bluuebunny/crossref_metadata_2025 huggingface dataset:
An excitatory body‐antral reflex in the sheep abomasum
Authors: Cottrell DF , Stanley HG
Published: December 2014

This paper describes an abomasal body‐antral excitatory reflex in acute experiments in sheep anaesthetized with chloralose. The abomasum was either surgically intact or acutely transected to form separate compartments of the abomasal body and antrum. Inflation of a balloon situated in the abomasal body and active contraction of the abomasal body increased the amplitude of antral contraction. In the intact preparation, inflation of the abomasal body increased the amplitude of antral contraction before and after extrinsic denervation. The antral response was reduced by 75% after extrinsic denervation. In the acutely transected preparation, inflation of the abomasal body and electrically induced contraction of the abomasal body also increased antral contraction amplitude. The antral response was abolished by bilateral section of the cervical vagus nerves in five of six experiments. Selective extrinsic neurotomy of either compartment abolished all responses. It was concluded that the neural mechanisms controlling abomasal motility in the sheep resemble those found in species with simple stomachs: excitation of in‐series tension receptors of the abomasal body causes an increase in antral contraction amplitude by vago‐vagal reflex pathways. Antral motility is also modulated by changes of tension in the abomasal body by intrinsic reflex pathways and reflexes involving abdominal preganglia may also be present. In a restricted number of experiments the splanchnic nerve was shown to play an important role.
Transfer of insulin‐like growth factors I and II from plasma to lymph in young goats
Authors: Prosser CG , Baucells MD , Fleet IR
Published: December 2014

The plasma clearance of intravenously injected 125I‐labelled insulin‐like growth factor I (IGF‐I, n = 13) and IGF‐II (n = 12) and their transfer into lymph draining the foreleg of 3.5‐ to 8‐week‐old British Saanen goats was studied. Both peptides were initially distributed into a volume equivalent to the plasma volume, while the final distribution spaces for IGF‐I and IGF‐II were 90 +/− 9.8 and 125 +/− 12 ml/kg live weight respectively. There were two phases to the plasma clearance of both IGF‐I and IGF‐II, with the half‐lives of both phases for IGF‐I (9.6 +/− 0.9 and 287 +/− 23 min, first and second phase respectively) being significantly (P less than 0.001) longer than those of IGF‐II (4.2 +/− 0.6 and 172 +/− 18 min, respectively). The radioactivity transferred into lymph originated from intact IGF‐I and IGF‐II as well as degraded products of these compounds, as assessed by precipitation with trichloroacetic acid and gel filtration. Levels of undegraded IGF‐I in lymph were 50% greater than IGF‐II. While more than 90% of either peptide was bound to specific IGF‐binding proteins in plasma, in lymph 34 +/− 2% of IGF‐I and 23 +/− 3% of IGF‐II remained in the free form 60‐80 min after injection. The plasma: lymph ratio for free IGF‐I was 2:1 and for bound IGF‐I, 8:1. The corresponding values for IGF‐II were 3:2 and 8:1 respectively. These results provide direct experimental evidence for transfer of undegraded IGF‐I and IGF‐II from blood into lymph of the foreleg, consistent with the ability of these factors to act in an endocrine role in growing tissues. Differences between plasma clearance and transfer of IGF‐II into lymph compared with IGF‐I may be due to its greater cellular uptake and/or degradation in vivo.
Actions of the phorbol ester, PMA, on ATP‐induced fluctuations in cytoplasmic calcium in single isolated bovine aortic endothelial cells
Authors: Lynch M , Gillespie JI , Greenwell  , Johnson C
Published: December 2014

Agonist‐evoked rises in [Ca2+]i were recorded from single bovine aortic endothelial cells in the middle of confluent monolayers by dual‐wavelength microspectrofluorimetry. Low doses of ATP (1‐5 microM) induced a transient rise in [Ca2+]i followed by a maintained plateau phase upon which were superimposed irregular fluctuations in [Ca2+]i. The mechanism underlying these fluctuations is not known. Addition of the phorbol ester, phorbol 12‐myristate 13‐acetate (PMA), to single cells displaying ATP‐induced fluctuations reduced the amplitude and frequency of these fluctuations but the maintained plateau phase was unaffected. Elevation of intracellular cAMP by activation of adenylate cyclase with forskolin, or application of dibutyryl cAMP did not affect the ATP‐induced fluctuations. These results suggest a possible role for the diacylglycerol limb of the phosphoinositide hydrolysis pathway, via activation of protein kinase C, but not cAMP, in the mechanism responsible for generating ATP‐induced fluctuations in [Ca2+]i.
Position sense at the proximal interphalangeal joint is distorted in patients with rheumatoid arthritis of finger joints
Authors: Ferrell WR , Crighton A , Sturrock RD
Published: December 2014

The results of this investigation demonstrate, using a position matching paradigm, that the ability of subjects to detect changes in the position of the proximal interphalangeal joint is impaired in patients with rheumatoid arthritis affecting this joint. In this group there is a systematic flexion bias in position judgements compared to an age‐ and sex‐matched control group. This bias becomes progressively more pronounced at more extended positions. These results suggest that chronic inflammatory joint disease significantly alters proprioceptive sensations at finger joints and this may be due to the loss or distortion of afferent feedback from mechanoreceptors innervating the affected joint.
Interdigestive gastric blood flow: the relation to motor and secretory activities in conscious dogs
Authors: Naruse S , Takagi T , Kato M , Ozaki T
Published: December 2014

Blood flow in the left gastric artery was measured with an electromagnetic flowmeter in nine conscious beagle dogs. In the fasting state gastric motility and secretion exhibited periodical changes with an average cycle interval of 115.4 +/− 9.7 min. During a quiescent period, when gastric motility and secretion were minimal, the mean blood flow was stable at 33.9 +/− 3.8 ml/min. During the contracting phase each peristaltic contraction was coupled with a rapid fall and rise in blood flow (from 10.5 +/− 1.9 ml/min below to 21.2 +/− 3.8 ml/min above the precontraction levels) in 20‐30 s. In addition there was a sustained elevation in blood flow (58.6 +/− 6.4 ml/min at the peak) lasting for 29.1 +/− 2.8 min. The onset of sustained blood flow elevation was preceded by that of motility in 63% of the cycles. In 23% of the cycles blood flow started to rise before the contracting phase began. Pepsin peaks coincided with blood flow peaks in two dogs and preceded the latter in the others. Feeding abolished periodic increases in motility and blood flow. It is concluded that left gastric arterial blood flow is not steady but exhibits dynamic changes in phase with periodic motor and secretory activities of the stomach in fasting conscious dogs.
Effects of intracellular ATP on calcium current in freshly dispersed single cells of guinea‐pig portal vein
Authors: Okashiro T , Tokuno H , Fukumitsu T , Hayashi H , Tomita T
Published: December 2014

In smooth muscle cells freshly dispersed from the guinea‐pig portal vein, inward currents were recorded with the whole‐cell clamp method in the presence of 2.4 mM Ca2+ under the condition in which outward K+ currents were suppressed and the effects of ATP in patch pipettes were studied. There was a large variation of the rate of current decay, the half‐decay time ranging from 20 to 80 ms, but it was difficult to demonstrate clearly the presence of fast (T‐type) and slow (L‐type) Ca2+ channels based on threshold, the effects of changing holding potential, and of nicardipine, a dihydropyridine Ca2+ channel blocker. Intrapipette ATP had a weak potentiating effect on inward current, but did not seem to influence the correlation between peak current amplitude and current configuration. Cyanide (0.5 mM) reduced inward currents, particularly when ATP concentration was low and only limited recovery was observed. It was concluded that the amplitude and the rate of current decay of inward currents are not only determined by intracellular ATP, but also significantly influenced by some other factor, such as that involved in 'run‐down' of Ca2+ currents.
Myoplasmic Mg2+ concentration in Xenopus muscle fibres at rest, during fatigue and during metabolic blockade
Authors: Westerblad H , Allen DG
Published: December 2014

Intracellular free Mg2+ concentration ([Mg2+]i) was measured in isolated single fibres of Xenopus muscle using the fluorescent Mg2+ indicator furaptra. In resting muscle the [Mg2+]i was 1.7 mM in a Mg(2+)‐free Ringer solution. There was no significant change in [Mg2+]i over 2 h in Mg(2+)‐free Ringer solution. Elevating extracellular [Mg2+] to 40 mM for 5 min caused a small rise (0.13 mM) in [Mg2+]i. There was no detectable rise in [Mg2+]i after 5 min in Na(+)‐free Ringer solution. These results suggest that the membrane is relatively impermeable to Mg2+ and that there was no detectable Na(+)‐Mg2+ exchange over 5 min. When muscle fibres were fatigued by repeated tetani continued until force declined to about 40% of control, [Mg2+]i showed characteristic changes. During the early period of fatigue when force first showed a small decline and then became almost stable, [Mg2+]i was unchanged; during the final period of fatigue when force declined more rapidly, [Mg2+]i increased by 0.8 mM. Recovery of [Mg2+]i took about 30 min. Recovery of force was complex: tetanic force first declined (post‐contractile depression) and then slowly recovered to control. Since the minimum force occurred at about the time when [Mg2+]i had recovered, it seems unlikely that post‐contractile depression is caused by elevated [Mg2+]i. Rigor, produced by inhibiting oxidative phosphorylation and glycolysis, was associated with a larger increase (1.6 mM) in [Mg2+]i than fatigue. The rise in [Mg2+]i during fatigue and metabolic blockade could be explained as release of Mg2+ normally bound to ATP. A model of the metabolic changes and the resulting increase in [Mg2+]i explains our results reasonably well.
Intracerebroventricular angiotensin II‐induced thirst and sodium appetite in rat are blocked by the AT1 receptor antagonist, Losartan (DuP 753), but not by the AT2 antagonist, CGP 42112B
Authors: Beresford MJ , Fitzsimons JT
Published: December 2014

In the rat, intakes of water and 1.8% NaCl induced by I.C.V. angiotensin II were inhibited by prior I.C.V. injection of the angiotensin subtype 1 receptor antagonist, Losartan, but not by the subtype 2 receptor antagonist, CGP 42112B. Drinking induced by I.C.V. carbachol was unaffected by either antagonist.
An investigation into the extent to which flare in human skin crosses the mid‐line
Authors: Mentis GZ , Lynn B
Published: December 2014

We investigated whether flare crossed the mid‐line in various positions in humans using laser Doppler flowmetry to confirm visual observations. On the back and forehead, flare crossed the mid‐line. However, on the posterior part of the neck, flare did not cross the mid‐line, an observation that may be related to the elongated shape of flare in this region.
Repetitive transients in intracellular Ca2+ in cultured human vascular smooth muscle cells
Authors: Gillespie JI , Otun H , Nicholls JA , Greenwell  , Dunlop W
Published: December 2014

Human uterine vascular smooth muscle cells have been isolated and maintained in culture. When these cells are exposed to bathing solutions with nominally zero sodium, using potassium, N‐methyl‐D‐glucamine or Tris as substitutes, repetitive transient increases in intracellular calcium are observed. These transients are abolished when the calcium concentration of the bathing solution is reduced to nominally zero suggesting a role for extracellular calcium in the activation or maintenance of the transients. The hypothesis is proposed that the underlying mechanism involves a calcium influx through the reversed operation of a sodium‐calcium exchange mechanism and the cyclical activation of calcium‐induced calcium release from the sarcoplasmic reticulum. Noradrenaline (10(‐6) M) and caffeine (20‐30 mM) reversibly inhibited the transients. The inhibitory action of these agents could not be mimicked by dibutyryl cAMP suggesting that cAMP does not mediate the inhibition. Caffeine alone had no effect on resting calcium. Thimerosal (1‐100 microM), an agent thought to activate a second type of calcium‐induced calcium release mechanism activated repetitive transient increases in intracellular calcium which behave in a similar manner to those activated by sodium removal. These data are consistent with the presence of a thimerosal‐activated calcium‐induced calcium release mechanism in these cultured human cells. It is proposed that this mechanism is different from the calcium‐induced calcium release mechanism, described in other cell types, which is activated by caffeine.
Modulation of voltage‐dependent calcium current in Helix aspersa buccal neurones by serotonin and protein kinase C activators
Authors: Hill-Venning C , Cottrell GA
Published: December 2014

In Helix aspersa, activation of the cerebral giant serotonin neurones (GSNs) evokes a biphasic, excitatory synaptic response in the M neurones of the buccal ganglia. Local application of serotonin to the current‐clamped M neurones also evokes fast and slow depolarizing responses. The slow response is thought to be dependent on calcium ions, whereas sodium ions have been implicated in the fast response. Here we provide further evidence that the slow response results from an increase in conductance to calcium ions, and show that okadaic acid, an antagonist of protein phosphatases 1 and 2A, potentiates the effect of serotonin, suggesting that the response is phosphorylation dependent. Further, agents known to activate protein kinase C, such as 1‐oleoyl‐2‐acetyl‐rac‐glycerol and active phorbol esters (but not an inactive one) were found to increase the calcium current (actually carried by barium ions) of the M neurones. Such data suggest that the slow synaptic response mediated by serotonin can occur by activation of protein kinase C and phosphorylation of the affected voltage‐sensitive calcium channels, or some closely associated protein(s).
Transcellular openings through microvascular walls in acutely inflamed frog mesentery
Authors: Neal CR , Michel CC
Published: December 2014

Openings in the endothelium of frog mesenteric microvessels associated with acute inflammation following mild thermal injury have been examined by reconstruction from serial ultrathin sections. While all the openings lay close to the intercellular junctions only a minority (seven out of thirty‐eight) were continuous with the intercellular clefts. The majority of gaps or openings (thirty‐one out of thirty‐eight) were transcellular and passed through the peripheral cytoplasm of one endothelial cell, separated from the intercellular cleft by a cellular process which was usually less than 2 microns wide.
Voltage‐sensitive elevation of cytosolic [Ca2+] in guinea‐pig cardiac myocytes elicited by calcitonin gene‐related peptide
Authors: Gill JS , Moonga BS , Huang CL , Lu F , Zaidi M , Camm AJ
Published: December 2014

We have studied the effect of the 37‐amino acid cardioactive peptide, calcitonin gene‐related peptide (CGRP) on cytosolic [Ca2+] in guinea‐pig ventricular myocytes following depolarization. Cytosolic [Ca2+] was measured in single myocytes using fura‐2. The application of 20 mM K+ led to a transient rise of cytosolic [Ca2+] followed by an exponential decline. The subsequent application of 2 nM CGRP resulted in a marked increase in cytosolic [Ca2+]. In contrast, no such response was obtained without prior depolarization. The results suggest a basis for the cardiotropic effects of CGRP through an influence on cytosolic [Ca2+].
Exercise‐induced cholesterol depletion and Na+,K(+)‐ATPase activities in human red cell membrane
Authors: Shanmugasundaram KR , Padmavathi C , Acharya S , Vidhyalakshmi N , Vijayan VK
Published: December 2014

Red cell membranes were isolated from blood samples obtained from athletes during exhaustive exercise on a bicycle ergometer and during the subsequent recovery period of 60 min. Plasma lactate levels were also determined. During exercise, cell membranes were progressively depleted of cholesterol and, at exhaustion, membrane cholesterol was less than 80% of the initial level. A parallel decline in Na+,K(+)‐ATPase was also noted, while phospholipid reduction was around 5%. During recovery, the erythrocyte membrane cholesterol and Na+,K(+)‐ATPase increased, but at a slow rate and were inversely proportional to plasma lactate content.
Properties of diazoxide and cromakalim‐induced activation of potassium channels in cultured rat and RINm5F insulin‐secreting cells; effects of GTP
Authors: Harding EA , Jaggar JH , Ayton BJ , Dunne MJ
Published: December 2014

Experiments have been carried out to examine the effects of GTP on the opening of K+ channels in insulin‐secreting cells by diazoxide (0.2 mM) and cromakalim (0.5 mM). Using rat pancreatic beta‐cells and RINm5F insulinoma cells, patch‐clamp recordings of unitary ATP‐sensitive potassium (K+ATP) channel currents were made in either the open cell or outside‐out patch recording configurations. Adding diazoxide or cromakalim to either the inside or the outside face of the membrane was found regularly to cause the activation of K+ATP channels in the presence of 0.5 mM ATP. We now demonstrate that in the absence of ATP but in the presence of GTP (0.5–1 mM), both diazoxide and cromakalim activate channels. Effects are rapid in onset, sustained and readily reversible. Both the diazoxide‐ and cromakalim‐induced activation of K+ATP channels were mediated by increases in channel open‐state probability, and were not associated with any significant change in either channel amplitude or by an increase in the number of channels in the patch. The actions of both diazoxide and cromakalim were not affected by overnight pretreatment of cells with pertussis toxin, suggesting that PTX‐sensitive GTP‐binding proteins are not involved in mediating the actions of either compound. These data indicate that diazoxide and cromakalim open K+ATP channels in a manner not solely dependent upon intracellular ATP, but by mechanisms involving other cytosolic nucleotides, including GTP.
The effects of increasing cell length on auxotonic contractions; membrane potential and intracellular calcium transients in single guinea‐pig ventricular myocytes
Authors: White E , Le Guennec JY , Nigretto JM , Gannier F , Argibay JA , Garnier D
Published: December 2014

Until recently the investigation of length‐dependent effects in cardiac muscle was restricted to multicellular preparations. We describe our experimental set‐up which for the first time, in single cardiac myocytes, permits the effects of changes in cell length on auxotonic contractions (measured by carbon fibre transducers) to be simultaneously recorded with the effects on membrane potential and/or changes in intracellular calcium concentration (using indo‐1 AM, acetoxylmethyl form). Consistent with previous findings (in experiments at 20‐25 degrees C and 0.25 Hz) we report that following a stretch there was an increase in passive tension and contraction. A stretch which increased sarcomere length by approximately 3% had no significant effect on resting membrane potential or action potential amplitude. There was, however, a significant decrease in the action potential duration (P < 0.01, n = 8). No significant change in the amplitude of the intracellular calcium transient was seen following a stretch but a reduction in its duration was observed (P < 0.025, n = 11). Our observations on intracellular calcium transients are consistent with the hypothesis that, in mechanically loaded preparations, their time course is more dependent on changes in tension than changes in length.
The effect of acidosis on beta‐adrenergic receptors in ferret cardiac muscle
Authors: Nimmo AJ , Than N , Orchard CH , Whitaker EM
Published: December 2014

Acidosis decreases the force of contraction of cardiac muscle in response to noradrenaline. The role of beta‐adrenergic receptors in this response to acidosis was investigated. Radioligand techniques were used to determine beta‐adrenergic receptor number and the degree of G‐protein coupling, and to see whether these were altered in tissues subject to acidosis. The effect of pH on agonist and antagonist binding to these receptors was also investigated. Tissue pre‐exposure to acidic conditions had no effect on numbers of beta‐adrenergic receptors and no effect on the affinity of [125I]iodocyanopindolol (ICYP) for the receptors. Agonist competition experiments indicated that there was no change in the affinity of isoprenaline for these receptors, and there was no change in the relative proportions of high and low affinity binding sites. When radioligand experiments were performed under acidic conditions, however, the total number of beta‐adrenergic receptors increased, and the affinity of these receptors for isoprenaline increased. This increase in agonist affinity might, therefore, minimize the shift to the right seen in the dose‐response curve to noradrenaline during acidosis.
The effect of age and voluntary contraction on presynaptic inhibition of soleus muscle Ia afferent terminals in man
Authors: Butchart P , Farquhar R , Part NJ , Roberts RC
Published: December 2014

Transmission in a pathway mediating presynaptic inhibition of soleus Ia afferent terminals was assessed from the reduction of soleus muscle H reflex amplitude brought about by a short conditioning vibration pulse applied to the anterior tibialis muscle. In a group of young subjects (aged between 21 and 37 years) the mean reduction in reflex size with the limb relaxed was to 29.2% of control, whereas in a group of older subjects (aged between 59 and 74 years) the reduction was significantly less, to 55.0% of control (P < 0.001, Student's t test). In the younger group the amount of presynaptic inhibition elicited was inversely related to the plantar‐flexor torque produced by tonic contraction of gastrocnemius‐soleus; often at higher torques no reduction in reflex size was seen. In contrast the older group showed only a slight reduction in presynaptic inhibition with increasing torque, so that at torques of 5 and 7 N m the amount of presynaptic inhibition elicited was similar in the younger and older groups. The older subjects were not able to sustain the higher torques produced by the younger subjects. These results suggest that the control of transmission in this spinal pathway changes with increasing age.
Control of tissue progastrin concentrations in the rat
Authors: Varro A , Yegen B , Dockray GJ
Published: December 2014

The influence of different physiological stimuli on plasma concentrations of the acid‐stimulating hormone gastrin and on the tissue concentrations of its precursor, progastrin, were examined in the conscious rat. Plasma concentrations were measured by radioimmunoassay using antibody specific for the C‐terminus of biologically active (amidated) gastrins, and tissue concentrations of progastrin were measured after size exclusion chromatography by radioimmunoassay using antibody specific for the C‐terminus of rat progastrin. Plasma and antral tissue were taken from control rats fed ad libitum, from rats fasted for 48 h, and from fasted or fed rats treated with the proton pump inhibitor omeprazole to reduce acid‐induced inhibition of gastrin release. Plasma gastrin concentrations were depressed 4‐fold by fasting and this was reversed by treatment with omeprazole; in rats fed ad libitum and treated with omeprazole plasma gastrin was elevated 8‐fold. Fasting did not significantly change the plasma clearance of gastrin, indicating that changes in endogenous circulating levels are attributable to altered secretion rather than metabolism. Tissue progastrin concentrations were depressed 3‐fold in fasted rats compared with rats fed ad libitum. Treatment of fasted rats with omeprazole produced a 2‐fold increase in tissue progastrin; but in spite of the substantial elevation of plasma gastrin in fed rats treated with omeprazole, tissue progastrin was elevated by only about 50%. Sulphation at Tyr103 of progastrin was not changed by fasting or omeprazole. An estimate of the conversion of progastrin to amidated gastrin was determined as the tissue progastrin clearance, i.e. the weight of antral mucosa in which progastrin is converted to amidated gastrin and secreted per minute to maintain plasma concentrations. Conversion rates were increased 7‐fold in fed omeprazole‐treated rats compared with controls; in fasted rats treated with omeprazole the rate of conversion was depressed 50% compared with controls. It is concluded that changes in the lumen of the stomach are able to influence the processes by which progastrin is converted to its active amidated products.
Calcium paradox in newborn and adult guinea‐pig hearts: changes in intracellular taurine and the effects of extracellular magnesium
Authors: Suleiman MS , Chapman RA
Published: December 2014

The isolated hearts of adult and neonatal guinea‐pigs have been compared for changes in intracellular amino acids during calcium depletion and the loss of cellular proteins on calcium repletion. Taurine, in freshly excised ventricles of neonatal guinea‐pig heart, at 10.5 +/− 0.5 mmol (kg wet weight)‐1 (n = 5) is less than in the adult heart (13.0 +/− 0.6 mmol (kg wet weight)‐1 (n = 5)) but still is the most abundant amino acid free in the sarcoplasm. A marked loss of tissue taurine in both neonatal and adult hearts (a fall to 3.5 +/− 0.25 mmol (kg wet weight)‐1 in neonatal and 4.9 +/− 0.6 mmol (kg wet weight)‐1 in adult hearts after 10 min) was induced by perfusion with Ca, Mg‐free Tyrode solution. A fall in several of the alpha‐amino acids was also seen during this manoeuvre. On reperfusion with normal Tyrode solution, a marked release of proteins (lactate dehydrogenase, creatine kinase and myoglobin) was observed, which showed a similar time course in both types of heart. Elevation of [Mg]o during calcium depletion reduced protein loss on calcium repletion in both neonatal and adult guinea‐pig hearts. This effect was consistent with an effect of Mg2+ on the rise of [Na]i. A second effect of [Mg]o was to shift the time to peak protein loss, an effect greater in neonatal hearts and more pronounced for the proteins with larger molecular weight (lactate dehydrogenase > creatine kinase > myoglobin). This latter effect of Mg2+ would seem not to be due to an effect on capillary permeability because the presence of bovine serum albumin in the perfusate failed to produce a similar effect. Neonatal and adult guinea‐pig hearts show a similar sensitivity to the calcium paradox and similar changes in tissue taurine during calcium depletion, and therefore contrast with rat and rabbit heart.
The role of the sodium pump and sodium‐calcium exchange in recovery from calcium overload in guinea‐pig ventricular myocytes
Authors: Minezaki KK , Chapman RA
Published: December 2014

A marked increase in [Ca2+]i is provoked in isolated guinea‐pig ventricular myocytes by return to normal Tyrode solution after a period of exposure to fluid free of divalent cations. When the sarcolemma of the myocyte remains intact, [Ca2+]i falls back towards initial levels over the next 5 to 10 min in spite of the strong irreversible contracture. This recovery fails to occur if either the Na+ pump or Na(+)‐Ca2+ exchange is inhibited once [Ca2+]i has risen.
Cardiac sympathetic nerve stimulation enhances cardiovascular performance during hyperkalaemia in the anaesthetized pig
Authors: O'Neill M , Dorrington KL , Paterson DJ
Published: December 2014

A rapid increase in arterial plasma potassium concentration to values seen during intense exercise depresses cardiac function at rest. Increasing the cardiac concentration of noradrenaline by right‐sided sympathetic stimulation in eleven anaesthetized pigs significantly augmented cardiovascular performance during hyperkalaemia, while electrical pacing of the right atrium at equivalent rates to sympathetic stimulation afforded no protection against the deleterious effects of hyperkalaemia. We conclude that the inotropic effect of sympathetic activation may be important in sustaining cardiac function during exercise‐induced hyperkalaemia.
The Wellcome Prize Lecture. A map of auditory space in the mammalian brain: neural computation and development
Authors: King AJ
Published: December 2014

The experiments described in this review have demonstrated that the SC contains a two‐dimensional map of auditory space, which is synthesized within the brain using a combination of monaural and binaural localization cues. There is also an adaptive fusion of auditory and visual space in this midbrain nucleus, providing for a common access to the motor pathways that control orientation behaviour. This necessitates a highly plastic relationship between the visual and auditory systems, both during postnatal development and in adult life. Because of the independent mobility of difference sense organs, gating mechanisms are incorporated into the auditory representation to provide up‐to‐date information about the spatial orientation of the eyes and ears. The SC therefore provides a valuable model system for studying a number of important issues in brain function, including the neural coding of sound location, the co‐ordination of spatial information between different sensory systems, and the integration of sensory signals with motor outputs.
Sympathetic innervation and beta‐adrenoceptor profile of blood vessels in the posterior region of the rabbit knee joint
Authors: Najafipour H , Ferrell WR
Published: December 2014

Experiments were performed to investigate the presence and nature of beta‐adrenoceptors in blood vessels supplying the posterior capsule of the rabbit knee joint. Electrical stimulation of the posterior articular nerve (PAN) and close intra‐arterial injection of adrenaline produced vasoconstriction which reversed to vasodilatation with administration of the alpha‐adrenoceptor antagonist phenoxybenzamine. In almost all animals close intra‐arterial injection of the beta‐adrenoceptor agonist isoprenaline resulted in vasodilatation. Injection of the more selective beta‐agonists dobutamine, salbutamol and terbutaline also produced vasodilatation with a rank potency order of isoprenaline > dobutamine > salbutamol > or = terbutaline. The beta‐adrenoceptor antagonist propranolol abolished the dilator responses to adrenaline and isoprenaline, and significantly reduced the dilator responses to PAN stimulation in phenoxybenzamine‐treated animals. Nerve‐mediated vasodilatation was also reduced by the substance P antagonist D‐Pro4 D‐Trp7,9,10 SP4‐11, suggesting that substance P contributes to this dilatation. Dobutamine, a selective beta 1‐agonist, produced vasodilatation which was abolished by administration of the selective beta 1‐antagonist atenolol. Isoprenaline‐induced vasodilatation was substantially reduced by atenolol. The dilator response to isoprenaline appeared to be unaffected by the selective beta 2‐antagonist ICI118551, but the weak dilator responses to the selective beta 2‐agonists salbutamol and terbutaline were significantly reduced by this antagonist. The results of this study suggest that beta‐adrenoceptors appear to be involved in the sympathetic regulation of rabbit knee joint blood flow, and that this is predominantly mediated via beta 1‐adrenoceptors.
Bombesin and gastrin‐releasing peptide stimulate electrogenic ion transport in cultured human endometrial epithelial cell layers
Authors: Matthews CJ , Redfern CP , Thomas EJ , Hirst BH
Published: December 2014

Electrogenic ion transport across human endometrial epithelial cells grown as polarized monolayers on permeable supports was measured as an inward short‐circuit current (Isc; 16.2 +/− 1.1 microA/cm2). Bombesin (10(−7) M) and human gastrin‐releasing peptide (GRP; 10(−7) M) caused transient enhancement of this Isc. These effects were largely restricted to the basolateral surface of the cells; responses to apical peptide were modest in comparison with those to basolateral peptide. GRP and other bombesin‐related peptides may have a role in regulation of endometrial epithelial ion transport in vivo and thereby influence the intra‐uterine environment.
Osteoclast function and its control
Authors: Zaidi M , Pazianas M , Shankar VS , Bax BE , Bax CM , Bevis PJ , Stevens C , Huang CL , Blake DR , Moonga BS , et al.
Published: December 2014

Bone resorption appears to be dependent on a range of processes. It requires an adequate number of osteoclasts to access bone mineral. These osteoclasts must be activated by a mechanism which is dependent upon prior osteoblastic stimulation. A range of factors then contribute to the formation of a functionally effective resorptive hemivacuole. These entail osteoclast adhesion to the bone surface leading to the formation of a sealing zone. Only then can subsequent processes such as H+ ion transport, enzyme secretion and matrix digestion become effective. Thus, any one process is potentially limiting to resorption and is a potential target for regulation. Long‐range regulation takes place through the action of hormones, of which the mode of action of calcitonin has been the subject of recent investigations in isolated osteoclasts. Such studies have shown a possible involvement of distinguishable receptor subtypes, the occupancy of which may activate at least two types of triggering mechanism. It is likely that an eventual influence on motility properties through G protein mediation accounts for the actions of this hormone and of related peptides such as amylin and CGRP at the cellular level. Similar pathways may contribute to shorter range modulation of osteoclast activity by increases in ambient Ca2+. Finally, there is recent evidence for a contribution of endothelial cell‐derived product to osteoclast regulation.
Spread of the dorsal root reflex in an isolated preparation of hamster spinal cord
Authors: Bagust J , Chen Y , Kerkut GA
Published: December 2014

In an isolated preparation of hamster spinal cord maintained at 27 degrees C, stimulation of a single dorsal root has been shown to evoke dorsal root reflexes in ipsilateral roots throughout the lumbar and thoracic cord. The dorsal root reflex was evoked by activity in low threshold dorsal root fibres, and left the cord through dorsal root fibres conducting at 5.9 m/s. The ipsilateral dorsal root reflex travelled equally well in both directions along the cord at a calculated velocity of 0.5 m/s at 27 degrees C. Comparison of the stimuli required to evoke dorsal root reflexes in adjacent and distant ipsilateral dorsal roots suggests that once this system is activated it operates largely in an all‐or‐none manner. The delay in the generation of the dorsal root reflex within the cord was calculated to be 4.7 +/‐ 0.2 ms at 27 degrees C, corresponding to approximately 2 ms at body temperature, suggesting that a trisynaptic pathway is involved in the generation of the dorsal root reflex at the segmental level.
Heart rate and blood pressure variability in subjects exposed to simulated increases in gravity
Authors: McKenzie I
Published: December 2014

The effect of simulated increases in gravity (G) force on blood pressure and heart rate variability was investigated in seven normal healthy subjects using a man‐carrying centrifuge. Subjects were exposed to G forces up to 3.6 times the gravity at the earth's surface (3.6 G). Blood pressure was measured non‐invasively using a finger cuff (Finapres), while the subjects breathed at a fixed rate and depth. The blood pressure waveform was digitized and systolic blood pressure, diastolic blood pressure and beat‐to‐beat intervals were extracted from these data. Power spectra were produced from these values. Increases in G force produced increases in spectral power of systolic blood pressure and diastolic blood pressure at the respiratory frequency (0.2 Hz) and less conspicuous but significant increases in spectral power at lower frequencies (0.045‐0.15 Hz). The spectral power of beat‐to‐beat interval did not change. It is postulated that the reduction in central blood volume produced by increased gravity is affecting blood pressure control in a similar way to that seen in hypovolaemic animals. The marked increase in blood pressure fluctuations induced by respiration at the higher G levels may be a result of the alteration in venous return to the right atrium, ultimately reflected as fluctuating left ventricular output and pressure.
Stimulation of taurine efflux from human placental tissue by a hypoosmotic challenge
Authors: Shennan DB , McNeillie SA , Curran DE
Published: December 2014

The fractional release of taurine from preloaded human placental tissue fragments was stimulated by a hypoosmotic challenge. This stimulation could not be attributed to a change in the Na+ gradient or the ionic strength of the medium. We suggest that taurine fluxes may play a role in placental cell volume regulation.
Differential effects of lipid and carbohydrate on enterocyte lactase activity in newborn piglets
Authors: Tivey DR , Le Dividich J , Herpin P , Brown D , Dauncey MJ
Published: December 2014

The influence of enteral feeding in the neonate on lactase‐phlorizin hydrolase activity in the small intestine has been determined in newborn piglets fed a series of modified colostra, with a controlled metabolizable energy intake, during the first 31.5 h of life. Striking differences were observed between lactase specific activity in mucosal homogenates and enterocyte lactase activity along the villus axis; compared with newborns, the former decreased after feeding colostrum, whereas the latter increased significantly. When lipid was present in adequate amount, the increase in enterocyte lactase activity occurred when carbohydrate was present as either lactose or galactose. However, when the lipid content of the diet was low, there was a specific effect of carbohydrate composition which was dependent on position along the villus axis: in the lower villus, colostra high in lactose or glucose stimulated an increase in lactase, but there was no such effect with a high galactose intake. It is concluded that colostrum increases enterocyte lactase activity during the first day of life, and that this is dependent on both the nutrient composition of the diet and the position of the enterocytes along the villus.
Effects of gadolinium on length‐dependent force in guinea‐pig papillary muscle
Authors: Lab MJ , Zhou BY , Spencer CI , Horner SM , Seed WA
Published: December 2014

The degree to which stretch‐activated channels operate during physiological length changes in multicellular heart preparations, or how much the channels could contribute to length‐dependent activation, is not known. We studied the relationship between muscle length and contractile force in guinea‐pig papillary muscles superfused with gadolinium chloride (10 microM), a stretch‐activated channel blocker, and compared the effects to those with nifedipine (0.25 microM), a calcium channel blocker. Gadolinium reduced contractile force statistically significantly more at the longer muscle lengths than at the short muscle lengths. This did not apply with nifedipine, although a marginally greater effect at longer lengths was perceptible. The results can only partly be explained by gadolinium having a non‐specific action via the calcium channel, or Na(+)‐Ca2+ exchange, and are consistent with the possibility that stretch‐activated channels contribute to length‐dependent activation in cardiac muscle, and thus to 'Starling's Law of the Heart'.
Electrical stimulation of the vagus increases extracellular glutamate recovered from the nucleus tractus solitarii of the cat by in vivo microdialysis
Authors: Allchin RE , Batten TF , McWilliam PN , Vaughan PF
Published: December 2014

Release of glutamate into the extracellular space of the cat nucleus tractus solitarii (NTS) was measured by in vivo microdialysis and high performance liquid chromatography. Perfusion of the probe with 100 mM potassium increased glutamate release by 211% (P < 0.001), while electrical stimulation of the cervical vagus increased release by 53% (P < 0.01). These results are compatible with the hypothesis that glutamate is a neurotransmitter released by vagal afferent nerve terminals in the NTS.
The effect of alcohol on physiological tremor
Authors: Lakie M , Frymann K , Villagra F , Jakeman P
Published: December 2014

Ethanol reduces the size of essential tremor. We here show that, contrary to a recent report, ethanol also causes a large decrease in the size of physiological tremor. As in the case of essential tremor, the frequency is not changed. The reduction in tremor probably explains the well‐known link between certain types of skilled activity and alcohol consumption.
The role of parathyroid hormone‐related protein in calcium homeostasis in the fetal pig
Authors: Abbas SK , Ratcliffe WA , Moniz C , Dixit M , Caple IW , Silver M , Fowden A , Care AD
Published: December 2014

The concentrations of plasma parathyroid hormone‐like bioactivity and parathyroid hormone‐related protein (1–86) (PTHrP) immunoreactivity were both higher in fetal pigs than in their mothers during the last 3 weeks of gestation. Both activities changed inversely with alterations in the plasma ionized calcium concentration. The data suggest that PTHrP may have a role in calcium homeostasis in the fetal pig, similar to its postulated role in sheep in the stimulation of calcium transport across the placenta.
Calcium influx and release in isolated rat osteoclasts
Authors: Shankar VS , Huang CL , Adebanjo OA , Pazianas M , Zaidi M
Published: December 2014

Intracellular and extracellular sources of cytosolic [Ca2+] elevation in isolated rat osteoclasts were explored by a comparison of fura‐2 signals in response to application of the Ca2+ ionophore, ionomycin, in Ca(2+)‐containing and in Ca(2+)‐free bathing solutions. Cytosolic [Ca2+] transients persisted in osteoclasts bathed in Ca(2+)‐free, EGTA‐containing solutions. They consisted of a peak cytosolic [Ca2+bd elevation followed by a full decay to baseline and were refractory to manipulations of surface membrane potential through changes in extracellular [K+]. They disappeared upon intracellular Ca2+ store depletion through repeated ionophore applications. They were therefore attributable solely to intracellularly stored Ca2+. In contrast, the fura‐2 peaks in osteoclasts exposed to Ca(2+)‐containing solutions decayed to sustained levels. Cytosolic [Ca2+] responses then persisted with repeated ionomycin application. These latter phenomena are accordingly attributable to extracellular Ca2+ entry. Finally, restoration of extracellular [Ca2+] to 1.25 mM following the depletion of intracellular Ca2+ stores by treatment with ionomycin elicited a cytosolic [Ca2+] 'overshoot' consistent with capacitative Ca2+ entry via a cytosolic route. These results demonstrate a refillable intracellular source of cytosolic Ca2+ that could function in osteoclastic regulation.
Effects of intracellular pH on calcium currents and intracellular calcium ions in the smooth muscle of rabbit portal vein
Authors: Iino S , Hayashi H , Saito H , Tokuno H , Tomita T
Published: December 2014

In smooth muscle cells freshly dispersed from the rabbit portal vein, effects of intracellular pH (pHi) on Ca2+ channel currents were studied with the whole‐cell clamp method using nystatin in the pipette. pHi was modified with ammonium chloride (NH4Cl) and propionate. Changes in intracellular Ca2+ concentration ([Ca2+]i) and pHi were also measured with the fluorescent indicator fura‐2 and a pH‐sensitive dye, respectively, together with the mechanical response in intact tissues. Intracellular alkalinization caused by an application of NH4Cl (20 mM) markedly potentiated and acidification caused by propionate (20 mM) inhibited inward Ca2+ channel currents, without much change in the kinetics. Tension development induced by 60 mM K‐ was inhibited by NH4Cl (20 mM) and potentiated by propionate (20 mM), whereas the peak [Ca2+]i level reached during K+ contracture was reduced in the presence of NH4Cl and increased in the presence of propionate. It was concluded that the modification of Ca2+ channel currents caused by pHi is not directly related to the effects of pHi on the mechanical response to excess K+. The direct effects of pHi on [Ca2+]i and on contractile machinery are considered to be mainly responsible for the mechanical effect of pHi.
Acid‐base transport systems in a polarized human intestinal cell monolayer: Caco‐2
Authors: Osypiw JC , Gleeson D , Lobley RW , Pemberton PW , McMahon RF
Published: December 2014

Acid‐base transport systems have been incompletely characterized in intact intestinal epithelial cells. We therefore studied the human cell line Caco‐2, cultured on Teflon membranes to form confluent monolayers with apical microvilli on transmission electron microscopy and progressive enrichment in microvillar hydrolases. Monolayers (16‐ to 25‐day‐old), loaded with the pH‐sensitive dye BCECF‐AM (2',7'‐bis (carboxyethyl)‐5‐carboxyfluorescein), were mounted in a spectrofluorometer cuvette to allow selective superfusion of apical and basolateral surfaces with Hepes‐ or HCO(3‐)‐buffered media. Intracellular pH (pHi) was measured by dual‐excitation spectrofluorimetry; calibration was with standards containing nigericin and 110 mM K+ corresponding to measured intracellular [K+] in Caco‐2 cell monolayers. In HCO(3‐)‐free (Hepes‐buffered) media, bilateral superfusion with 1 mM amiloride or with Na(+)‐free media reversibly inhibited pHi recovery from an intracellular acid load (NH4Cl pulse) by 86 and 98% respectively. Selective readdition of Na+ to the apical or basolateral superfusate also induced a pHi recovery, which was inhibited by ipsilateral but not by contralateral amiloride (1 mM). The pHi recovery induced by apical Na+ readdition had a Michaelis constant (Km) for Na+ of 30 mM and a relatively high inhibitor constant (Ki) for amiloride of 45.5 microM. Initial pHi in HCO(3‐)‐buffered media was lower than in the absence of HCO3‐ (7.35 vs. 7.80). pHi recovery from an acid load in HCO3‐ was Na‐ dependent but was inhibited only 18% by 1 mM amiloride. The amiloride‐independent pHi recovery was inhibited 49% by pre‐incubation of cells in 5 mM DIDS (4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonic acid). These data suggest that Caco‐2 cells possess: (a) both apical and basolateral membrane Na(+)‐H+ exchange mechanisms, the apical exchanger being relatively resistant to amiloride, similar to apical Na(+)‐H+ exchangers in several normal epithelia; and (b) a Na(−)‐dependent HCO3‐ transport system, either Na(+)‐HCO3‐ cotransport or Na(−)‐dependent Cl(−)‐HCO3‐ exchange.
A new approach to measuring transepithelial potentials in the bovine lens reveals a chloride‐dependent component
Authors: Zhang JJ , Jacob TJ
Published: December 2014

A new approach was used to measure anterior and posterior potentials and resistances of the bovine lens. Segments of the anterior, central and posterior lens were studied by mounting a disc of tissue from either the front or the back of the lens in a double chamber. At 35 degrees C the isolated anterior epithelial preparation exhibited a high potential of 9 mV and a low resistance of 279 omega cm2. The lens epithelium can therefore be classified as a ‘leaky’ or low resistance epithelium. Amiloride, benzamil and furosemide (frusemide) all reduced the anterior transepithelial potential and increased the resistance, amphotericin B (aqueous side) abolished the potential, whereas SITS (4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐disulphonic acid) had no effect. The posterior lens preparation was found to have a ‘transepithelial’ of ‐4 mV. This potential and a proportion of the anterior potential were not sensitive to ouabain, amiloride, furosemide, Na+ removal or raised K+, but were abolished by lowering [Cl‐] and reduced by the Cl‐ channel blocker NPPB. We conclude that chloride plays a significant role in the maintenance of transepithelial potentials at both the anterior and posterior surfaces of the lens.