bluuebunny/crossref_metadata_2025 huggingface dataset:
Local vasoactivity of oxygen and carbon dioxide in the right coronary circulation of the dog and pig.
Authors: Ely S W , Sawyer D C , Scott J B
Published: December 2014

1. Eight mongrel dogs were anaesthetized with sodium thiamylal and chloralose‐urethane, ventilated, vagotomized and heparinized. Five Poland‐China pigs were anaesthetized with sodium thiamylal and nitrous oxide, ventilated, vagotomized and heparinized. 2. Extracorporeal perfusion of the right coronary artery at constant pressure (100 mmHg) was instituted. A lung from a donor animal was interposed in the coronary perfusion circuit to effect changes in CO2 and O2 tensions in the coronary arterial blood while systemic blood gases were maintained at normal levels. 3. Local hypoxia (PO2 range 17‐22 mmHg) produced a 25‐75% decrease in coronary vascular resistance (P less than 0.05) and a 0‐24% (not significant) decrease in right ventricular dP/dt. 4. Local changes in PCO2 over the range 8‐105 mmHg were associated with a 17‐58% decrease in coronary vascular resistance (P less than 0.05), a 19‐24% decrease in right ventricular dP/dt (P less than 0.05) with no change in right ventricular end‐diastolic pressure, and a 1‐18% (not significant) decrease in heart rate. 5. These studies suggest that local decreases in O2 or increases in CO2 tensions produce decreases in right coronary vascular resistance that are in the opposite direction to those that would be expected from the observed changes in heart rate and contractility (two primary determinants of myocardial oxygen consumption). 6. These data support the hypothesis that CO2 and O2 are locally vasoactive in the coronary circulation.
Effects of hypoxia on catecholamine synthesis in rabbit carotid body in vitro
Authors: Fidone S. , Gonzalez C. , Yoshizaki K.
Published: December 2014

1. Unanaesthetized, unrestrained rabbits were exposed for 3 hr in a chamber to either air, hypoxic gas mixtures (10% or 14% O2 in N2) or a hyperoxic gas mixture (50% O2 in N2). The carotid bodies were then removed and incubated for 3 hr in modified Tyrode media equilibrated with 100% O2 and containing either [3H]tyrosine or [3H]DOPA. The contents of [3H]DA and [3H]NA in the tissue were determined as described in the preceding paper.

2. When [3H]DOPA was used as precursor, neither labelled dopamine (DA) or noradrenaline (NA) synthesis was increased in carotid bodies from rabbits exposed to 10% O2 in N2. Following exposure to 10% O2 in N2 and incubation with [3H]tyrosine, however, [3H]DA synthesis was increased by 72% above control (air) values while [3H]NA synthesis was unchanged. Less severe hypoxia, 14% O2 in N2, resulted in a smaller increase in [3H]DA synthesis, i.e. 53% above control value. Again, [3H]NA synthesis was unchanged. Similar experiments with the superior cervical ganglion involving exposure of the animals to either 10% or 14% O2 in N2 did not produce any change in the amounts of [3H]DA or [3H]NA synthesized from [3H]tyrosine when compared to control animals breathing air.

3. Sympathectomy of the carotid body or transection of the carotid sinus nerve 12‐15 days prior to hypoxic exposure (10% O2 in N2) did not alter the increase in [3H]DA synthesis compared to normally innervated carotid bodies.

4. Carotid bodies incubated with [3H]tyrosine for 2 hr in an alternating O2/N2 sequence (5 min in media equilibrated with 100% O2 followed by 3 min in media equilibrated with 100% N2) synthesized 37% more [3H]DA than control carotid bodies similarly exposed to an alternating O2/O2 sequence. [3H]NA synthesis was unchanged. However, tissue levels of non‐metabolized [3H]tyrosine were reduced by 19% in the carotid bodies exposed to the O2/N2 sequence.

5. Exposure of rabbits for 3 hr to 50% O2 in N2, followed by incubation of their carotid bodies in [3H]tyrosine, resulted in a 19% decrease in the absolute value for [3H]DA synthesis compared to control carotid bodies, but this difference was not significant (P > 0·05). However, [3H]NA synthesis was significantly reduced (51%; P < 0·05) in the hyperoxic carotid bodies. Similar experiments with the superior cervical ganglion showed that [3H]DA and [3H]NA synthesis were unchanged under control vs. hyperoxic conditions.

6. Carotid bodies incubated with [3H]tyrosine for 3 hr, then transferred for 1 hr to unlabelled media equilibrated with 10% O2 in N2, released 81% more [3H]DA, and contained 38% less [3H]DA, than similarly treated carotid bodies exposed to 100% O2. [3H]NA was not detectable in the media, and tissue levels of [3H]NA were the same in both hypoxic and control carotid bodies.
Effects of low oxygen on the release of dopamine from the rabbit carotid body in vitro
Authors: Fidone S. , Gonzalez C. , Yoshizaki K.
Published: December 2014

1. Rabbit carotid bodies were pre‐loaded with [3H]dopamine (DA) synthesized from [3H]tyrosine and then mounted in a vertical drop‐type superfusion chamber which permitted simultaneous collection of released [3H]DA and recording of chemoreceptor discharge from the carotid sinus nerve.

2. The time course of the spontaneous release of [3H]DA (superfusion with media equilibrated with 100% O2) in the presence of monoamine oxidase inhibitors exhibited two linear components, an initial steep phase followed after 3‐4 hr by a later slower phase of release.

3. When a 5 min low O2 stimulus was delivered during the initial steep linear component of resting [3H]DA release, there was an abrupt increase in release, the magnitude of which was stimulus‐dependent.

4. The efflux of total radioactivity from the preparation declined exponentially with time; under resting conditions it was principally non‐metabolized [3H]tyrosine. During stimulation, however the efflux increased, and 60‐80% of the radioactivity could be attributed to [3H]DA.

5. For a given low O2 stimulus, the ratio of [3H]DA release during the stimulus period over that in the preceding control period remained approximately the same throughout a single experiment. Ratios for different low O2 stimuli (50, 40, 30, 20, 10 and 0% O2 in N2) yielded a parabolic relationship when plotted against stimulus intensity.

6. Transection of the carotid sinus nerve or removal of the superior cervical ganglion 12‐15 days prior to the experiment did not affect the release of [3H]DA at moderate stimulus intensities (superfusion with media equilibrated with 30% or 10% O2 in N2) but both procedures significantly depressed release at the highest stimulus intensity (100% N2).

7. Chemoreceptor discharge and [3H]DA release were simultaneously monitored in experiments using superfusion media free of monoamine oxidase inhibitors. In these experiments, the efflux of [3H]dihydroxyphenyl acetic acid (DOPAC) was also measured. The increase in peak chemosensory discharge was closely correlated with the increase in total release ([3H]DA + [3H]DOPAC) during stimulation with a series of low O2 stimuli.

8. Release of [3H]DA was almost completely abolished during superfusion with Ca2+‐free, high Mg2+ (2·1 mM) media, and the stimulus‐related efflux of [3H]DOPAC was significantly reduced. However, chemoreceptor discharge was diminished by only 55%. These data are discussed with respect to their implications for DA as a chemosensory transmitter in rabbit carotid body.
Free magnesium in sheep, ferret and frog striated muscle at rest measured with ion‐selective micro‐electrodes
Authors: Hess P. , Metzger P. , Weingart R.
Published: December 2014

1. Neutral carrier‐based liquid membrane micro‐electrodes were constructed which are suitable for continuous measurements of [Mg2+]i in cardiac and skeletal muscle preparations.

2. The electrodes show a Nernstian behaviour in pure MgCl2 solutions. In the presence of a constant ionic background chosen to simulate the cytoplasmic composition, the calibration function flattens progressively with lower [Mg2+], due to the interference of K+ and Na+. The response to changes in [Mg2+] is less than 0·5 sec.

3. In quiescent preparations at room temperature (23 °C), the following basal [Mg2+]i were determined: 3·5 mM (sheep Purkinje fibres), 3·1 mM (sheep ventricular muscle), 3·0 mM (ferret ventricular muscle) and 3·3 mM (frog skeletal muscle).

4. In cardiac tissue, electrical stimulation does not measurably affect the basal [Mg2+]i.

5. In the presence of 0·5 mM‐Mg2+o, the calculated Mg2+ equilibrium potentials, EMg, are in the range of ‐23 to ‐25 mV, suggesting that Mg2+ is not passively distributed across the sarcolemma in striated muscle.

6. Further studies were performed on sheep Purkinje fibres to investigate the effect of various experimental interventions on [Mg2+]i.

7. Elevating [Mg2+]o from 0·5 to 10 mM resulted in a reversible increase of [Mg2+]i. The initial rate of increase corresponds to a Mg2+ influx of 0·42 p‐mole/cm2.sec, or a magnesium permeability, PMg, of 1·6 × 10−8cm/sec.

8. Increasing PCO2 from nominally 0 to 100 mmHg (Tris‐buffered vs. bicarbonate‐buffered Tyrode solution) produced a reversible decrease in [Mg2+]i by roughly 0·45 mM, probably due to Mg2+ binding the newly formed intracellular HCO3−.

9. The effect of metabolic poisoning on [Mg2+]i was assessed by exposure to cyanide, iodoacetic acid and 2‐4‐dinitrophenol. No significant increase in [Mg2+]i indicative of a liberation of Mg2+ from ATP was observed.
Electrophysiology and innervation of the smooth muscle of dog inferior vena cava.
Authors: Mekata F , Nagatsu I
Published: December 2014

1. Electrical properties of outer and inner muscles of three portions of dog inferior vena cava and their catecholaminergic innervation were investigated by microelectrode recording and an immunohistochemical technique. 2. There was no difference in the electrical properties of outer and inner muscles of the supradiaphragmatic (portion a) or the infrarenal (portion c) segments which had a quiescent membrane potential, delayed rectification, strong outward going rectification and no action potential. 3. In the longitudinal muscle which made up most of the segment (portion b) between the liver and renal veins, some of the outermost cells fired slow discharges and others action potentials in response to depolarizing current, but no cells from the innermost layer of longitudinal muscle of this portion did so. 4. All smooth muscle portions of the inferior vena cava showed a current spread in the direction of the long axis of the cell. Mean values of space constant of portions a, b and c were 2.25, 1.15 and 0.99 mm, respectively. 5. Noradrenergic nerve terminals were widely distributed in the longitudinal muscle layer of portion b and the circular muscle layer of portion c. Few nerve terminals were seen in any part of portion a. 6. The results suggest that a tendency to repetitive electrical activity was associated with outer smooth muscle aligned longitudinally, though a low space constant may have been associated with noradrenergic innervation.
Properties of junctional and extrajunctional acetylcholine‐receptor channels in organ cultured human muscle fibres
Authors: Cull‐Candy S. G. , Miledi R. , Uchitel O. D.
Published: December 2014

1. Current noise, obtained during steady ionophoretic application of acetylcholine (ACh) to voltage‐clamped human fibres has been analysed to derive properties of end‐plate channels and also extrajunctional ACh‐activated channels which are present at the muscle—tendon junction of normal fibres. In addition, ACh‐receptor channels present at the end‐plate and tendon region in organ cultured muscles have been compared with those in fresh muscles.

2. Extrajunctional channels in the tendon region of fresh fibres have a longer mean life‐time, τ, and a smaller single channel conductance, γ, than the junctional channels. τ was 1·71 ±0·11 msec and γ was 25·05 ± 1·18 pS for junctional channels; τ was 3·16 ± 0·33 msec and γ was 12·76 ± 1·29 pS for extrajunctional channels.

3. Properties of channels in the end‐plate and tendon region were unchanged during short‐term (< 7 days) organ culture at 23 or 36 °C. The voltage sensitivity of the mean channel life‐time was similar at junctional and extrajunctional sites.

4. In muscles organ cultured for 7 days at 36 °C, double component noise spectra were obtained at some end‐plates. The fast and slow time constants underlying the noise appeared to correspond to simultaneous activation of junctional and extrajunctional channels.

5. After organ culture for 3‐4 weeks at 23 °C the mean life‐time of the end‐plate channels was prolonged while their single channel conductance was unchanged, τ = 3·58 ± 0·16 msec; γ = 22·11 ± 0·83 pS (Vm = ‐80 mV, T = 21 °C).

6. As end‐plate channel properties were unchanged in short‐term cultures it was possible to assess post‐junctional sensitivity by comparing miniature end‐plate current (m.e.p.c.) amplitudes in both normal and myasthenia gravis affected muscles. No evidence was found for a change in post‐synaptic sensitivity during organ culture at 23 °C of normal or myasthenia gravis muscle fibres, which seems to rule out reversible block of receptors by anti‐receptor antibody as playing an important role in myasthenia gravis.
The pCa‐tension and force‐velocity characteristics of skinned fibres isolated from fish fast and slow muscles
Authors: Altringham J. D. , Johnston I. A.
Published: December 2014

1. Single fast fibres and small bundles of two to six slow fibres were dissected from the myotomal muscles of the cod, Gadus morhua, and the dogfish, Scyliorhinus canicula. Fibres were chemically skinned with the non‐ionic detergent Brij 58.

2. The isometric tension properties were investigated. Maximal isometric tensions (mean ± S.E. of mean) were 18·65±1·18 (n = 11) and 8·34±0·98 (n = 13) N cm−2 for cod fast and slow fibres, and 18·34±0·88 (n = 28) and 8·24±0·39 (n = 12) N cm−2 for dogfish fast and slow fibres respectively. The values are comparable to those observed in mammalian and amphibian skinned fibres. The lower tensions generated by the slow fibres cannot be fully explained on the basis of their lower myofibrillar fractional volume.

3. In common with previous studies, a steep sigmoid relationship between pCa and tension was observed. The threshold for tension generation was around pCa 7·2. Half‐maximal pCas were 6·08 and 6·42 for cod fast and slow muscle, and 6·41 and 6·50 for dogfish fast and slow fibres respectively. Cod fibres were maximally activated at around pCa 5·18, and dogfish fibres at pCa 5·62.

4. Contraction‐induced residual tensions were observed in cod fast fibres after return to relaxing solution. This phenomenon is a feature common to many skinned fibre studies, but the mechanism behind it has yet to be resolved.

5. The force‐velocity characteristics of fast and slow fibres have been investigated (at 8 °C).

6. Points below 0·6 P0 on the P-V curves could be fitted to a linear form of the Hill equation. Extrapolated Vmaxs were calculated as follows: cod fast fibre Vmax = 1·01 muscle length sec−1 (Lsec−1) (a = 0·21 P0; b = 0·21 Lsec−1). Slow fibre = 0·53 Lsec−1 (a = 0·28P0; b = 0·21 Lsec−1). Dogfish fast fibre Vmax = 2·34 Lsec−1 (a = 0·06 P0; b = 0·14 Lsec−1). Slow fibre = 0·67 Lsec−1 (a = 0·19 P0; b = 0·13 Lsec−1).

7. Contraction velocity in cod slow fibres decreased continuously to produce markedly non‐linear velocity transients, similar to those reported for amphibian slow fibres.

8. The effect of altering Ca2+ concentration on the shape of the isotonic velocity curve (at low loads) was studied in dogfish fast fibres (0·5‐1 °C). Contraction velocity decreased continuously during shortening, at both maximal and half‐maximal Ca2+ concentration. The rate of decay of velocity with shortening was greater at low Ca2+ concentration.
Effect of stimulation of the vagus nerve in bursts on gastric acid secretion and motility in the anaesthetized ferret.
Authors: Grundy D , Scratcherd T
Published: December 2014

1. The effect of electrical stimulation of the vagus nerve with different patterns of impulses (the total number of stimuli remaining constant) on gastric acid secretion and gastric motility were investigated in the anaesthetized ferret. Three stimulus patterns were used: continuous, bursts at ten times the continuous frequency but for a tenth of the time, and a natural burst pattern obtained from a recording of vagal efferent fibre discharge. 2. The natural burst pattern gave rise to gastric contractions of larger amplitude than either the artificial burst or continuous stimulation, while continuous stimulation gave rise to larger changes in tonus. Acid secretion, however, was reduced by the natural pattern of stimulation as compared to the output during continuous stimulation, but to a lesser extent than that due to artificial burst stimulation. 3. Burst stimulation at 10 impulses/sec resulted in a larger output of acid and greater amplitude of gastric contraction than the equivalent continuous stimulation. This potentiation was lost at stimulation frequencies above 30 impulses/sec. 4. At burst frequencies of 60 and 120 impulses/sec there was a marked reduction in acid output and amplitude of contraction as compared with continuous stimulation at 6 and 12 impulses/sec respectively. 5. These results are discussed in relation to the functional significance of the different patterns of vagal discharge seen in the anaesthetized ferret.
The thermoregulatory effects of noradrenaline, serotonin and carbachol injected into the rat spinal subarachnoid space
Authors: Lopachin Richard M. , Rudy T. A.
Published: December 2014

1. We have examined the effects on thermoregulation in the rat of noradrenaline bitartrate (NA), 5‐hydroxytryptamine hydrochloride (5‐HT) and carbamylcholine chloride (CCh) injected into the lumbar spinal subarachnoid space via a chronic indwelling catheter.

2. Intrathecal injections of the monoamines and CCh reproducibly affected thermoregulation, whereas injections of control solutions had no effect.

3. Intrathecal injections of NA (0·01‐0·30 μmol) produced a dose‐dependent hypothermia associated with a decrease in tail skin vasomotor tone. Shivering activity was not depressed during the hypothermia and sometimes increased. Intrathecal administration of the α‐adrenergic agonist clonidine (0·0175‐0·070 μmol) elicited changes in Tc and Tsk similar to those induced by intrathecal NA.

4. Intrathecal 5‐HT (0·030‐0·90 μmol) elicited a dose‐dependent hyperthermia accompanied by increased tail skin vasomotor tone and increased shivering.

5. CCh injected intrathecally (0·001‐0·06 μmol) evoked a dose‐dependent hyperthermia. During the period when core temperature was rising, tail skin vasomotor tone increased and shivering‐like activity was present. Once the maximum core temperature had been reached, tail skin vasodilatation occurred. Vasodilatation persisted until core temperature had returned to normal.

6. Intravenous injections of 5‐HT (0·30 and 0·90 μmol) or CCh (0·006 and 0·03 μmol) caused no thermoregulatory effect. The effects of these agents injected intrathecally were therefore not due to an action in the periphery.

7. Intravenous infusions of NA (0·06 and 0·10 μmol) produced hypothermia and transient tail skin vasodilatation. We suggest that an action at peripheral sites may have contributed to the effects produced by intrathecal injection of this monamine.

8. These findings suggest that spinal noradrenergic, serotonergic and cholinergic synapses may be importantly involved in the control of body temperature in the rat. The possible functional roles of these synapses and the putative spinal sites of action of the injected substances are discussed.
Facial thermal input in the caudal trigeminal nucleus of rats reared at 30 degrees C.
Authors: Dawson N J , Hellon R F , Herington J G , Young A A
Published: December 2014

1. Rats reared from birth in air at 30 degrees C showed a decreased ability to maintain colonic temperature when exposed to 10 degrees C as compared with rats reared at 20 degrees C. This difference was not due to physical factors affecting heat loss, such as surface area or fur thickness. 2. In anaesthetized rats extracellular recordings were made in trigeminal nucleus caudalis from higher order neurones with input from facial cold and warm receptors. A systematic search on a grid pattern showed there was no difference between heat‐reared and control rats in facial receptive fields or in the abundance, extent and somatotopic distribution of thermal neurones in the nucleus. In both groups almost all the neurones were excited only by facial cooling. 3. When single cold neurones were tested quantitatively by the application of controlled temperature changes to their receptive fields on the face there was no difference in the static temperature/discharge rate relationship between the two groups of rats. 4. The results suggest that the observed difference in ability to regulate body temperature is not attributable to differences in skin‐temperature reception at the level of the trigeminal nucleus.
The milk ejection reflex in the pig
Authors: Ellendorff F. , Forsling M. L. , Poulain D. A.
Published: December 2014

1. The milk ejection reflex in response to suckling was studied in conscious sows by continuous recording of intramammary pressure, radioimmunoassay of plasma concentrations of neurohypophysial hormones, and observation of the behaviour of the sows and piglets.

2. A regular pattern of nursing, suckling and milk ejection was observed. The mean duration of the suckling period was 6·3 min. Over 144 suckling periods, 113 milk ejections were recorded. Each milk ejection was characterized by a sudden rise in intramammary pressure reaching 20‐49 mmHg, and lasting 8‐41 sec. Milk ejections occurred only once per suckling period, at a mean interval of 44·3 min.

3. Each milk ejection occurred with a mean latency of 2·4 min from the onset of a period of initial massage of the udders by the piglets, and was coincident with a period of quiet suckling when the piglets were consuming milk. The onset of nursing was signalled by the sows grunting in a rhythmic manner. In most cases, the frequency of grunts, at first low, increased suddenly 23 sec before milk ejection.

4. During eighteen suckling periods leading to milk ejection, neurohypophysial hormone assays performed on serial blood samples showed an increase in plasma concentration of oxytocin up to 30 sec before milk ejection. The concentration of lysine—vasopressin did not rise above basal levels.

5. In 21·4% of the suckling periods, no rise in intramammary pressure was observed. In these ‘incomplete sucklings’, the sow usually failed to grunt rapidly, and the piglets obtained no milk. For three of these periods, hormone assay showed no increase in oxytocin or vasopressin concentrations in blood.

6. Oxytocin given intravenously produced variations in intramammary pressure which depended on the dose and the rate of injection. Rapid injections of 25‐50 m‐u. oxytocin, caused milk ejections similar to those induced by suckling. When oxytocin was administered at different rates, the faster the injection, the shorter the latency and the higher the amplitude of the response. Plasma concentrations of oxytocin after injection of 25 m‐u. were similar to those observed during reflex milk ejection.

7. Trains of electrical pulses were applied to the posterior pituitary of four anaesthetized sows. At frequencies of stimulation above 10 Hz, a rise in intramammary pressure and an increase in plasma oxytocin and vasopressin concentrations were observed. At frequencies of stimulation of 30‐50 Hz, the response of the mammary gland and the time course of the variations in oxytocin plasma concentrations were similar to those observed during natural reflex milk ejection.

8. It is concluded that reflex milk ejections during suckling in the pig are caused by the intermittent and spurt‐like release of about 25 m‐u. oxytocin, without concomitant vasopressin release. It is postulated that the release of oxytocin is probably precipitated by a brief and massive activation of oxytocin‐secreting neurones in the hypothalamus. Central mechanisms controlling the intermittent release of oxytocin are discussed.
The effects of low concentrations of cardiotonic steroids on membrane currents and tension in sheep Purkinje fibres
Authors: Hart G. , Noble D. , Shimoni Y.
Published: December 2014

1. Simultaneous measurements of voltage‐clamp currents and tension were made in shortened sheep Purkinje fibres exposed to various concentrations of strophanthidin, ouabain and digoxin.

2. In 5·4 mM‐K moderate doses (mean 2·4 × 10−7M) of the drugs produced an inward shift of the current—voltage relationship at very negative potentials, consistent with an increase in cleft K concentration (Cohen, Daut & Noble, 1976b), which was always accompanied by an increase in tension. This change, which has been attributed to Na—K pump inhibition, was often better correlated with an increase in voltage‐dependent tonic tension than in twitch tension.

3. Exposure to dihydro‐ouabain gave a monotonic increase in tension but a delayed increase in inward current. This suggests (cf. Lee, Kang, Sokol & Lee, 1980) that minor changes in pump activity may not always change the current—voltage relationship.

4. Low concentrations of strophanthidin (5 × 10−9 to 5 × 10−7 M) produced an outward current shift at very negative potentials, this change becoming smaller with a more rapid onset and reversing on increasing the dose. This change is attributed to pump stimulation.

5. The outward current shift was often associated with a negative inotropic effect, which always reversed either spontaneously or on removal of the drug.

6. The alternative response at a narrower dose range (1 × 10−8 to 2 × 10−7 M) was an increase in twitch (not tonic) tension, termed the low‐dose positive inotropic effect.

7. After a low concentration of cardiotonic steroid had given an early negative inotropic effect the bulk Ca concentration was reduced and the drug re‐applied. The low‐dose positive inotropic mechanism was then observed.

8. Outward current shifts and negative inotropy were also obtained with low concentrations of the clinically used glycosides digoxin and ouabain.

9. Low concentrations of strophanthidin applied to externally stimulated sheep ventricular trabeculae produced negative inotropy with lengthening of the action potential duration. Positive inotropy and action potential shortening occurred with higher doses.

10. A computer model of ionic currents and distributions in Purkinje fibres satisfactorily reproduced the changes in membrane currents and ionic gradients observed with cardiotonic steroids. The only perturbations capable of explaining our results were Na pump stimulation and inhibition.

11. It is concluded that cardiotonic steroids possess two inotropic mechanisms. The first is a low‐dose positive inotropic mechanism causally unrelated to changes in sodium pump activity and possibly a direct release of a membrane‐associated calcium fraction. Should this mechanism be unavailable then net pump stimulation at low doses will produce negative inotropy. The second mechanism is the well known Na‐lag process.
Neural units in the superior cervical ganglion of the guinea‐pig.
Authors: Purves D , Wigston D J
Published: December 2014

The size and arrangement of the set of neurones innervated by individual preganglionic axons (the neural unit) has been investigated in the superior cervical ganglion of the guinea‐pig. 1. Based on the ratio of preganglionic neurones to ganglion cells, and the average number of axons contacting each ganglion cell, we estimated that individual preganglionic axons innervate on the order of 50‐200 superior cervical ganglion cells. 2. Of 562 pairs of ganglion cells examined with intracellular recording, forty‐seven (8.4%) were innervated by one or more common axons. 3. Pairs of ganglion cells innervated by the same axon were not necessarily near each other. Although nearby cells were more likely to share innervation than neurones far apart, cells sharing innervation were often found several hundred micrometers apart, and were occasionally separated by the largest dimension of the ganglion (about 1‐2 mm). 4. The incidence of cell pairs that shared innervation from more than one axon was greater than expected from the frequency of pairs sharing at least one axon. 5. Extracellular recordings from small fascicles of the cervical sympathetic trunk showed that preganglionic axons from different segmental levels intermingle extensively en route to the superior cervical ganglion. 6. Taken together, these findings support the view that sets of ganglion cells are innervated in common not because of any special topographic relationship within the ganglion, but because they share one or more properties that make them especially attractive to particular preganglionic axons.
Effects of extracellular potassium concentration on the excitability of the parallel fibres of the rat cerebellum.
Authors: Kocsis J D , Malenka R C , Waxman S G
Published: December 2014

1. Field potentials and extracellular potassium concentration, [K+]o, were recorded from the rat cerebellar cortex using ion‐selective micro‐electrodes, following micro‐stimulation of the cerebellar surface. The compound action potential of the parallel fibres (p.f.s) showed changes indicative of a supernormal period (s.n.p) when conditioned by a previous p.f. volley, and was studied in relation to [K+]o. 2. Repetitive stimulation of the p.f.s (greater than 10 Hz) elicited an alternation in p.f. excitability from supernormality to subnormality simultaneous to a steady increase in [K+]o. 3. Superfusion with various levels of K+ led to changes in the p.f. conduction properties. Small increases in [K+]o above the resting 3.0 mM level led to an increase in p.f. conduction velocity while greater increases led to conduction slowing and eventually block. 4. Repetitive activation of a row of p.f.s elicited increases in [K+]o in the vicinity of neighbouring non‐activated fibres. These fibres displayed an increase in excitability that was quantitatively related to [K+]o. 5. After introduction of 4‐aminopyridine (4‐AP; 100 microM) into the superfusate, a single stimulus would elicit relatively large (up to 15 mM) increases in [K+]o around neighbouring non‐activated p.f.s. The excitability of the adjacent non‐activated fibres was either increased or decreased, and was quantitatively related to [K+]o. 6. Strophanthidin application (15 microM) led to a slow and continuous increase in [K+]o. The excitability of the p.f.s initially increased as [K+]o increased, but subsequently decreased, eventually resulting in conduction block. 7. These experiments are consistent with the hypothesis that small increases in [K+]o may elicit an increase in p.f. excitability while greater increases lead to a decrease in p.f. excitability.
Colonic motor and vascular responses to pelvic nerve stimulation and their relation to local peptide release in the cat.
Authors: Andersson P O , Bloom S R , Järhult J
Published: December 2014

1. The effects of stimulation of the pelvic nerves in atropinized cats at continuous, low frequencies from 1 to 16 Hz (continuous stimulation) were compared with those of stimulation at higher frequencies (10‐160 Hz) delivered in 1 s bursts at 10 s intervals (stimulation in bursts), the latter simulating a commonly observed discharge pattern in vivo. Both types of stimulation evoked a transient vasodilatation. Stimulation in bursts at 20 and 40 Hz evoked more pronounced vasodilatations than continuous stimulation delivering exactly the same number of impulses over the whole period of excitation. 2. Stimulation of the pelvic nerves in bursts failed to elicit an effective contraction of the colon at any frequency tested, whereas continuous stimulation invariably evoked a contraction. 3. There was a clear‐cut increase in the output of vasoactive intestinal polypeptide during both continuous and intermittent stimulation of the pelvic nerves. Stimulation in bursts caused a small but significant increase in the output of somatostatin but there was no change in the output of substance P in response to either type of pelvic nerve stimulation. 4. The colonic muscular contraction in response to continuous stimulation of the pelvic nerves was not affected by somatostatin when infused intra‐arterially at the large dose of 1.0 microgram/min. 5. It is concluded that the colonic responses of atropinized cats to pelvic nerve stimulation can be substantially altered merely by changing the pattern of stimulation. Thus, whereas continuous stimulation produces both muscular contraction and vasodilatation, stimulation in bursts favours vasodilatation but is ineffective in eliciting colonic contraction.
The contracture produced by sodium removal in the non‐pregnant rat myometrium.
Authors: Masahashi T , Tomita T
Published: December 2014

1. Mechanical responses to Na removal were investigated in the circular and longitudinal muscles of the non‐pregnant rat myometrium at 35 degrees C. In both muscles, reduction of the external Na concentration to less than 20 mM produced an initial acceleration of phasic contractions and a sustained tonic contracture. No difference was found with different Na substitutes (Tris‐hydroxymethyl aminomethane, choline, dimethyl diethanol ammonium). However, when Mg was substituted for Na, only the tonic contracture was produced without the phasic contractions. 2. Readmission of 5‐10 mM‐Na, after exposure to Na‐free solution, relaxed the contracture produced by Na removal. The degree of relaxation was dependent on the Na concentration readmitted and on the period of pre‐treatment with Na‐free solution, being stronger with longer pre‐treatment. 3. In the presence of Na, excess Ca failed to increase the muscle tone. In the absence of Na, the tension development was closely related to the external Ca concentration up to 20 mM. In the absence of both Ca and Na, some tension remained. Even after pre‐treatment with Ca‐free solution containing 0.1‐0.5 mM EGTA, removal of Na caused some mechanical response. A similar small tension development was observed when Na removal was repeated during prolonged absence of external Ca for more than 3 h. 4. Verapamil (2 X 10(‐4) M) markedly suppressed the response to Na removal, but it did not block it, either in the presence or in the absence of Ca. Ouabain (10(‐3) M) in the presence of verapamil potentiated the early phasic component of the response to Na removal, but the tonic component was little affected or even slightly reduced. 5. The results indicate that there are three components in the mechanical response to Na removal: the phasic and tonic components, which are highly Ca‐dependent, and the third small tonic component, which is independent of external Ca. Most of the phasic and tonic responses seem to be due to an increase in Ca permeability, but this may be secondary to membrane depolarization. A Na‐Ca exchange mechanism is also considered to contribute to the transient phase of the response to Na removal and to Na readmission.
Blood flow through arteriovenous anastomoses and its thermal function in the laying hen.
Authors: Wolfenson D
Published: December 2014

1. Total (arteriovenous anastomoses + capillary) blood flow (t.b.f.) and capillary blood flow (c.b.f.) distribution were determined by 52 and 15 micron microspheres respectively, in body organs of six unanaesthetized laying hens, exposed to thermoneutral air temperatures. 2. Statistically significant differences between t.b.f. and c.b.f. were only found in the unfeathered metatarsal skin, comb and wattles. The c.b.f. constituted 22, 42 and 45% of t.b.f. respectively, indicating significant arteriovenous anastomoses (a.v.a.) blood flow. Differences between t.b.f. and c.b.f. were small in the two larger ovarian follicles and digestive tract and were negligible in reproductive tract, liver and kidney. 3. Microspheres of different size have been injected into the external ischiadic artery in order to examine the vasomotor responses of leg tissues in twenty‐one hens kept in thermoneutral, cold or hot conditions. 4. In cold, thermoneutral and hot conditions 1, 16 and 35% of whole leg blood flow respectively passed through a.v.a. Only c.b.f. was present in bone and muscle in either treatment; cold and heat reduced it in bones and cold increased it in muscles. Arteriovenous anastomoses blood flow appeared mostly in unfeathered skin; it constituted 17, 53 and 83% of t.b.f. to this tissue in cold, thermoneutral and hot conditions, while t.b.f. increased from 1.4 to 14% and 30% of whole leg blood flow respectively. Blood flow to feathered skin decreased during heat and cold.
Calcium action potentials in rat fast‐twitch and slow‐twitch muscle fibres.
Authors: Chiarandini D J , Stefani E
Published: December 2014

Slow action potentials were evoked in twitch fibres of rat extensor digitorum longus (e.d.l.) and soleus muscles after drastically reducing the Cl and K conductances of the muscle fibres. Cl conductance was eliminated by exposing the muscles to a Cl‐free saline in which methanesulphonate replaced Cl. K conductance was reduced by adding tetraethylammonium (TEA) and 3,4‐diaminopyridine (3,4‐DAP) to the Cl‐free saline or by overnight incubation of the muscles in a saline containing Cs and TEA. The delayed rectifier was markedly blocked by TEA and 3,4‐DAP. In contrast, the inward rectifier was blocked only by TEA. Depolarization with pulses of increasing amplitude triggered slow responses which had a threshold of ‐30 to ‐10 mV and a peak amplitude of 50‐60 mV. In e.d.l. muscles the time course of the response was sustained for the duration of the pulses and was not affected by repeated stimulation. In soleus muscles the first evoked response was sustained in about 60% of the fibres and transient in the rest. Transient responses reached a peak amplitude and were followed by a hyperpolarization. Repeated stimulation irreversibly transformed the sustained responses of soleus fibres into transient ones. The responses were blocked when the Ca in saline was replaced by Mg (10 mM) or Co (5 mM) or by the addition of Cd (0.1‐1.0 mM) or nifedipine (5‐6 microM). Tetrodotoxin did not affect the responses. These results strongly suggest that Ca is the main carrier of current during the response. Nifedipine blocked both the Ca response and the subsequent hyperpolarization, suggesting that the latter is due to the activation of a Ca‐dependent K conductance.
Acidotic depression of cyclic AMP accumulation and phosphorylase b to a transformation in skeletal muscle of man.
Authors: Chasiotis D , Hultman E , Sahlin K
Published: December 2014

Intravenous infusion of adrenaline was performed in three healthy subjects on two occasions. In one case subjects performed a maximal isometric contraction before infusion. Biopsies were taken from the quadriceps femoris muscle before and after infusion for 0.5 and 2 min, and analysed for muscle pH, cyclic AMP, metabolites and activities of glycogen phosphorylase and synthetase. Isometric contraction resulted in a decrease of muscle pH to 6.60 (normal value at rest 7.0‐7.1). By this experimental procedure the effect of adrenaline infusion could be studied on a muscle with normal pH and one with low pH. Cyclic AMP increased from 3 to about 9.5 mumol per kg dry weight after 0.5 min of adrenaline infusion. When isometric contraction preceded the infusion, cyclic AMP increased more slowly and was about 5.5 mumol per kg dry weight after the same time of infusion. Phosphorylase a constituted about 22% of total phosphorylase in resting muscle but increased rapidly to 80% after 0.5 min infusion. When exercise preceded infusion phosphorylase a decreased and was still lower after 2 min infusion. The results can be explained by inhibition of adenylcyclase and phosphorylase b kinase at low muscle pH.
Actions on gamma‐motoneurones elicited by electrical stimulation of group I muscle afferent fibres in the hind limb of the cat.
Authors: Appelberg B , Hulliger M , Johansson H , Sojka P
Published: December 2014

The reflex actions, elicited by graded electrical stimulation of hind‐limb muscle, skin and joint nerves were studied in an extended series of experiments in extra‐and intracellular recordings from 120 lumbar gamma‐motoneurones of cats anaesthetized with chloralose. The present report deals with the action of group I muscle afferent fibres, which was examined in ninety‐five gamma‐cells. Of the gamma‐cells 83% were classified as either static or dynamic by stimulation in the mesencephalic area for dynamic control. The general responsiveness (i.e. number of input nerves with effect/number of input nerves tested) of the cells was very high (89.9%). The responsiveness to stimulation of group I muscle afferent fibres was extremely low, both in flexor and extensor gamma‐motoneurones and irrespective of whether they were static or dynamic. There was no difference, as regards the low incidence of group I muscle reflex action, between stimulation of autogenetic and heteronymous nerves. Among the rare reflex effects elicited from group I muscle fibres inhibition was four times as frequent as excitation. Inhibitory effects could be provoked from the autogenetic as well as from the heteronymous nerves. In contrast, excitatory effects were almost always autogenetic. The scarcity of group I muscle action on gamma‐motoneurones is in striking contrast to the well known and powerful reflex actions of Ia and Ib fibres on alpha‐motoneurones. These findings are discussed in relation to the concept of alpha‐gamma linkage, and it is concluded that skeletomotor and fusimotor activity cannot be rigidly linked under all conditions.
Kinetics of sodium‐dependent solute transport by rabbit renal and jejunal brush‐border vesicles using a fluorescent dye.
Authors: Schell R E , Stevens B R , Wright E M
Published: December 2014

The kinetics of Na‐coupled solute transport by renal and jejunal brush‐border vesicles in the rabbit were examined using the potential‐sensitive fluorescent dye diS‐C3‐(5). All organic solutes known to be transported across these membranes by Na‐coupled mechanisms increase the fluorescence of the dye in the presence of Na, but not K. An increase in fluorescence (delta F) corresponds to a depolarization of the electrical potential difference (5‐60 mV) across the brush‐border membrane in the intact cell. delta F was independent of the valency of the transported solute. The fluorescence response was saturable, and for twelve solutes the Kf, i.e. the concentration of the substrate generating 50% of the maximal response, agreed quite closely with the Kt values reported from tracer studies. For six solutes increasing the Na concentration decreased Kf, and this agrees with the effect of Na on the kinetics of succinate transport in renal vesicles. We conclude that D‐glucose, neutral amino acids and imino acids are co‐transported with Na across both renal and jejunal brush‐border membranes, and that carboxylic acids, beta‐amino acids, and dibasic amino acids are co‐transported with Na across the renal, but not jejunal, membranes.
Analysis of potassium dynamics in mammalian brain tissue.
Authors: Gardner‐Medwin A R
Published: December 2014

Equations are derived for potassium (K+) dynamics in simplified models of brain tissue. These describe K+ movement in extracellular space, transfer of K+ associated with current flow through cells (the so‐called spatial buffer mechanism) and equilibration between extracellular space and cytoplasm. Numerical calculations show that the principal data on K+ dynamics from various laboratories can be accounted for with simple assumptions about spatial buffer action and uptake. Much of the data is inconsistent with extracellular diffusion being the main mechanism for K+ flux through brain tissue, including some that has earlier been cited in support of this hypothesis. The buffering actions of spatial buffer transfer of K+ and of cytoplasmic equilibration, in which these mechanisms reduce rises of [K+]o that would otherwise occur, are analysed quantitatively for specific K+ source distributions and for spatial and temporal frequency components of general disturbances. Spatial buffer action has most effect in reducing [K+]o rises with net release over extensive zones of tissue (greater than ca. 200 micron in diameter) for periods of the order of minutes. Reductions greater than 75% may be achieved. With localized but prolonged release, the maximum [K+]o rise is little affected but the volume of tissue affected by more moderate rises is substantially reduced. Cytoplasmic K+ uptake also has most effect with widespread release, but its effect diminishes with prolonged periods of release. The effects of the buffering mechanisms and of K+ re‐uptake into active neurones in determining the decline of [K+]o after a period of stimulation are considered. Re‐uptake is unlikely to be the major factor responsible for [K+]o decline when this has a time course of only a few seconds. The properties necessary for the cells mediating the spatial buffer mechanisms, possibly glial cells, are assessed.
The effects of changes of pH on intracellular calcium transients in mammalian cardiac muscle.
Authors: Allen D G , Orchard C H
Published: December 2014

The calcium‐sensitive photoprotein aequorin was micro‐injected into cells of rat, ferret, rabbit and cat papillary muscles. Aequorin light emission is a function of free intracellular calcium concentration. The changes in intracellular calcium concentration [( Ca2+]i) and tension accompanying changes of pH have been studied. When the solution perfusing the papillary muscle was changed from Tyrode solution equilibrated with 5% CO2 to Tyrode solution equilibrated with 15% CO2, developed tension showed a rapid fall followed by a slower rise to a steady state which was less than the control. However the calcium transient associated with each contraction increased monophasically to a new steady state. When the external pH was held constant during exposure to 15% CO2 (by increasing the [HCO3‐]), the initial fall of tension was reduced and the slow recovery of tension was greater than when CO2 alone was changed. The amplitude of the calcium transient increased monophasically to a new steady state which was greater than control, but less than when [CO2] alone was increased. If [HCO3‐] was decreased while maintaining [CO2] at 5%, there was a slow monophasic decline in developed tension, and a small increase in peak light. Alkaloses produced by changing the [HCO3‐]/[CO2] ratio produced similar results but the changes observed were in the opposite direction to those described above. The effects of changes of pHo can be explained if pHi affects tension by two mechanisms. The first mechanism, which is responsible for the rapid change in tension, is not associated with a change in [Ca2+]i. The second mechanism leads to a slower and smaller change in tension, in the opposite direction to the first, and is due to a change in the intracellular calcium transient.