The effects of a 2 h exposure to 250 and 400 p.p.m. of SO2 delivered via an endotracheal tube on the reactivity of the dog lung have been studied. Forty‐eight hours after exposure to 250 p.p.m. SO2 base‐line values of total lung resistance and dynamic lung compliance were unchanged but there was an increase in the bronchoconstrictor response to histamine (20 micrograms/kg I.V.). This enhanced response was vagally dependent. The response of lung irritant receptors to histamine (20 micrograms/kg I.V.) was also increased in these animals. Forty‐eight hours after exposure to 400 p.p.m. SO2 resting total lung resistance had increased and resting dynamic lung compliance had fallen. Vagotomy produced a small but insignificant fall in resting total lung resistance. Changes in total lung resistance produced by acetylcholine (40 micrograms/kg I.V.) histamine (20 micrograms/kg I.V.) and 5‐hydroxytryptamine (20 micrograms/kg I.V.) were all increased after exposure and these increases were significantly reduced by vagotomy. The falls in dynamic lung compliance produced by these agents were not enhanced by exposure to SO2. The rise in total lung resistance by bilateral vagal stimulation was increased 48 h after exposure to 400 p.p.m. SO2. Exposing dogs to SO2 produced an increase in the reactivity of the lung principally by the enhancement of reflexes. The mechanisms involved are discussed.
Renin‐induced sodium appetite: effects on sodium balance and mediation by angiotensin
Authors: Avrith D. B. , Fitzsimons J. T.
Published: December 2014

1. Injection of pig renin or purified renin from the mouse submaxillary gland into the preoptic region or third ventricle of the rat caused thirst within a minute or so of injection followed shortly afterwards by increased sodium appetite. Renin from two widely different sources produced identical responses.

2. The stimulating effect of renin on intake of water and hypertonic (2·7%) NaCl was continuous and persisted for at least a week after the largest (265 ng) dose of purified renin.

3. The stimulating effect was also very large. A single preoptic injection of less than 0·75 pmol (26·5 ng) purified mouse renin caused mean intakes of 250·4 ± 26·2 ml water and 44·8 ± 12·5 ml 2·7% NaCl by five naive rats in 24 h. After the largest dose (265 ng) intakes of water and 2·7% NaCl reached about 80% and 20% body weight respectively.

4. Weekly injections of renin resulted in progressively larger intakes of NaCl and water in response to the injections.

5. Even after repeated injections, carbachol did not stimulate sodium appetite. The stimulating effect on water intake was quickly over and showed no progressive increase with repeated injections. Overnight intake of water was generally depressed after carbachol.

6. Preoptic injection of renin caused some increase in sodium excretion but this was small compared with the stimulating effect on sodium appetite.

7. Detailed temporal analysis of fluid and sodium balance shows that the increased intakes of water and 2·7% NaCl were not secondary to renin‐induced urinary losses. Increased intakes of water and 2·7% NaCl caused by renin resulted in the rats going into and remaining in positive fluid and sodium balance throughout the 24 h experiment.

8. Renin‐induced sodium appetite and thirst were inhibited by the converting enzyme inhibitors teprotide or captopril, or by the angiotensin antagonist saralasin. Inhibition was longer lasting after captopril. Carbachol‐induced thirst was unaffected.

9. In conclusion, renin injected into the preoptic region or third ventricle is a potent stimulus to sodium appetite as well as thirst. The effect is mediated by local generation of angiotensin II and it is not secondary to increased urinary loss.
Contractions induced by sodium withdrawal in crab (Callinectes danae) muscle fibres.
Authors: Madeira A C , Suarez‐Kurtz G
Published: December 2014

A study was made of the effects of Na removal on the resting tension of single muscle fibres of the crab Callinectes danae. Reduction of [Na]o (replacement with Li, Tris or choline) below a threshold value, typical for each fibre, induced spontaneous, local contractions randomly dispersed along the fibres; this was followed by propagated contractile waves and tension oscillations. Sustained contractures were occasionally seen at threshold [Na]o and were consistently observed when [Na]o was further reduced. The Na withdrawal contractions depended on [Ca]o and were abolished in Ca‐free media; they were restored within seconds after the addition of Ca (3‐12 mM) or Sr (15‐25 mM), but not Ba (10‐100 mM), to the media. Caffeine (0.2‐1.0 mM) facilitated, whereas La (2‐5 mM), procaine (1 mM) or lidocaine (10 mM) inhibited the Na‐withdrawal contractions. It is concluded that increased Ca influx across the sarcolemma and release of stored Ca from the sarcoplasmic reticulum are involved in the contractions induced by Na‐deficient solutions in crab fibres.
The directional sensitivities of the Stiles’ colour mechanisms.
Authors: Alpern M , Kitahara K
Published: December 2014

Field sensitivities of the three IIj (j = 3, 4, 5) mechanisms of Stiles were measured for monochromatic backgrounds of different wave numbers (mu)‐1 traversing the eye through different points (r) displaced along a horizontal chord through the centre of the entrance pupil. Each mechanism shows an insensitivity to the direction of retinal incidence of short‐wave backgrounds not previously described. The spectral densities of the centre‐most part of the lens and of the macular pigment were measured on this eye. With reasonable assumptions the former allowed for correction at the receptor level of the directional sensitivity; together with the latter it allowed correction for the spectral sensitivity as well. No correction for the attenuation of the high spatial frequencies of the background as it traversed the pupil at different r was needed. The anomalies of section 2 (above) disappear after correction for losses in the eye media. After these corrections, for every mu and r, the results are well described by the parabola ‘tentatively’ suggested by Stiles (1939) for each mechanism, allowing only a small amount of variance attributable to experimental imprecision alone. Each mechanism is most sensitive to backgrounds going through essentially the same point of the pupil, independent of background. This result is inconsistent with a qualitative explanation of the ‘hue shift’ suggested by Safir, Hyams & Philpot (1971). The field sensitivity spectra for backgrounds traversing the pupil at this most effective point and at the 3.5 mm margin, are the data needed to predict this observer's brightness and colour matches of monochromatic lights passing through the entrance pupil at these two points according to a unified theory of the two Stiles‐Crawford effects. In the following paper these predictions are quantified and confronted with results of the matching experiments (Alpern, Kitahara & Tamaki, 1982).
The effect of palmitate and lactate on mechanical performance and metabolism of cat and rat myocardium.
Authors: Drake‐Holland A J , Elzinga G , Noble M I , ter Keurs H E , Wempe F N
Published: December 2014

Fourteen isolated ejecting hearts were perfused with a suspension of red cells in Tyrode solution. In five hearts comparison was made between glucose alone as substrate and glucose plus free fatty acid (palmitate). In five hearts the effect of additional lactate was studied. In the remaining hearts no substrate changes were made (controls). There were only transient changes in cardiac output of the hearts (at fixed mean aortic pressure) when the perfusion media were switched from one to another. There were no consistent steady‐state changes in myocardial oxygen consumption, mean external power, efficiency, cardiac output or coronary blood flow associated with any of the changes in substrate consumption. Thus we were unable to confirm an increase in oxygen consumption and decrease in efficiency associated with either free fatty acid or lactate as substrates. Isolated rat trabeculae were deprived of exogenous substrate; their mechanical performance remained constant for approximately 10 min. Subsequent deterioration was restored by any of the three exogenous substrates. We conclude that there is no oxygen wasting effect of these substrates as has previously been postulated, nor any deleterious effect of changing exogenous or endogenous carbohydrate or lipid substrate.
Electromyogram, force and relaxation time during and after continuous electrical stimulation of human skeletal muscle in situ.
Authors: Hultman E , Sjöholm H
Published: December 2014

A technique for recording the surface electromyogram (e.m.g.) simultaneously with electrical stimulation of human skeletal muscle is described. During a fatiguing electrical stimulation the e.m.g. amplitude and force decreased in the same proportion. During recovery the e.m.g. was quickly normalized whereas force remained at a reduced level. Relaxation time increased during the stimulation and helps substantially in keeping up tension during a fatiguing contraction. In the recovery phase the rapid normalization of relaxation time counteracts recovery of tension. It is concluded that e.m.g. measurements alone can be misleading as an index of contraction force and that muscular fatigue during electrical stimulation can be attributed to excitation failure only to a lesser extent.
Distribution of chloride and potassium in cellular and luminal compartments of control and drug‐treated turtle thyroid.
Authors: Chow S Y , Woodbury D M , Yen‐Chow Y C
Published: December 2014

Chloride and potassium activities inside the lumen and the transepithelial potentials of control and drug‐treated turtle thyroid follicles were determined simultaneously by ion‐selective and conventional 3 M‐KCl micro‐electrodes, respectively. Water and electrolyte contents of these thyroid tissues were determined chemically after each experiment. Cellular and luminal concentrations of Cl‐ and K+ in control and drug‐treated thyroid glands were derived from the data obtained. Both Cl‐ and K+ equilibrium potentials across the follicular cell membranes calculated from their concentration gradients are not identical to their corresponding membrane potentials measured directly. Thus, transport of both ions occurs. Thyrotrophin, SITS and ouabain increased both cellular and luminal Cl‐ concentrations. Acetazolamide increased the cellular but did not alter the concentrations. Furosemide and perchlorate markedly increased the cellular but decreased the luminal Cl‐ concentrations. There is a discrepancy in the intracellular K+ concentration between values derived from electrometric data as measured by ion‐selective micro‐electrodes and those calculated from the chemical analyses. The electrometrically determined intracellular K+ concentration is smaller. Intracellular Cl‐ concentrations derived from measurements with the Cl‐ ion‐selective micro‐electrodes were in the same range as those calculated from chemical analyses. Thus, either method provides accurate values for intracellular Cl‐ concentrations.
Upper airway dynamics during breathing and during apnoea in fetal lambs.
Authors: Fewell J E , Johnson P
Published: December 2014

We have done experiments to determine the site(s) of resistance to the outward flow of lung fluid during apnoea and the inward flow of fluid during breathing in fetal lambs. Pressures were measured at various sites in the upper airway of ten chronically instrumented fetal lambs. Three fetuses were tracheostomized, two fetuses had nasopharyngeal tubes, one fetus had a tube through the body of its larynx only and four fetuses were studied with their upper airway intact. During apnoea, oropharyngeal pressure as well as tracheal pressure was greater than amniotic pressure. Tracheostomy or insertion of a nasopharyngeal tube (that extended from the amniotic cavity to the oropharynx) eliminated the standing pressure gradient between trachea and amniotic cavity. During normal breathing, negative phasic changes in oropharyngeal pressure occurred only when there was substantial posterior cricoarytenoid activity. Tracheostomy substantially attenuated phasic changes in tracheal pressure during breathing. From these data we conclude that the larynx provides a substantial resistance to the movement of fluid towards the lungs during normal breathing despite the presence of laryngeal abductor activity but does not offer a resistance to the secretion of lung fluid. The small positive tracheal pressure during apnoea most likely results from the secretion of lung fluid into a closed pharyngeal and buccal cavity or against a high nasal and oral resistance.
Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit.
Authors: Bradbury M W , Westrop R J
Published: December 2014

Experiments have been made to determine the main route by which radio‐iodinated albumin reaches deep cervical lymph from cerebrospinal fluid (c.s.f.) in the anaesthetized rabbit. Other factors, influencing drainage through this pathway, have been investigated. After single injection of [125I]albumin into a lateral ventricle of control rabbits, a mean of 14.8% of the radioactivity lost from brain‐c.s.f. was recovered during 6 hr in the lymph of the cannulated jugular trunk of one side. Injection of kaolin into the olfactory fossa or sealing of the cribriform plate with cyanoacrylate glue reduced the recovery of [125I]albumin to 3.3% and 1.9% respectively at 2‐3 weeks after the procedure designed to block the cribriform plate. This confirms the traditional view that the major connexions between c.s.f. and deep cervical lymph is via prolongations of subarachnoid space around the olfactory nerves, leading into the interstitial spaces of the nasal submucosa. The dense lymphatic plexus in this tissue is known to drain into the retropharyngeal (deep cervical) lymph nodes. Constant infusion of artificial c.s.f. into a lateral ventricle at 10 microliters/min or 30 microliters/min, in order to approximately double or quadruple flow through the system respectively, decreased the recovery of intraventricular [125I]albumin to 8.1% and 6.9% respectively. It also appeared that the increased c.s.f. pressures induced forced relatively more radioactivity from inside the skull into the c.s.f. spaces of the spinal cord. Maintaining the rabbit prone but at 20 degrees from the horizontal caused recoveries of [125I]albumin in lymph of 17.6% (head‐up position and 6.6% (head‐down). The amounts of radioactivity in nose and spinal cord markedly increased and decreased respectively in the head‐down position. They changed in the opposite directions in the head‐up position. The amounts of [51Cr]EDTA, [125I]metrizamide and [14C]inulin in deep cervical lymph were negligible after intraventricular injection. Estimations of the ratio of [51Cr]EDTA/[125I]albumin in various tissues on the pathway into lymph, together with measurements of arterio‐venous fluxes across the retropharyngeal nodes, indicate that [51Cr]EDTA passed from c.s.f./lymph into blood within both the nose and the lymph nodes.
Dendritic plateau potentials evoked in Purkinje cells by parallel fibre volleys in the cat.
Authors: Campbell N C , Ekerot C F , Hesslow G , Oscarsson O
Published: December 2014

Responses evoked in Purkinje cell dendrites by parallel fibre volleys and climbing fibre impulses were investigated by intra‐ and extracellular recording from cat cerebellar cortex. The depth distribution of recording sites suggested that the intracellular recordings were predominantly from proximal dendrites whereas the extracellular recordings were predominantly from distal dendrites. Parallel fibre stimulation evoked monosynaptic excitation and disynaptic inhibition in the dendrites and, at higher strength, prolonged plateau‐like responses in distal dendrites but only rarely in proximal dendrites. However, when the inhibitory synapses were blocked with topically applied picrotoxin, parallel fibre volleys evoked plateau potentials also in proximal dendrites. The duration of the parallel‐fibre‐evoked plateau potentials in distal dendrites was prolonged by increasing the intensity of the eliciting stimulus or by increasing the number of stimuli. A similar prolongation in the duration of climbing‐fibre‐evoked plateau potentials was observed when brief repetitive stimulation was applied to the inferior olive. The investigation provided evidence that under physiological conditions plateau potentials in Purkinje cell dendrites are exclusively evoked by climbing fibre impulses.
An analysis of transmission from cones to hyperpolarizing bipolar cells in the retina of the turtle.
Authors: Ashmore J F , Copenhagen D R
Published: December 2014

Voltage noise was recorded from centre‐hyperpolarizing bipolar cells in the retina of the snapping turtle. The identity of the cells was confirmed by intracellular staining. The variance of the voltage fluctuations of the membrane potential present in the dark was suppressed by up to 30‐fold by 100 microns diameter light spot stimuli centred on the cell's receptive field. Such noise reduction is expected when light hyperpolarizes the photoreceptors and reduces the rate of release of transmitter from the terminals. The spectra of the fluctuations were analysed as the sum of two components: (a), a component with power band width limited to below approximately 10 Hz, and (b), a component Sh(f) of the form Sh(f) = Sh(0)/(1 + (f/f0)2)2, with f0 = 27 Hz. The two components were attributed (a) to the noise generated in the cones and transmitted through the synapse to the bipolar cells and (b) to the action of transmitter on the bipolar cell membrane. The component Sh(f) attributed to the action of transmitter on the bipolar cells corresponded to an event approximately 14 ms in duration. The event had a peak amplitude in the range 17.6‐223 microV with a mean of 69.5 microV. It is estimated that, in the dark, the number of such events contributing to the noise is about 9200 s‐1. It is estimated that each elementary noise event in the cones controls approximately thirty of the transmitter‐related events at the synapse. Responses to flashes of darkness applied on steady illumination were analysed by a method of matched filtering. The responses fluctuated in amplitude, and the analysis of this fluctuation suggested an elementary event of approximately the same amplitude as found from the noise analysis. Enlarging the diameter of the stimulus spot to 1500 microns repolarized the bipolar cells with an associated increase in voltage noise. Implications for the synaptic mechanisms of the centre‐surround organization are discussed.
Voltage‐dependent drug blockade of L‐glutamate activated channels of the crayfish.
Authors: Dekin M S , Edwards C
Published: December 2014

The actions of d‐tubocurarine (d‐TC) and local anaesthetics on the L‐glutamate activated channel at the voltage‐clamped crayfish neuromuscular junction were studied. The effect of d‐TC and local anaesthetics on the dose‐response relationship between ionophoretically applied L‐glutamate and synaptic current suggested that both acted as non‐competitive inhibitors. The amount of inhibition was voltage dependent, and increased as the membrane potential was hyperpolarized. This voltage‐dependent block was also manifest in a flattening of the I‐V relationship between L‐glutamate induced current and membrane potential in the presence of d‐TC. However, the reversal potential for the L‐glutamate activated channel was not affected; it was about +7 mV in both the presence and absence of d‐TC. The neurally evoked excitatory post‐synaptic current (e.p.s.c.) was depressed in the presence of these drugs and this effect was also voltage dependent. The time course of the e.p.s.c. was affected, but less so than expected if the L‐glutamate activated channel were identical to the channel opened by acetylcholine at the vertebrate neuromuscular junction. Possible reasons for this discrepancy are discussed.
The effect of vasopressin on renal blood flow and its distribution in the rat.
Authors: Azzawi S A , Shirley D G
Published: December 2014

Anaesthetized Brattleboro rats with hereditary diabetes insipidus were infused with vasopressin at three different doses (1.3, 13 or 130 mu./hr) in order to study the effect of the hormone on renal blood flow and its distribution. Radioactive microspheres were used to determine intrarenal blood flow. The plasma vasopressin level during infusion of the lowest dose was calculated to be within the physiological range. At this dose vasopressin was antidiuretic but was without effect on arterial blood pressure or solute excretion, whereas the two higher doses were both pressor and natriuretic. All doses of vasopressin increased renal vascular resistance and decreased renal blood flow. The vasoconstrictor effect of the lowest dose was confined to the outer cortex, whereas the two higher doses affected the entire cortex. In separate experiments, [1‐(beta‐mercapto‐beta, beta‐cyclopentamethylenepropionic acid), 2(O‐methyl) tyrosine] arginine vasopressin, an antagonist of the vascular action of vasopressin, was administered to anaesthetized Long Evans or Brattleboro rats. In the Long Evans rats the antagonist caused a decrease in renal vascular resistance and a consequent increase in renal blood flow, this effect being restricted to the outer cortex. In Brattleboro rats the antagonist had no effect on renal vascular resistance or renal blood flow. It is concluded that physiological levels of vasopressin influence the distribution of renal blood flow by causing vasoconstriction in the outer region of the renal cortex. Higher levels of the hormone increase vascular resistance throughout the cortex.
Effects of capsaicin applied perineurally to the vagus nerve on cardiovascular and respiratory functions in the cat.
Authors: Jancsó G , Such G
Published: December 2014

The effects of capsaicin applied perineurally to the cervical vagus nerves have been studied on cardiovascular and respiratory functions in urethane anaesthetized cats. Application of capsaicin resulted in a moderate but significant decrease in the mean arterial blood pressure and in changes of the heart rate whose direction and magnitude depended on the initial cardiac frequency. Subsequent to these alterations, which may be attributed to a direct stimulation by capsaicin of vagal afferents, a transient block of impulse propagation was observed. Three to five days after pre‐treatment of the cervical vagus nerves with capsaicin, phenyldiguanidine and veratrine given intravenously invariably evoked bradycardia, hypotension and apnoea, while the reflex responses to intravenous injection of capsaicin and some of its pungent congeners were greatly reduced or even abolished. It is suggested that vagal afferent fibres mediating cardiovascular and respiratory chemo‐reflexes are separated into chemo‐specifically different populations. Perineural application of capsaicin may be a useful tool for elucidating the role of different populations of peptide‐containing vagal afferent fibres in the regulation of cardiovascular and respiratory functions.
The action of alcohols and other non‐ionic surface active substances on the sodium current of the squid giant axon.
Authors: Haydon D A , Urban B W
Published: December 2014

The effects of several n‐alkanols and n‐alkyl oxyethylene alcohols, methyl octanoate, glycerol 1‐monooctanoate and dioctanoyl phosphatidylcholine on the ionic currents and electrical capacity of the squid giant axon membrane have been examined. The peak inward current in voltage‐clamped axons was reduced reversibly by each substance. For n‐pentanol to n‐decanol the concentrations required to suppress the peak inward current by 50% were determined. From these data, it was estimated that the standard free energy per CH2 for adsorption to the site of action was ‐3.04 kJ mole‐1, as compared with ‐3.11 kJ mole‐1 for adsorption into phospholipid bilayers or an n‐alkane/aqueous solution interface. The membrane capacity at 100 kHz was not greatly by any of the test substances at concentrations which reduced the inward current by 50%. Na currents under voltage clamp were recorded in intracellularly perfused axons before, during and sometimes after exposure to the test substances and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady‐state activation and inactivation parameters (m infinity and h infinity) against membrane potential, changes in the peak heights of the activation and inactivation time constants (tau m and tau h) and reductions in the maximum Na conductance (gNa) have been tabulated. All of the test substances shifted the voltage dependence of the steady‐state activation in the depolarizing direction and lowered the peak time constants for both activation and inactivation. The origins of these effects, and of the differences in the present results from those of the hydrocarbons (Haydon & Urban, 1983), have been discussed in terms of the physico‐chemical properties of the two groups of substances and with reference to their effects on artificial membranes.
Analysis of glycine‐activated inhibitory post‐synaptic channels in brain‐stem neurones of the lamprey.
Authors: Gold M R , Martin A R
Published: December 2014

Voltage‐clamp techniques were used to measure fluctuations in membrane current produced by the application of glycine to Müller cells in the brain stem of the lamprey. The power density spectrum of the glycine‐induced current ‘noise’ was consistent with the hypothesis that glycine activated a single population of conductance channels with open times determined by first‐order kinetics. In normal bathing solution the channel conductance was 73 +/‐ 12 pS (mean +/‐ S.D.) and the channel open time 34 +/‐ 6 msec at 5 degrees C. The reversal potential for the response was 66 +/‐ 5 mV. Neither channel conductance nor mean open time was voltage‐dependent. Replacement of Cl‐ in the bathing solution by isethionate and sulphate reversibly abolished the response to glycine. Increasing intracellular Cl‐, either by using Cl‐ ‐filled micropipettes or by raising extracellular K+, decreased channel conductance. This unexpected decrease was a direct effect of intracellular Cl‐ and was not related to coincident changes in reversal potential. Channel open time was unaffected by intracellular Cl‐ concentration. Reducing extracellular Cl‐ concentration from 126.5 to 31 mM reduced channel conductance at all levels of intracellular Cl‐ without affecting open time. Increasing the temperature of the preparation resulted in increase in channel conductance and a decrease in mean open time. Q10S for the effects were of the order of 1.3 and ‐2.3 respectively in the range 4‐14 degrees C.
A transient calcium‐dependent chloride current in the immature Xenopus oocyte.
Authors: Barish M E
Published: December 2014

Ionic currents were studied in immature full‐grown Xenopus oocytes using the two‐micro‐electrode voltage‐clamp technique. Recordings of total membrane current showed a transient outward peak during depolarizations from the approximate resting voltage (‐70 or ‐80 mV) to voltages more positive than ‐20 mV. The current‐voltage relation for peak outward current was U‐shaped, with a maximum at about 0 mV. Replacement of external Cl with methanesulphonate reversed this transient outward current to a transient inward current. Current relaxations recorded after the membrane potential was stepped to different voltages at the time of the peak showed a component that inverted at about ‐25 to ‐30 mV. This value was close to ECl as determined by measurement of the intracellular Cl ion concentration. The reversal potential for these current relaxations changed with the external Cl concentration as predicted by the Nernst relation. Replacement of external Ca with Mg, Sr or Ba, or addition of low concentrations of Ni in the presence of Ca, eliminated the transient outward current. Increasing the external Ca concentration increased the amplitude of the transient outward current without affecting the amplitude of the steady‐state current. It was concluded that the outward peak in records of total membrane current represented the contribution of a transient outward current carried by Cl ions which was dependent on the entry of external Ca. It will be noted as ICl(Ca). Decay of ICl(Ca) could be described at the normal Ca concentration by a single exponential function whose time constant showed a shallow U‐shaped voltage dependence. ICl(Ca) was maximally activatable by depolarizations from a holding potential of about ‐100 mV, but could not be activated by depolarizations from ‐40 mV. The amplitude of ICl(Ca) showed a large temperature dependence as compared to the steady‐state current, suggesting complex control of its activation.
Sites of dipeptide hydrolysis in relation to sites of histidine and glucose active transport in hamster intestine.
Authors: Wiseman G
Published: December 2014

The effects of dipeptides and amino acids on the active transport of L‐histidine and D‐glucose by sacs of everted small intestine of the hamster have been used to determine the sites of final hydrolysis of the dipeptides in relation to the sites of active transport of L‐histidine and D‐glucose. The results, plus earlier observations (Wiseman, 1977), show that (a) dipeptide active transport occurs at a superficial site, followed by progressively deeper sites for (b) final hydrolysis of glycyl‐phenylalanine and phenylalanyl‐glycine, then deeper (c) L‐histidine active transport, then (d) final hydrolysis of alanyl‐alanine, alanyl‐leucine, glycyl‐alanine, glycyl‐proline, leucyl‐alanine and leucyl‐leucine, then (e) D‐glucose active transport, then (f) final hydrolysis of alanyl‐glycine, alanyl‐valine, glycyl‐glycine, prolyl‐glycine, valyl‐alanine and valyl‐valine. The site of D‐glucose active transport (2e) and all the sites superficial to it (2a‐d) lie in the intestinal epithelial cell's brush‐border. The location within the cell of site(s) 2f is not known; it may lie in the cytosol. All the dipeptides appeared to inhibit L‐histidine active transport by the release of free amino acid and not by action of intact dipeptide, supporting the view that dipeptides and free amino acids do not share a common transport pathway in the epithelium of the small intestine.
Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb.
Authors: Brown M J , Olver R E , Ramsden C A , Strang L B , Walters D V
Published: December 2014

In the chronically catheterized fetal lamb, intravenous infusion of adrenaline at 0.5 microgram/min produced slowing of the secretion of lung liquid or its absorption, an effect which increased exponentially with advancing gestation. Between 120 and 130 days, the characteristic response was slowing of secretion, whereas after 130 days it was absorption. Stimulus‐response curves, relating secretion or absorption rate to plasma adrenaline concentration, were obtained by infusing adrenaline into the fetus intravenously at rates between 0.1 and 1.0 microgram/min (0.55‐5.5 nmol/min). These curves allowed estimation of the minimum concentration of adrenaline required to inhibit secretion [( Ai]) and this was found to decrease from 0.43 ng/ml. (2.35 nM) at 132‐4 days' gestation to 0.029 ng/ml. (0.16 nM) at gestations above 140 days. During spontaneous labour there was a slowing of lung liquid secretion in the early stages followed by absorption during the last 50‐150 min. The mean concentration of adrenaline in plasma increased from 0.087 ng/ml. (0.48 nM) in early labour to 6.86 ng/ml. (37.5 nM) in the last 50 min and to 7.17 ng/ml. (39.2 nM) in the early post‐natal period. Mean noradrenaline levels at the same times were 1.71 ng/ml. (10.1 nM), 12.14 ng/ml. (71.8 nM) and 9.10 ng/ml. (53.9 nM). The relationship between the plasma adrenaline concentration and the rate of absorption during labour was similar to that found when adrenaline was infused at various rates into the non‐labouring fetus of comparable gestational age. The upper airway of the fetus was shown to be capable of acting as a one‐way valve allowing outflow but not inflow of liquid. Thus withdrawal of liquid at 5‐20 ml./hr from the fetal trachea below the larynx caused closure of the upper airway and this result was obtained both when the recurrent laryngeal nerves were intact and when they were divided.
Facial sensitivity to rates of temperature change: neurophysiological and psychophysical evidence from cats and humans.
Authors: Davies S N , Goldsmith G E , Hellon R F , Mitchell D
Published: December 2014

The dynamic responses in a thermal afferent pathway to rates of temperature change have been studied in anaesthetized cats. Recordings were made in the caudal trigeminal nucleus from neurones with a synaptic input from facial cold receptors. Five rates of cooling and warming ranging from 0.05 degrees C/sec to 1 degree C/sec were applied to the receptive fields of the neurones. Several measures of the dynamic response were computed but the most representative was the maximum rate during cooling or the minimum rate during warming. During cooling the maximum rate increased with increasing cooling rates between 0.05 degrees C/sec and 0.25 degrees C/sec, but did not increase at faster rates. Minimum activity during warming reached near zero at rates of 0.25 degrees C/sec and faster. The total number of impulses generated during cooling or absent during warming was unrelated to rate of temperature change. The same thermal stimuli were applied to the cheeks of human subjects. They were able to sense cooling or warming changes at 0.05 degrees C/sec. They could also distinguish the faster of two cooling changes when these were slow, but not when they were fast. Warming rates could not be distinguished, except from an adapting temperature of 35 degrees C, when warm receptors would have been activated. There was good agreement between the responses of the cat neurones and the human sensations. Slow rates of cooling could be detected or distinguished. Fast rates appeared to saturate the neuronal and sensory mechanisms.
Burst kinetics of single calcium‐activated potassium channels in cultured rat muscle.
Authors: Magleby K L , Pallotta B S
Published: December 2014

Burst kinetics of single Ca‐activated K channels in excised patches of surface membrane from cultured rat muscle were studied using the patch‐clamp technique. Channel activity was separated into bursts using a calculated gap derived from the distribution of shut intervals. Shut intervals greater than the calculated gap were taken as gaps between bursts. The distribution of burst duration was described as the sum of two exponentials with mean durations of about 0.8 and 24 msec (1 microM‐Cai, + 20 mV), suggesting two classes of bursts (short and long). The composition of short and long bursts was determined from comparisons of the distributions of open intervals, unit bursts (bursts of single openings), and openings/burst. Short bursts consisted mainly of single openings to the open channel state of short mean lifetime. Long bursts consisted of one or more openings to the (compound) open‐channel state of long mean lifetime, plus, in fewer than 70% of the long bursts, one or more openings to the short open‐channel state. The frequency of occurrence of bursts from each class first increased and then decreased with increasing [Ca]i, with the number of long bursts increasing at a greater rate than the number of short bursts. The number of openings/short burst was relatively independent of [Ca]i, while the number of openings/long burst increased, often more than linearly, with increasing [Ca]i. This increase arose almost entirely from an increase in openings to the long open state. These results suggest that openings to the long open state typically require the binding of three or more Ca ions, and openings to the short open state typically require the binding of at least one Ca ion. This is the case whether the openings occur in isolation as bursts of single openings or in bursts composed of both types of openings. An obvious burst of channel activity would occur when the channel opens and closes several times without losing all its bound Ca. The power relationship between [Ca]i and the percentage of time spent in the open state is accounted for in terms of the effects of [Ca]i upon mean channel open time, openings/burst, and burst rate. A model is presented that describes quantitatively many features of the burst kinetics of the Ca‐activated K channel for constant [Ca]i.
Effects of denervation on sodium, potassium and [3H]ouabain binding in muscles of normal and potassium‐depleted rats.
Authors: Clausen T , Kjeldsen K , Nørgaard A
Published: December 2014

K depletion leads to a selective loss of K from skeletal muscles, which is associated with a decrease in the number of [3H]ouabain binding sites. The significance of the nerve supply for these changes has been assessed in denervation experiments with K‐depleted rats. In K‐depleted rats (age 4‐12 weeks) denervation led to a partial recovery of the K contents in soleus (46‐77%), gastrocnemius (23%) and extensor digitorum longus (e.d.l.) muscles (19%) within 24 h. These effects were not prevented by beta‐adrenoceptor blockade or mimicked by alpha‐adrenoceptor blockade. In K‐depleted rats the number of [3H]ouabain binding sites was not increased following denervation. In K‐depleted rats 24 h of plaster immobilization of the entire hind limb caused 51% recovery of the total K content in soleus, whereas gastrocnemius and e.d.l. showed 49 and 16% recovery, respectively. Tenotomy for 3 h caused a rise in total K content of 33% in soleus muscles from K‐depleted rats. Anaesthesia for 3 h increased the total K content by 23%. The recovery of K induced by denervation, immobilization in plaster, tenotomy or anaesthesia was associated with an equivalent decrease in Na content. Denervation performed before K depletion reduced the loss of K from soleus, but not from gastrocnemius and e.d.l. In both soleus and e.d.l. the number of [3H]ouabain binding sites, however, decreased to the same level as in the contralateral innervated muscles. Denervation reduced, but did not prevent, the increase in the number of [3H]ouabain binding sites seen after re‐administration of K to K‐depleted rats. It is concluded that the changes in Na‐K contents seen after denervation in K‐depleted rats are the outcome of cessation of muscle activity. The results give no support to the idea that the effects of K depletion on the K content and the number of [3H]ouabain binding sites in skeletal muscle are mediated by the peripheral nerves.