bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of osmolality and carbohydrate content on the rate of gastric emptying of liquids in man.
Authors: Vist G E , Maughan R J
Published: December 2014

1. The effect of osmolality and carbohydrate content on the rate of gastric emptying was assessed by using the double sampling gastric aspiration technique to measure the rate of gastric emptying of isoenergetic and isosmotic solutions of glucose and glucose polymer. Six healthy male subjects were each studied on four separate occasions using a test drink volume of 600 ml. 2. The half‐emptying time (t1/2, mean +/‐ S.E.M.) for a dilute (40 g l‐1) solution of glucose (LG, 230 mosmol kg‐1) was 17 +/‐ 1 min. This was greater than that (14 +/‐ 1 min) for a glucose polymer solution with the same energy content (LP, 42 mosmol kg‐1). A concentrated (188 g l‐1) glucose polymer solution (HP, 237 mosmol kg‐1) emptied faster (t1/2 = 64 +/‐ 8 min) than the corresponding isoenergetic glucose solution (HG, 1300 mosmol kg‐1, t1/2 = 130 +/‐ 18 min). 3. The dilute (40 g l‐1) glucose solution emptied faster than the concentrated (188 g l‐1) glucose polymer solution with the same osmolality (LG, 230 mosmol kg‐1; HP, 237 mosmol kg‐1). 4. The two dilute solutions (40 g l‐1) delivered a similar amount of carbohydrate to the small intestine, whereas the concentrated (188 g l‐1) glucose polymer solution delivered a greater amount of carbohydrate at 20, 40 and 50 min than the isoenergetic glucose solution. 5. These results indicate that both osmolality and carbohydrate content influence gastric emptying of liquids in man, but the carbohydrate content appears to have greater influence than osmolality.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Ca2+ channel blockers on transmitter release and presynaptic currents at the frog neuromuscular junction.
Authors: Katz E , Ferro P A , Cherksey B D , Sugimori M , Llinás R , Uchitel O D
Published: December 2014

1. The effects of the calcium channel blockers, funnel‐web spider toxin (FTX), omega‐agatoxin IVA (omega‐Aga IVA) and omega‐conotoxin GVIA (omega‐CgTX), were tested on transmitter release and presynaptic currents in frog motor nerve endings. 2. Evoked transmitter release was blocked by FTX (IC50 = 0.02 microliter ml‐1) and omega‐CgTX (1 microM) but was not affected by omega‐Aga IVA (0.5 microM). When FTX (0.1 microliter ml‐1) was assayed on spontaneous release either in normal Ringer solution or in low Ca(2+)‐high Mg2+ solution, it was found not to affect miniature endplate potential (MEPP) amplitude but to increase MEPP frequency by approximately 2‐fold in both conditions. 3. Presynaptic calcium currents (ICa), measured by the perineurial technique in the presence of 10 mM tetraethylammonium chloride (TEA) and 200 microM BaCl2 to block K+ currents, were blocked by omega‐CgTX (5 microM), partially blocked by FTX (1 microliter ml‐1) and not affected by omega‐Aga IVA (0.5 microM). 4. The presynaptic calcium‐activated potassium current (IK(Ca)) measured by the perineurial technique in the presence of 0.5 microM 3,4‐aminopyridine (DAP) to block voltage‐dependent K+ currents, was strongly affected by charybdotoxin (ChTX) (300 nM) and completely abolished by BaCl2 (200 microM). This current was also blocked by omega‐CgTX (5 microM) and by CdCl2 (200 microM) but was not affected by FTX (1 microliter ml‐1). The blockade by omega‐CgTX could not be reversed by elevating [Ca]o to 10 mM. 5. The results suggest that in frog synaptic terminals two omega‐CgTX‐sensitive populations might coexist. The transmitter release process seems to be mediated by calcium influx through a omega‐CgTX‐ and FTX‐sensitive population.
Repetitive firing properties of developing rat brainstem motoneurones.
Authors: Viana F , Bayliss D A , Berger A J
Published: December 2014

1. The repetitive firing properties of neonatal and adult rat hypoglossal motoneurones (HMs) were investigated in a brainstem slice preparation. Neonatal HMs could be classified into two main groups: (1) neurones with a decrementing or adapting firing pattern (type D); exhibiting an early and a late phase; and (2) neurones with an incrementing or accelerating firing pattern (type I). 2. The pattern of repetitive firing changed markedly during development. While most HMs recorded from young rats (< postnatal day (P) 4) were type D, the majority of HMs recorded during the second postnatal week were type I. In adults (> P21), nearly all HMs had a decrementing firing pattern, characterized by a brief period of adaptation and high steady‐state firing rates. 3. The calcium‐dependent after‐hyperpolarization (AHP) was shortest in type I neonatal HMs, and decreased in amplitude during trains of action potentials (APs). In type D neurones, these same trains caused a slight enhancement of AHP amplitude. In adult HMs, with a decrementing firing pattern, trains of APs also caused summation of the AHP. 4. Type D neonatal HMs showed a progressive prolongation of the AP during repetitive firing. In contrast, type I neonatal HMs had almost no change in AP duration. In adult HMs the AP was short and experienced only a modest increase in duration during fast repetitive firing. 5. The function relating steady‐state firing frequency to injected current (f‐I curve) was linear. The mean steady‐state f‐I slope was significantly higher in neonates than in adults (approximately 30 vs. approximately 20 Hz nA‐1), and was weakly correlated with input resistance. The f‐I slope was negatively correlated with AHP duration in neonatal HMs only. In addition, for a given AHP duration the slope was higher in neonatal HMs. 6. Two threshold behaviours were observed among neonatal HMs: (a) a progressive rhythmic firing threshold, and (b) a sudden transition from subthreshold to regular repetitive firing. Current threshold for repetitive firing was strongly correlated with cell input conductance. Type I neonatal HMs had higher minimal steady firing rates (fmin) than type D HMs. In neonates, fmin was strongly correlated with AHP duration. Adult HMs showed a weaker correlation between these two parameters, and fmin was higher than predicted by AHP duration. 7. In summary, HMs responded to depolarizing current pulses with different firing patterns during postnatal development.(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence favouring different descending pathways to soleus motoneurones activated by magnetic brain stimulation in man.
Authors: Nielsen J , Petersen N
Published: December 2014

1. In resting subjects low‐intensity magnetic stimulation of the brain evoked an inhibition of the soleus H reflex at short latency (conditioning‐test interval, ‐2 to +1 ms) followed approximately 10 ms later by a period of facilitation. During voluntary dynamic or tonic plantar flexion the same stimulus evoked a facilitation with a shorter latency than the inhibition (conditioning‐test interval, ‐5 to ‐1 ms). 2. At the onset of ramp‐and‐hold plantar flexion the short‐latency facilitation was seen at lower intensities of stimulation than the long‐latency facilitation in six of seven subjects. At rest and/or during tonic plantar flexion the opposite was observed in four of the subjects, whereas the two facilitations had approximately the same threshold in the remaining subjects. 3. The short‐latency facilitation decreased approximately 100 ms after the onset of ramp‐and‐hold plantar flexion in all of eight subjects. The long‐latency facilitation, in contrast, either had the same size throughout the ramp phase or even increased around the end of the ramp phase. 4. The short‐latency facilitation of the reflex was significantly larger at the onset of a fast ramp‐and‐hold plantar flexion (10 N m (150 ms)‐1) than at the onset of a slow contraction (10 N m (600 ms)‐1), whereas the opposite was the case for the long‐latency facilitation. 5. As the short‐ and long‐latency facilitations had different thresholds and were differently regulated during voluntary movement, it is suggested that they are caused by activation of different descending pathways by the magnetic stimulus.
Ingestion of branched‐chain amino acids and tryptophan during sustained exercise in man: failure to affect performance.
Authors: van Hall G , Raaymakers J S , Saris W H , Wagenmakers A J
Published: December 2014

1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched‐chain amino acids (BCAAs) affect performance. Ten endurance‐trained male athletes were studied during cycle exercise at 70‐75% maximal power output, while ingesting, ad random and double‐blind, drinks that contained 6% sucrose (control) or 6% sucrose supplemented with (1) tryptophan (3 g l‐1), (2) a low dose of BCAA (6 g l‐1) or (3) a high dose of BCAA (18 g l‐1). 2. These treatments greatly increased the plasma concentration of the respective amino acids. Using the kinetic parameters of transport of human brain capillaries, BCAA supplements were estimated to reduce brain tryptophan uptake at exhaustion by 8‐12%, while tryptophan ingestion caused a 7‐ to 20‐fold increase. Exercise time to exhaustion was not different between treatments (122 +/‐ 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise or that manipulation of serotoninergic activity functionally does not contribute to mechanisms of fatigue.
Calcium current reactivation after flash photolysis of nifedipine in skeletal muscle fibres of the frog.
Authors: Feldmeyer D , Zöllner P , Pohl B , Melzer W
Published: December 2014

1. L‐type calcium currents were activated by depolarization of cut muscle fibres of the frog. The current was blocked by the dihydropyridine compound nifedipine (5‐10 microM) and reactivated by flash photolysis of the drug. 2. In the presence of nifedipine, increasing the time interval between the onset of depolarization and the flash resulted in progressively faster kinetics of the flash‐induced current. This change developed with a slow time course similar to that of normal current activation. 3. A fast gating mode of the normally slow L‐type channel was induced by conditioning activation (500 ms prepulses) applied 80 ms before a test step to the same potential. After block by nifedipine, flash‐photolysis was carried out 40 ms before the end of the long conditioning pulse. The flash‐induced current had the same rapid time course as the current activated by the subsequent test voltage step. 4. Similarly, the time course of current activation was comparable for the voltage‐induced fast mode activation (flash applied 5 ms before the test step) and the flash‐induced activation 40 ms after the onset of the test depolarization. 5. Our data suggest that in frog skeletal muscle nifedipine inhibits calcium current activation by blocking a rapid channel gating step while the slow conformational change that normally limits the rate of activation of the L‐type calcium channel remains unaffected. UV flash illumination results in a fast reactivation indicating that the channels need not be inactivated to be blocked by nifedipine.
Investigating the origin of cyclic changes in limb volume using mercury‐in‐silastic strain gauge plethysmography in man.
Authors: Christ F , Raithel P , Gartside I B , Gamble J , Peter K , Messmer K
Published: December 2014

1. Vasomotion, a phenomen frequently observed in skeletal muscle microcirculation, has been observed under physiological conditions and found enhanced during critical reduction of tissue perfusion due to hypoxic hypoxia, haemorrhage and local hypotension. We used a computer assisted non‐invasive plethysmographic method to investigate periodic changes of limb volume (volumotion), which we previously found in critically ill patients. The current study was designed to investigate the origin of volumotion. 2. Simultaneous recordings of limb circumference of both calves were obtained. In patients with peripheral vascular disease and patients with minor surgery the cross‐correlation with spontaneous breathing was investigated. In patients who had undergone major abdominal or vascular surgery we analysed for cross‐correlations between MSG plethysmography signals of both legs and changes in central venous, arterial and ventilation pressures. In this group the effects of positive‐pressure ventilation and positive end‐expiratory pressure (PEEP) were also studied. 3. No ventilation‐related volumotion was observed during spontaneous breathing. During positive‐pressure ventilation a ventilation‐related peak was found in the Fourier transform in agreement with the ventilation frequency applied. The amplitude of ventilation‐related volumotion decreased significantly after a pressure cuff applied to the thigh was inflated above central venous pressure. We observed a significant increase in the amplitude of ventilation‐related volumotion when PEEP was applied. 4. Ventilation‐related volumotion showed significant cross‐correlation between both legs. Slow wave volumotion (0.5‐7 cycles min‐1) was frequently observed, but always appeared unilaterally. Whilst we looked for correlations between slow wave volumotion and changes in central venous pressure and arterial blood pressure, respectively, significant cross‐correlation with the MSG plethysmography recordings was only observed at the frequency of the positive‐pressure ventilation. 5. The fact that periodic changes of limb circumference matching the frequency of the positive‐pressure ventilation were detectable with the MSG plethysmography system demonstrates that small volume changes (less than 0.02 ml (100 ml tissue)‐1) can be assessed using this system. As slow wave volumotion was observed unilaterally and revealed no correlation either with breathing, ventilation or arterial and central venous pressure, we suggest that slow wave volumotion is a local event most likely reflecting arteriolar vasomotion.
Different spatial patterns of [Ca2+] increase caused by N‐ and L‐type Ca2+ channel activation in frog olfactory bulb neurones.
Authors: Bischofberger J , Schild D
Published: December 2014

1. The intracellular calcium concentration ([Ca2+]i) in cultured olfactory bulb neurones of Xenopus laevis tadpoles was imaged using the calcium indicator dyes fluo‐3 and Fura Red as well as a laser scanning microscope. 2. Upon extracellular application of brief pulses of a solution with high potassium concentration (high [K+]o), an increase in [Ca2+]i occurred in all neurones observed. During the first 2 days in culture this increase was highest. At later stages (more than 2 days in culture) the increase in [Ca2+]i was non‐homogeneous and highest in the dendritic processes. 3. Nifedipine (10 microM) reduced the high [K+]o‐induced increase in [Ca2+]i. The reduction was greatest in somata and proximal dendrites. 4. With nifedipine in the bath, the high [K+]o‐induced increase of [Ca2+]i was further reduced by the application of omega‐conotoxin GVIA (1 microM). The omega‐conotoxin‐sensitive Ca2+ influx occurred predominantly on dendritic processes. 5. Noradrenaline (NA), as well as the alpha 2‐adrenergic receptor agonist clonidine, reduced the high [K+]o‐induced increase of [Ca2+]i. This reduction occurred mainly on dendritic processes. 6. Our results suggest a highly non‐homogeneous spatial distribution of voltage‐gated Ca2+ channels in cultured olfactory bulb neurones. L‐type channels were found mainly on somata and their density seemed to decrease on the dendrites with increasing distance from the soma. In contrast, nifedipine‐insensitive N‐type channels were mainly observed on dendrites and were blocked by omega‐conotoxin. NA, as well as clonidine, markedly blocked Ca2+ influx through dendritic N‐type Ca2+ channels.
Volume regulation in a toad epithelial cell line: role of coactivation of K+ and Cl‐ channels.
Authors: Nilius B , Sehrer J , De Smet P , Van Driessche W , Droogmans G
Published: December 2014

1. We have measured changes in cell volume, membrane potential and ionic currents in distal nephron A6 cells following a challenge with hypotonic solutions (HTS). 2. The volume increase induced by HTS is compensated by a regulatory volume decrease (RVD), which is inhibited by both 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB) and quinine. Quinine (500 microM) completely blocked RVD, whereas 100 microM NPPB delayed and attenuated RVD. 3. The resting potential in A6 cells was ‐52.3 +/‐ 4.8 mV (n = 53), and shifted to ‐35.1 +/‐ 2.2 mV (n = 33) during HTS. 4. Resting membrane current in A6 cells was 0.35 +/‐ 0.12 pA pF‐1 at ‐80 mV and 0.51 +/‐ 0.16 pA pF‐1 at +80 mV (n = 5). During cell swelling these values increased to 11.5 +/‐ 1.1 and 29.3 +/‐ 2.8 pA pF‐1 (n = 29), respectively. 5. Quinine (500 microM) completely blocked the HTS‐activated current at ‐15 mV, the reversal potential for Cl‐ currents, but exerted only a small block at ‐100 mV (K+ equilibrium potential). NPPB (100 microM) inhibited the current at both potentials almost to the same extent. The HTS‐induced net current reversed at ‐41 +/‐ 2.5 mV (n = 15), which is close to the measured resting potential during HTS. 6. The quinine‐insensitive current reversed near the Cl‐ equilibrium potential. The quinine‐sensitive current reversed near the K+ equilibrium potential. The respective conductances activated by HTS at the zero‐current potential were 2.1 +/‐ 0.7 nS for K+ and 5.2 +/‐ 1.3 nS for Cl‐ (n = 15). 7. Single channel analysis unveiled activation of at least two different channels during HTS. A 36 pS channel reversing at the Cl‐ equilibrium potential showed increased open probability at depolarized potentials. HTS also activated a K+ channel with a 29 pS conductance in high‐K+ extracellular solutions (130 mM) or 12 pS in 2.5 mM K+. 8. This coactivation of K+ and Cl‐ channels shifts the membrane potential towards a value between EK and ECl (the reversal potentials for K+ and Cl‐), where a net efflux of Cl‐ (Cl‐ inward current) and K+ (K+ outward current) under zero‐current conditions occurs. Block of either the K+ or the Cl‐ conductance will shift the zero‐current potential towards the equilibrium potential of the unblocked channel, preventing net efflux of osmolytes and RVD. This coactivation of K+ and Cl‐ currents causes a shift of osmolytes out of the cells, which almost completely accounts for the observed RVD.
Light adaptation and the rising phase of the flash photocurrent of salamander retinal rods.
Authors: Jones G J
Published: December 2014

1. Both theory and analysis of photocurrents in retinal rods show that phosphodiesterase activity after a flash rises initially as a delayed ramp. 2. The effect of light adaptation on the flash‐induced rise in phosphodiesterase activity deduced from photocurrent responses was investigated. 3. Background adaptation reduces the deduced rate of rise of phosphodiesterase activity. The effect is most prominent for bright backgrounds and moderate flashes. There is little reduction for bright flashes, even in bright backgrounds. There is no effect for weak backgrounds. 4. Light adaptation after bleaching visual pigment produces a reduction in the deduced rise of phosphodiesterase activity for all flashes. For bright flashes, the reduction is explained by the reduction in quantum catch. For moderate flashes, there is an extra reduction, similar to the reduction produced by the equivalent background. 5. The results provide support for the idea that a reduction in the amplification step of phototransduction functions as part of the mechanism of light adaptation in rods. The dependence on flash intensity of the background‐induced reduction in phosphodiesterase activation could imply a feedback mechanism on the activation steps of phototransduction.
Medullary‐evoked EPSPs in neonatal rat sympathetic preganglionic neurones in vitro.
Authors: Deuchars S A , Morrison S F , Gilbey M P
Published: December 2014

1. Whole‐cell patch clamp recordings were made from twenty‐three sympathetic preganglionic neurones (SPNs) in the upper thoracic segments of a neonatal rat brainstem‐spinal cord preparation to study their synaptic responses to stimulation of the rostral ventrolateral medulla (RVLM) and the receptors involved. 2. SPNs were identified by their antidromic activation following stimulation of a ventral root, their morphology and their location in the spinal cord. 3. Electrical stimulation within the RVLM elicited EPSPs in all SPNs tested (n = 23). These EPSPs consisted of one or more components that had different time courses, voltage relationships and pharmacological sensitivities. 4. All SPNs responded to RVLM stimulation with a constant‐latency fast EPSP that increased in size as the membrane was hyperpolarized. This EPSP was reduced in amplitude by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (10‐20 microM). 5. In thirteen SPNs the response to RVLM stimulation was a complex EPSP consisting of a fast EPSP and a slow EPSP that either followed or summed with the fast EPSP. The amplitude of the slow EPSP was (i) either reduced in size or not affected as the membrane was hyperpolarized, and (ii) reduced by the NMDA receptor antagonist, D, L‐2‐amino‐5‐phosphonovaleric acid (50 microM). 6. Selective activation of neuronal cell bodies in the RVLM by chemical stimulation elicited slow depolarizations and increases in synaptic activity in SPNs. 7. These results provide evidence that an excitatory amino acid is involved in transmitting sympathoexcitatory drive from the RVLM, partly via a monosynaptic pathway. Both non‐NMDA and NMDA receptors play a role in mediating this drive.
Intracellular calcium and force in single mouse muscle fibres following repeated contractions with stretch.
Authors: Balnave C D , Allen D G
Published: December 2014

1. The role of the myoplasmic free Ca2+ concentration ([Ca2+]i) in the reduction of muscle force following contractions with stretch was investigated in single fibres from mouse toe muscle. Muscle fibres were either stretched by 25% of their optimum length (Lo) for ten tetani (Protocol I) or stretched by 50% of Lo for between ten and thirty tetani (Protocol II). Indo‐1 was used to measure [Ca2+]i. 2. In each protocol the stretch series was compared with isometric controls; the stretch series always resulted in greater changes in muscle properties than in the isometric controls. The observed changes were (i) reduced tetanic force, (ii) reduced tetanic [Ca2+]i, (iii) increased resting [Ca2+]i and (iv) the greater relative reduction in force at low stimulus frequencies (30 and 50 Hz) compared with high (100 Hz). These changes were maintained for up to 60 min. 3. Stretching a resting muscle fibre had no effect on the subsequent [Ca2+]i or force. 4. Following Protocol I 10 mM caffeine restored tetanic force to pre‐stretch levels. Tetanic [Ca2+]i vs. force curves were constructed pre‐ and post‐stretch and showed that neither the maximum Ca(2+)‐activated force nor the Ca2+ sensitivity of the muscle fibres post‐stretch was significantly different from control. The force reduction, therefore, appears to be the result of reduced tetanic [Ca2+]i. 5. The more severe stretching regimen of Protocol II resulted in a much greater reduction in force than Protocol I. Ten millimolar caffeine did not restore control force. Comparison of the [Ca2+]i‐force relationships pre‐ and post‐stretch showed that the reduction in tetanic force was caused by a combination of a reduced tetanic [Ca2+]i, reduced maximum Ca(2+)‐activated force and reduced Ca2+ sensitivity. 6. Following both protocols the resting [Ca2+]i showed a small rise which persisted for at least 60 min. This elevated [Ca2+]i was associated with a reduction in the pump rate of the sarcoplasmic reticulum Ca2+ pump. 7. This study establishes that reduced Ca2+ release and reduced Ca2+ sensitivity contribute to the reduction in force generating capacity of single mammalian muscle fibres following active stretches.
Modulation of erythropoietin formation by changes in blood volume in conscious dogs.
Authors: Ehmke H , Just A , Eckardt K U , Persson P B , Bauer C , Kirchheim H R
Published: December 2014

1. A possible influence of the filling of the circulatory system on the plasma concentration of erythropoietin, which is the major regulator of erythrocyte formation, was investigated in conscious dogs. 2. Over an experimental period of 5 h, the animals were subjected to either haemorrhage (hypovolaemia), blood volume expansion (hypervolaemia), or exchange transfusion of blood with dextran (isovolaemic anaemia). 3. A reduction of blood volume by 20% induced by haemorrhage increased plasma erythropoietin levels approximately 1.5‐fold in the absence of significant changes in haematocrit. 4. An expansion of blood volume by 12% induced by an intravenous infusion of dextran did not change plasma erythropoietin levels, although the haematocrit decreased by 0.04. 5. A reduction of the haematocrit by 0.12 in the absence of changes in blood volume induced by an isovolaemic exchange transfusion (dextran vs. blood) increased plasma erythropoietin levels approximately 3‐fold. 6. Total renal oxygen supply did not change in any of the three experimental protocols. 7. These data indicate that in dogs the erythropoietin production rate is modulated by changes in blood volume, and suggest a possible role of erythropoietin in the regulation of blood volume.
Role of antral intramural neural pathways in control of gastric emptying in the pig.
Authors: Anvari M , Yu P , Dent J , Jamieson G G
Published: December 2014

1. The role of antral intramural pathways in the control of antropyloric motility and gastric emptying was evaluated in five conscious pigs equipped with chronic gastric and duodenal cannulae. Neural pathways were divided by transection and re‐anastomosis of the antrum 2 cm proximal to the pylorus. Concurrent measurements of gastric emptying, transpyloric flow and antropyloric motility were performed before and 6 weeks after surgery. 2. Antral transection retarded gastric emptying, only 36% of 1000 ml saline being emptied in 30 min compared with 62% before transection. Transection did not alter the number of transpyloric flow pulses (22.0 +/‐ 4.0 cf. 24.4 +/‐ 3.2 pre‐transection), but reduced (P < 0.01) the volume of flow pulses substantially (8.6 +/‐ 0.4 cf. 18.7 +/‐ 1.5 ml pre‐transection). 3. Antral transection was associated with a reduction in the rate of distal antral pressure waves (P < 0.05), but no alteration in the rate of phasic low level pressurization of the entire gastric content by gastric contractions (gastric common cavity pressure waves). However, transection was associated with a significant (P < 0.05) shortening of the interval between the onset of gastric common cavity pressure waves, and the onset of lumen‐occlusive pyloric pressure waves generated by the same contraction sequence (3.2 +/‐ 0.3 cf. 7.9 +/‐ 0.6 s). 4. Transection did not alter the inhibition of antral pressure waves, stimulation of localized pyloric pressure waves, and retardation of gastric emptying produced by infusion of 25% dextrose into the duodenum. 5. These studies suggest that antral intramural nerves regulate the emptying of liquids from the stomach by modulating the timing of pyloric closure in relation to phasic gastric antral and corpus contractions. 6. Distal antral intramural neural pathways do not appear to play a major role in the suppression of antral motor activity produced by duodenal glucoreceptors.
Some effects of vagal blockade on abdominal muscle activation and shortening in awake dogs.
Authors: Leevers A M , Road J D
Published: December 2014

1. The mechanisms of abdominal muscle activation are thought to be different during expiratory threshold loading (ETL) compared with hypercapnia. Our objectives in the present study were to determine the effects of removing excitatory vagal feedback on abdominal muscle activation, shortening and pattern of recruitment during ETL and hypercapnia. Six tracheotomized dogs were chronically implanted with sonomicrometer transducers and fine wire EMG electrodes in each of the four abdominal muscles. Muscle length changes and EMG activity were studied in the awake dog during ETL (6 dogs) and CO2 rebreathing (3 dogs), before and after vagal blockade. 2. Following vagal blockade, the change in volume (increase in functional residual capacity, FRC) during ETL was greater and active phasic shortening of all the abdominal muscles was reduced, when shortening was compared with a similar change in lung volume. Similarly, at comparable minute ventilation, abdominal muscle active shortening was also reduced during hypercapnia. The internal muscle layer was recruited preferentially in both control and vagally blocked dogs during both ETL and hypercapnia. 3. The degree of recruitment of the abdominal muscles during ETL and hypercapnia in awake dogs is influenced by vagal feedback, but less so than in anaesthetized dogs. These results illustrate the importance of the vagi and abdominal muscle activation in load compensation. However, vagal reflexes are apparently not contributing to the preferential recruitment of the internal muscle layer. In awake dogs during vagal blockade abdominal muscle recruitment still occurs by extravagal mechanisms.
Effects of age on aneural regeneration of soleus muscle in rat.
Authors: Lewis D M , Schmalbruch H
Published: December 2014

1. The ability of autografted soleus muscles to regenerate without innervation was investigated in young (two groups: 17 days or 35 g and 5 weeks or 100 g) and old (10 weeks or 300 g and 19 months or 700 g) rats. 2. Tetanic force and fibre area of the regenerated muscles were followed in 35, 100 and 300 g rats and found to reach a maximum 10‐15 days after the operation and then declined. 3. Maximal tetanic force and fibre area were greater in old than in young rats; the largest increase was seen between 100 and 300 g rats. The relaxation phase of the twitch became shorter in the 700 g animals. The force per cross‐sectional area appeared to fall with age. The length of the new fibres, inferred from the width of the length‐force curve, increased only slightly with age. 4. Ten days after grafting, autophagocytosis of necrotic fibres was completed in young but not in old rats. The new fibres in young rats had one central nucleus per cross‐section and fibre size was unimodally distributed; fibres in old rats had multiple internal nuclei and the size distribution was bimodal due to the presence of large fibres. 5. Previous results indicating greater muscle regeneration in young than in old rats may reflect more vigorous reinnervation in young animals rather than a greater myogenic potential. Increased fibre size of regenerated muscles of old compared with young rats may be attributed to the larger amount of necrotic material which is mitogenic for satellite cells, or to age‐dependent changes of the expression of cell adhesion molecules. Enhanced lateral fusion of myotubes would give rise to large fibres with multiple internal nuclei.
Potassium conductances underlying repolarization and after‐hyperpolarization in rat CA1 hippocampal interneurones.
Authors: Zhang L , McBain C J
Published: December 2014

1. The roles of multiple potassium conductances underlying action potential repolarization and after‐hyperpolarization (AHP) in visually identified st. oriens‐alveus (st. O‐A) inhibitory interneurones of neonatal rat CA1 hippocampal slices were determined using whole‐cell patch clamp techniques. 2. 4‐Aminopyridine dose‐dependently prolonged the action potential repolarization. The effects of 4‐AP persisted in Ca(2+)‐free conditions. Action potentials evoked from hyperpolarized potentials possessed an increased rate of repolarization. These data suggest an involvement of the rapidly activating transient current, IA, in spike repolarization. 3. Action potential duration was increased in the presence of Ca(2+)‐free, Cd(2+)‐containing solution, iberiotoxin or 1 mM TEA. The fast component of the AHP was attenuated by these agents suggesting that the Ca(2+)‐activated K+ conductance, IC, underlies both the spike repolarization and fast AHP. 4. In Ca(2+)‐free conditions, TEA (> 1 mM) dose‐dependently prolonged the action potential duration by blocking a late conductance in action potential repolarization, suggesting a role for the sustained current, IK. 5. The slow AHP was attenuated by Ca(2+)‐free medium, apamin or the Ca2+ chelator EGTA, suggesting a role for the Ca(2+)‐activated K+ conductance, IAHP. 6. We conclude that action potential repolarization and AHP of st. O‐A interneurones result from the activation of pharmacologically distinct, temporally overlapping potassium conductances. These findings are discussed with reference to the voltage clamp data presented in the preceding manuscript.
A study of the role of corticosterone as a mediator in exercise‐induced stimulation of murine macrophage phagocytosis.
Authors: Forner M A , Barriga C , Rodriguez A B , Ortega E
Published: December 2014

1. It is generally accepted that physical activity provokes changes in the immune system. Previous studies have demonstrated that the stress of physical activity (swimming until exhaustion) increases the phagocytic activity of peritoneal macrophages. However, the precise mechanisms remain unknown. 2. Two experiments were performed in the present study. (A) Peritoneal macrophages from control mice were incubated with plasma from three different groups of mice: (1) mice subjected to swimming until exhaustion with no previous training, (2) mice subjected to the same activity but with 1 month of training (30 min day‐1), and (3) a control (non‐exercised) group. The differences in the resulting phagocytic (attachment and ingestion) capacity were measured. (B) Changes in the concentration of plasma corticosterone after exercise were also measured, and the effect of incubation with the postexercise plasma corticosterone level on the phagocytic activity of peritoneal macrophages was then studied in vitro. 3. The results were: (A) incubation with plasma from both groups of exercised mice (with and without previous training) led to increased levels of phagocytic capacity (number of C. albicans cells ingested per 100 macrophages). (B) Incubation with a corticosterone concentration of 0.72 mumol l‐1 (similar to that observed in plasma immediately after exercise) raised the phagocytic capacity (144 +/‐ 12 after incubation with 0.72 mumol l‐1 vs. 93 +/‐ 19 after incubation with 0.24 mumol l‐1). This increase was also significantly greater than that observed with 7.2 mumol l‐1 corticosterone. 4. It is concluded that corticosterone may mediate the increased phagocytic function of peritoneal macrophages induced by exercise.
alpha‐Adrenergic inhibition of the beta‐adrenoceptor‐dependent chloride current in guinea‐pig ventricular myocytes.
Authors: Iyadomi I , Hirahara K , Ehara T
Published: December 2014

1. alpha 1‐Adrenoceptor‐mediated inhibition of the beta‐adrenoceptor‐dependent Cl‐ current was investigated in guinea‐pig ventricular myocytes using the patch clamp technique. The Cl‐ conductance activated by noradrenaline (0.1‐10 microM) with an alpha 1‐blocker (prazosin, 5 microM) was significantly greater than that activated by noradrenaline alone. Phenylephrine and methoxamine, alpha 1‐agonists, exerted an inhibitory effect on the Cl‐ conductance activated by isoprenaline. The dose‐response relationship for isoprenaline and the Cl‐ current activation was shifted to higher doses in the presence of phenylephrine (30 microM). 2. The interaction of alpha 1‐ and beta‐agonists on Cl‐ current was also observed on the single channel level; in some of the outside‐out membrane patches, phenylephrine (50 microM) depressed the activity of the single Cl‐ channel which was induced by 5 microM adrenaline. 3. Phenylephrine had no effect on the Cl‐ conductance induced by forskolin (0.5‐5 microM), an activator of adenylate cyclase. The Cl‐ conductance activated persistently by isoprenaline in GTP gamma S‐loaded cells was also insensitive to phenylephrine. The results suggest that the observed alpha 1‐adrenergic attenuation of the beta‐adrenergic response is not primarily due to inhibition of adenylate cyclase activity. The alpha 1‐adrenergic action may interfere with the processes leading to enzyme activation in the beta‐adrenergic pathway.
Effects of cyclic AMP and theophylline on chloride conductance across toad skin.
Authors: Katz U , Nagel W
Published: December 2014

1. The effects of the phosphodiesterase inhibitors theophylline and isobutylmethylxanthine (IBMX) on baseline and voltage‐activated Cl‐ conductance (gCl) of toad skin were compared with those of the potent 2‐chlorophenylthio analogue of cAMP (CPT‐cAMP). 2. Using intact and split skins of Bufo viridis we confirmed that theophylline and IBMX raised the voltage‐activated gCl with a pattern identical to that seen under control conditions. This effect was small or missing if gCl was already high in the control. 3. CPT‐cAMP, in contrast, increased the Cl(‐)‐specific conductance by up to 6 mS cm‐2 at short circuit. The characteristic time‐dependent, slow activation of gCl by serosa‐positive clamp potentials was completely lost under these conditions. 4. Coinciding with the loss of voltage activation of gCl the plateau value of the Lorentzian component of fluctuation in current at serosa‐positive clamp potentials decreased by almost 50%. The corner frequencies were not notably different. 5. After CPT‐cAMP, the sigmoidal voltage‐conductance relation that is characteristic of control conditions or after theophylline disappeared; the patterns were variable and incompatible with voltage activation. 6. The voltage‐activated gCl under control conditions and with theophylline was blocked by mucosal NO3‐, I‐ or SCN‐, the last two being almost equally effective. In the presence of CPT‐cAMP, mucosal NO3‐ had minimal influence on tissue conductance, whereas the effects of I‐ and SCN‐ were essentially unchanged. Br‐ on the mucosal side could substitute for Cl‐ under all conditions. 7. The results suggest that protein phosphorylation by supramaximal concentrations of cAMP induces maximal conductance through anion‐specific routes, while the voltage sensitivity of this pathway is lost. The effects of theophylline and IBMX on the voltage‐activated Cl‐conductance of toad skin cannot be explained solely by inhibition of the phosphodiesterase.
Carbohydrate ingestion and glycogen utilization in different muscle fibre types in man.
Authors: Tsintzas O K , Williams C , Boobis L , Greenhaff P
Published: December 2014

1. The effect of carbohydrate (CHO) ingestion on muscle glycogen utilization during exercise was examined on seven male subjects completing two 60 min treadmill runs at 70% maximum oxygen uptake (VO2,max), 1 week apart. On each occasion the subjects consumed either water or a 5.5% CHO‐electrolyte solution immediately before and during exercise. Muscle samples were obtained from the vastus lateralis by needle biopsy before and immediately after exercise. Venous blood samples were also collected from an ante‐cubital vein at rest and at 10, 20, 40 and 60 min into the run. 2. Higher blood glucose concentrations (P < 0.01) were observed throughout the run during the CHO trial compared with the water trial. Serum insulin concentration was only higher after 20 min of exercise (P < 0.01). 3. A 28% reduction in mixed glycogen utilization was observed as a result of CHO ingestion when compared with water ingestion (108.7 +/‐ 16.3 vs. 150.9 +/‐ 19.9 mmol (kg dry matter)‐1, respectively; P < 0.01). 4. The ingestion of the CHO solution resulted in sparing of glycogen in type I (slow twitch) fibres only (38 +/‐ 7% degradation of glycogen as opposed to 66 +/‐ 3% during the water trial; P = 0.01).
Major difference between rat and guinea‐pig ureter in the ability of agonists and caffeine to release Ca2+ and influence force.
Authors: Burdyga T V , Taggart M J , Wray S
Published: December 2014

1. We have investigated the internal Ca2+ store and its ability to affect contraction by simultaneously measuring force and Ca2+ in the ureter from guinea‐pig and rat. Both species responded in a similar manner to electrical stimulation and depolarization with high‐K+, generating plateau‐type action potentials and increasing intracellular calcium ([Ca2+]i) and force. 2. In the guinea‐pig, carbachol had no effect on [Ca2+]i and force in the resting ureter. In contrast, resting rat ureter always responded with a large [Ca2+]i rise and maintained force to carbachol in Ca(2+)‐containing solution, and in Ca(2+)‐free solution it showed a transient increase in [Ca2+]i and force. This Ca2+ release and force development was also present in both polarized and high‐K(+)‐depolarized preparations and was insensitive to nifedipine, suggesting the presence of a receptor‐coupled pathway of Ca2+ release in rat ureter. 3. Caffeine was able to produce a release of Ca2+ from the internal store of guinea‐pig ureter and elicit contraction. However, rat ureter failed to respond to caffeine. In the presence of La3+, the caffeine response in the guinea‐pig ureter and carbachol response in the rat ureter, elicited in Ca(2+)‐free solutions, were always increased and prolonged and could be repeatedly evoked, suggesting similarity in Ca2+ uptake behaviour of the store in both species. 4. Ryanodine blocked the caffeine responses of the guinea‐pig ureter elicited both in Ca(2+)‐containing and Ca(2+)‐free solutions, both in the absence and presence of La3+. However, ryanodine failed to prevent the rat ureter responding to carbachol, suggesting that carbachol was releasing Ca2+ from a ryanodine‐insensitive channel in the sarcoplasmic reticulum (SR). 5. Cyclopiazonic acid, which inhibits the SR Ca(2+)‐ATPase, abolished the effects of both caffeine and carbachol in Ca(2+)‐free solutions in guinea‐pig and rat, respectively. 6. We conclude that there is a major difference in the mechanisms of Ca2+ release in the internal Ca2+ store of smooth muscle from guinea‐pig and rat ureter. The data suggest that the guinea‐pig store is purely a calcium‐induced calcium release (CICR)‐type store and that the rat store is a pure receptor‐operated Ca2+ store.
Ca2+ activation and Ca2+ inactivation of canine reconstituted cardiac sarcoplasmic reticulum Ca(2+)‐release channels.
Authors: Schiefer A , Meissner G , Isenberg G
Published: December 2014

1. Calcium‐release channels (ryanodine receptors) of canine cardiac sarcoplasmic reticulum (SR) were incorporated into lipid bilayer membranes at the tip of a patch pipette. Using symmetrical 150 mM KCl solutions, [Ca2+] > 0.3 microM activated single channels of 627 pS conductance. The kinetics of Ca(2+)‐mediated channel activation, deactivation and inactivation were studied by stepwise changes in pCa (‐log[Ca2+]) and analysis of current means. 2. Steps of [Ca2+] activated the channel open probability (Po) along a time course which could be fitted by a single exponential. The activation time constant was dependent on [Ca2+], which decreased from 4.9 ms at pCa 6.5 to 0.2 ms at pCa 3. Subsequent rapid reduction in [Ca2+] decreased Po along a mono‐exponential deactivation time course, the time constant of which was independent of the [Ca2+] during the preceding activation period. Further analysis yielded the rate constants kon of 2 x 10(8) (M s)‐1 and koff of 2 x 10(2) s‐1, an apparent dissociation constant (KD) of 1 microM, and a Hill coefficient of 1.05. 3. The open probability increased with [Ca2+], reaching a peak at about pCa 5.5. At pCa < or = 5.5, Po decreased time dependently, the time constants decreasing along with [Ca2+] from 1 s at 3 microM to 0.2 s at 1 mM. During the 0.5 s period at 3 microM Ca2+, Po fell by 13% due to an extension of the closed times. At 1 mM Ca2+, Po ‘inactivated’ by 72%, which was due mostly to long closures. These differences suggest that the Ca(2+)‐mediated decay of Po was dependent on Ca2+ binding to an intermediate (KD, 3 microM) and a low affinity site (KD, 360 microM). On the return of pCa from 3 to > 8, the channels briefly re‐opened. 4. A ‘refractory’ behaviour of the channel was not observed for 20 ms steps between < 10 nM and < 10 microM [Ca2+] (25 Hz). For steps between 10 nM and 1 mM, however, such behaviour was marked by infrequent and irregular channel openings. 5. The results are described by a three Ca2+ binding site model and compared with the literature.
Activation of store‐operated calcium influx at resting InsP3 levels by sensitization of the InsP3 receptor in rat basophilic leukaemia cells.
Authors: Parekh A B , Penner R
Published: December 2014

1. Patch clamp and fura‐2 AM measurements were performed to study the effects of sensitizing the inositol 1,4,5‐trisphosphate (InsP3) receptor to InsP3 on the activation of Ca2+ release‐activated Ca2+ current (ICRAC) in rat basophilic leukaemia (RBL) cells. 2. The sensitizing agent thimerosal (1 microM) triggered Ca2+ release, and this was followed by Ca2+ influx. With no added InsP3 in the patch pipette, thimerosal activated ICRAC; this was prevented by heparin. ICRAC activated by thimerosal was very similar to that evoked by InsP3 or ionomycin. 3. Dialysing cells either for short (30 s) or long (600 s) periods of time prior to application of thimerosal did not affect the subsequent activation of ICRAC, even though no InsP3 was included in the patch pipette. 4. These results suggest that sensitizing the InsP3 receptor can result in large Ca2+ influx in the presence of resting InsP3, and that stores closer to the membrane may contribute more to activation of ICRAC than stores further away.
Potassium currents underlying the oscillatory response in hair cells of the goldfish sacculus.
Authors: Sugihara I , Furukawa T
Published: December 2014

1. Ionic currents underlying the oscillatory response of membrane potential were studied in oscillatory‐type hair cells isolated from the goldfish sacculus with the whole‐cell recording method using a patch pipette. 2. Bath application of 4‐aminopyridine (4‐AP; 10 mM) reversibly produced moderate depolarization of the resting potential along with complete suppression of the oscillatory response. Sustained injection of a small depolarizing current also suppressed the oscillatory response. 3. A 4‐AP‐sensitive atypical A‐type K+ current which had a high threshold voltage for inactivation (IA(H)) was found to be a major outward current underlying the oscillatory response. 4. IA(H) was activated with a time constant of 0.4‐10 ms and was inactivated slowly with a time constant of 0.6‐2 s. IA(H) activation and inactivation occurred mostly at membrane potentials more positive than ‐70 mV. 5. There was a clear correlation between activation speed of IA(H) and the frequency of pulse‐evoked oscillation. A ‘hump’‐type response was produced in about one‐quarter of the oscillatory‐type hair cells.