bluuebunny/crossref_metadata_2025 huggingface dataset:
TEMPERATURE‐DEPENDENCE OF A FAST MOTILE RESPONSE IN ISOLATED OUTER HAIR CELLS OF THE GUINEA‐PIG COCHLEA
Authors: Ashmore J. F. , Holley M. C.
Published: December 2014

Isolated outer hair cells (OHC) of the cochlea exhibit a motility which can be driven at acoustic frequencies (Ashmore, 1987). The temperature‐dependence of the movement is reported here for the range 20‐37 °C. OHC are shown to be motile at 37 °C. The temperature‐dependence is quite weak, with Q10 = 1·33. The observation is difficult to reconcile with mechanisms involving an intermediate biochemical messenger, including those based on actomyosin.
SYNOVIAL FLUID ‐ ITS MASS, MACROMOLECULAR CONTENT AND PRESSURE IN MAJOR LIMB JOINTS OF THE RABBIT
Authors: Knox P. , Levick J. R. , McDonald J. N.
Published: December 2014

Synovial fluid from rabbit elbow, shoulder, hip and knee was analysed to establish the normal levels of parameters relevant to fluid exchange ‐ viz. fluid mass per joint, hydraulic pressure, temperature, colloid osmotic pressure (COP), protein, albumin and glycosaminoglycan (GAG) concentrations. Fluid mass was greatest in the least congruous joint, the shoulder (43 ± 4 mg), cf. 6 ± 2 mg in the highly congruous hip. In the knee (24 ± 4 mg) the mean thickness of the fluid layer was calculated to be 30 µm. Fluid pressure was subatmospheric in all joints (mean ‐2·8 ± 0·4 cmH2O, elbow, to ‐5·7 ± 0·3 cmH20, knee), as in many other interstitial spaces. Colloid osmotic pressure was substantial (mean 11·4 ± 0·9 cmH2O, shoulder, to 13·1 ± 1·0 cmH2O, elbow), being 40‐46% of serum level. Comparison of synovial fluid results with COP versus concentration curves in vitro indicated that the fluid's COP was primarily generated by its protein content (22‐30 g l−1, 64% albumin) rather than GAG (4·0‐5·8 g l−1). The GAG was 95% hyaluronate and 5% sulphated GAG. Algebraic summation of the hydraulic and colloid osmotic pressures of synovial fluid and serum indicated a net filtration gradient from blood to joint cavity. When serum COP was reduced by intravenous saline infusion, synovial fluid mass increased, in accordance with the ultrafiltration hypothesis of synovial fluid formation. The fluid's colloid concentration declined as volume increased. The relation was not a simple dilution curve, but indicated that the newly formed synovial fluid contained ≥ 8 g protein 1−1 (14·5% serum concentration); and that hyaluronate was entering the synovial cavity at a rate of ≥ 6·5 µg h−1 per joint.
ETHANOL INGESTION AND THE DEVELOPMENT OF POST‐EXERCISE KETOSIS IN NON‐ALCOHOLIC HUMAN SUBJECTS
Authors: Hadley W. , Koeslag J. H. , De V. Lochner J.
Published: December 2014

Alcoholic ketosis occurs in alcoholics, who have been shown also to be more predisposed than normal to post‐exercise ketosis (Chalmers, Sulaiman & Johnson, 1977). We therefore studied post‐exercise ketosis in ten normal people who drank 1·6 mol ethanol at 18.00‐21.00 h, and then did a 12 km walk at 07.00 h the next morning. (The timing of the alcohol ingestion was prompted by the finding that alcoholic ketosis usually develops after the blood ethanol concentrations have fallen to zero.) Ten subjects who had not drunk alcohol for 60 h, acted as controls. All subjects were observed till 16.00 h. The blood 3‐hydroxybutyrate level rose from 0·034 ± 0·006 to 0·336 ± 0·073 mmol/l (P 〈 0·001) during the 9 h observation period in the controls, and from 0·038 ± 0·009 to 0·352 ± 0·127 mmol/l (P 〈 0·001) in the test subjects. The differences between the two groups are not significant. Plasma free fatty acid concentrations, and insulin/glucagon ratios of the two exercise groups did not differ signficantly from each other, or from those of a sedentary group (n = 16). Acute ethanol ingestion (1·6 mol/person) therefore does not predispose normal, non‐alcoholic subjects to ketosis, even when ketogenesis is further stimulated by exercise.
REACTIVE HYPERAEMIA IN THE HUMAN FOREARM
Authors: Imms F. J. , Lee Wen-Sen , Ludlow P. G.
Published: December 2014

Reactive hyperaemia in the human forearm has been studied following 5, 10 and 15 min occlusion of the circulation using mercury‐in‐rubber strain gauges. Following 5 min occlusion the initial high blood flows declined exponentially with a half‐life ranging from 14 to 45 s. After 10 and 15 min occlusion the flow pattern is represented by a plateau followed by an exponential of similar time course to the above. Flows did not decay totally along this exponential but deviated onto a second, slower exponential with half‐lives ranging from 50 to 560 s. The hyperaemia represented by the area under the second exponential makes a greater contribution to the total flows in non‐muscular tissues. It is suggested that this phase of the hyperaemia may be the result of tissue warming during the initial period of high flows.
THIXOTROPY: STIFFNESS RECOVERY RATE IN RELAXED FROG MUSCLE
Authors: Lakie M. , Robson Lesley G.
Published: December 2014

The stiffness of relaxed frog muscle is affected by its previous history of movement. The extent of this thixotropic effect is dependent on the size of the applied force (Lakie & Robson, 1988). The stiffness recovery following movement has now been studied at two temperatures, and has been shown to proceed at a logarithmically declining rate.
PROLONGED PRESSOR RESPONSES TO INTRAVENOUSLY INJECTED VASOPRESSIN IN ANAESTHETIZED BRATTLEBORO RATS
Authors: Obika L. F. O. , Laycock J. F.
Published: December 2014

Randomized intravenous injections of arginine vasopressin, 0·02 to 0·62 , µg/kg, administered to anaesthetized Brattleboro rats genetically lacking vasopressin, produced significantly greater, prolonged dose‐dependent pressor responses than those produced in normal animals of the parent Long‐Evans strain. Dose‐related decreases in cardiac output were transient in both groups of animals but were greater in Brattleboro rats. It is concluded that the enhanced pressor effects in these animals were associated with greater and prolonged increases in the total peripheral resistance.
RESOLUTION OF OUABAIN‐SENSITIVE AND EXTRACELLULAR K+‐ACTIVATED Na+ EXTRUSION IN CARDIAC TISSUE
Authors: Achenbach C.
Published: December 2014

Intracellular sodium activity (aiNa) was measured in sheep cardiac Purkinje fibres exposed inter‐ mittently to calcium‐free solutions containing 1·3 mM‐Na+ with 0‐16 mM‐K+ and 0‐0·2 mM ouabain. In potassium‐free solution (0 K+) mean maximum Na+ pump activity (i.e. excluding Na+ influx and Na+‐Ca2+ exchange) was 61% of that in the 4 mM‐K+ control solution; in 0·2mM‐ouabain‐4 mM‐K+ it was still 44% of control. This high ouabain concentration abolished Na+ extrusion only in 0 K+ while reducing it by the same absolute amount at all other extracellular K+ concentrations. The Na+ pump may therefore have two independent components in cardiac tissue.
THE EFFECTS OF REDUCED DIETARY PHOSPHATE INTAKE ON PLASMA OSTEOCALCIN LEVELS IN SHEEP
Authors: Corlett S. C. , Care A. D.
Published: December 2014

Six sheep were fed a diet with normal phosphorus content for 1 month after which plasma inorganic phosphorus (Pi), calcium, osteocalcin (BGP) and alkaline phosphatase concentrations were measured over a 48 h period. The same animals were then fed a low phosphorus diet for a further month prior to a second sampling period. Plasma Pi and BGP concentrations were significantly reduced after the low phosphorus diet; there was a statistically non‐significant rise in plasma calcium but no change in alkaline phosphatase concentrations.
COMPARISON OF THE EFFECTS OF OXYGEN, 5‐HYDROXYTRYPTAMINE, BRADYKININ AND ADRENALINE IN ISOLATED HUMAN UMBILICAL ARTERY SMOOTH MUSCLE
Authors: McGrath J. C. , MacLennan S. J. , Whittle M. J.
Published: December 2014

The actions of 5‐HT, bradykinin and adrenaline on the isolated human umbilical artery (HUA) were examined in paired isometric and isotonic preparations and in paired isometric and perfused preparations at both low (∼20 mmHg) and high (∼120 mmHg) oxygen tensions. The response to each agonist was potentiated by the higher oxygen tension in all test systems. The relative potency of the three agonists studied was similar using each of the experimental techniques. The contractions to stepped increments in oxygen tension were compared in isometric and isotonic preparations. The thresholds were found to be 20 and 28 mmHg respectively. The maximum contraction occurred at 234 and 199 mmHg respectively. In the perfused (constant flow rate) preparations, oxygen did not evoke any increase in perfusion pressure unless the vessel was held under longitudinal tension, in which case the pressor responses were similarly concentration dependent as for isometric and isotonic preparations. Responses to 5‐HT, bradykinin and adrenaline in the perfused preparation were similar with or without application of longitudinal tension. It is concluded that oxygen may contract only the longitudinal muscle whereas 5‐HT, bradykinin and adrenaline act on both longitudinal and circular muscle. The possible roles which these agonists may play in the regulation of umbilical blood flow are discussed.
THE EFFECT OF SODIUM PUMP BLOCKADE AND DENERVATION ON THE STEADY‐STATE SODIUM PERMEABILITY OF MOUSE SKELETAL MUSCLE FIBRES
Authors: Seabrooke S. R. , Ward M. R. , White N. K.
Published: December 2014

The Na+ pump inhibitor ouabain produced a 25 mV depolarization of mouse extensor digitorum longus muscle fibres in 2 h. Approximately 40% of this depolarization could be prevented by the inclusion of tetrodotoxin (TTX) in the incubation fluid, and the membrane potential of ouabain‐depolarized fibres increased when external Na+ ion concentration was reduced. TTX and Na+ reduction were without effect on fibres incubated for 2 h in the control saline or on fibres depolarized by raising extemal K+ ion concentration. Ouabain induced a fall in input resistance in fibres of reduced chloride conductance. Part of the depolarization induced in the majority of fibres by K+‐free solutions was also TTX sensitive. These results suggest that the steady‐state Na+ permeability of muscle fibres is increased after Na+ pump blockade. The ouabain‐induced depolarization of skeletal muscle therefore cannot be taken as evidence for a significant contribution of an electrogenic Na+ pump to the resting membrane potential. TTX also reverses much of the depolarization which occurs after denervation of skeletal muscle. Denervation and ouabain both increase the steady‐state Na+ permeability of the sarcolemma, possibly by an action on the same population of Na+ channels.
EFFECTS OF SYNTHETIC BOVINE PARATHYROID HORMONE (1‐34) AND ITS ANALOGUES ON 45Ca UPTAKE AND ADENYLATE CYCLASE ACTIVATION IN BONE AND PLASMA CALCIUM LEVELS IN THE CHICK
Authors: Dacke C. G. , Shaw A. J.
Published: December 2014

We have previously demonstrated that intravenous injection of synthetic bovine parathyroid hormone (1‐34) (bPTH(1‐34)), but not necessarily bPTH(l‐84), into chicks rapidly (3 min) inhibits skeletal uptake of an acute 45Ca label. In the present study hydrogen peroxide oxidation of bPTH(1‐34) abolished this response and reduced its ability to activate adenylate cyclase in bone and kidney. Oxidised bPTH(1‐34) did, however, exhibit the full hypercalcaemic activity of untreated hormone. In contrast, the analogue [Nle8, Nle18, Tyr34]‐bPTH(l‐34)amide reduced chick bone 45Ca uptake but failed to raise plasma Ca levels. Cyclic AMP formation in response to this analogue was also slight. Another analogue, [Nle8, Nle18, Tyr34]‐bPTH(3‐34)amide, failed to inhibit 45Ca uptake or stimulate cyclic AMP formation in chick bone. It was also without hypercalcaemic activity. These data suggest that the hypercalcaemic response to bPTH(1‐34) in chicks is not merely a reflection of its inhibitory effect on bone 45Ca uptake. They also question the relevance of cyclic AMP in the former action. A model is proposed by which PTH could rapidly inhibit bone net 45Ca uptake by stimulating release and turnover of intracellular calcium stores in bone lining cells, thereby creating a gradient for Ca out of bone.
MYOSIN LIGHT CHAINS IN REGENERATING RAT SKELETAL MUSCLE FOLLOWING CHRONIC, LOW‐FREQUENCY, ELECTRICAL STIMULATION
Authors: Rosenblatt J. David , Kuzon William M. , Houston Michael E. , McKee Nancy H. , Plyley Michael J.
Published: December 2014

Ten days of chronic, low‐frequency, electrical stimulation of regenerating rat extensor digitorum longus muscle causes an increase in the percentage of slow, phosphorylatable myosin light chains with a complementary decrease in the total fast light chain content. This altered light chain expression is similar to that observed when electrical stimulation is applied to a developing muscle in vivo.
DIURESIS FROM ATRIAL RECEPTORS AFTER HYPOPHYSECTOMY AND LOCAL ABLATION WITH NO CHANGES IN PLASMA VASOPRESSIN
Authors: Bennett K. L. , Linden R. J.
Published: December 2014

Stimulation of the left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and natriuresis. The efferent limb of this reflex is thought to have at least three components: nervous, haemodynamic and humoral. The present study was designed to investigate the humoral component in dogs anaesthetized with chloralose; to determine whether a humoral agent, other than vasopressin, might be causative in this reflex diuresis. The nervous and haemodynamic components were prevented by pharmacological denervation. Any possible contribution to the diuresis by a decrease in the plasma concentration of vasopressin was prevented by the removal of the pituitary gland. In animals in which a spontaneous diuresis followed hypophysectomy, an infusion of arginine vasopressin sufficient to maintain urine flow in the normal range for these dogs anaesthetized with chloralose was given. Distension of small balloons at the pulmonary vein‐atrial junctions and in the left atrial appendage discretely to stimulate the atrial receptors in eleven dogs anaesthetized with chloralose resulted in a significant diuresis. It was concluded that a blood‐borne agent other than vasopressin was responsible for the observed diuresis. At the moment it is not known whether vasopressin or the diuretic agent, or both, are involved in the diuresis accompanying the stimulation of atrial receptors.
REFLEX RESPONSES OF VASCULAR RESISTANCE IN ANAESTHETIZED DOGS TO INDEPENDENT CHANGES IN VENTRICULAR SYSTOLIC PRESSURE AND CARDIAC INOTROPIC STATE
Authors: Tutt S. M. , Al-Timman J. K. A. , Hainsworth R.
Published: December 2014

Responses of systemic arterial perfusion pressure to changes in ventricular systolic pressure were determined before and after administration of dobutamine, then after propranolol, to determine whether the effective stimulus to left ventricular receptors was the change in ventricular systolic pressure or inotropic state. The results showed that increases in ventricular systolic pressure resulted in reflex vasodilatation which was unaffected by inotropic state, indicating that changes in ventricular systolic pressure provided the more potent stimulus.
TISSUE ELECTROLYTES IN THE RABBIT FOLLOWING CHRONIC DIETARY POTASSIUM DEPLETION
Authors: Ward Jeremy P. T.
Published: December 2014

Tissue electrolytes were estimated in rabbits following chronic dietary K+ depletion, and after a week of subsequent K+ repletion. The heart, liver and brain all exhibited protection against K+ loss following K+ depletion, whereas skeletal muscle did not. Both Na+ and total magnesium were elevated in quadriceps, but not in other tissues. After 1 week of K+ repletion the heart and liver both showed a significant overshoot in tissue K+, but no change in total magnesium. It is suggested that the liver may have a similar adaptation to depletion as that reported for the heart (Ward & Cameron, 1984).
A NEW FORM OF ASYMMETRY IN EPITHELIA: KINETICS OF APICAL AND BASAL SULPHATE TRANSPORT IN HUMAN PLACENTA
Authors: Bustamante J. C. , Yudilevich D. L. , Boyd C. A. R.
Published: December 2014

Sulphate transport into and out of membrane vesicles prepared from both the brush‐border and basal surfaces of the human placental trophoblast has been studied. For both surfaces of this epithelium clear evidence of trans‐stimulation of influx is seen but for efflux, acceleration of labelled sulphate movement by addition of external sulphate is seen only in basal and not in brush‐border membrane vesicles. This kinetic asymmetry may underlie the previously observed, but unexplained, finding that the concentration of sulphate is greater in the fetal than in the maternal circulation.
POST‐TRANSLATIONAL MODIFICATION OF PEPTIDE MESSENGERS IN THE GUT
Authors: Dimaline R.
Published: December 2014

Recombinant DNA technology has enabled valuable information to be obtained on the precursors of gastrointestinal regulatory peptides. A number of precursors such as progastrin and proCCK contain a single recognized biologically active sequence, while others contain multiple active sequences. Some of the latter group such as proenkephalin contain repeated copies of a single peptide sequence, some such as proVIP and proglucagon contain related, but not identical, biologically active peptides, and others such as proopiomelanocortin contain unrelated active sequences. However, while cDNA sequencing studies reveal the potential secretory products available within precursors, they provide no information on the actual cleavages and prosthetic modifications that occur. Some prediction of processing events can be made from the occurrence of consensus sequences of amino acids, but confirmation is possible only by isolation and characterization of the products of the post‐translational processing.

This is of particular physiological significance because in many instances processing occurs in a cell‐specific manner, such that a single precursor may give rise to several products with a range of biological activities. For this reason it is important that studies of post‐translational processing keep pace with the ever increasing number of precursor sequences deduced by recombinant DNA technology.
MECHANISMS RESISTING FATIGUE IN ISOMETRICALLY CONTRACTING HUMAN SKELETAL MUSCLE
Authors: Gibson H. , Cooper R. G. , Edwards R. H. T. , Stokes M. J.
Published: December 2014

Human adductor pollicis was fatigued during circulatory occlusion by supramaximal stimulation via the ulnar nerve using intermittent trains of stimuli in ascending (1, 10, 20, 50 and 100 Hz) and descending (100, 50, 20, 10 and 1 Hz) frequencies to investigate the contribution of relaxation rate slowing and post‐tetanic potentiation (PTP) to fatigue resistance. At 50 and 100 Hz force was initially well maintained despite a marked loss of excitation as indicated by EMG, demonstrating the operation of a high‐frequency ‘safety factor’ which appeared independent of the pattern of stimulation. At 10 Hz, force was initially potentiated before declining during both activity series. Potentiation was greater during the descending frequency series and the rate of decline of force, or fatigability, was reduced. The ‘extra’ low‐frequency potentiation at 10 Hz was not simply the result of PTP of twitch force, since this declined more during the descending than during the ascending series, nor the result of maximal relaxation rate changes which were identical for both fatiguing series. It is hypothesized that the extra potentiation and reduced fatigability at low stimulation frequencies, when preceded by high frequency, is the result of increased myofibrillar Ca2+ availability and/or sensitivity. These findings may have important practical implications in relation to functional electrical stimulation techniques as used in paraplegia and in other areas of muscle research where fatigue is to be minimized.
A STUDY OF THE RENAL RESPONSES IN THE RAT TO ELECTRICAL STIMULATION OF THE AFFERENT NERVES OF THE BRACHIAL PLEXUS
Authors: Handa Rajash K. , Johns Edward J.
Published: December 2014

Brachial nerve stimulation at 3 Hz in sodium pentobarbitone‐anaesthetized rats, with constant renal arterial pressure, increased systemic blood pressure, did not alter glomerular filtration rate but reduced renal blood flow, absolute and fractional sodium excretions and urine flow. In renally denervated animals, stimulation caused similar changes in blood pressure and renal haemodynamics but significantly smaller reductions in sodium and water excretions. Brachial nerve stimulation at 30 Hz caused changes in blood pressure and renal function identical to those obtained with low‐frequency stimulation but these responses were not modified by renal denervation. The results show that renal nerves are necessary to promote sodium and water reabsorption in response to low‐but not high‐frequency stimulation of the brachial nerves in the rat.
INHIBITION OF BRAIN STEM NEURONAL ACTIVITY BY CARDIAC AND PULMONARY VAGAL AFFERENT FIBRES IN THE CAT
Authors: Bennett J. A. , Goodchild C. S. , Kidd C. , McWilliam P. N.
Published: December 2014

Recordings have been made of the activity of 311 neurones in the nucleus tractus solitarius (NTS) and dorsal motor vagal nucleus (DMVN) which responded to stimulation of the cardiac or pulmonary vagal branches in the anaesthetized cat. Eighty‐one neurones showed inhibitory effects to vagal branch or vagal trunk stimulation which were exhibited in three different ways. First, the responses of forty neurones evoked by stimulation of one vagal branch were reduced or abolished by stimulation of another vagal branch or the vagal trunk. Second, the spontaneous activity of six neurones, not excited by branch stimulation, was reduced or abolished by vagal branch stimulation, and third, thirty‐five neurones showed evidence of reduced excitability to a second stimulus pulse applied to the same branch. The inhibitory effects were characterized by a long time course (mean 932 ms, range 4‐10000 ms), and the latency to onset suggests that both myelinated and non‐myelinated afferents are capable of such actions. Inhibitory effects were observed on neuronal elements activated both synaptically, i.e. interneurones, and non‐synaptically, i.e. efferent motoneurones or afferent fibres, although no pattern of branches mediating particular effects could be discerned. The possible physiological implications of these observations are discussed.
EFFECT OF MAGNESIUM INFUSION ON CALCIUM HANDLING IN THE RAT KIDNEY
Authors: Shafik I. , Green R.
Published: December 2014

Anaesthesized rats were infused with 100 µl min-1 of 0·9% saline or saline containing 2 or 4 mmol l−1 of magnesium chloride and renal function was studied. Magnesium had no effect on urine flow rate, excretion of sodium or potassium, or glomerular filtration rate (GFR). Infusion of either dose of magnesium increased calcium excretion and calcium concentration in the urine. The increased urinary calcium excretion is due to a decrease in tubular reabsorption of calcium.
THE EFFECTS OF MONENSIN ON THE ABUNDANCE OF mRNA(α) AND OF SODIUM PUMPS IN HUMAN CULTURED CELLS
Authors: Cramb G. , Cutler C. P. , Lamb J. F. , McDevitt Trudi , Ogden Patricia H. , Owler D. , Voy Carol
Published: December 2014

HeLa or MRC5‐VI cells were grown for up to 1 day in media containing monensin at concentrations up to 10 µM. We measured the sodium pump density of the plasma membrane with [3H]ouabain and the mRNA for the α‐subunit of the pump by hybridization to a cDNA probe. The sodium and potassium concentrations were measured under similar conditions, and in some experiments the rate of internalization of the sodium pumps estimated by using [3H]ouabain uptake into the cell. We found that the relationship between sodium pump density and [Na+]i was well described by Michaelis‐Menten kinetics with a Km of 12 mM‐[Na+]i and a Vmax twice the normal value. There was no obvious relationship between cell potassium and pump density. The relationship between sodium pump density and [Na+]i was the same as that found by growing the cells in low‐potassium medium, so we conclude that the manner of raising [Na+]i is not important, merely the final value. In conditions of raised intracellular sodium there was an increase in the mRNA for the α‐subunit of the pump, but there was no slowing of the rate of internalization of the pumps from the plasma membrane. We conclude that the increased density of pumps is due to an increased synthesis rather than a decreased internalization rate of pumps, suggesting that the cell can control the method of upregulation.
INFLUENCE OF HALOTHANE ON CONTRACTION AT POSITIVE MEMBRANE POTENTIALS IN SINGLE CELLS ISOLATED FROM GUINEA‐PIG VENTRICULAR MUSCLE
Authors: Terrar D. A. , Victory J. G. G.
Published: December 2014

Actions of halothane were investigated under voltage‐clamp conditions in single cells from guinea‐pig ventricular muscle. Contraction (measured by an optical method) evoked by step depolarization to 0 mV was consistently reduced by halothane. At positive membrane potentials (+60 mV) 2% halothane did not cause a consistent depression of peak contraction, and in the majority of cells contraction was enhanced. Two per cent halothane increased the time‐to‐peak contraction at +60 mV. However, when a pre‐pulse to 0 mV was applied to inactivate calcium current through L‐channels, any effect of 2% halothane on the time‐to‐peak of contraction was reduced or abolished. A halothane‐induced increase in time‐to‐peak contraction was also observed at membrane potentials in the range of the action potential plateau (+20 and +40 mV). In double‐pulse experiments contraction during a ‘test’ depolarization to +60 was measured following a ‘conditioning’ depolarization to 0 mV. Contraction at +60 mV was slightly reduced at brief interpulse intervals (less than 400 ms) following the ‘conditioning’ depolarization to 0 mV, and recovered as the interval was prolonged; in cells exposed to halothane contraction at +60 mV was no longer influenced by the interval between the pulses. Isoflurane (3·2%) had qualitatively similar but less potent effects than halothane on contraction at +60 mV. These observations are consistent with the suggestion that mechanisms for calcium entry may vary with the membrane potential: at 0 mV, the major pathway for calcium entry may be through halothane‐sensitive L‐type calcium channels, while at +60 mV entry may be through additional pathways which are relatively resistant to halothane. Actions of halothane on the time‐to‐peak of contraction may be accounted for by its influence on the sarcoplasmic reticulum to decrease net uptake and release of calcium. These actions of halothane might be of importance during the action potential plateau.
ON THE RELATION OF CALCIUM TO OVINE PAROTID SECRETION
Authors: Wright R. D. , Blair-West J. R. , Nelson J. F.
Published: December 2014

The effects of Ca2+‐active agents on ovine salivary flow rate and composition were measured in parotid glands under several conditions: no stimulation, submaximal stimulation of the secretomotor nerve, or stimulation by the cholinergic agents carbachol or bethanechol. Agents were infused into the arterial blood supply of parotid glands and those investigated were: calcium chloride, the calcium ionophores Bay K8644 and A23187, the calcium chelators EGTA and EDTA, the voltage‐dependent calcium channel blocker verapamil and congeners, the calmodulin inhibitor trifluoperazine (TFP) and congeners. None of the agents affected the flow rate of saliva from unstimulated or pharmacologically stimulated glands. Increased plasma [Ca2+] and the ionophores did not affect salivary flow in nerve‐stimulated glands. In nerve‐stimulated glands, EGTA and TFP reduced salivary flow rate and verapamil increased it. The effect of EGTA was reversed by restoring plasma [Ca2+] to normal (1·0‐1·2 mmol/l) or above, but the responses to TFP and verapamil were not reversed by increasing plasma [Ca2+]. In all three conditions of stimulation, infusions of EGTA, verapamil or TFP increased salivary [HPO42−] and reduced [HCO3−] and pH. The ionophores had the opposite effects but increased plasma [Ca2+] had no effect. At the same time, EGTA, verapamil or TFP increased salivary [Na+ + K+], Bay K8644 had the opposite effect but increased plasma [Ca2+] had no effect. The osmolality of the saliva was not altered in any of these circumstances. Salivary [Ca2+] was increased by Ca2+ infusion and reduced by EGTA. Glandular blood flow increased with infusion of agents which increased salivary [HPO42−], fell with infusion of ionophores, and was unchanged by increased plasma [Ca2+]. Thus, there appear to be three calcium‐related activities in ovine parotid salivary gland in vivo: (1) salivary flow rate by action at the neuroeffector site, (2) salivary composition by alteration of the ratio of HPO42−:HCO3−, and (3) rate of blood flow through the gland by altering vascular resistance.
DRINKING AND VASOPRESSIN RELEASE FOLLOWING CENTRAL INJECTIONS OF ANGIOTENSIN II IN MINIPIGS
Authors: Thornton S. N. , Baldwin B. A. , Forsling M. L.
Published: December 2014

Angiotensin II (AII; 300 ng) injected into the lateral cerebral ventricle produced significant drinking responses and also stimulated release of lysine vasopressin (LVP) in conscious, water replete, unrestrained minipigs. Plasma LVP concentration, measured by a specific radioimmunoassay, was decreased by drinking. At the end of the experiment the level was inversely proportional to the volume of water drunk in response to the AII, and not to changes in plasma osmolality. These findings suggest that AII‐stimulated LVP release is influenced by a negative feed‐back mechanism, probably involving oropharyngeal receptors.
MECHANISM OF POTENTIATION OF CONTRACTION BY DEPOLARIZATION DURING ACTION POTENTIALS IN GUINEA‐PIG VENTRICULAR MUSCLE
Authors: Terrar D. A. , White E.
Published: December 2014

Action potentials were recorded from guinea‐pig ventricular cells and contraction recorded by an optical technique. When the plateau of a single action potential was depolarized (by 70–120 pA applied 100 ms after the upstroke for 100 ms), contraction associated with the following normal action potential was potentiated. This potentiation was not seen in cells exposed to 10 mM‐caffeine. The observations are consistent with potentiation of subsequent contraction by increased loading of caffeine‐sensitive calcium stores, as a consequence of reduced Ca2+ extrusion or possibly Ca2+ entry via Na+−Ca2+ exchange during a depolarized plateau.
EFFECT OF PHOSPHATE ON WATER AND GLUCOSE TRANSPORT IN MOUSE EVERTED GUT SACS
Authors: Mary P. L. , Rao J. Prakasa
Published: December 2014

Everted sacs prepared from proximal and distal parts of mouse intestine were used to study water and glucose transport in phosphate media. In the presence of high phosphate, glucose was found to increase water transport in the proximal segment but to decrease it in the distal segment. The possible mechanism of this action is discussed.
MECHANISMS OF WATER TRANSPORT BY EPITHELIAL CELLS
Authors: Tripathi Subrata , Boulpaep Emile L.
Published: December 2014

Isosmotic transport of fluid across epithelial cell layers occurs by intraepithelial mechanisms that are not fully understood. Newer methods of measuring water flows across epithelia with higher resolution should now permit some key issues regarding solute‐linked water transport to be clarified. Unstirred‐layer effects are not likely to be serious sources of error in these measurements with judicious choice of experimental conditions.

Progress in ultrastructural stereology has shown that in the proximal tubule most of the transporting membrane is located in the basal aspects of cells, making models based on a hyperosmolar lateral compartment less relevant. The current models of simple transcellular osmosis, though appealing for this simplicity, fail to account for some major experimental findings. Experimental design and methodological limitations have not yet achieved rigorous testing of whether or not epithelia can produce a perfectly isosmotic absorbate without any transepithelial driving forces.

A better understanding of the mechanism of translocation of water through the lipid bilayer, the plasma membrane proteins, and special membrane structures like the tight junctions would significantly contribute to our knowledge of the mechanisms and intraepithelial routes by which water is transported by epithelia.
SPONTANEOUS CONTRACTILE ACTIVITY OF GUINEA‐PIG GALL‐BLADDER IN VITRO
Authors: Mancinelli R. , Racanicchi C. , Mingrone G. , Mastromattei E. Arcieri , Greco A. V.
Published: December 2014

Some parameters of rhythmic mechanical and electrical events of guinea‐pig gall‐bladder were investigated. Pressure‐volume (P-V) responses, extracellular electrical activity and gall‐bladder morphology were recorded. Rhythmic gall‐bladder activity consisted of waves of pressure at intraluminal volumes between 0·5 and 1·8 ml. The pressure waveforms developed in a single contraction were usually oscillatory, containing two or more peaks which were more or less separated. The maximum amplitude value of phasic pressure waves was 1·8 ± 0·6 cmH2O. Bursts of spike potentials appeared at three equidistant electrodes along the longitudinal diameter of the bladder with variable delays indicating absence of propagation of the fast electrical activity. By analysing the morphological changes of gall‐bladder silhouette during the P−V curve it was evident that the maximum amplitude and duration of contractile events occurred when the whole muscular wall was stretched. Tetrodotoxin added to the bath solution did not abolish rhythmic activity ‐ indicating its myogenic nature ‐ and shifted the P−V curve to the left of the control, confirming the inhibitory role of the intrinsic nervous plexus of guinea‐pig gall‐bladder.
ANABOLIC EFFECTS OF INSULIN IN GROWING LAMBS
Authors: Wolff J. E. , Dobbie P. M. , Petrie D. R.
Published: December 2014

Romney cross‐bred wether lambs (aged 16–56 weeks and weighing 16–36 kg) were fed a concentrate diet ad lib. and surgically prepared with catheters in the left and right external iliac arteries and veins, inserted via the ipsilateral medial saphenous artery and vein. Sterile saline was continuously infused through all catheters and after appetite had fully recovered, bovine insulin was infused into one arterial catheter at rates of 5, 10 or 20 mU min−1 for periods of 15, 30 or 45 days in different lambs. At the end of the infusion the lambs were slaughtered to measure the composition of each hindquarter by tissue dissection and chemical analysis. As a result of the insulin infusions, plasma insulin concentrations were increased in venous blood sampled downstream from the infusion site and the arteriovenous concentration differences of glucose were greater across the treated than the contralateral limb. At the 10 and 20 mU min−1 infusion rates, systemic plasma insulin concentrations were increased and glucose concentrations decreased. Pooling results from all the treated lambs showed that intra‐arterial insulin infusion increased weight of the hindquarter by 7%, weight of muscle by 5%, weight of dissected fat by 12% and weight of chemical fat by 11% when compared with the contralateral limb. No significant differences were detected among infusion rates or times of infusion. Much of the variation in response between lambs was negatively correlated to their age and/or liveweight when they entered the study. The results demonstrate that tissues in the hindlimb respond to local concentrations of a circulating hormone, provide strong evidence that insulin is an anabolic hormone in the growing postnatal lamb and suggest that such responses diminish with age.
VASOPRESSIN REDUCES FOOD INTAKE IN GOATS
Authors: Meyer A. H. , Langhans W. , Scharrer E.
Published: December 2014

The effect of arginine vasopressin (VP) on cumulative food intake and meal pattern was tested in pygmy goats. VP injected intraperitoneally (I.P.) (0·75, 1·5 and 3·0 µg kg‐1 body weight) appeared to reduce food intake in a dose‐dependent manner by reducing the size of the first meal and by increasing the first intermeal interval (IMI). The hypophagic effect of VP was reversed by both a V1−receptor antagonist and an α‐adrenergic antagonist. Exogenous VP (0·75 and 1·5 µg kg−1 body weight I.P.) produced increases in plasma VP concentration which also may occur in stressful situations. VP might therefore be related to stress−induced anorexia.
CHARACTERIZATION OF DILATATION INDUCED BY ELECTRICAL FIELD STIMULATION IN MAMMALIAN CEREBRAL AND PERIPHERAL VESSELS
Authors: Hardebo J. E. , Kåhrström J. , Owman Ch.
Published: December 2014

The ability of electrical field stimulation in releasing transmitter from isolated blood vessels in vitro, during recordings of constrictor or dilator responses, is dependent upon an appropriate choice of stimulation parameters which avoid concomitant change in tone due to a direct effect on the vascular smooth muscle membrane. In many species, including man, small arteries such as pial arteries frequently respond to electrical field stimulation with a dilatation which is TTX‐resistant. Such dilatations occur even with stimulus parameters of 7·5 V/60 mA at 0·1 ms, 6 Hz. The stimulation parameters required to induce the TTX‐resistant response are just above those needed to obtain a purely neurogenic contractile or dilatory response in vessels equipped with a dense net of adrenergic nerves, such as rabbit central ear artery, and, in addition, highly sensitive postsynaptic α‐ or β‐adrenergic receptors, such as the buccal segment of the facial vein. This prompted us to characterize further the nature of the response. It was tested whether the relaxation, despite being TTX‐resistant, might be neurogenic in origin. 4‐Aminopyridine, in doses that usually enhance the transmitter release from nerves, did not affect the response. Blockade by a variety of dilator antagonists, the presence of excess amounts of known dilators or removal or emptying of known vasodilator nerves did not inhibit the response. Removal of extracellular calcium did not abolish the response. Therefore, it is highly unlikely that neuronal release is involved to any measurable extent in this response. The relaxation was not significantly affected by removal of endothelium, blockade of endothelium‐derived relaxing factor, or interference with mast cells. At modest stimulatory parameters (12−13 V/96−104 mA at 0·1 ms, 7∓8 V/56−64 mA at 0·3 ms, at 6 Hz) chlorine gas bubbles could be seen forming at the electrode or mounting hook; this gas is toxic to the musculature and relaxes a pre‐contracted vessel. At stronger stimulation (〉 12 V/96 mA, 〉 0·3 ms at 6 Hz) a relaxation supervened that was almost prevented by scavengers of oxygen free‐radical metabolites. This relaxation was partly irreversible, indicating damage to the contractile elements. We conclude that when studying electrically induced release of vasodilator transmitters in vessels not equipped with an highly effective transmitter/receptor function, even a small rise in stimulatory parameters ‐ in order to enhance transmitter release ‐ causes relaxations that are non‐neurogenic. At these and higher parameters the electrical field starts generating chlorine gas, as well as free radicals, which causes relaxation of the vessels. Therefore, stimulation at supramaximal voltage, commonly utilized in such studies to assure an effective neuronal activation, is not suitable when changes in vascular tone are used as a parameter.
THE EFFECT OF DISTENSION OF THE URINARY BLADDER ON ACTIVITY IN EFFERENT VAGAL FIBRES IN ANAESTHETIZED DOGS
Authors: Ramadan Mohamed R. M. , Drinkhill Mark J. , Mary David A. S. G.
Published: December 2014

Experiments were performed in anaesthetized dogs to find out whether the response of decreases in vagus nerve activity to distension of the urinary bladder is affected by changes in carotid sinus pressure. The carotid sinuses were vascularly isolated and perfused with blood at constant flow. Both ureters were cannulated and the urinary bladder was distended with warm Ringer solution. In eight dogs, all eleven efferent vagus fibres which responded to changes in carotid sinus pressure also responded to distension of the urinary bladder by a decrease in activity. This response of a decrease in activity was obtained at all levels of carotid sinus pressure between 8·4 and 30 kPa, and was greater at high than at low carotid sinus pressure. In the same vagus fibres, a relation was shown between progressive decreases in activity and either increases in intravesical pressure up to 8·7 kPa or reductions in carotid sinus pressure between 9 and 30 kPa. The decreases in activity were greater at high than at low carotid sinus pressure. These findings have shown that the inhibition of vagus nerve activity caused by bladder distension was affected by the level of carotid sinus pressure.
ABSORPTION OF DISSOCIATED AND UNDISSOCIATED SHORT‐CHAIN FATTY ACIDS ACROSS THE COLONIC EPITHELIUM OF GUINEA‐PIG
Authors: Rönnau K. , Guth D. , Engelhardt W. V.
Published: December 2014

Diffusion potentials for Na+, Cl-, acetate (Ac−), propionate (Pr−) and butyrate (Bu-) across the isolated epithelium of the proximal and the distal colon of guinea−pig were measured with flowing electrodes in Ussing chambers. Permeabilities of the anions are expressed in relation to the permeability of sodium. Unidirectional fluxes of Na+ and short‐chain fatty acids (SCFAs) were estimated. Fluxes of SCFA anions and of undissociated SCFAs were calculated from relative permeabilities and flux values. In the proximal colon of guinea‐pig 50% of SCFAs were transported in the dissociated and 50% in the undissociated form; transport rates of the three SCFAs were similar. In the distal colon SCFA transport was based primarily on diffusion of the free acids; the ratios of fluxes were: HAc/Ac‐ = 2·4; HPr/Pr− = 6·9; HBu/Bu− = 9·3, and transport rates increased with chain length of the SCFA.
FLUID BALANCE DURING HEAT STRESS IN LACTATING GOATS
Authors: Olsson Kerstin , Dahlborn Kristina
Published: December 2014

Fluid balance and thermoregulation were studied during an acute heat load (maximal daily temperature, 38 ± 1 °C; night temperature, 27 ± 1 °C) in six goats during lactation and nonlactation. The goats had free access to water for 1 day, followed by 29·5 h of water deprivation and then water was returned. With water available the goats increased water intake and urinary and milk water losses, while plasma and milk osmolality decreased. Water deprivation caused plasma osmolality and vasopressin concentration to increase most in lactating goats. Milk osmolality rose to values similar to plasma osmolality. Plasma cortisol increased in lactating goats at the end of dehydration. Renal Na+ excretion increased during dehydration in lactating goats. Evaporative heat loss was larger in lactating goats when hydrated, but became less than in non‐lactating goats during dehydration. Lactating goats exhibited higher respiratory frequency and rectal temperature than non‐lactating goats. In conclusion, our results show that goats increase the water turnover during heat stress if allowed to drink ad libitum, but when they are deprived of water lactating goats reduce water loss in urine, milk and by evaporation, and rectal temperature reaches higher levels than in non‐lactating animals. This saving of water could allow milk production to be maintained for a longer time during heat stress.
INJURY TO SKELETAL MUSCLES OF MICE BY FORCED LENGTHENING DURING CONTRACTIONS
Authors: Faulkner John A. , Jones David A. , Round Joan M.
Published: December 2014

Our purpose was to determine the amount of injury to extensor digitorum longus (EDL) and anterior tibial (ATB) muscles of mice from 1 h to 30 days following passive shortening and lengthening, shortening contractions and lengthening contractions. The shortening‐lengthening cycle was of 600 ms duration and was repeated every 5 s for 30 min. Contractions were produced during either the shortening or lengthening phase with stimulation at 100 Hz for 300 ms. The amount of injury was evaluated by the decrease in the number of fibres in a cross‐section of the muscle and in the maximum isometric tetanic force (P0). Passively shortened and lengthened and actively shortened EDL and ATB muscles showed no evidence of injury. At 3‐5 days after lengthening contractions, EDL and ATB muscles showed an inflammatory response. At 3‐5 days, the number of fibres in the cross‐section of the injured EDL muscles was 65% of that of the contralateral control EDL muscle, whereas no change was observed in the number of fibres in the injured ATB muscles. By 3 days, the presence of myoblasts, myotubes and central nuclei indicated regeneration of fibres. One hour after shortening contractions, the P0 of EDL and ATB muscles decreased to about 75% of the contralateral control value, but recovered completely by 3 days. In contrast, 1 h after lengthening contractions the P0 of EDL and ATB muscles decreased to 52 and 40% respectively of the contralateral control value and then both recovered to about 65% within 3 h. For the ATB muscle, the P0 showed a secondary decrease to 49% of the contralateral control value at 1 day and for the EDL muscle, to 47% at 3 days. Each muscle recovered gradually and by 30 days the number of fibres and the P0 of the injured muscles were not significantly different from values for contralateral control muscles.
REFLEX ACTIONS OF SELECTIVE STIMULATION OF SURAL NERVE C FIBRES IN THE RABBIT
Authors: Clarke R. W. , Ford T. W. , Taylor J. S.
Published: December 2014

Selective electrical stimulation of the non‐myelinated C fibres of the sural nerve in the decerebrated, spinalized rabbit evoked long‐latency (76‐160 ms), long‐lasting (〉 100 ms) reflex responses in the ipsilateral ankle extensor gastrocnemius medialis (GM). Activation of the same fibres elicited little or no response from the ipsilateral knee flexor semitendinosus (ST). Reflex responses were evoked in both GM and ST muscle nerves by stimulation of the Aβ afferents of the sural nerve. The Aβ‐elicited reflex in GM was enhanced, and that in ST depressed by prior activation of sural nerve C fibres. Strychnine, but not picrotoxin or mecamylamine, blocked C fibre‐induced inhibition of the flexor reflex. Pinching the heel with serrated forceps produced an immediate reflex discharge in GM motoneurones, whereas ST responded upon termination of the stimulus. Pinching the second toe evoked reflex activity in ST but not in GM. After strychnine (0·5 mg kg−1), both sets of motoneurones responded simultaneously to stimulation of either the heel or the toe. These data show that sural and other afferent fibres from the heel excite ipsilateral GM motoneurones and inhibit ST reflex responses. One interpretation of these findings is that fine sural afferents activate parallel inhibitory and excitatory pathways, of which the former is sensitive to strychnine and therefore probably mediated by glycine.