bluuebunny/crossref_metadata_2025 huggingface dataset:
THE HISTOLOGY OF THE ISOLATED PERFUSED LUNG
Authors: Trowell O. A.
Published: December 2014

A description is given of the histological changes found in the isolated perfused lungs of dogs. The perfusion was carried out with heparinised blood under negative pressure ventilation for 3½ to 7 hours. The main findings were:

(1) Œdema: comprising alveolar exudate, distension of periarterial lymphatics and œdema of arterial walls.

(2) Periarterial and peribronchial hæmorrhage.

(3) Collections of polymorphonuclear leucocytes in the small pulmonary blood vessels.

(4) Dilation of bronchi and bronchioles.

(5) Vascular congestion of bronchial walls (except in experiments in which the outflow was allowed to drain from the open pulmonary veins).

The alveolar walls, bronchial epithelium and vascular endothelium were normal and there was no pulmonary vascular congestion. It is pointed out that changes (1) and (2) have been recorded in other types of experimental lung damage and they seem to represent a common reaction of the lung to various modes of injury. The possible causes of these changes are discussed.

The histological changes which have been described in the lung of the heart‐lung preparation were for the most part not found in the isolated perfused lung.

The perfusion experiments which provided the material for this investigation were performed by Miss Catherine Hebb, and the author is indebted to her and to Professor de Burgh Daly for much helpful discussion.
THE BEHAVIOUR OF CHOLESTEROL AND LECITHIN TOWARDS NORMAL HÆMOLYTIC SERUM
Authors: Lee Jui‐Shuan , Tsai Chiao
Published: December 2014

1. Cholesterol is able to inhibit the hæmolytic action of normal serum from a large number of mammalian species towards a variety of mammalian red blood cells. The only exception was found in the sera of some rabbits.

2. The sera of most of the local rabbits does not exhibit lytic property against dog cells; only that of a few, especially of the black variety, possesses this lytic action. The lytic activity of the sera of some of these rabbits is inhibited by cholesterol, but that of others is not.

3. This inhibitory action of cholesterol towards normal hæmolytic serum is due to the inactivation of the complement. Similar behaviour has also been observed with lecithin. Unlike cholesterol, lecithin is able to reinforce amboceptor activity, but this occurs only in the absence of complement.

4. The inactivation of complement by cholesterol and by lecithin are both reversible; i. e. when the complement is destroyed by heat, the anti‐hæmolytic potency of cholesterol and of lecithin is recovered quantitatively.
THE BEHAVIOUR OF CHOLESTEROL TOWARDS HÆMOLYTIC IMMUNE SERUM
Authors: Lee Jui‐Shuan , Tsai Chiao
Published: December 2014

1. A specific property that antagonizes the anti‐hæmolytic action of cholesterol, or may even reverse it to an accelerating one on hæmolysis, has been demonstrated in the sera of rabbits, goats, and dogs immunized with dog cells, dog cells and rabbit cells respectively.

2. This property is always associated with the acquired sensitizers, but its development does not run exactly parallel with them.

3. The specificity of the anti‐cholesterol property is demonstrated by the fact that it acts only in the presence of specific antigen and complement.

4. It is not related to the agglutinating property or process of the immune serum.
FACTORS IN PANCREATIN WHICH INFLUENCE THE NUCLEOPROTEIN CONTENT OF FIBROBLASTS GROWING IN VITRO
Authors: Davidson J. N. , Waymouth C.
Published: December 2014

Material has been prepared from pancreatin which influences the growth of fresh explants of the 9‐day chick embryo heart in roller‐tubes. Cultures grown in a mixture of this material and embryo‐extract show a much higher nucleoprotein phosphorus (N. P. P.) content than do control cultures grown in embryo‐extract alone. They also have a characteristic dense compact appearance and are composed of well‐nourished polyhedral cells with numerous mitotic figures.

A method for the partial purification of the factor (or factors) responsible for these phenomena is described. It appears that at least two components are involved, one of which is responsible for the characteristic morphological changes in the cells, while the other can produce even in the absence of embryo‐juice a very marked rise in N. P. P., as great as that produced under similar conditions by a very concentrated extract of embryonic tissue. Such nucleoprotein synthesis appears to be a necessary preliminary to cell division in cultures stimulated by the factor. This would be in accordance with the views of Willmer [1942 b, 1943].

Some chemical properties of the purified material are described. It appears to consist mainly of polypeptides and nucleotide derivatives. Crude preparations of lecithinase A from pancreatin and snake venom produce the morphological changes described, and this enzyme may be one of the active components.

Our grateful thanks are due to Mr. E. N. Willmer of Cambridge and to Lt.‐Col. W. F. Harvey of the Royal College of Physicians Laboratory, Edinburgh, for much valuable advice, to Dr. F. W. Landgrebe for photographic assistance, and to Dr. G. R. Barker and Messrs. Boots Pure Drug Co. for samples of snake venom.

A grant for scientific assistance from the Medical Research Council and an expenses grant from the Carnegie Trust for the Universities of Scotland to one of us (J. N. D.) are gratefully acknowledged.
OBSERVATIONS RELATING TO CARDIAC HYPERTROPHY PRODUCED IN THE RABBIT BY ARTERIO‐VENOUS ANASTOMOSIS: THE EFFECT OF CLOSURE OF THE ANASTOMOSIS
Authors: Drury Alan N.
Published: December 2014

In a series of animals in which a carotid jugular anastomosis had been patent for three months, the anastomosis was tied off. The hearts of these animals, with one exception, were found almost, if not entirely, to have returned to their normal weight within eight weeks, the auricles reaching normal values before the ventricles. The area of the X‐ray cardiac shadow indicated that many of the hearts were twice the normal weight when the anastomosis was tied off.
THE EFFECTS OF SKIN CONTAMINATION WITH LIQUID MUSTARD‐GAS ON WATER BALANCE IN ANIMALS
Authors: Cameron G. R. , Courtice F. C.
Published: December 2014

The lymph flow from the skin of dogs contaminated with mustardgas increases, and the lymph protein concentration approaches that in the plasma.

The lymph taken after contamination inhibits the growth of bonemarrow fragments in tissue culture, indicating the presence of mustardgas or a toxic derivative.

The effect of local œdema is to produce hæmoconcentration and hypoproteinæmia lasting 1 to 2 days in goats and rabbits.

The absorption of mustard‐gas leads often to diarrhœa, with loss of fluid from the bowel. This causes dehydration without hypoproteinæmia. The dehydration results in loss of body‐weight, increased protein breakdown, and rise in blood urea.

We are indebted to Mr. F. W. Randoll for his assistance in the experiments with tissue culture. Our acknowledgments are also due to the Chief Scientist, Ministry of Supply, for permission to publish this investigation.
THE ADAPTATION OF THE LUNG CIRCULATION TO THE VENTILATION
Authors: Dirken M. N. J. , Heemstra H.
Published: December 2014

In normal circumstances 55 per cent. of the total blood supply to the lungs of the rabbit is directed to the right and 45 per cent. to the left lung. On lowering the alveolar oxygen tension in one lung its blood circulation may be gradually reduced to less than half of the original value. while the circulation of the other lung shows a corresponding increase.

A drop in the alveolar oxygen percentage of 2 to 2·5 per cent. in one lung may reduce the blood‐flow by 15 per cent. of the original value.

The significance of these results with reference to an adaptation of the circulation to the unequal ventilation of the lungs is discussed.
INTRACORPUSCULAR METHÆMOGLOBIN FORMATION AND ITS RELATION TO THE RATE OF OXYGEN RELEASE
Authors: Fegler G.
Published: December 2014

1. The relative rate of O2 release from horse r.b.c. suspensions (pH 7·0–7·4) measured with a slow reaction method was investigated in relation to the methæmoglobin formation.

2. A straight‐line relationship was found between the relative rate of methæmoglobin formation by sodium nitrite and the increase in the rate of O2 release.

3. A close relationship was also found between the increase in the rate of O2 release and the relative rate of the spontaneous methæmoglobin formation caused by exposure of the r.b.c. suspensions to N2 + CO2 gas mixtures.

4. A methæmoglobin formation uninterrupted by the reduction develops in the suspensions poisoned by sodium azide. The phenomenon is probably caused by a combination between sodium azide and spontaneously formed methæmoglobin [Keilin], this compound being resistant to the intracorpuscular enzymatic reduction of the preformed methæmoglobin. Sodium azide also causes an increase in the rate of O2 release from r.b.c. suspensions.

5. A suggestion is forwarded of a possible part played by the spontaneous methæmoglobin formation as a factor promoting deoxygenation.
SOME EFFECTS OF AN ACUTE TOXIC SUBSTANCE FORMED BY SOLUTION OF METHYL‐BIS (B‐CHLOROETHYL) AMINE IN WATER AFTER INJECTION IN ANIMALS
Authors: Foss George L.
Published: December 2014

Water contaminated with nitrogen mustard—methyl‐bis (B‐chloroethyl) amine—was found to contain a heat stabile acutely toxic substance, probably methyl B‐hydroxyethyl ethylenimonium chloride. When injected subcutaneously into experimental animals an acute neurotoxic syndrome was observed. The essential features of this were rapidly progressive muscular hypotonia, inco‐ordination and tremor, followed later by ophthalmoplegia and finally paralysis of respiration.

Ingestion of this solution did not produce this picture at all, but on the contrary was followed more gradually by symptoms of systemic nitrogen mustard poisoning.

With smaller toxic doses complete recovery sometimes occurred after exhibition of hypotonia for some hours, but sometimes death occurred several days later, again from systemic nitrogen mustard poisoning.

From admittedly incomplete evidence it is suggested that the action of this interesting poison may be on the anterior horn cells.

I am indebted to Professors Lovatt Evans, Gaddum, Cameron, Boyland, and Liddell for their advice, and to the Chief Scientific Officer, Ministry of Supply, for permission to publish.
PULMONARY VASOMOTOR FIBRES IN THE SYMPATHETIC CHAIN AND ITS ASSOCIATED GANGLIA IN THE DOG
Authors: Daly I. de Burgh , Duke Helen , Hebb Catherine O. , Weatherall Josephine
Published: December 2014

In the perfused living animal, under conditions which eliminate cardiac and bronchomotor effects, stimulation of the upper thoracic sympathetic chain, the stellate ganglion, the middle cervical ganglion, and the thoracic vagosympathetic nerves causes a rise in pulmonary arterial pressure of 10–15 per cent. at constant pulmonary blood inflow. More rarely a fall in pulmonary arterial pressure takes place. Stimulation of these same nerve structures at constant pulmonary arterial pressure perfusion may cause a diminution in lung blood‐flow by as much as 30 per cent.

The rise in pulmonary arterial pressure is not due to changes in the amount of blood transferred from the bronchial to the pulmonary vascular bed, nor is it dependent upon the method used for artificial ventilation of the lungs.

Results are described which are consistent with the view that the upper thoracic chain, stellate ganglion or middle cervical ganglion, and thoracic vagosympathetic nerves constitute a pre‐ganglionic‐ganglionic‐post‐ganglionic path for adrenergic pulmonary vasoconstrictor fibres. The same path probably carries pulmonary vasodilator fibres, the nature of which is discussed.
REFLEX REBOUND IN EXTENSOR MUSCLES
Authors: Del Castillo‐Nicolau J. , Schweitzer A.
Published: December 2014

1. Three types of reflex rebound contractions were studied in the quadriceps muscle of decerebrate cats: rebound following reflex inhibition, rebound after reflex contraction caused by ipsilateral afferent stimulation, and rebound after reflex contraction caused by contralateral afferent stimulation.

2. The strength of rebound contractions following reflex inhibition and reflex contraction after ipsilateral sensory stimulation increased with an augmentation of the stretching force previously applied to the muscle.

3. These types of rebound contractions could not be produced after complete deafferentation of the muscle. Transection of the sixth posterior lumbar root usually sufficed to abolish rebound; in those cases where rebound persisted, although decreased in force and inconstant, transection of the seventh posterior lumbar root finally abolished it.

4. There was no evidence that the fourth and fifth lumbar posterior root participated in the production of quadriceps rebound.

5. Reflex rebound, under the conditions studied, is explained as a phenomenon originating in the proprioceptors of the muscle.
COMMUNICATING BLOOD VESSELS BETWEEN BRONCHIAL AND PULMONARY CIRCULATIONS IN THE GUINEA‐PIG AND RAT
Authors: Rakshit Prabhaschandra
Published: December 2014

1. In the guinea‐pig, the ease with which injection masses into the aorta find their way into the pulmonary circulation has been confirmed.

2. Evidence is presented which indicates that in the guinea‐pig and rat the bronchial arteries supply the bronchi, the lymph glands and the interstitial tissue of the lungs. They also give rise to the vasa vasorum.

3. In the guinea‐pig and rat, casts of vessels connecting the bronchial artery and pulmonary artery casts are found in the region of the lung hilus. Reasons are given for the belief that they represent communicating vessels and not vasa vasorum.
ON HISTIDINURIA
Authors: Kapeller‐Adler R.
Published: December 2014

1. L‐histidine was given intravenously and orally to pregnant and non‐pregnant women, and was estimated in the blood by a modified diazo reaction and by its reaction with bromine in the urine.

2. On intravenous as well as on oral application, L‐histidine disappeared only very slowly from the blood‐stream of pregnant women as compared with non‐pregnant women, large amounts of it being simultaneously excreted in the urine. This observation does not confirm the results of Page, who found that on intravenous injection L‐histidine leaves the blood‐stream of pregnant women at least as quickly as that of non‐pregnant persons. It seems, moreover, to support the previously suggested theory of a reduced activity of histidase in human pregnancy.

3. In severe toxæmia of pregnancy no histidine could be detected in the urine even after the injection or ingestion of histidine although the blood levels remained high. This indicates a retention of L‐histidine by the kidney.

4. The results obtained in mild pregnancy toxæmia were intermediate between those found in severe toxæmia and in normal pregnancy.
PHYSIOLOGICAL AND PATHOLOGICAL RESPONSES IN THE BLOOD‐VESSELS OF THE LIVER
Authors: Seneviratne R. D.
Published: December 2014

The circulation in the intact liver and its reaction to various stimuli were studied in frogs, mice and rats by a modification of Knisely's transillumination technique.

Characteristic patterns in the anatomy and distribution of the portal and hepatic veins are described. Sinusoids appear as thin‐walled collapsible tubes with complete linings. Arteriovenous anastamoses are frequent, and reconcile the rarity of infarcts from embolism with the frequency of pyæmic abscesses and metastatic deposits. The behaviour of circulating dyes and toxic agents suggest the presence of functional zones in the liver lobule. Certain structural differences, too, are noticed in the centrilobular areas.

Under normal conditions the liver circulation shows an irregularly intermittent rhythmicity. Blood‐flow is under sympathetic control, but there is no evidence of a parasympathetic supply. A chemical control is suggested by the effects of hormones such as adrenalin, acetylcholine and histamine, while respiration has a very definite influence.

Stimuli such as obstruction of the vessels, mechanical trauma, hæmorrhage, heat and cold induce rapid responses in the liver circulation. Indeed the centrally important observation is the readiness with which it reacts to stimuli, and this may have a significant bearing on the pathogenesis of liver diseases.
THE DETERMINATION OF THE RENAL CLEARANCE OF DIODONE AND THE MAXIMAL TUBULAR EXCRETORY CAPACITY FOR DIODONE IN MAN
Authors: Robson J. S. , Ferguson M. H. , Olbrich O. , Stewart C. P.
Published: December 2014

1. The principles devised by the authors [1949] for the determination of the renal clearance of inulin have been applied to the determination of the renal clearance of diodone and the tubular excretory capacity for diodone.

2. Following the intravenous injection of diodone in amounts suitable for the measurement of both renal clearance and tubular excretory capacity, the volume of distribution of diodone continues to increase for the duration of the experiments. It is concluded that equilibration of diodone between the plasma and the extravascular component of the volume of distribution does not occur under the conditions of the experiment.

3. Formulæ are derived for the renal clearance of diodone and the maximal tubular excretory capacity for diodone incorporating functions which are demanded by the failure of the establishment of equilibration.

4. The formula for the renal clearance of diodone is applied to fourteen subjects possessing widely different clearance values, and the formula for the maximal tubular excretory capacity for diodone is applied to twelve of these subjects. The values calculated by the formulæ agree closely in every case with the average values experimentally determined, following intravenous injections of diodone.

5. The calculative errors introduced into the formulæ by the simplifying assumption that the volume of distribution of diodone is linearly related to time, between defined limits of time, are shown to be of similar magnitude to the limits of the error in the chemical determination of diodone in the plasma.

6. The formulæ can be applied without the need for accurate urine collection over short clearance periods. They necessitate the passage of urine approximately 25 and 120 minutes (for the maximal tubular excretory capacity for diodone) and 20 and 60 minutes (for the renal clearance of diodone) after the injection of known amounts of diodone, and a minimum of two blood samples for each determination taken at the time of urine passage.

7. The errors introduced in the determinations of inulin and diodone clearance and the maximal tubular excretory capacity for diodone by sampling venous blood are discussed briefly.

8. The results of a further five estimations of inulin clearance employing the authors' method (loc. cit.), and their comparison with average values experimentally determined, are also included.
THE EFFECT OF CERTAIN ANALGESIC DRUGS ON SYNAPTIC TRANSMISSION AS OBSERVED IN THE PERFUSED SUPERIOR CERVICAL GANGLION OF THE CAT
Authors: Hebb Catherine O. , Konzett Heribert
Published: December 2014

1. In the perfused superior cervical ganglion of the cat the administration of morphine does not affect the size of the contraction of the nictitating membrane produced by pre‐ganglionic stimulation, injection of acetylcholine or of KCI when the pre‐ganglionic fibres are normally functional, but after degenerative section of the cervical sympathetic nerve, morphine in large doses potentiates the contraction elicited by injections of acetylcholine and of KCI.

2. Pethidine and amidone strongly depress the responses of the membrane to pre‐ganglionic stimulation and to injections of acetylcholine or KCI. Both drugs have a similar depressant action on responses to acetylcholine and KCI after denervation of the ganglia. In these actions, 1‐amidone is the most powerful and pethidine the least powerful, while dl‐amidone is intermediate between the other two substances.

3. Of the three analgesics tested, none have the power to excite a response of the nictitating membrane when injected into the ganglion.

4. The effects of morphine, amidone and pethidine on the responses of the frog rectus abdominis muscle to acetylcholine are analogous to their effects on the responses of the denervated superior cervical ganglion to acetylcholine.
AN INSTRUMENT FOR THE STUDY OF VASCULAR FACTORS IN THE PHYSIOLOGY AND PATHOLOGY OF THE HUMAN MAMMARY GLAND
Authors: Pickles V. R.
Published: December 2014

An instrument is described for the investigation of vascular factors in human mammary physiology, for which hitherto no suitable technique has existed. It involves a modification of the plethysmographic method.
VASOMOTOR NERVE FIBRES TO THE MAMMARY GLANDS OF THE CAT AND DOG
Authors: Linzell J. L.
Published: December 2014

1. The existence of sympathetic vasoconstrictor fibres in the spinal nerves to the mammary glands of the cat and dog has been demonstrated in experiments involving blood flow measurements, plethysmography, perfusion of the isolated gland, and microscopical examination of the living vessels.

2. In the cat, vasoconstriction was only observed in the small arteries and arterioles, vessels which, on histological examination, were found to have much smooth muscle in the medial coat and were innervated by fine unmyelinated nerve fibres.

3. The nerve endings concerned are thought to be adrenergic, because—

(a) adrenaline has the same action in very small doses;

(b) their effects are unaffected by eserine, atropine and nicotine;

(c) are potentiated by cocaine and tannic acid;

(d) abolished or reversed by ergot preparations.

4. No convincing evidence has been obtained of the existence of active vasodilator fibres in the spinal nerves studied, or of parasympathetic innervation of the mammary gland.

5. The mammary blood vessels are very sensitive to cooling, to which they react by vasoconstriction.

6. Two types of spontaneous volume waves seen in plethysmograph experiments are described and their causes discussed.
THE EFFECTS OF OBSTRUCTING THE BLOOD‐FLOW THROUGH THE PULMONARY VESSELS: AN EXPERIMENTAL STUDY IN RATS
Authors: Cheng Kwok‐Kew
Published: December 2014

1. Total ligation of the left pulmonary artery by means of a new technique results in slight atrophy of the affected lung, with occasional fibrosis, new capillary formation near bronchi, and the development of fibrovascular strands between pleura and peribronchial or perivascular spaces. Bronchial arteries, pleural vessels, and vessels of pleural adhesions become congested and dilated.

2. Simultaneous ligation of the pulmonary artery and vein produces haemorrhagic infarction in the lung, with ultimate fibrosis.

3. Total ligation of the pulmonary vein leads to haemorrhagic infarction of the lung. Partial ligation of pulmonary vein often gives the same change.

4. The bearing of these experimental results on pulmonary infarction in chronic valvular diseases is discussed, and it is suggested that some lung infarcts may be due to circulatory stasis and venous thrombosis alone without the intervention of embolism.
THE SYMPATHICO‐ADRENAL SYSTEM AND THE PHAGOCYTOSIS OF THE LEUCOCYTES
Authors: Kokas F. , Ludtny G. , Vajda J.
Published: December 2014

1. Blood serum from anaesthetized dogs was tested for its stimulant action on phagocytosis.

2. Stimulation of the splanchnic nerves increases the action of blood collected from the femoral veins. This effect is partly due to the release of some substance from the adrenals, since it is abolished by ligation of the adrenal veins, and since blood collected from the adrenal veins has high activity, which is increased by splanchnic stimulation.

3. The effect is also partly due to another mechanism, since the injection of adrenaline also increases the action, even in the absence of the adrenals. Desoxycorticosterone and an extract of adrenal cortex did not have this effect.

4. These effects were not directly due to changes in the concentration of adrenaline or histamine in the blood. Desoxycorticosterone and an extract of adrenal cortex has no action in vitro.

5. The substances producing these effects act partly as opsonins and partly by direct stimulation of the leucocytes.
BAROPLETHYSMOGRAPHY: A METHOD OF ESTIMATING BLOOD FLOW
Authors: Pickles V. R.
Published: December 2014

1. A baroplethysmographic method proposed previously for measuring human mammary blood flow is summarized and its reliability examined.

2. Experiments on the human hand, in comparison with occlusion plethysmography, show fair agreement between the two methods, except for the fact than an approximately constant quantity, possibly representing movement of tissues other than blood, is included in the estimates given by baroplethysmography.

3. The possible sources of error, and ways of overcoming some of them, are discussed. The method is not recommended for use on organs whose blood flow can be measured by occlusion plethysmography, but it can give useful estimates of human mammary blood flow.
Slowing of relaxation during fatigue in single mouse muscle fibres.
Authors: Westerblad H , Lännergren J
Published: December 2014

1. In the preceding paper we analysed the force decline in fatigue of isolated mouse muscle fibres. Using the same preparation and stimulation scheme we have now examined another aspect of muscle fatigue, namely slowing of relaxation. 2. Relaxation at the end of a tetanic contraction can usually be divided into two phases, an initial nearly linear force decline, followed by an exponential phase. We have analysed the initial phase in terms of decline rate and duration. In rested fibres the decline rate after a 350 ms tetanus was not affected by a 30% reduction of tetanic tension (obtained by decreasing the stimulation frequency). 3. Relaxation became gradually slower during fatiguing stimulation with a maximum reduction at the time when tetanic tension was reduced to about 75% of the original (end of phase 2, see preceding paper). At this time the decline rate of the linear phase had fallen to 55.2 +/‐ 2.9% (mean +/‐ S.E.M., n = 25) and its duration had increased to 151.3 +/‐ 14.2% of the control (unfatigued 350 ms, 70 Hz tetanus). 4. Short rest periods (duration = 10s), given at various times during fatiguing stimulation, resulted in a clear, but partial, normalization of the relaxation parameters; at the time of maximum slowing the mean decline rate increased from 50.3 to 58.7% and the duration decreased from 167.9 to 144.0% of the control (n = 14). 5. The influence of intracellular acidosis on relaxation was studied by exposing rested fibres to 30% CO2 instead of the normal 5%. This resulted in a decline rate of 43.0 +/‐ 2.6% and a duration of 221.1 +/‐ 13.1% of the control (n = 7). 6. In amphibian muscle relaxation is known to become gradually slower during a single, prolonged tetanus. The existence of such an effect also in the present preparation was studied by giving ‘interrupted’ tetani with a total duration of about 2 s. In rested fibres the mean rate of relaxation was found to fall from 140.9 to 71.8% (n = 11) of the control (end of 350 ms stimulation) with a time constant of about 0.5 s. Thus, a marked slowing during a long tetanus occurs also in mammalian muscle. 7. A distinct slowing of relaxation during prolonged tetani was observed also in the fatigued and in the acidified state. Under these two conditions the mean rate of relaxation fell from 87.0 to 34.0% (n = 3) and from 74.0 to 23.0% (n = 5) of the control, respectively, with time constants similar to that in the rested state.(ABSTRACT TRUNCATED AT 400 WORDS)
The actions of calcium on the mechano‐electrical transducer current of turtle hair cells.
Authors: Crawford A C , Evans M G , Fettiplace R
Published: December 2014

1. Mechano‐electrical transducer currents evoked by deflections of the hair bundle were recorded in turtle isolated hair cells under whole‐cell voltage clamp. The outcome of perfusing with solutions of reduced Ca2+ concentration was investigated. 2. The transducer current was roughly doubled by lowering the concentration of divalent cations from normal (2.2 mM‐Mg2+, 2.8 mM‐Ca2+) to 0 Mg2+, 0.5 mM‐Ca2+. No significant effects on the current's kinetics or reversal potential, or on the current‐displacement relationship, were noted. 3. If the Ca2+ concentration was lowered to 50 microM (with no Mg2+), there was about a threefold increase in the maximum current but other changes, including loss of adaptation and a decreased slope and negative shift in the current‐displacement relationship, were also observed. As a result, more than half the peak transducer current became activated at the resting position of the hair bundle compared to about a tenth in the control solution. 4. The extra changes manifest during perfusion with 50 microM‐Ca2+ had also been seen when the cell was held at positive potentials near the Ca2+ equilibrium potential. This supports the view that some consequences of reduced external Ca2+ stem from a decline in its intracellular concentration. 5. With 20 microM‐Ca2+, a standing inward current developed and the cell became unresponsive to mechanical stimuli, which may be explained by the transducer channels being fully activated at the resting position of the bundle. 6. The results are interpreted in terms of a dual action of Ca2+: an external block of the transducer channel which reduces the maximum current, and an intracellular effect on the position and slope of the current‐displacement relationship; the latter effect can be modelled by internal Ca2+ stabilizing one of the closed states of the channel. 7. During perfusion with 1 microM‐Ca2+, the holding current transiently increased but then returned to near its control level. There was a concomitant irreversible loss of sensitivity to hair bundle displacements which we suggest is due to rupture of the mechanical linkages to the transducer channel. 8. Following treatment with 1 microM‐Ca2+, single‐channel currents with an amplitude of ‐9 pA at ‐85 mV were sometimes visible in the whole‐cell recording. The probability of such channels being open could be modulated by small deflections of the hair bundle which indicates that they may be the mechano‐electrical transducer channels or conductance about 100 pS. 9. Open‐ and closed‐time distributions for the channel were fitted by single exponentials, the mean open time at rest being approximately 1 ms. The mean open time was increased and the mean closed time decreased for movements of the hair bundle towards the kinocilium.(ABSTRACT TRUNCATED AT 400 WORDS)
Release of endothelial mediators and sympathetic transmitters at different coronary flow rates in rabbit hearts.
Authors: Wennmalm A , Benthin G , Karwatowska‐Prokopczuk E , Lundberg J , Petersson A S
Published: December 2014

1. The release of three endothelial mediators, namely, endothelial‐derived relaxing factor (EDRF), prostacyclin (PGI2) and endothelin, and of two sympathetic neurotransmitters, noradrenaline and neuropeptide Y (NPY), from resting or sympathetically stimulated rabbit Langendorff hearts was investigated at normal or elevated coronary flow. The sympathetic nerves to the hearts were stimulated at 5 Hz for 30 s and the cardiac effluent was analysed for nitrite (metabolite of EDRF) with electron paramagnetic resonance spectrometry, for 6‐keto‐PGF1 alpha (metabolite of PGI2) with gas chromatography/mass spectrometry, for endothelin‐ and NPY‐like immunoreactivity with radioimmunoassay, and for noradrenaline and purines with liquid chromatography. 2. During perfusion of the hearts at normal flow (35 +/‐ 1.4 ml min‐1) the effluent concentration of nitrite was 0.15 +/‐ 0.02 microM, that of 6‐keto‐PGF1 alpha 0.74 +/‐ 0.08 nM, and that of endothelin‐like immunoreactivity 0.18 +/‐ 0.01 pM. Nerve stimulation augmented the release of 6‐keto‐PGF1 alpha from 76 +/‐ 8 to 99 +/‐ 10 pmol (3 min)‐1 (P less than 0.05), but did not affect the release of nitrite or endothelin‐like immunoreactivity. Nerve stimulation also facilitated the outflow of noradrenaline and of NPY‐like immunoreactivity by 52 +/‐ 11 pmol (3 min)‐1 and 19 +/‐ 7 fmol (3 min)‐1, respectively. 3. Elevation of the coronary flow to 79 +/‐ 3.2 ml min‐1 did not affect the effluent concentrations of nitrite, 6‐keto‐PGF1 alpha and endothelin‐like immunoreactivity, implying that their outflows were augmented. Sympathetic stimulation at elevated coronary flow did not further augment the outflow of endothelial mediators or of NPY‐like immunoreactivity, but increased the outflow of noradrenaline by 62 +/‐ 12%, in comparison to stimulation at normal flow. Perfusion of the heart with the noradrenaline uptake blocker desipramine (5 microM) completely abolished the promoting effecting of elevated coronary flow on noradrenaline outflow during sympathetic stimulation. 4. These data indicate that an increase in coronary flow in perfused rabbit hearts is paralleled by a corresponding facilitation of the formation of the endothelial mediators, EDRF, prostacyclin and endothelin. Such an elevation of mediator formation does not affect nerve stimulation‐induced release of sympathetic transmitters in the heart.
The transient K+ current in rat ventricular myocytes: evaluation of its Ca2+ and Na+ dependence.
Authors: Dukes I D , Morad M
Published: December 2014

1. The transient outward K+ current (Ito) was studied in enzymatically isolated rat ventricular myocytes using the whole‐cell patch clamp technique. 2. At holding potentials between ‐100 and ‐60 mV, depolarizing pulses activated outward current which was composed of transient and maintained components. These components differed from each other in their activation voltage range as well as in their kinetics of inactivation. 3. The transient component, in turn, appeared to be composed of rapidly and slowly inactivating components. Subtraction of ICa from the total current, or nifedipine pre‐treatment, eliminated the slowly inactivating component of Ito indicating that the time course of inactivation of Ito may be contaminated by ICa. 4. Reduction of the holding potential from ‐100 mV to less negative holding potentials reduced all components of Ito, such that at holding potentials of ‐40 mV, very little or no Ito could be measured. 5. Elevation of [Ca2+]o activated Ito at holding potentials of ‐40 mV, and substitution of external Ca2+ by Sr2+ suppressed Ito, consistent with findings from other preparations and in support of a Ca(2+)‐activated component of Ito. 6. Elevations of [Ca2+]o, however, also shifted the steady‐state activation and inactivation parameters of the transient K+ current, such that a greater proportion of Ito channels were activated at the less negative holding potentials. 7. The shifts in the activation and inactivation parameters of the transient outward current were not mimicked by equivalent changes in external Mg2+. 8. Modulators of Ca2+ release from the sarcoplasmic reticulum (SR) such as caffeine and ryanodine suppressed Ito regardless of whether the myocytes were dialysed with low or high concentrations of Ca2+ buffers (EGTA or BAPTA, 0.5‐14 mM) or whether nifedipine was used to block ICa. 9. 4‐Aminopyridine (4‐AP) blocked Ito in a dose‐dependent manner, completely suppressing it at 10 mM. Similarly, tedisamil, a new K+ channel blocker, completely and reversibly blocked Ito at 5‐20 microM concentrations. 10. TTX (10 microM) or removal of external Na+ decreased Ito, consistent with the idea that a component of Ito was Na+ activated. Both interventions, however, also shifted the voltage dependence of the activation and inactivation of Ito to more negative potentials, such that at ‐100 mV neither intervention had a significant effect on Ito. Alterations in [Na+]i had no effect on Ito.(ABSTRACT TRUNCATED AT 400 WORDS)
Long‐term potentiation induced by a sustained rise in the intraterminal Ca2+ in bull‐frog sympathetic ganglia.
Authors: Minota S , Kumamoto E , Kitakoga O , Kuba K
Published: December 2014

1. The mechanism of a long‐term potentiation of transmitter release (pre‐LTP) induced by a tetanic stimulation (33 Hz for 1‐30 s) applied to the preganglionic nerve was examined by intracellularly recording the fast excitatory postsynaptic potentials (fast EPSPs) in bull‐frog sympathetic ganglia. 2. Short‐term facilitation induced by paired pulses was decreased during the course of pre‐LTP; the extent of reduction paralleled with the magnitude of pre‐LTP. 3. The frequency of miniature EPSPs increased after tetanic stimulation that produced the pre‐LTP. 4. The Ca2+ ionophore, A23187, increased both the amplitude and quantal content of fast EPSPs and frequency of miniature EPSPs while it decreased short‐term facilitation. 5. A Ca2+ chelating agent, Quin‐2, loaded as acetoxymethyl ester, reduced the amplitude and quantal content of fast EPSPs and short‐term facilitation, and blocked the generation of pre‐LTP. 6. Activators of protein kinase C, phorbol 12,13‐dibutyrate and 1‐oleoyl‐2‐acetyl‐rac‐glycerol, and its inhibitors, H‐7 and staurosporine, did not block the generation of pre‐LTP, while the activators enhanced transmitter release. 7. Inhibitors of calmodulin, trifluoperazine and W‐7, blocked the generation of pre‐LTP, whereas the amplitude and quantal content of fast EPSPs were not influenced. 8. These results suggest that the pre‐LTP results from a sustained rise in the basal level of intraterminal Ca2+ and an activation of the Ca(2+)‐calmodulin‐dependent process in the preganglionic nerve terminals.
Pharmacology of nicotinic receptor‐mediated inhibition in rat dorsolateral septal neurones.
Authors: Wong L A , Gallagher J P
Published: December 2014

1. Intracellular electrophysiological techniques were employed to investigate the effects of nicotinic receptor stimulation on rat dorsolateral septal nucleus (DLSN) neurones in a submerged rat brain slice preparation. 2. Acetylcholine (in the presence of the muscarinic antagonist, atropine), nicotine or dimethylphenylpiperazinium (DMPP), applied either by pressure ejection or superfusion, produced predominantly a membrane potential hyperpolarization. 3. Following concentration‐response comparisons, DMPP appeared to exhibit fewer desensitizing properties and greater efficacy than nicotine with half‐maximal hyperpolarizing responses attainable at 3 and 10 microM, respectively. 4. Pharmacological analyses revealed that the agonist‐induced membrane hyperpolarization was sensitive to antagonism by mecamylamine (50‐100 microM) and neuronal bungarotoxin (0.2‐0.3 microM), but not alpha‐bungarotoxin (0.5‐1.0 microM), curare (10‐50 microM) or dihydro‐beta‐erythroidine (50‐100 microM). 5. Hyperpolarizing responses to DMPP were found to reverse near the equilibrium potential for potassium and were sensitive to changes in extracellular potassium concentration as predicted by the Nernst equation. Under single‐electrode voltage clamp, application of DMPP produced an outward current (75‐100 pA) which approached reversal at around ‐88 mV. These findings indicated that the hyperpolarizing response to nicotinic receptor stimulation was mediated by changes in membrane permeability to potassium. 6. DMPP‐induced membrane hyperpolarization resulted from a direct action on postsynaptic DLSN neurones since the response persisted under conditions of superfusion with calcium‐free/high‐magnesium media or tetrodotoxin; both conditions blocked orthodromically induced neurotransmission. The hyperpolarizing response remained unaltered in TTX but was diminished in calcium‐free/high‐magnesium media. Further studies revealed blockade of the DMPP response following intracellular injection of EGTA. This response was also sensitive to antagonism by various calcium‐dependent potassium channel blockers including apamin, barium and tetraethylammonium. 7. Our studies reveal a novel class of CNS nicotinic receptor whose action upon stimulation by an agonist results in a membrane hyperpolarization via a calcium‐dependent increase in potassium ion conductance.
Electrophysiology of dopaminergic and non‐dopaminergic neurones of the guinea‐pig substantia nigra pars compacta in vitro.
Authors: Yung W H , Häusser M A , Jack J J
Published: December 2014

1. The membrane properties of substantia nigra pars compacta neurones were studied using an in vitro slice preparation of guinea‐pig midbrain. 2. Neurones were divided into two classes based on their electrophysiological properties: bursting neurones displayed a burst of several rapidly accommodating action potentials in response to relaxation of hyperpolarizing current injected through the microelectrode, while non‐bursting neurones produced regularly spaced action potentials. These neuronal types were found to be electrophysiologically distinct from those recorded in the substantia nigra pars reticulata and the subthalamic nucleus. 3. Non‐bursting neurones, which comprised ca 85% of the sampled cells, were characterized by a slow, pacemaker pattern of firing at rest, broad action potentials, a pronounced spike after‐hyperpolarization, long membrane time constants, and strong transient outward and time‐dependent inward rectification. 4. Bursting neurones, comprising ca 15% of the sample, displayed rapid firing rates at rest, fast action potentials, a shallow spike after‐hyperpolarization and briefer membrane time constants. All of these parameters were significantly different from those of the non‐bursting type. Bursting neurones lacked transient outward or time‐dependent inward rectification. 5. Both types of cells were capable of generating pronounced calcium‐dependent, low‐threshold spikes in the presence of tetrodotoxin (TTX). However, only the non‐bursting type displayed calcium‐dependent rhythmic oscillations in membrane potential near resting potential in the presence of TTX. The firing rate, action potential shape and after‐hyperpolarization of non‐bursting neurones were strongly influenced by calcium‐dependent currents. 6. The majority of cells were injected with biocytin, which allowed morphological reconstruction of the neurones and confirmation of their location within the pars compacta. Non‐bursting neurones had variable soma shapes and their dendrites were mostly directed in a medio‐lateral direction. Many cells extended some of their dendrites into the pars reticulata. Bursting neurones were mainly fusiform in shape with their dendrites oriented in a medio‐lateral direction; a few had dendrites extending into the pars reticulata. 7. Thirty‐six neurones were also double labelled using a combination of biocytin or Lucifer Yellow injection with tyrosine hydroxylase (TH) immunohistochemistry. Non‐bursting neurones all displayed TH immunofluorescence, while none of the bursting neurones were TH positive.(ABSTRACT TRUNCATED AT 400 WORDS)
Single calcium channels in rat and guinea‐pig hippocampal neurons.
Authors: O'Dell T J , Alger B E
Published: December 2014

1. Calcium (Ca2+) channels were studied under whole‐cell clamp and in cell‐attached patch recordings from acutely isolated and tissue‐cultured rat hippocampal neurons. Under whole‐cell voltage clamp of tissue‐cultured neurons the current‐voltage plot for Ca2+ channel current was biphasic, with a ‘hump’ on the descending phase of the plot when the cell was held at ‐80 mV and stepped to various command potentials. When determined from a holding potential of ‐40 mV the plot was no longer biphasic. 2. In cell‐attached patch experiments extracellular isotonic potassium gluconate was used to zero the cell membrane potential. When the patch electrode solution contained monovalent cations (150 mM‐Li+ in most experiments) and no Ca2+, a small channel (approximately 13 pA) could be clearly distinguished in tissue‐cultured neurons from a large dihydropyridine‐sensitive channel (approximately 36 pS). With Ba2+ as the charge carrier it was more difficult to resolve small channel openings. The small channel was activated during voltage steps from negative holding potentials (‐80 to ‐100 mV) over a range of potentials (‐70 mV and less negative). The channels inactivated rapidly (time constants of 20‐40 ms) during the voltage step. Steady‐state inactivation and activation functions were well fitted by single Boltzmann equations of the form y = 1/[1 + exp [V‐V0.5)/k)] and y = 1/[1 + exp [V0.5‐V)/k)], where V0.5 = ‐82.9 +/‐ 2.4 and ‐55.2 +/‐ 1.5 mV and k = 4.5 +/‐ 0.6 and 4.9 +/‐ 0.6 mV, respectively. These small channels were not found in acutely isolated adult cells. 3. Ensemble averages of small‐channel activity in numerous sweeps were very similar in time course to the T currents recorded in the whole‐cell mode. Often small channels occurred in clusters, with many channels in a single patch. In these multichannel patches the voltage dependence of the kinetics of the channel was clearly revealed. 4. Small channels were insensitive to the dihydropyridine nifedipine (20 microM) and to TTX (1‐5 microM), but the Li+ current through this channel was readily blocked by including 2 mM‐Ca2+ in the recording pipette. Small‐channel activity persisted for minutes in off‐cell patches, and in cell‐attached patches was not affected by phorbol esters. 5. The large channel was studied with electrodes filled with 110 mM‐Ca2+ or Ba2+ (single‐channel conductance approximately 24 pS in Ba2+). Activity of this channel was dramatically increased by the dihydropyridine Bay K 8644 and suppressed by nifedipine.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhibition of caudal medullary expiratory neurones by retrofacial inspiratory neurones in the cat.
Authors: Anders K , Ballantyne D , Bischoff A M , Lalley P M , Richter D W
Published: December 2014

1. Comparisons between the spike discharge of inspiratory neurons within the retrofacial area (RFN), and the membrane potential of expiratory neurones within the caudal medulla were made in pentobarbitone‐anaesthetized, vagotomized, artificially ventilated cats. Spike‐triggered averaging (STA) of synaptic potentials, triggered by the discharge of inspiratory RFN neurones, was utilized to test for synaptic connectivity. 2. Eighty‐nine neurons with respiratory‐phased discharge patterns were recorded in the vicinity of the RFN. Fifty‐four neurones discharged at or slightly before the onset of the inspiratory burst activity of the phrenic nerve and continued firing throughout inspiration. Two continued to fire during post‐inspiration. Forty‐five of fifty‐four inspiratory RFN neurones exhibited incrementing discharge patterns, six discharged with a plateau pattern, while only three neurones had a decrementing discharge pattern. 3. The membrane potential trajectories of caudal expiratory neurones revealed a typical wave of early inspiratory hyperpolarization. Occasionally, a second wave of hyperpolarization occurred during late inspiration, in conjunction with increased phrenic nerve activity. 4. Spike‐triggered averaging revealed averaged inhibitory postsynaptic potentials (IPSPs), indicative of inhibitory synaptic connections, between eight and sixty‐three pairs of RFN inspiratory and caudal expiratory neurones. 5. Inhibitory postsynaptic potentials detected by STA exhibited a relatively long latency and a slow time course. The IPSPs began, on average, 3.8 ms after an RFN action potential. The rise times, half‐widths and durations of IPSPs were longer than expected for a monosynaptic somal input from myelinated axons of inspiratory RFN neurones. It is suggested that an inhibitory relay neurone in the immediate vicinity of the expiratory neurones is activated by a collateral of the RFN inspiratory neurone. 6. Retrofacial inspiratory neurones were antidromically activated only when high‐intensity electrical stimulation was applied in the vicinity of caudal expiratory neurones. 7. The averaged IPSPs were preceded by diphasic and triphasic 'spike potentials'. The averaged spike potentials were highly entrained to the action potentials of RFN inspiratory neurones which triggered IPSPs. The spike potentials may be terminal potentials recorded from axons of RFN inspiratory neurones. 8. Evidence for convergence of synaptic inputs was obtained from STA tests in a caudal expiratory neurone receiving IPSPs from four RFN neurones. 9. The functional significance of this observation is discussed. We conclude that RFN inspiratory neurones exert a moderate inhibitory influence and act conjointly with other types of medullary inspiratory neurones.