bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between secretin and acetylcholine in the regulation of fluid secretion by isolated rat pancreatic ducts.
Authors: Evans R L , Ashton N , Elliott A C , Green R , Argent B E
Published: December 2014

1. Interlobular ducts were isolated from the rat pancreas and maintained in short‐term tissue culture. Fluid secretion from these isolated ducts was measured using micropuncture techniques, intracellular calcium concentration ([Ca2+]i) by fura‐2 microspectrofluorimetry, and cyclic AMP by radioimmunoassay. 2. Applying secretin and ACh simultaneously to ducts caused either a stimulation or an inhibition of fluid secretion depending on the doses employed. 3. The inhibitory effect of secretin and ACh could be relieved by atropine, and by the protein kinase C (PKC) inhibitors staurosporine and 1‐(5‐isoquinolinylsulphonyl)‐2‐methyl‐piperazine (H‐7). 4. Activation of PKC by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and phorbol 12, 13‐dibutyrate (PDBu) inhibited secretin‐evoked fluid secretion. 5. ACh and TPA also inhibited fluid secretion stimulated by the adenylate cyclase activator, forskolin. 6. Neither secretin nor the PKC activators and inhibitors had any effect on either the increase in [Ca2+]i evoked by ACh or the increase in intracellular cyclic AMP evoked by secretin and forskolin. 7. We conclude that the inhibitory effect of combined doses of secretin and ACh on ductal fluid secretion is probably mediated by PKC at a point in the secretory mechanism distal to the generation of intracellular messengers.
Delayed sympathetic efferent responses to coronary baroreceptor unloading in anaesthetized dogs.
Authors: Drinkhill M J , McMahon N C , Hainsworth R
Published: December 2014

1. We previously reported that, although stimulation of coronary arterial baroreceptors results in reflex vasodilatation of a magnitude and a time course similar to that seen in response to carotid baroreceptor stimulation, the vasoconstriction that occurs when the stimulus to coronary baroreceptors is removed develops more slowly. We now report the results of experiments designed to investigate the site on the reflex are that is responsible for the delayed vasoconstriction. 2. In alpha‐chloralose anaesthetized, artificially ventilated dogs, a perfusion circuit allowed independent control of pressures to the aortic root, including the coronary arteries, the aortic arch and the carotid sinuses. Electrophysiological recordings were made of afferent discharge in nerve fibres dissected from the vagus nerve, which responded to changes in coronary pressure, and from renal and lumbar efferent sympathetic nerves. Reflex vascular responses were assessed from changes in perfusion pressure to the systemic circulation, which was perfused at constant flow. 3. The afferent discharge from the coronary baroreceptors responded rapidly to both increases and decreases in coronary perfusion pressure. This indicates that prolonged activation of the coronary receptors cannot be the cause of the delayed vasoconstriction. 4. An increase in pressure to the coronary baroreceptors resulted in an immediate decrease in activity in either renal or lumbar sympathetic nerves. A decrease in coronary pressure, however, was followed by a slow gradual increase in sympathetic discharge. This contrasts with the responses to decreases in carotid or aortic arch pressures, which were followed by rapid increases in efferent discharge, often with an overshoot. 5. We conclude that the slow recovery of efferent sympathetic activity following a reduction in coronary pressure is likely to explain the previously reported slow recovery of vascular resistance.
Glutamate as a candidate retrograde messenger at interneurone‐Purkinje cell synapses of rat cerebellum.
Authors: Glitsch M , Llano I , Marty A
Published: December 2014

1. Depolarization‐induced suppression of inhibition (DSI) is a form of synaptic plasticity which involves a retrograde messenger. We have performed experiments in Purkinje cells of rat cerebellar slices to determine the nature of this messenger. 2. DSI is mimicked by 2‐(2,3‐dicarboxycyclopropyl)‐glycine (DCG‐IV), a specific agonist of group II metabotropic glutamate receptors (mGluRs). 3. DSI is reduced if transmitter release is inhibited by saturating doses of DCG‐IV. 4. Both DSI and DCG‐IV‐induced inhibition are inhibited by L‐2‐amino‐3‐phosphonopropionic acid (L‐AP3), a drug which interferes with several subtypes of mGluRs. 5. DSI is reduced if synaptic activity is enhanced by application of forskolin. 6. We propose that glutamate or a glutamate‐like substance is the retrograde messenger implicated in DSI, and that the inhibition resulting from presynaptic glutamate binding is mediated by a decrease in the presynaptic concentration of cAMP.
Effects of body immersion on postural adjustments to voluntary arm movements in humans: role of load receptor input.
Authors: Dietz V , Colombo G
Published: December 2014

1. The effect of body immersion on postural adjustments was studied in ten healthy subjects. Reaction times, for pushing or pulling a rigid handle, in response to a visual stimulus were measured. In addition EMG recordings were taken from upper arm and lower leg muscles during three levels of body immersion while standing on a platform (immersed to spinal levels: lumbar nerve root 2 (L2); thoracic nerve root 4 (T4); and cervical nerve root 7 (C7)), while floating and while standing or sitting out of water. 2. With increasing levels of body immersion there was a near linear reduction in the amplitude of the gastrocnemius (GM) EMG activity before (200 ms) the onset of a force signal from pulling, but immersion had a significantly weaker effect on the amplitude of the tibialis anterior (TA) EMG during pushing movements. There was no significant difference in the effect of body immersion on biceps femoris (BF) and rectus femoris (RF). Under free‐floating conditions postural adjustments did not occur in response to pull or push movements. There were no adaptational changes of EMG adjustments during successive trials at a given immersion level. 3. Under non‐immersed conditions reaction times were significantly shorter during sitting than during standing. This difference is assumed to be due to the postural adjustments required while standing before the onset of a voluntary arm movement. While standing, reaction times were significantly longer for pull compared with push movements. Under all conditions of body immersion the reaction times remained longer compared with the sitting condition, even when no leg muscle EMG adjustments were present. 4. It is assumed that the differential effect of body immersion on the antagonistic leg muscles is due to the differential neuronal control of antagonistic leg muscles with a strong influence from proprioceptive input (most probably from load receptors) on the leg extensors. The longer reaction times seen during body immersion, where no postural adjustments were evident, suggests that a supraspinal command to the leg muscles precedes the voluntary arm movement. However, because of the changed/decreased afferent input no postural adjustments are generated.
The effect of passive tilting on microvascular parameters in the human calf: a strain gauge plethysmography study.
Authors: Gamble J , Christ F , Gartside I B
Published: December 2014

1. Cumulative small steps in venous congestion pressure were used to study the effect of passive tilt on vascular parameters in dependent tissues. Using this protocol we have non‐invasively assessed venous pressure (Pv,est), isovolumetric cuff pressure (Pv,i), which is the congestion cuff pressure (Pcuff) that has to be exceeded to induce fluid filtration. We have also assessed microvascular filtration capacity (Kf), which is the linear relationship between filtration rate (Jv) and Pcuff, when Pcuff > Pv,i, and is the product of the available exchange vessel surface area and wall conductance. 2. Subjects were passively tilted to increase the venous pressure at the level of the calf by 47.4 +/‐ 2.4 mmHg (mean +/‐ S.E.M.). The value of Pv,i increased from 20.6 +/‐ 1.8 to 48.5 +/‐ 3.8 mmHg after the imposition of the tilt. This change may reflect the increased colloid osmotic pressure at the microvascular interface that is known to occur in response to this manoeuvre. 3. The pre‐tilt value of Kf did not change after the imposition of the passive tilt, the values being 3.2 +/‐ 0.4 x 10(‐3) and 3.6 +/‐ 0.4 x 10(‐3) ml min‐1 (100 ml‐1) mmHg‐1, respectively, (n = 13). 4. These results support the notion that passive postural change alters the pre‐capillary resistance, thereby altering the pressure and flow characteristics within the exchange vessels, but does not alter the surface area available for fluid exchange in the calf, contrary to previous findings in the dependent human foot using a single‐step venous occlusion protocol.
Exercise‐induced stimulation of murine macrophage chemotaxis: role of corticosterone and prolactin as mediators.
Authors: Ortega E , Forner M A , Barriga C
Published: December 2014

1. Exercise provokes changes in the immune system, including macrophage activity. Chemotaxis is a necessary function of macrophages if they are to reach the focus of infection and strenuous acute exercise may modulate chemotaxis. However, the precise mechanisms remain unknown. 2. Three experiments were performed in the present study. (1) The effect of strenuous acute exercise (swimming until exhaustion) on the chemotactic capacity of macrophages was evaluated. (2) Peritoneal macrophages from control mice were incubated with plasma from exercised mice or control (no exercise) mice. The differences in the resulting chemotactic capacity were measured. (3) Changes in the concentration of plasma corticosterone and prolactin after exercise were also measured, and the effect of incubation with the post‐exercise levels of plasma corticosterone and prolactin on the chemotactic capacity of the peritoneal macrophages was then studied in vitro. 3. Exercise induced an increase in the macrophage chemotaxis index (103 +/‐ 8 vs. 47 +/‐ 11 in controls). Incubation with plasma from exercised mice led to an increased level of chemotaxis (68 +/‐ 18 vs. 40 +/‐ 6 with plasma from controls). Incubation with concentrations of corticosterone and prolactin similar to those observed in plasma immediately after exercise (corticosterone, 0.72 mumol l‐1; prolactin, 88 pmol l‐1) raised the chemotactic capacity with respect to that following incubation with the basal concentrations of the hormones in control animals (90 +/‐ 9 vs. 37 +/‐ 4 for corticosterone; 72 +/‐ 9 vs. 41 +/‐ 4 for prolactin). 4. It is concluded that corticosterone and prolactin may mediate the increased chemotaxis of peritoneal macrophages induced by exercise.
Oscillation of gap junction electrical coupling in the mouse pancreatic islets of Langerhans.
Authors: Andreu E , Soria B , Sanchez-Andres J V
Published: December 2014

1. Pancreatic beta‐cells oscillate synchronously when grouped in islets. Coupling seems essential to maintain this oscillatory behaviour, as isolated cells are unable to oscillate. This allows the islet to be used as a model system for studying the role of coupling in the generation of oscillatory patterns. 2. Pairs of beta‐cells were intracellularly recorded in islets. beta‐Cells oscillated synchronously. Propagated voltage deflections were observed as a function of glucose concentration and of the distance between the recording electrodes. Space constants were smaller in the silent than in the active phases, suggesting a higher intercellular connection in the active phases. 3. Coupling coefficients and estimated coupling conductances were larger in the active than in the silent phases. 4. Coupling coefficients and coupling conductances changed dynamically and in phase with the membrane potential oscillations, pointing to an active modulation of the gap junctions. 5. We hypothesize a role for coupling in the generation of the oscillatory events, providing different levels of permeability dependent on the state of conductance during the oscillatory phases.
Stimulation of a nicotinic ACh receptor causes depolarization and activation of L‐type Ca2+ channels in rat pinealocytes.
Authors: Letz B , Schomerus C , Maronde E , Korf H W , Korbmacher C
Published: December 2014

1. Membrane voltage (Vm) recordings were obtained from isolated rat pinealocytes using the patch‐clamp technique. In parallel to the electrophysiological experiments, intracellular Ca2+ measurements were performed using fura‐2. 2. The resting Vm averaged ‐43 mV and replacement of extracellular NaCl by KCl completely depolarized the cells. This indicates that the resting Vm is dominated by a K+ conductance. Single‐channel recordings revealed the presence of a large conductance Ca(2+)‐activated charybdotoxin‐sensitive K+ channel. 3. Application of ACh (100 microM) depolarized the pinealocytes on average by 16 mV. The depolarizing effect of ACh was mimicked by nicotine (50 microM) and was prevented by tubocurarine (100 microM). 4. The ACh‐induced depolarization was largely abolished in the absence of extracellular Na+, but was not significantly affected by extracellular Ca2+ removal. 5. Application of ACh (100 microM) caused an increase in [Ca2+]i. This increase was completely dependent on the presence of extracellular Ca2+ and was largely reduced after extracellular Na+ removal. Nifedipine (1 microM) reduced the ACh‐induced increase in [Ca2+]i by about 50%. 6. Our findings indicate that in rat pinealocytes stimulation of a nicotinic ACh receptor (nAChR) induces depolarization mainly by Na+ influx via the nAChR. The depolarization then activates L‐type Ca2+ channels, which are responsible for the nifedipine‐sensitive portion of the intracellular Ca2+ increase. Ca2+ influx via the nAChR probably also contributes to the observed rise in [Ca2+]i.
Delayed rectifier current of bullfrog sympathetic neurons: ion‐ion competition, asymmetrical block and effects of ions on gating.
Authors: Block B M , Jones S W
Published: December 2014

1. The delayed rectifier (DR) K+ channel pore was probed using different permeant and blocking ions applied intra‐ and extracellularly. Currents were recorded from bullfrog sympathetic neurons using whole‐cell patch‐clamp techniques. 2. With intra‐ and extracellular Cs+ (0 K+), there were large, tetraethylammonium (TEA)‐sensitive currents. Adding K+ back to the extracellular solution revealed that the current with Cs+i was K+ selective (permeability ratio PCs/PK = 0.17 +/‐ 0.02, n = 4) and showed a strong anomalous mole fraction effect. 3. There were also large non‐inactivating currents with Na+i and Na+o (0 K+). The current with Na+i was K+ selective (Na+o vs. K+o: PNa/PK = 0.022 +/‐ 0.005, n = 5), and was TEA sensitive with K+o but not with Na+o. 4. Permeant ions affected gating kinetics. DR currents activated faster in K+ than in Cs+, and activated faster with increasing concentrations of either K+ or Cs+. Deactivation was slowed by increased K+ or Cs+ concentration, with no difference between K+ and Cs+. 5. The pore was also characterized using intracellular blocking ions. A wide variety of monovalent cations (TEA, N‐methyl‐D‐glucamine, arginine, choline, CH3NH3+, Li+, Cs+ and Na+) blocked DR channels from the inside in a voltage‐dependent manner: KD at 0 mV was 2.9 mM for TEA and 134‐487 mM for the others, at apparent electrical distances (delta) of 0.33‐0.79. There was no detectable block by 10 mM Mgi2+. Apart from TEA, the organic cations did not block from the outside. 6. The permeability to Na+ in the absence of K+, and the strong anomalous mole fraction effects observed for Cs+o + K+o mixtures, suggest that DR channels select for K+ using ion‐ion competition. The block by large intracellular cations shows that the pore is asymmetrical. The loss of high affinity TEAo block with Na+i and Na+o, and the effects of permeant ions on gating, suggest that channel conformation may be affected by ions in the pore.
Effect of pancreatic polypeptide on rat dorsal vagal complex neurons.
Authors: McTigue D M , Hermann G E , Rogers R C
Published: December 2014

1. Pancreatic polypeptide (PP) microinjected into the dorsal vagal complex (DVC) elevates gastric activity through a vagal mechanism. Thus, it was hypothesized that PP alters the activity of nuclei comprising the DVC, i.e. the nucleus tractus solitarii (NTS) and the dorsal motor nucleus (DMN). 2. In vivo and in vitro approaches were used. For in vivo studies, micropipettes were used for recording and injecting vehicle or PP. Neurons were identified as NTS or DMN using orthodromic and antidromic activation, respectively, following vagal stimulation. Gastric‐related DVC neurons were located using antral inflation. For in vitro studies, DMN neurons were recorded from medullary slices. 3. Of the twenty‐eight NTS and DMN neurons identified, fifteen were activated, six inhibited and seven unaffected after PP microinjection. Forty‐two gastric‐related neurons were located in the DVC, of which twenty‐five were stimulated by PP and seventeen exhibited no change. No gastric‐related cells were inhibited. 4. For in vitro studies, 66% of DMN neurons were activated by PP (n = 27/47) while the remaining 33% were inhibited (n = 14/47). Similar results were obtained in normal or synaptic blockade media. 5. These results support the hypothesis that PP alters DVC neuronal activity, which may thereby lead to the previously observed alterations in gastric activity.
Effect of metabolic inhibition on intracellular Ca2+, phosphorylation of myosin regulatory light chain and force in rat smooth muscle.
Authors: Taggart M J , Menice C B , Morgan K G , Wray S
Published: December 2014

1. The effect of the inhibition of oxidative phosphorylation on intracellular calcium concentration ([Ca2+]i), phosphorylation of the 20 kDa regulatory light chain of myosin (MLC20) and contractility was investigated in isolated longitudinal smooth muscle from rat uteri. 2. Cyanide (2 mM) application to normally polarized preparations resulted in an elevation of basal [Ca2+]i but an inhibition of [Ca2+]i transients and the accompanying contractions. 3. Depolarization with high‐K+ solution (40 mM KCI) resulted in elevation of [Ca2+]i and maintained force production. Phosphorylation of MLC20 was transiently increased followed by a steady‐state augmentation above resting levels. 4. Carbachol (100 microM) produced a transient elevation of [Ca2+]i and force of depolarized tissues followed by a steady‐state augmentation of both parameters. PGF2 alpha (1 microM) did not significantly potentiate [Ca2+]i or force in depolarized preparations. Both carbachol and PGF2 alpha potentiated phosphorylation of MLC20 in depolarized tissues. 5. Addition of cyanide to depolarized preparations, in the presence or absence of carbachol or PGF2 alpha, resulted in significant attenuation of force under each condition. The magnitude and normalized rates of force inhibition by cyanide were not significantly different for each stimulus condition. MLC20 phosphorylation levels were unaltered by cyanide treatment. However, cyanide increased the maintained level of [Ca2+]i under each experimental protocol. 6. It is concluded that the inhibition of oxidative phosphorylation with cyanide results in dissociation of both the [Ca2+]i‐force and MLC20 phosphorylation‐force relationships in rat uterine smooth muscle.
Interstitial PCO2 and pH, and their role as chemostimulants in the isolated respiratory network of neonatal rats.
Authors: Voipio J , Ballanyi K
Published: December 2014

1. CO2‐H(+)‐sensitive microelectrodes were used for simultaneous measurements of the partial pressure of CO2 (PCO2) and extracellular pH (pHo) in the ventral respiratory group (VRG) of the isolated brainstem‐spinal cord of neonatal rats. Some of the data were analysed using diffusion equations. 2. With increasing recording depth within the boundaries of the VRG (300‐600 microns below the tissue surface), PCO2 increased from 77 to 95 mmHg and pHo fell from 7.0 to 6.8 at steady state in standard saline equilibrated with 5% CO2 and 95% O2. 3. Elevating bath CO2 from 5 to 10‐12.5% produced a mean increase in PCO2 of 18 mmHg, a fall in pHo of 0.13 pH units, and a 50‐250% increase in the frequency of respiration‐related spinal (C2) nerve bursts. Similar effects on C2 activity and pHo were observed upon lowering bath [HCO3‐] from 25 to 10 mM, leading to a mean decrease in PCO2 of 4.4 mmHg in the VRG. 4. Raising bath [HCO3‐] to 50 mM produced a substantial frequency decrease, a rise in pHo of 0.24 pH units and an elevation in PCO2 of 9.3 mmHg. C2 activity was not profoundly affected upon doubling the CO2‐HCO3‐ content, leading to a mean increase in pHo of 0.13 pH units and elevation of PCO2 by 30 mmHg. 5. In a CO2‐HCO3(‐)‐free, Hepes‐buffered solution, PCO2 decreased to 18 mmHg in the VRG and pHo fell by 0.15 pH units with no major effect on rhythmic activity. Subsequent anoxic exposure for more than 15 min produced a further fall in PCO2 to below 1 mmHg, a decrease in pHo of 0.55 pH units, and blockade of respiration‐related activity. In three out of the six preparations tested, C2 activity could be restored by reapplication of CO2‐HCO3‐ in the absence of O2. 6. C2 activity persisted at a reduced frequency, even up to 30 min, during anoxia in the CO2‐HCO(‐)‐buffered saline,leading to an elevation in PCO2 of 15 mmHg and a fall in pHo of 0.18 pH units. 7. The diffusion coefficient of CO2 in the tissue was found to be equal to that in saline. Two mean estimates for anoxic tissue of the function lambda 2/ alpha of tortuosity (lambda) and extracellular volume fraction (alpha), affecting extracellular diffusion of bicarbonate, were 4.7 and 4.1. The mean rate of acid production by anoxic tissue was 1.1 mequiv 1‐1 min‐1. 8. The results suggest that extracellular H+ is the primary stimulating factor in central chemosensitivity, which may often mask the less evident effects of CO2. A model of diffusion of acid equivalents in brain tissue is proposed.
Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.
Authors: Kwiecien R , Tseeb V , Kurchikov A , Kordon C , Hammond C
Published: December 2014

1. The effects of brief applications of growth hormone‐releasing hormone (GHRH) to male rat somatotrophs in culture were analysed with the perforated patch clamp technique to record changes in potential or with fura‐2 imaging techniques to measure variations of cytosolic Ca2+ concentration ([Ca2+]i). 2. Silent somatotrophs (n = 61) had a mean resting potential of ‐37 +/‐ 1 mV and a mean basal [Ca2+]i of 30 +/‐ 4 nM. Brief GHRH applications (30 nM, 40 s) triggered rhythmic action potentials (23.6 +/‐ 0.9 mV, 613 +/‐ 82 ms, 0.21 +/‐ 0.02 Hz) and [Ca2+]i increase (to 352 +/‐ 30 nM) followed by rhythmic [Ca2+]i transients (to 138 +/‐ 6 nM) that persisted up to 90 min after the last GHRH application. Both action potentials and [Ca2+]i transients were totally and reversibly blocked by removing external Ca2+ or Na+ or by adding inorganic Ca2+ channel blockers or nifedipine (3 microM). 3. Somatostatin (1‐300 nM), carbamylcholine (0.1‐1 microM) and muscarine (0.1‐1 microM) each had a dose‐dependent inhibitory effect, from a decrease of Ca2+ spike duration and frequency to a complete block of the GHRH‐evoked action potentials. 4. The present results show that somatotrophs in culture have intrinsic membrane properties that allow them to sustain a pacemaker activity and subsequent long‐lasting sequences of [Ca2+]i oscillations triggered by short pulses of GHRH and inhibited by somatostatin and muscarinic agonists.
Gating charge and ionic currents associated with quinidine block of human Kv1.5 delayed rectifier channels.
Authors: Fedida D
Published: December 2014

1. The mechanism of quinidine‐induced ionic and gating current inhibition was studied in human Kv1.5 (hKv1.5) delayed rectifier channels expressed in human embryonic kidney cells. In the steady state, quinidine produced a voltage‐dependent block between +30 and +120 mV (Kd at +60 mV = 7.2 microM) with an equivalent electrical distance, delta, of 0.29 +/‐ 0.06 and 0.26 +/‐ 0.05 at 10 and 50 microM quinidine, respectively. The apparent affinity at 0 mV (Kd) was 25 microM at 10 microM quinidine and 38 microM at 50 microM quinidine. The data suggested a quinidine binding site that sensed 20‐30% of the transmembrane electrical field, from the inside. Non‐steady‐state measurements indicated rapid open channel block with mean time constants of 2.1 +/‐ 0.9 and 1.2 +/‐ 0.2 ms at 10 and 50 microM quinidine, respectively. 2. ‘On’ gating current (on‐Ig) was unaffected over a wide range of potentials and between 10 and 100 microM quinidine. On‐gating charge (Qon) was similarly conserved in the steady state between ‐100 and +50 mV. On return to ‐100 mV, quinidine slowed the off‐gating current (off‐Ig) after depolarizations more positive than ‐25 mV. After depolarizations to +50 mV, only 59 +/‐ 3.4% (10 microM quinidine) and 6.6 +/‐ 9.5% (100 microM quinidine) of the charge returned within 25 ms, compared with 100% in control. Due to the conservation of Qon in subsequent pulses, the remaining charge must have returned during the subsequent 10 s interpulse interval. 3. A threshold for quinidine action on off‐Ig was established positive to ‐25 mV. The voltage dependence of Qoff immobilization at more positive potentials than +20 mV had an equivalent electrical distance of 0.32 +/‐ 0.04 (10 microM quinidine) and 0.20 +/‐ 0.32 (100 microM quinidine) with calculated Kd values of 21.6 +/‐ 4.6 and 16.2 +/‐ 8.4 microM at 10 and 100 microM quinidine, respectively. These characteristics of block are in good agreement with values obtained from ionic data. 4. Simultaneous measurements of ionic and gating currents confirmed, after subtraction, an ionic current threshold at ‐21.8 +/‐ 1.8 mV. The gating current data confirm directly that ionic current block by quinidine occurs by binding at a site on the hKv1.5 channel that becomes accessible when the channel opens. There was no evidence for action of quinidine on kinetic states prior to the open state at concentrations of quinidine up to 100 microM.
Membrane‐delimited modulation of NMDA currents by metabotropic glutamate receptor subtypes 1/5 in cultured mouse cortical neurons.
Authors: Yu S P , Sensi S L , Canzoniero L M , Buisson A , Choi D W
Published: December 2014

1. Modulation of NMDA receptors by metabotropic glutamate receptors (mGluRs) in cultured mouse cortical neurons was investigated using whole‐cell and single‐channel recordings. 2. NMDA whole‐cell current was reversibly attenuated by selective mGluR1/5 agonists (S)‐3‐hydroxyphenylglycine (3HPG; 10‐200 microM), (S)‐3,5‐dihydroxyphenylglyeine (S‐DHPG; 100 microM) and other mGluR agonists: (1S,3R)‐1‐aminocyclopentane‐1,3‐decarboxylic acid (1S,3R‐ACPD; 200 microM), quisqualate (10 microM) and (2S,1'S,2'S)‐2‐(carboxycyclopropyl)glycine (L‐CCG‐I; 100 microM). 3. The attenuation of NMDA current by 3HPG was totally eliminated by the mGluR antagonist (RS)‐alpha‐methyl‐4‐carboxyphenylglycine (MCPG; 500 microM) and by the selective mGluR1/5 antagonist (S)‐4‐carboxyphenylglycine (4CPG; 300 microM). 4. mGluR2/3 agonists (2S,1'R,2'R'3'R)‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV; 3 microM), (S)‐4‐carboxy‐3‐hydroxyphenylglycine (4C3HPG; 100‐200 microM) and (S)‐4‐carboxyphenylglycine (4CPG; 300 microM) did not reduce NMDA current. 5. The NMDA‐induced increase in intracellular free Ca2+ measured by fura‐2 Ca2+ imaging was attenuated by 3HPG (300 microM). 6. The suppression of NMDA current by 3HPG was not affected by treatments that altered intracellular Ca2+ or cAMP levels, or by the protein kinase inhibitor, staurosporine (0.1‐0.5 microM). 7. The open probability (NPo) of the NMDA receptor channel in excised outside‐out patches was attenuated by 3HPG but not by 4C3HPG. This 3HPG effect was blocked by MCPG. 8. The 3HPG‐induced reduction of NMDA whole‐cell and single‐channel currents was prevented by GDP beta S (200‐400 microM). Intracellular dialysis of GTP gamma S (100 microM) also reduced NMDA whole‐cell current, and rendered irreversible further reduction induced by 3HPG. 9. These data suggest that a selective activation of mGluR1/5 downmodulates the NMDA receptor channel in a membrane‐delimited manner, mediated by G proteins, but not by diffusible second messengers.
Kinetic properties of unitary Na+‐dependent K+ channels in inside‐out patches from isolated guinea‐pig ventricular myocytes.
Authors: Mistry D K , Tripathi O , Chapman R A
Published: December 2014

1. Single Na+‐activated K+ channels (K(Na)) were investigated by means of the inside‐out patch clamp technique in ventricular myocytes isolated from the guinea‐pig heart. 2. Na+‐activated K+ channels were observed at very low density (< 9% of patches). In symmetrical (60/60 mM) K+ solutions, K(Na) channels had a mean slope conductance of 75 pS and in asymmetrical (150/70 mM; outside/inside) K+ solutions, they had a mean slope conductance of 220 pS. The reversal potentials obtained under these two ionic conditions were close to the equilibrium potential for K+, suggesting K+ selectivity. 3. In high (98 mM) [Na+]i, the channel showed two open states and up to four closed states, and K(Na) channels also displayed long closures (of the order of seconds). The opening probability (Po) was not voltage dependent. Transient sublevels between 8 and 86% of the main state were identified and appeared to be a common feature of K(Na) channels. 4. Decreasing the activating [Na+]i, reduced Po and this was associated with both an increase in mean closed times and a decrease in mean open times. Lowering [Na+]i also increased the longer closed‐time constants and their relative proportions. The first open‐time constant was more sensitive to alterations in [Na+]i. 5. Distributions of burst duration, between burst duration and openings within bursts were best described by the sum of two exponentials. Lowering [Na+]i decreased the burst duration and the duration of openings within burst. 6. These observations show that the Na+‐activated K+ channel from guinea‐pig ventricular myocytes has complex gating and bursting behaviour.
Thyroid hormone regulates postnatal expression of transient K+ channel isoforms in rat ventricle.
Authors: Shimoni Y , Fiset C , Clark R B , Dixon J E , McKinnon D , Giles W R
Published: December 2014

1. The ability of thyroid hormone to regulate the postnatal changes of the Ca2+‐independent transient outward K+ current (It) was studied in rat ventricular myocytes. 2. In rat ventricle, It is very small at birth and then increases markedly between postnatal days 8 and 20. The time course of this increase in current density is similar to that of a significant rise in plasma thyroid hormone (T3) levels. 3. During early development, the density of expression of It can be altered by changes in thyroid hormone levels. Eight days after birth the density of It measured at +50 mV in control animals is 2.2 +/‐ 0.4 pA pF(‐1). This value is about 3‐fold larger (6.5 +/‐ 0.8 pA pF(‐1)) in myocytes from age‐matched hyperthyroid animals. When the plasma T3 level in newborn rats is not allowed to increase, or is decreased by making animals hypothyroid, this age‐dependent increase in It fails to occur. 4. Using RNase protection assays, Kv4.2 and Kv4.3 mRNA levels were measured in ventricular tissues obtained from age‐matched 8‐day‐old control and hyperthyroid rats. In hyperthyroid animals, where an approximately 3‐fold increase in It was identified, increases in the mRNA levels for Kv4.2 and Kv4.3 were 1.6‐fold and 2.6‐fold, respectively. 5. These results show that thyroid hormone can regulate the development of It in rat ventricle. Direct measurements of It density and mRNA levels as a function of development and thyroid hormone levels also strongly suggest that the Kv4.2 and Kv4.3 channels are essential components of It in rat ventricular cells.
The effect of intracellular pH on contractile function of intact, single fibres of mouse muscle declines with increasing temperature.
Authors: Westerblad H , Bruton J D , Lännergren J
Published: December 2014

1. The effect of altered intracellular pH (pHi) on isometric contractions and shortening velocity at 12, 22 and 32 degrees C was studied in intact, single fibres of mouse skeletal muscle. Changes in pHi were obtained by exposing fibres to solutions with different CO2 concentrations. 2. Under control conditions (5% CO2), pHi (measured with carboxy SNARF‐1) was about 0.3 pH units more alkaline than neutral water at each temperature. An acidification of about 0.5 pH units was produced by 30% CO2 and an alkalinization of similar size by 0% CO2. 3. In acidified fibres tetanic force was reduced by 28% at 12 degrees C but only by 10% at 32 degrees C. The force increase with alkalinization showed a similar reduction with increasing temperature. Acidification caused a marked slowing of relaxation and this slowing became less with increasing temperature. 4. Acidification reduced the maximum shortening velocity (V0) by almost 20% at 12 degrees C, but had no significant effect at 32 degrees C. Alkalinization had no significant effect on V0 at any temperature. 5. In conclusion, the effect of pHi on contraction of mammalian muscle declines markedly with increasing temperature. Thus, the direct inhibition of force production by acidification is not a major factor in muscle fatigue at physiological temperatures.
Protein kinase C requirement of Ca2+ channel stimulation by intracellular ATP in guinea‐pig basilar artery smooth muscle cells.
Authors: McHugh D , Beech D J
Published: December 2014

1. Smooth muscle cells were isolated from guinea‐pig basilar artery and conventional whole‐cell recordings of Ca2+ channel activity were made at room temperature within 7 h of the isolation procedure. The purpose of the study was to investigate the mechanism of the stimulatory action of intracellular ATP on Ca2+ channels. 2. High (millimolar) concentrations of ATP were needed to produce stimulation of Ca2+ channels, and neither ADP nor AMP mimicked the action of ATP. 3.The ATP effect was not mimicked by stable ATP derivatives (AMP‐PNP or AMP‐PCP) and was abolished by incubation of cells in non‐specific protein kinase inhibitors (staurosporine or H‐7) or specific protein kinase C inhibitors (GF109203x, calphostin C or chelerythrine) but not by tyrosine kinase inhibitors (tyrphostin B42 and genistein). 4. The data suggest that ATP‐induced stimulation of L‐type Ca2+ channels requires functional activity of a protein kinase C isozyme.
Stimulation of pulmonary C fibres by lactic acid in rats: contributions of H+ and lactate ions.
Authors: Hong J L , Kwong K , Lee L Y
Published: December 2014

1. The contributions of H+ and lactate ions to the stimulation of single pulmonary C fibres by lactic acid were examined in anaesthetized and artificially ventilated rats. 2. Lactic acid injected into the right atrium caused a transient decrease in arterial blood pH (pHa) and a short but intense burst of afferent activities in pulmonary C fibres, whereas sodium lactate had no effect. The fibre activity usually reached a peak within 1‐1.5 s, with an onset latency of < 1 s, and returned to the baseline in 5 s. 3. The injection of hydrochloric acid at the same pH as that of lactic acid did not significantly decrease pHa, nor did it stimulate any C fibres studied. 4. Formic acid has a pKa value (the negative logarithm of the dissociation constant) almost identical to that of lactic acid; thus, its injection decreased pHa to the same degree as did the injection of lactic acid. However, the response of C fibres to lactic acid was 134% stronger than that to formic acid. 5. We conclude that H+ is primarily responsible for the activation of pulmonary C fibres by lactic acid, probably through a direct effect of H+ on these afferent endings. The lactate ion, by itself, does not activate C fibres, but it seems to potentiate the stimulatory effect of H+ on these afferents.
Active and passive forces of isolated myofibrils from cardiac and fast skeletal muscle of the frog.
Authors: Colomo F , Piroddi N , Poggesi C , te Kronnie G , Tesi C
Published: December 2014

1. Force measurements in isolated myofibrils (15 degrees C; sarcomere length, 2.10 microns) were used in this study to determine whether sarcomeric proteins are responsible for the large differences in the amounts of active and passive tension of cardiac versus skeletal muscle. Single myofibrils and bundles of two to four myofibrils were prepared from glycerinated tibialis anterior and sartorius muscles of the frog. Skinned frog atrial myocytes were used as a model for cardiac myofibrils. 2. Electron microscope analysis of the preparations showed that: (i) frog atrial myocytes contained a small and variable number of individual myofibrils (from 1 to 7); (ii) the mean cross‐sectional area and mean number of myosin filaments of individual cardiac myofibrils did not differ significantly from those of single skeletal myofibrils; and (iii) the total myofibril cross‐sectional area of atrial myocytes was on average comparable to that of bundles of two to four skeletal myofibrils. 3. In maximally activated skeletal preparations, values of active force ranged from 0.45 +/‐ 0.03 microN for the single myofibrils (mean +/‐ S.E.M.; n = 16) to 1.44 +/‐ 0.24 microN for the bundles of two to four myofibrils (n = 9). Maximum active force values of forty‐five cardiac myocytes averaged 1.47 +/‐ 0.10 microN and exhibited a non‐continuous distribution with peaks at intervals of about 0.5 microN. The results suggest that variation in active force among cardiac preparations mainly reflects variability in the number of myofibrils inside the myocytes and that individual cardiac myofibrils develop the same average amount of force as single skeletal myofibrils. 4. The mean sarcomere length‐resting force relation of atrial myocytes could be superimposed on that of bundles of two to four skeletal myofibrils. This suggests that, for any given amount of strain, individual cardiac and skeletal sarcomeres bear essentially the same passive force. 5. The length‐passive tension data of all preparations could be fitted by an exponential equation. Equation parameters obtained for both types of myofibrils were in reasonable agreement with those reported for larger preparations of frog skeletal muscle but were very different from those estimated for multicellular frog atrial preparations. It is concluded that myofibrils are the major determinant of resting tension in skeletal muscle; structures other than the myofibrils are responsible for the high passive stiffness of frog cardiac muscle.
Novel activation stimulus of chloride channels by potassium in human osteoblasts and human leukaemic T lymphocytes.
Authors: Steinert M , Grissmer S
Published: December 2014

1. The whole‐cell recording mode of the patch‐clamp technique was used to study the effect of extracellular K+ and Rb+ on membrane currents in human osteoblasts, in a human osteoblast‐like cell line, and in the Jurkat human leukaemic T cell line. 2. Increasing the extracellular concentration of K+ increased the membrane conductance of the cells in a concentration‐dependent manner. This increase in membrane conductance was due to the activation of a Cl‐ conductance. Rb+ also induced this conductance, but conductance was less than half that seen in K+. 3. The Cl‐ channel blockers 4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonic acid (DIDS) and 4‐acetamido‐4'‐isothiocyanatostilbene 2,2'‐disulphonic acid (SITS) blocked the K(+)‐induced Cl‐ current in a voltage‐dependent manner. The degree of blockade increased with membrane depolarization to a maximum level at 40 mV. At potentials above this value the block appeared to decrease. 4. Both tonicity and K+ were required for maximal activation of the Cl‐ conductance since the K(+)‐induced Cl‐ conductance could be inhibited by hypertonic solutions and the activation of a volume‐sensitive Cl‐ conductance by hypotonic solutions could be enhanced by extracellular K+. 5. We conclude that an outwardly rectifying Cl‐ conductance can be activated either upon osmotic swelling or by an increase in extracellular K+. Both activation pathways may be involved in cell volume regulation and seem to apply to volume‐sensitive Cl‐ channels in general since we observe this phenomenon in two different cell types, in human osteoblasts as well as in human leukaemic T lymphocytes.
Review of Correlations of Flow Boiling Heat Transfer Coefficients for Nitrogen
Authors: Wang Hao , Fang Xiande
Published: December 2014

As an excellent cryogenic cooling medium, Nitrogen (N2) has been used in a variety of engineering fields, where the determination of N2 two-phase flow boiling heat transfer is required. There were some studies evaluating the correlations of flow boiling heat transfer coefficient for N2. However, either the number of correlations covered or the number of data used was limited. This work presents a comparative review of existing correlations of flow boiling heat transfer coefficients for N2 applications. A database of N2 flow boiling heat transfer containing 1043 experimental data points is compiled to evaluate 45 correlations of two-phase flow boiling heat transfer. The experimental parameters cover the ranges of mass flux from 28.0 to 1684.8 kg/m2s, heat flux from 0.2 to 135.6 kW/m2, vapor quality from 0.002 to 0.994, saturation pressure from 0.1 to 3.16 MPa, and channel inner diameter from 0.351 to 14 mm. The results show that the best correlation has a mean absolute deviation of 31.8% against the whole database, suggesting that more efforts should be made to study N2 flow boiling heat transfer to develop a more accurate correlation.
Investigating and Modeling the Correlation of Pressurization and Electron Acceleration Inside a Micro Arc-Jet Thruster
Authors: Groll Rodion , Gomez Juan E.
Published: December 2014

Fuel mass is one of the main economical and technical restrictions while designing space propulsion systems. Given the high costs related to the transport of mass into space, the necessary fuel mass for accomplishment of the mission should be minimized. For an optimum thrust/fuel consumption ratio the gas exit velocity must be maximized. In this research this is achieved through the heating of the micro gas flow by an electrical arc inside the sub-sonic region of the propulsion system. The electrical arc induces a partial ionization of the propellant gas. Because of the very low mass flow the gap of the plasma channel has a width of just a few hundred microns. The electrical arc consists of electrons being accelerated through this small gap by the charged walls of the microchannel. The electrons move in a cross flow compared to the propellant gas.

In order to study this approach an experimental rig is built up inside a vacuum chamber. The relation between electrical power and mechanical pressurization is investigated experimentally. The won data are compared with computational results of the electrodynamic behavior inside the micro gap. The computational model consists of the coupling of the micro gas flow in the trans-sonic thruster application (e.g. [1]) with the heating mechanism of the electron motion including the partial ionization of the subsonic flow of the electric propulsion system.

The computational results are validated with the experimental data. Through this investigation a very efficient form of electrodynamic heating-modeling is developed. The very good results show the quality of the present method and encourage further utilization and development. For this reason this model will be used for the optimization and the computational engineering pre-development of future thermo-electric propulsion systems.
Simultaneous Investigation of PEMFC Performance and Water Content at Different Flow Rates and Relative Humidities
Authors: Hasheminasab Mohammadreza , Bozorgnezhad Ali , Shams Mehrzad , Ahmadi Goodarz , Kanani Homayoon
Published: December 2014

In order to prevent membrane dehydration and flooding in proton exchange membrane fuel cells (PEMFC), appropriate water management must be done. Therefore, accurate knowledge of the effects of various parameters on cell water content is needed. This knowledge helps to achieve optimum cell performance. The effects of both anode and cathode stoichiometry and relative humidity on single serpentine PEMFC performance and flow channel water content are surveyed experimentally. All tests conducted on transparent fuel cell with serpentine flow field channels and 25cm2 MEA active areas. Digital image processing is performed on the captured images of cathode channel to detect accumulated water at that side. The results indicate that there is a correlation between water content of cathode flow channels and cell performance. Increasing cathode water content causes membrane hydration which leads to better cell performance, but high water content causes flooding. It is concluded that both stoichiometry and relative humidity have significant effect on cell performance. Increasing reactant relative humidity improves water transport mechanisms within the cell, but fully humidified reactants may causes flooding. Although high stoichiometry rate prevents flooding and facilitate reactants transport within catalyst layer, high anode and cathode stoichiometry leads to membrane dehydration. Experimental observation shows that both stoichiometry and relative humidity have optimum value.
Effect of Inclination Angle on Pulsating Heat Pipe Performance
Authors: Paudel Sagar Babu , Michna Gregory J.
Published: December 2014

Micro-electronic devices are creating ever-increasing demands on their thermal management systems due to their decreasing size and increasing power. Pulsating heat pipes (PHPs) are one possible solution for electronics cooling applications. A PHP is a passive, two-phase heat transfer system which has been shown to have the advantages of the ability to accommodate very high heat fluxes and of relatively low cost, due to its wickless construction. In this investigation, a 20-turn PHP was constructed out of 1.6-mm inner diameter copper tubing. The PHP was operated in vertical and horizontal positions with a filling ratio of 77%. PHP pressure variations, indicating PHP operation, were first observed when the power was increased to 16 W for the vertical orientation (90°). For angles orientations, in general more power was required to induce pulsation. For the 60°, 45°, and 30° orientations, the required startup power was similar to that for the vertical case. In the PHP in the horizontal orientation (0°), pulsation did not begin until a heater input of 30 W was applied, and the thermal resistance only decreased slightly upon startup. Under steady-state operation at the highest heat fluxes, the thermal resistance was lowest for the vertical orientation.
Thermal and plasma enhanced atomic layer deposition of TiO2: Comparison of spectroscopic and electric properties
Authors: Das Chittaranjan , Henkel Karsten , Tallarida Massimo , Schmeißer Dieter , Gargouri Hassan , Kärkkänen Irina , Schneidewind Jessica , Gruska Bernd , Arens Michael
Published: December 2014

Titanium oxide (TiO2) deposited by atomic layer deposition (ALD) is used as a protective layer in photocatalytic water splitting system as well as a dielectric in resistive memory switching. The way ALD is performed (thermally or plasma-assisted) may change the growth rate as well as the electronic properties of the deposited films. In the present work, the authors verify the influence of the ALD mode on functional parameters, by comparing the growth rate and electronic properties of TiO2 films deposited by thermal (T-) and plasma-enhanced (PE-) ALD. The authors complete the study with the electrical characterization of selected samples by means of capacitance–voltage and current–voltage measurements. In all samples, the authors found a significant presence of Ti3+ states, with the lowest content in the PE-ALD grown TiO2 films. The observation of Ti3+ states was accompanied by the presence of in-gap states above the valence band maximum. For films thinner than 10 nm, the authors found also a strong leakage current. Also in this case, the PE-ALD films showed the weakest leakage currents, showing a correlation between the presence of Ti3+ states and leakage current density.