bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of 45calcium with rat mast cells stimulated by 48/80: effects of inactivation, calcium and metabolic inhibition
Authors: Cochrane David E. , Distel Daniel L.
Published: December 2014

1. Stimulation by compound 48/80 of mast cells deprived of Ca released histamine when Ca was subsequently added. This secretory response was accompanied by a pronounced increase in the amount of cell‐associated 45Ca.

2. The level of cell‐associated 45Ca declined as the interval between stimulation by compound 48/80 and the introduction of 45Ca increased.

3. This decline in the amount of 45Ca paralleled the decline in histamine secretion that is called inactivation and each curve could be fitted by linear regression to a first‐order equation with a half‐life of between 1 and 2 min.

4. When histamine secretion was held constant, the amount of cell‐associated 45Ca steadily and significantly declined as the interval between stimulation and the addition of 45Ca increased. This decline in the level of 45Ca was significantly reduced when fully inactivated cells were used.

5. The amount of cell‐associated 45Ca could not be significantly reduced by repeated or prolonged washing with EGTA or LaCl3.

6. The addition of the ionphore, A23187, or compound 48/80, to mast cells loaded with 45Ca by prior stimulation with 48/80 and bathed in Ca‐free media, significantly reduced the level of cell‐associated 45Ca. This effect of 48/80 but not of A23187 was prevented by including either dinitrophenol or 45Ca in the extracellular solution.

7. When [3H]N‐methyl‐methoxy‐inulin was included with the 45Ca or added alone, no significant change in the level of cell‐associated [3H]inulin was found during the course of inactivation.

8. Increasing the Ca concentration increased the amount of cell‐associated 45Ca when Ca was added 10 sec after stimulation by 48/80 but not when Ca was added 10 min after stimulation.

9. Incubation of mast cells in media containing deoxyglucose and either antimycin A or dinitrophenol prevented both histamine release and any increase in the level of cell‐associated 45Ca in response to stimulation by 48/80. A similar result was obtained using sensitized mast cells stimulated by antigen. The addition of the ionophore, A23187, to the mast cells prompted a significant increase in the level of cell‐associated 45Ca.

10. These results are considered to be support for the hypothesis that the process of inactivation to compound 48/80 results from a time‐dependent decay in membrane permeability. It is suggested that those events associated with initiating changes in membrane permeability are effected by metabolic inhibition and calcium.
Nasal conductance and effective airway diameter.
Authors: Hey E N , Price J F
Published: December 2014

1. Transnasal pressure (delta p) in Pa and gas flow in cm3 s‐1 were measured in men breathing gases of different density, assuming flow through each nostril (f) to be half the measured total flow. Measurements were also made in children with allergic rhinitis before and after nasal antigen challenge. 2. Flow always showed evidence of turbulence when transnasal pressure exceeded 40‐80 Pa breathing air and Reynolds number exceeded 2400 (1800 in the presence of nasal obstruction). 3. Changes in effective mean nasal airway diameter (D) after nasal challenge can be determined at points of similar pressure from the relation log (D2/D1) = 0.368 log (f2/f1) when flow is turbulent. 4. Absolute estimates of airway diameter in cm can be obtained from the relation 4.75 log D = 1.75 log f‐‐log delta p+log L‐‐4.756 breathing air when flow is turbulent (since the relation between pressure and flow approximates to that found in a long cylinder) and these estimates are only marginally affected by differing assumptions about nasal airway length (L). 5. Because pressure and flow are non‐linearly related, and changing nasal dimensions have a profound effect on the flow at which turbulence occurs, it is suggested that measures of nasal conductance at delta p greater than or equal to 0.1 kPa are preferable to the more conventional measures of nasal resistance at a specified flow rate.
Reflex response of the rabbit hind‐limb muscle vascular bed to baroreceptor stimulation and its modification by pregnancy.
Authors: Humphreys P W , Joels N
Published: December 2014

1. The pressure‐‐flow relationship of the blood‐perfused skinned hind limb has been compared in primigravid pregnant and virgin non‐pregnant rabbits while pressure within the vascularly isolated carotid sinus was held at a series of non‐pulsatile values. 2. At each level of sinus pressure the slope of the pressure‐‐flow relationship was steeper in the pregnant animals. Thus, at all but the very lowest flows, the same flow was achieved at a lower perfusion pressure in the pregnant rabbits. 3. When hind‐limb vascular resistance at constant flow was plotted against carotid sinus pressure it could be seen that at each level of sinus pressure vascular resistance was less in the pregnant rabbits. 4. The reflex responses of the hind‐limb bed to changes in sinus pressure were compared in pregnant and non‐pregnant animals; there was little difference in the threshold and saturation values of carotid sinus pressure. There seemed to be a small reduction in the range and gain of the reflex in the pregnant group but this was not statistically significant. 5. We have previously shown total peripheral resistance in the pregnant rabbit to be less than that in the non‐pregnant rabbit at the same level of sinus pressure. The lower hind‐limb vascular resistance of the pregnant rabbit at any given sinus pressure must contribute to this reduced total peripheral resistance.
The appearance and development of chemosensitivity in Rohon—Beard neurones of the Xenopus spinal cord
Authors: Bixby John L. , Spitzer Nicholas C.
Published: December 2014

1. We have examined the onset and subsequent development of chemosensitivity in Rohon—Beard neurones from the Xenopus spinal cord. These cells become sensitive to bath‐applied γ‐aminobutyric acid (GABA) around stage 25 (early tailbud, about 1 d old), and remain so at least until stage 49 (9 d old). In contrast, a number of other neurotransmitter candidates tested caused no potential or conductance change during the same period.

2. We examined ionophoretic dose—response relations of the cells at stage 26, a couple of hours after the first acquisition of GABA sensitivity. Sensitivities as high as 450 mV/nC were recorded. Comparable sensitivities were recorded between stages 46‐49 (5‐9 d old).

3. Measurements of ionophoretic sensitivities and input resistances during several periods from stage 26 to maturity show that the underlying conductance change for a given GABA dose is likely to increase steadily during this time. A ‘sensitivity index’ (ionophoretic sensitivity/input resistance) was calculated, which is low at stage 26, higher at intermediate stages (stages 31‐42), and highest for mature cells (stages 46‐49; 5‐9 d of development).

4. The reversal potential of the ionophoretic GABA response is the same at stage 26 (‐30 mV) as it is in mature cells. Ion substitution experiments show that Na+ and K+, but not Cl− or Ca2+, are involved in the response.

5. GABA responses at stage 26 are pharmacologically similar to those of mature cells. The responses are blocked by 10 μM‐picrotoxin or curare, and muscimol is an agonist in concentrations as low as 1 μM.

6. GABA responses at stage 26 desensitize in a manner similar to that seen for mature cells, either with prolonged bath application of GABA or with repetitive ionophoretic application.

7. Nearly half of the cells tested at stage 26 respond to glycine, in concentrations as low as 5 μM. This sensitivity is absent by 3½ d of development.

8. The responses of Rohon—Beard neurones to GABA are similar to those of other cells in that they involve a conductance increase, are mimicked by muscimol, and are blocked by picrotoxin. These responses are different in that they do not involve Cl− and are blocked by low concentrations of curare.

9. Many of the characteristics of GABA receptors, i.e. the reversal potential, desensitization, and pharmacology, are constant during development. However, the sensitivity of the cells to GABA and the spectrum of transmitters to which they are sensitive appear to change.
Physiological compartmentation of fluid within the synovial cavity of the rabbit knee.
Authors: Knight A D , Levick J R
Published: December 2014

1. The relationship between pressure in the suprapatellar region (Psp) of the synovial cavity of the rabbit knee, and volume of fluid (oil or saline) infused into that region displayed a pressure plateau (15 . 5 cm H2O) between 1 . 2 and 2 . 0 ml. 2. No pressure plateau occurred when fluid was infused simultaneously into the suprapatellar and posteromedial regions of the synovial space. 3. Pressure in the posteromedial region (Ppm) did not respond to suprapatellar fluid infusions until onset of the suprapatellar pressure plateau. During the plateau phase, Ppm rose steadily towards Psp. At the end of the plateau phase the two pressures were almost equal and rose in parallel. 4. The plateau phenomen also occurred during aspiration of volume‐expanded joints; and was present at all joint angles. 5. It was concluded that the joint space, although anatomically continuous, is divided into two hydraulically separate compartments at physiological pressures. 6. The sites of communication between the two compartments at pathological pressures were explored by casts of the synovial cavity.
Resistance of a crayfish sensory interneurone to hyperinnervation by acceptable afferents.
Authors: Krasne F B , Lee S H
Published: December 2014

1. Intact normal innervation of muscle fibres and other peripheral targets usually prevents regenerating nerves from forming synapses with the targets. Whether intact innervation similarly prevents synapse formation on central target neurones has rarely been tested. This question was examined here for interneurone A of the crayfish last abdominal ganglion. 2. Interneurone A normally receives synaptic input from mechanoreceptor neurones distributed over the side of the tailfan ipsilateral to interneurone A's axon and unilateral dendrites. When the five nerve roots carrying mechanoreceptor axons of one side are cut and central and peripheral ends of one or more are sutured together, regeneration and reinnervation of interneurone A occurs over some two to six weeks. If peripheral ends of roots from the ‘wrong’ (contralateral) side of the body are sutured to ipsilateral central stumps, they also form connexions with interneurone A. When roots from the two sides of the body are simultaneously tied to a central stump, functional connexion formation occurs equally well for afferents from both sides. Therefore, roots of the two sides seem to be equivalent in their ability to reinnervate interneurone A. 3. If peripheral ends of roots from one side of the tailfan are tied to roots on the intact opposite side of the body, the cut axons appear to grow into the last ganglion but usually do not form functional synapses there. The intact innervation therefore seems to exclude further innervation by other acceptable afferents. 4. It is known that mechanoreceptors are added to the tailfan at moult. Exclusion of extra innervation often broke down partially in animals that moulted during the present experiments. This suggests the possibility that synapse formation or exchange may be controlled by moult‐inducing hormones.
Modification of the response to nerve stimulation in small arteries of guinea‐pig caused by distension of the artery.
Authors: Keef K , Neild T O
Published: December 2014

1. Intracellular recordings of membrane potential were made from the smooth muscle of small arteries taken from the guinea‐pig ear. The arteries were internally perfused at constant pressures ranging from 0 to 60 mmHg. 2. The resting membrane potential of the smooth muscle was not affected by altering the perfusion pressure. 3. At the higher pressures the smooth muscle membrane showed an enhanced ability to generate rapidly rising action potentials. 4. The amplitude of the excitatory junction potential evoked by a single stimulus to the perivascular nerves was increased when the perfusion pressure was raised. 5. Excitatory junction potentials and action potentials could be recorded in the presence of tetrodotoxin (3 x 10(‐6) M) although increased stimulus voltages were required. These responses were abolished by guanethidine (2 x 10(‐5) M). 6. The effects of increased perfusion pressure could still be observed in tetrodotoxin.
The effects of intracochlear and systemic furosemide on the properties of single cochlear nerve fibres in the cat
Authors: Evans E. F. , Klinke R.
Published: December 2014

1. Tuning properties and spontaneous discharge rate of single cochlear fibres in the anaesthetized cat were determined during short‐ and long‐term poisoning of the cochlea by locally and systemically applied furosemide.

2. With intra‐arterial administration of furosemide, short‐term reversible elevation occurred of the low threshold sharply tuned ‘tip’ segment of the frequency threshold (‘tuning’) curve (f.t.c.) by up to 40 db, without substantial changes in the threshold of the low frequency ‘tail’ segment of the f.t.c. These changes could occur in part without changes in the spontaneous activity and entirely without changes in the maximal evoked activity. These effects were observed in all fibres examined, the characteristic frequencies of which ranged from 3·5 to 31 kHz.

3. Intracochlear administration of furosemide in 0·9 mM concentrations produced similar changes, but these were not reversible.

4. The changes correlated with the depression of the amplitude of the gross cochlear action potential. The cochlear microphonic potential, however, was either unchanged, or only slightly reduced.

5. In long‐term furosemide poisoning of the cochlea, fibres with anomalous response properties were found alongside fibres having normal tuning. The former exhibited either reduced excitability of the low threshold tip segment, or a tip segment attenuated in both excitability and threshold.

6. It is concluded that the selective effects of furosemide on the tip segment of cochlear fibre f.t.c.s offer further evidence for a physiologically vulnerable ‘second filter’ in the cochlea. The selective influence of the furosemide on the low threshold tip segment provides support for the hypothesis that the normal f.t.c. is generated by two largely independent processes: one vulnerable, low threshold and sharply tuned, and the other less vulnerable, but high threshold and more broadly tuned.

7. The findings, obtained with an agent known to produce reversible impairment of hearing in man, provide direct physiological evidence in support of the hypothesis that in sensorineural hearing loss of cochlear origin the frequency selectivity of cochlear nerve fibres is impaired.
Distribution of transported amino acid within rabbit ileal mucosa.
Authors: Paterson J Y , Sepúlveda F V , Smith M W
Published: December 2014

1. Pieces of rabbit distal ileum, incubated for short periods of time in solutions containing tritiated amino acids, have been processed for autoradiography and the profiles of amino acid concentration across the villi determined by microdensitometry. 2. The concentration profiles of a series of amino acids could be described in terms of two descending exponentials, one extending from the brush border to the basal membrane of the enterocyte and the other from the base of the epithelial layer to the centre of the villus. 3. Exponential coefficients describing the steepness of these gradients were highest for basic amino acids. Coefficients for short‐chain amino acids were greater than for long‐chain neutral amino acids. None of these values changed for times of incubation varying from 5 to 180 sec. 4. Enterocytes accumulated amino acids in the apical cytoplasm, against a concentration gradient, within the first few seconds of incubation. This step‐up in concentration decreased as the external concentration was increased, in a manner dependent on the amino acid used. 5. It is suggested that amino acid concentration gradients within enterocytes arise by diffusion and that the amino acid specificity of this process originates from an ability of the more lipophilic amino acids to permeate structures acting as barriers to the more hydrophilic molecules.
Amino acid efflux from rabbit ileal enterocytes.
Authors: Paterson J Y , Sepúlveda F V , Smith M W
Published: December 2014

1. A method is described for converting tissue concentrations of amino acid, determined autoradiographically using sections of rabbit distal ileum, into measurements of total uptake. 2. Using this method the quantity of amino acid recovered from the villus core following short‐term incubation with tritiated amino acid was shown to be directly related to the intra‐enterocyte concentration of amino acid determined at a site immediately adjacent to the basal membrane. No evidence was obtained for saturation of efflux across the basal membrane of the enterocyte. 3. Amino acid efflux from the mucosa to the villus core, calculated for a constant intra‐enterocyte concentration of substrate, was found to be greater for methionine and leucine than for alanine, serine, lysine or arginine. 4. The distribution of amino acids within the core of the villus following efflux from the enterocyte could not be explained by diffusion alone. 5. It is suggested that quantitative autoradiography can be used as an alternative method to study mechanisms responsible for amino acid movement across the basal membranes of enterocytes. Advantages and limitations of the technique are discussed.
Electromyographic responses to imposed sinusoidal movement of the human thumb.
Authors: Brown T I , Rack P M , Ross H F
Published: December 2014

1. The interphalangeal joint of the thumb was driven through sinusoidal flexion‐extension movements while electromyograms were recorded from over the flexor pollicis longus muscle. 2. When the subject relaxed his thumb the movement generated no detectable e.m.g. response. When, however, he exerted a voluntary flexing force electrical activity could be recorded from the flexor pollicis longus, the amplitude of which was modulated at the frequency of the movement. 3. As the driving frequency was increased, the maximal e.m.g. activity occurred progressively later in the cycle of movement; for frequencies above about 6 Hz the timing of the averaged e.m.g. was compatible with a reflex delay of 55‐65 msec. 4. The frequency‐phase plot was not, however, the perfect straight line that would arise from a simple and constant reflex delay. There were some consistent departures from linearity and some random variations. In either case, the timing of the e.m.g. and the timing of the reflex force (Brown, Rack & Ross, 1982a) changed together in ways that increased confidence in each of the measurements. 5. The amplitude of the e.m.g. signal was more deeply modulated by movements at 8‐14 Hz than by higher or lower frequencies, and it was concluded that the stretch reflex responds particularly readily to signals in that frequency range.
A range of different stretch reflex responses in the human thumb
Authors: Brown T. I. H. , Rack P. M. H. , Ross H. F.
Published: December 2014

1. Imposed sinusoids were used to assess the resistance to movement at the thumb interphalangeal joint.

2. The resistance to high‐frequency movements (> 12 Hz) increased when the subject exerted a large voluntary flexing force; this increase was attributable to a greater non‐reflex resistance of the contracting flexor muscles. This resistance was essentially ‘visco‐elastic’, and the force was phase‐advanced on joint position. At moderately large forces (up to half maximal), however, the resistance changed with changing frequency, and over a range 4‐12 Hz the vectors which represented joint stiffness described the wide path that is characteristic of an active stretch reflex (Brown, Rack & Ross, 1982a). At frequencies between about 4 and 6 Hz the force was sometimes phase‐delayed on position, and the joint exhibited a negative viscous stiffness. When the voluntary flexing force was very large the reflex contributed less to the resisting force, which was then phase‐advanced on position at all frequencies of movement.

3. Large amplitude movements did not generate correspondingly large reflex responses; as the amplitude of movement was increased, the reflex component of the resisting force became relatively smaller and the total resisting force was then phase‐advanced on joint position at all frequencies.

4. The reflex component of the resisting force (as indicated by the excursion of the joint stiffness vectors) varied from subject to subject and from time to time; the reflex usually became more active late in an experiment when the subject had exerted flexing forces against the imposed movement for some minutes. Extreme fatigue, however, diminished the amount of reflex force.

5. In some subjects the joint‐stiffness records indicated a particularly vigorous reflex response at 8‐11 Hz, in contrast to a rather feeble response at 6 or 7 Hz. It is suggested that the reflex pathways then had a relatively low impedance to afferent signals that were modulated at 8‐11 Hz, related perhaps to the firing patterns of the most recently recruited motoneurones.

6. Under the conditions of these experiments, it appears that the stretch reflex has too small a gain to function as a very effective error‐controlled position servo‐mechanism.
Central innervation of neurones in the inferior mesenteric ganglion and of the large intestine of the cat
Authors: Krier J. , Schmalz P. F. , Szurszewski J. H.
Published: December 2014

1. Segmental, lumbar sympathetic outflow to neurones in the cat inferior mesenteric ganglion and to the large intestine were studied. Synaptic responses of neurones in the inferior mesenteric ganglion were recorded intracellularly, in vitro, during electrical stimulation of preganglionic fibres in the lumbar white rami. Synaptic responses consisted of excitatory post‐synaptic potentials and/or action potentials.

2. None of the neurones tested received synaptic input from spinal cord segment L1. There was synaptic input from segments L2‐L5 of the spinal cord. The strongest synaptic input arose from spinal cord segments L3 and L4.

3. 42% of the neurones tested received synaptic input from only one spinal cord segment. 54% of the neurones tested received convergent synaptic input from two, three or four adjacent lumbar segments.

4. Electrophysiological measurements indicated that the number of preganglionic fibres in any lumbar white ramus communicans which provided synaptic input ranged from one to thirteen. Each lumbar white ramus contained, on average, five preganglionic fibres which provided synaptic input to neurones in the inferior mesenteric ganglion.

5. Changes in intraluminal colonic pressure were measured in vivo during electrical stimulation of preganglionic fibres in the different lumbar white rami and lumbar ventral roots. Electrical stimulation of white rami L3 and L4 abolished phasic changes in intraluminal colonic pressure and reduced basal pressure to near zero. Electrical stimulation of preganglionic fibres in lumbar ventral roots L3 and L4 abolished phasic changes in intraluminal colonic pressure and reduced basal pressure to near zero. Stimulation of ventral roots L1, L2 and L5 had little to no effect on intraluminal pressure.

6. Based on the data obtained in this study, two hypotheses are proposed. First, spinal cord segments L3, L4 and L5 are the primary sources of central synaptic input to neurones in the inferior mesenteric ganglion. Secondly, spinal cord segments L3 and L4 control colonic motility.
Synaptic inhibition of the M‐current: slow excitatory post‐synaptic potential mechanism in bullfrog sympathetic neurones.
Authors: Adams P R , Brown D A
Published: December 2014

1. Slow muscarinic excitatory post‐synaptic currents (slow e.p.s.c.s) generated by preganglionic nerve stimuli were recorded in voltage‐clamped bullfrog sympathetic neurones. 2. IM‐‐an outward, voltage‐dependent, K+‐current‐‐was inhibited during the slow e.p.s.c., and membrane conductance was reduced in a voltage‐dependent manner. 3. The slow e.p.s.c. was associated with reduced outward rectification in the steady‐state current‐‐voltage (I/V) curve at membrane potentials more positive than‐‐60 m V, with no change in the shape of the non‐rectifying part of the I/V curve at more negative potential. 4. The amplitude of the slow e.p.s.c. was reduced by membrane hyperpolarization, to zero at membrane potentials equal to, or more negative than, ‐60 m V. The voltage sensitivity of the slow e.p.s.c. accorded with that of IM. 5. It is concluded that the slow e.p.s.c. results from a selective inhibition of IM.
Effects of some drugs and peptide hormones on the responsiveness of the rabbit isolated gall‐bladder to cholecystokinin.
Authors: Johnson A G , Marshall C E , Wilson I A
Published: December 2014

1. The efficacies of some standard preparations of CCK were compared and the effects of some drugs and peptide hormones on the responsiveness of the rabbit isolated gall‐bladder to cholecystokinin were studied with an established automatic method of estimating cholecystokinin. 2. Atropine, propranolol, phentolamine mesylate and lignocaine were shown to have no effect on the responsiveness of the rabbit isolated gall‐bladder. 3. Glucagon, somatostatin, pentagastrin, pancreatic polypeptide, motilin and the Karolinska preparation of secretin had no effect on the preparation alone and caused only slight changes when given with cholecystokinin. 4. The Boots preparation of secretin exhibited a small cholecystokinin effect when given alone, but considerably inhibited cholecystokinin‐induced contractions. 5. The desulphated C‐terminal octapeptide of cholecystokinin also exhibited inhibitory effects.
The patterns of discharge of static and dynamic gamma motoneurones in the decerebrate rabbit.
Authors: Murphy P R
Published: December 2014

1. The effect of natural stimulation of the limbs (usually pinching the forepaws) on the discharges of muscle spindle primary and secondary afferents and gamma motoneurones of the gastrocnemius medialis muscle were examined in the precollicular decerebrate rabbit, paralysed with gallamine triethiodide to prevent extrafusal muscle contraction. 2. The afferents showed only excitation in response to natural stimulation. The same stimulus strongly inhibited some gamma motoneurones and, at the same time, predominantly excited others. 3. Since extrafusal muscle contraction was prevented using gallamine triethiodide, intrafusal contraction was responsible for the afferent excitation, and could only have been evoked by those gamma motoneurones excited by natural stimulation. The distribution of effects from gamma motoneurones that were strongly inhibited by natural stimulation could not be deduced from afferent recordings. 4. On the basis of these afferent and efferent recordings, and the known structure of the muscle spindle, gamma motoneurones were identified as static or dynamic. 5. The results are discussed in relation to the patterns of discharge of static and dynamic gamma motoneurones.
The influence of injected cyclic AMP protein kinase catalytic subunit on the sodium efflux in barnacle muscle fibres
Authors: Bittar E. Edward , Chambers Geoffrey , Fischer Edmond H.
Published: December 2014

1. A study has been made of the response of the Na efflux in single barnacle muscle fibres to the injection of cyclic AMP protein kinase catalytic subunit (CSU).

2. (i) Injected CSU stimulates the Na efflux in unpoisoned and ouabain‐poisoned fibres. (ii) Stimulation in both situations is always sustained, and (iii) stimulation of the ouabain‐insensitive Na efflux is observed with as low a concentration as 10−7 M‐CSU.

3. (i) The response to injected CSU depends on [Ca]o but is unaffected by prior external application of verapamil. (ii) An effect fails to occur in fibres cooled to 0 °C.

4. (i) Injection of 5′‐guanylylimidodiphosphate (Gpp(NH)p) following peak stimulation by CSU causes a further sustained stimulatory response. (ii) Injection of CSU following peak stimulation by Gpp(NH)p causes a further sustained stimulatory response. (iii) Injection of undialysed cholera toxin following CSU causes little or no effect, whereas injection of dialysed cholera toxin causes a stimulatory effect. Injection of CSU following undialysed cholera toxin causes little or no effect, whereas its injection after dialysed cholera toxin causes a fairly appreciable effect.

5. (i) The response to CSU is reduced by prior injection of protein kinase type 2 regulatory subunit (RII) but not when RII is injected following peak response to CSU. (ii) Injection of protein kinase inhibitor partially reverses the response to CSU.

6. (i) Injection of Mg2+ fully reverses the response to CSU. (ii) Fe and Zn cause only partial reversal.

7. (i) External imipramine but not trifluoperazine reduces the response to CSU. (ii) Diphenylhydantoin is ineffective.

8. These results support the view that CSU behaves as a modulator of the ouabain‐insensitive Na efflux and that Mg2+, Fe and Zn are inhibitors of the catalytic reaction.
Reinnervation of the amphibian cardiac ganglion after complete or partial denervation.
Authors: Ko C P , Roper S
Published: December 2014

The interactions between regenerating and sprouted nerve terminals during reinnervation of neurones were tested in the parasympathetic cardiac ganglion in frogs. 1. After partial (unilateral) vagotomy, remaining intact preganglionic vagal axons rapidly sprouted and innervated the entire ganglion. At later intervals after nerve damage, regenerating vagal axons were able to reinnervate ganglion cells despite the presence of synapses from sprouted nerve terminals. 2. When vagal reinnervation took place after unilateral vagotomy, synaptic input from the sprouted vagus nerve declined. 3. The presence of synapses from intact and sprouted nerve terminals in the ganglion after partial denervation measurably delayed the rate of vagal reinnervation. 4. After complete denervation (bilateral vagotomy), ganglionic reinnervation was rapid and complete. However, cells initially received an excessive number of preganglionic inputs and an abnormal distribution of left/right vagal innervation in the ganglion. 5. At long intervals (up to 85 weeks) after ganglionic reinnervation, some reduction of excess vagal inputs took place, indicating there was a slow re‐organization of ganglionic synapses. 6. The number of boutons per cell body as revealed by zinc iodide‐osmium staining remained constant after vagal reinnervation, despite an initial excessive synaptic reinnervation and subsequent synaptic remodelling.
Free and bound acetylcholine in frog muscle.
Authors: Miledi R , Molenaar P C , Polak R L
Published: December 2014

1. Frog sartorius muscles were divided into end‐plate containing (e.p.) and end‐plate‐free (non‐e.p.) segments or homogenized in Ringer solution at 0 degrees C in the presence or absence of added acetylcholinesterase from electric eel. ACh was extracted from the tissue or from the homogenates and measured by mass fragmentography. 2. The concentration of ACh in non‐e.p. segments was about six times lower than that in e.p. segments. 3. Homogenization of muscles in Ringer caused the hydrolysis of a small fraction (‘free‐1’) of total ACh; addition of extra acetylcholinesterase caused hydrolysis of another, greater, fraction (‘free‐2’ ACh). The esterase‐resistant (‘bound’) ACh was stable at 0 degrees C up to 15 min of incubation. 4. Denervation for 15 days, which caused the disappearance of the nerve terminals, did not influence ACh in non‐e.p. segments, but reduced total and bound ACh by about 75%, and free‐2 ACh by 90%. 5. Treatment with La3+ ions, which caused the disappearance of synaptic vesicles, did not influence total ACh, but reduced bound ACh by 75%, whereas free‐1 and free‐2 ACh were increased. 6. Electrical stimulation of the nerve at 5 sec‐1 or incubation with 50 mM‐KCl did not affect ACh in the non‐e.p. segments, but reduced by roughly 60% total, bound, and free ACh. 7. It is concluded that about 75% of bound ACh derives from synaptic vesicles, corresponding to 11,000 molecules per vesicle, and 25% from non‐neural ACh; that free‐1 and free‐2 ACh derive mainly from the nerve terminal cytoplasm, although they may be contaminated by vesicular ACh.
Characteristics of the electrical response to dopamine in neuroblastoma cells.
Authors: Kato E , Narahashi T
Published: December 2014

1. The characteristics of the electrical response to dopamine in the mouse neuroblastoma cell line N1E‐115 were studied. 2. Neuroblastoma cells responded to ionophoretically applied dopamine by generating a transient depolarization. Under voltage‐clamp conditions, a transient inward current was recorded in response to dopamine application. 3. The receptor was more effectively activated by dopamine than by noradrenaline. Haloperidol blocked the dopamine‐induced current with an apparent dissociation constant of 40 nM. Phentolamine was much less potent than haloperidol, and propranolol had no effect. 4. The dopamine‐induced current was increased in amplitude by hyperpolarizing the membrane, decreased by depolarization, and reversed its polarity at + 14 mV. 5. When the external sodium concentration was decreased from 125 to 94 mM, the reversal potential was shifted in the direction of hyperpolarization by 10 mV. 6. Increasing the external potassium concentration from 0.2 to 20 mM caused a shift of the reversal potential by 13 mV in the direction of depolarization. 7. Replacement of external chloride with isethionate or glutamate caused little or no shift in the reversal potential, but increased the amplitude of the current. 8. Increase in external calcium concentration caused a block of the dopamine‐induced current with an apparent dissociation constant of 1.3 mM, without altering its reversal potential. 9. It is concluded that the ionic channel activated by dopamine undergoes a conductance increase to both sodium and potassium but not to chloride or calcium.
Voltage‐clamp analysis of peptidergic slow depolarizations in bullfrog sympathetic ganglion cells.
Authors: Katayama Y , Nishi S
Published: December 2014

1. The membrane currents during the late slow excitatory post‐synaptic potential (late slow e.p.s.c.s) and luteinizing hormone‐releasing hormone (LHRH)‐induced depolarization of nicotinized and atropinized bullfrog lumbar sympathetic ganglion cells were studied with voltage‐clamp methods. 2. Two types of late slow e.p.s.c. were observed. The Type I response was associated with a decreased conductance and was depressed by membrane hyperpolarization. The Type II response was accompanied by an increased conductance and was augmented by membrane hyperpolarization. 3. LHRH also induced two types of responses. The nature of the LHRH‐induced current and the late slow e.p.s.c. in each neurone was similar, if not identical. 4. The Type I response appeared to be produced primarily by a suppression of the M current (Brown & Adams, 1980) and partially by a depression of the resting K+ conductance. The Type II response is probably due to an increased conductance to Na+ or Na+ and some other cations.
The contribution of the electrogenic sodium—potassium pump to the electrical activity of toad rods
Authors: Torre Vincent
Published: December 2014

1. The membrane potential of rods in the isolated toad retina was recorded while changing the ionic composition of the extracellular medium.

2. Caesium (Cs+) at a concentration of 1 mM was sufficient to completely block the sag from the peak to the plateau in the bright‐flash voltage response.

3. In the presence of 10 mM‐Cs+ the bright‐flash response increased in amplitude to about 90 mV, thus reaching an absolute membrane potential of between ‐110 and ‐135 mV. These responses consisted of an initial fast component of about 35 mV followed by a much slower component which could be as large as 50 mV.

4. At the peak of the initial fast component the rod membrane conformed closely to the behaviour of a K+ electrode with a PNa/PK ratio of 0·023. On average the amplitude of the slow component was about 35 mV in the presence of 2·6 mM‐K+ and was reduced to about 25 mV in a K+‐free Ringer.

5. Addition of 100 μM‐strophanthidin to the perfusate induced several reversible changes in the electrical activity of rods. The dark resting membrane potential depolarized by about 5 mV and the kinetics of the voltage response to dim flashes of light slowed down. The voltage sensitivity initially increased by about 30%, but the peak of the response to a bright flash of light was reduced by about 13 mV.

6. In rods treated with 10 mM‐Cs+ the slow component present in the bright flash response was abolished by strophanthidin with an apparent Km of 3 μM.

7. The amplitude of the slow component decreased with a time lag of about 2 min when external Na+ was reduced. A previous exposure of the retina to a Na+‐free Ringer solution for at least 3 min modified the voltage photoresponse in a way similar to that observed in the presence of 100 μM‐strophanthidin.

8. When external Ca2+ concentration ([Ca2+]o) was increased from 2 to 5 mM the slow component decreased by about 30%. When [Ca2+]o was reduced the slow component increased. A twofold increase was observed when [Ca2+]o was lower than 10−4 M.

9. It is suggested that the slow component of the voltage response in the presence of external Cs+ is caused by an electrogenic current driven by the Na+—K+ transport system, during a voltage‐dependent block of external Cs+ of some K+ channels.
Nerve impulse blockage in squid axons by n‐alkanes: the effect of axon diameter.
Authors: Haydon D A , Hendry B M
Published: December 2014

1. The anaesthetic effects of aqueous solutions of the n‐alkanes pentane to nonane on the propagated action potential of squid axons have been investigated for a range of axon diameters. 2. By the use of small axons (approx. 200 microns diameter) to minimize effects due to long diffusion times and alkane depletion it was found that n‐pentane and n‐hexane caused a rapid reversible inhibition of the impulse, while higher homologues had progressively less effect, n‐nonane being apparently inert. 3. The rate of action potential decline due to the n‐alkanes was found to be strongly dependent on axon diameter. For n‐hexane, n‐heptane and n‐octane the rate of decline was inversely proportional to the square of the axon diameter. 4. The mechanisms which may underly the increased sensitivity of small axons to impulse blockade by n‐alkanes are discussed. A quantitative comparison is made between the effects of n‐hexane, n‐heptane and n‐octane on the action potential. It is argued that this supports the idea of a real decline in anaesthetic potency on ascending the homologous series, rather than an effect due to long diffusion times and solution depletion.
Some determinants of optic terminal localization and retinotopic polarity within fibre populations in the tectum of goldfish.
Authors: Horder T J , Martin K A
Published: December 2014

1. The reorganization of the retinotectal projection which results after partial ablation of tectal tissue was examined in goldfish using electrophysiological methods. 2. Regardless of the size of a unilateral ablation of caudal tectum, an orderly and virtually complete, ‘compressed’, visual projection re‐formed on the remaining tectum after crushing the optic nerve and allowing it to regenerate. 3. If the optic nerve was left intact after ablations of caudal tectum, compressed projections were only found when the ablations were small. Large caudal ablations involving half or more of the dorsal tectum resulted in the cut fibres transposing onto the remaining tectum and forming an overlaid, ‘duplicate’, projection on the remaining intact projection. 4. In approximately one third of cases the duplicate projection lay in a reversed polarity along the rostrocaudal axis of the tectum. In the remaining cases the polarity of the duplicate projection was normal. 5. Transposed projections of reversed rostrocaudal polarity could be consistently obtained by ablating temporal retina and caudal tectum, leaving an intact strip of fibres terminals along the caudal edge of the tectal remnant. 6. Compression and duplication occurred in the same way if fish were maintained in constant light. 7. After ablations of lateral tectum, leaving the optic nerve intact, compression and some disorderly duplications were found. 8. Reversed projections could be induced across the mediolateral axis of dorsal tectum by denervating the medial tectum and ablating a strip of lateral tectum. 9. Projections of normal polarity were found after the optic nerve was allowed to regenerate into tecta which had previously supported reversed polarity projections.
Presence and axonal transport of cholinoceptor, but not adrenoceptor sites on a cat noradrenergic neurone
Authors: Alonso F. G. , Ceña V. , García A. G. , Kirpekar S. M. , Sánchez‐García P.
Published: December 2014

1. Noradrenaline release and radioligand binding studies were carried out in the cat hypogastric nerve ligated in vito 2 cm distal to the inferior mesenteric ganglion for different time periods, and in different effector organs.

2. Large quantities of noradrenaline and dopamine β‐hydroxylase (DBH) accumulated in the segments of nerve immediately proximal (P1) and distal (D1) to the ligation, with rates of about 100 and 25 mm/24 hr for the orthograde and retrograde transport, respectively.

3. Nicotine evoked the release of noradrenaline from P1 and atrial slices; the secretory response to nicotine was completely antagonized by mecamylamine. [3H]α‐bungarotoxin biding to membranes from P1 allowed the estimation of a KD of 2·97 n
m and a Bmax of 1639 f‐mole/mg protein.

4. Acetylcholine inhibited the release of endogenous noradrenaline evoked by high K+ stimulation in atrial slices, but not in P1 segments. Similarly, carbachol decreased [3H]noradrenaline release induced by electrical stimulation (twenty‐six shocks, 2 Hz, 5 msec) in the atrium but not in P1.

5. [3H]Quinuclydinilbenzylate ([3H]QNB) specifically binds to membranes from P1 and vas deferens, following a saturation curve. In the case of P1 segments taken 48 hr after ligation a KD of 0·35 n
m and a Bmax of 129 f‐mole/mg protein were found.

6. The fact that the Bmax in P1 and D1 increased with the time of ligation suggests that orthograde and retrograde axonal transports of muscarinic binding sites exist in this nerve, with approximate rates of transport of 15 and 8 mm/24 hr, respectively.

7. As far as adrenoceptors are concerned, we observed that yohimbine or phentholamine did not modify transmitter release from P1, evoked by high K+ or electrical stimulation. However, yohimbine enhanced the release of [3H]noradrenaline induced by electrical stimulation from splenic slices of the same animals.

8. [3H]Clonidine, [3H]dihydroergocryptine or [3H]dihydroalprenolol ([3H]DHA) did not specifically bind to membranes from P1, in spite of the fact that they showed typical saturation curves for specific binding in cortex and atrial membranes from the same cats.

9. In conclusion, these data (a) further show that the ligated hypogastric nerve is a good model of noradrenergic nerve terminal free of effector cell; (b) provide direct evidence for the neural location of nicotinic receptors whose activation trigger noradrenaline release from noradrenergic neurones; (c) demonstrate the neural location and axonal transport of muscarinic receptor sites, but leave certain doubts about its functional role in this noradrenergic neurone; and (d) do not support the hypothesis that α and β‐adrenoceptors which modulate noradrenaline release from peripheral noradrenergic nerve terminals are neurally (or prejunctionally) located.
Calcium transients evoked by action potentials in frog twitch muscle fibres
Authors: Miledi R. , Parker I. , Zhu P. H.
Published: December 2014

1. Intracellular Ca2+ transients were recorded from frog twitch muscle fibres in response to action potentials and repetitive stimulation, using ionophoretically injected arsenazo III as a Ca2+ monitor. A dual wave‐length optical system was used to measure absorbance changes of the injected dye from small areas of single fibres within the cutaneous pectoris muscle.

2. The absorbance spectrum of the injected arsenazo III in a resting fibre was consistent with an intracellular free Mg2+ level of a few hundred micromolar, assuming an intracellular pH of 7·1. The resting free Ca2+ concentration was below the limit of resolution.

3. The wave‐length dependence of the arsenazo light absorbance signal during twitches followed that expected for Ca2+ binding to the dye. Recordings made at wave‐lengths where the dye is maximally sensitive to pH or Mg2+ concentration changes indicated that interference from these sources is minimal at the usual wave‐length pair (650‐700 nm) used for Ca2+ recordings.

4. Over a wide range of intracellular dye concentrations, the size of the arsenazo response to an action potential increased linearly with dye concentration (100‐1000 μM), although there were deviations from this relationship at low and high concentrations.

5. An approximate estimate of 8 μM was obtained for the peak free Ca2+ concentration change following a single action potential. Changes in temperature (6‐25 °C) did not significantly affect the size of the free Ca2+ transient. During maximal tetanic stimulation the signal rose to about three times higher than the twitch response. An approximate minimum estimate of the increase in total cytoplasmic Ca2+ concentration during a twitch gave a value of 220 μM.

6. A latency of about 1·5 ms (at 10 °C) was observed between the foot of an action potential and the onset of the arsenazo response. Recordings made using a narrow measuring light slit, placed either at the edge or the centre of a fibre, suggested that only a small part of this latency could be due to inward conduction of the action potential along the T‐tubules.

7. The decay phase of the arsenazo response to an action potential followed an exponential time course, with a time constant of 71 ms at 10 °C. This time constant was strongly temperature‐dependent, with a Q10 of about 2·4. An Arrhenius plot of the decay time constant gave a straight line.

8. During repetitive stimulation, the arsenazo responses evoked by successive impulses showed two changes: a progressive decrease in amplitude and a slowing of the decay. The extent to which successive responses summated during a tetanus depended upon the balance between these two effects.