bluuebunny/crossref_metadata_2025 huggingface dataset:
The interplay between hydrogen ions, bicarbonate ions and osmolarity in the anterior duodenum modulating gastric function in the conscious calf
Authors: Bell F. R. , Nouri M. , Webber D. E.
Published: December 2014

1. Gastric emptying, gastric acid and pepsinogen secretion were assessed simultaneously in the conscious calf using the test meal and duodenal perfusion technique (Bell & Mostaghni, 1975).

2. Duodenal infusion of NaCl at a constant osmolality of 300 m‐osmole/kg, but with pH ranging from 2·0 to 12·0, did not alter the high level of gastric emptying and secretion already reported for isotonic NaCl or NaHCO3 alone (Bell & Mostaghni, 1975; Bell & Webber, 1979). Gastric function, therefore, is either unaffected by gastric chyme at pH 2·0‐12·0 entering the duodenum, or else isotonicity is dominant over pH in activating duodenal receptors which increase motor activity.

3. When the pH of the isotonic NaCl was reduced by the addition of HCl to below pH 2·0, inhibition of gastric function occurred in direct proportion to the amount of titratable acid present in the infusate. The H+ moiety of isotonic duodenal infusates of pH < 2·0 dominates activation of osmoreceptors and so inhibits motor activity.

4. When the same amount of acid but at differing concentrations and infusion rates was introduced into the duodenum uniform inhibition of gastric function occurred. This result indicates that duodenal acid receptors respond to acid concentration and flow rate to produce an integrated response in proportion to the amount (concentration × volume) of acid present.

5. Isotonic NaHCO3 solutions adjusted to pH 8·1‐12·0 by the addition of NaOH, like isotonic NaCl infusions, did not affect gastric function until pH 11·0‐12·0, when significant inhibition occurred. This inhibitory effect of isotonic NaHCO3 at high pH is probably due to CO32−, since Na2CO3 and Li2CO3, but not LiCl, produce a similar inhibitory effect on gastric function.

6. The inhibitory effect of carbonate gives some support to the existence of a CO2‐sensor as suggested by Hunt & Knox (1972), whereby increased PCO2 produced by intracellular or intercellular neutralization of CO32- by duodenal H+ activates acid receptors. But other experiments reported here, where simultaneous perfusion of HCl and excess NaHCO3 produced a rise in intraluminal PCO2, did not inhibit gastric function, which is contrary to the idea of a direct intraluminal effect of CO2 on duodenal receptors.

7. The pH, PO2, PCO2, HCO3− and base excess of venous blood showed no detectable change during duodenal infusion of either acidic or alkaline solutions. Metabolic acidosis or alkalosis, therefore, cannot be considered to play any part in controlling gastric function. The results thus corroborate the notion that the receptors controlling gastric function are localized in the intestinal mucosa.

8. Our results suggest that interplay between acid and osmolality of gastric chyme occurs in the rostral part of the duodenum to produce a graded inhibitory effect which by negative feedback modulates the gastric effectors that normally activate smooth muscle, parietal cells and zymogen cells.
Electrical activity of the pulmonary vein and its interaction with the right atrium in the guinea‐pig.
Authors: Cheung D W
Published: December 2014

1. The tunica media of the proximal segments of the pulmonary vein is made up of cardiac muscle cells. The electrical activity of this cardiac portion of the pulmonary vein was studied with intracellular micro‐electrodes in isolated preparations. 2. All‐or‐none action potentials were recorded in all cardiac muscle cells in response to electrical stimulation. These action potentials did not propagate into the adjoining smooth muscle cells. 3. There were differences in properties between cells at the distal end of the cardiac pulmonary vein close to the smooth muscle and those close to the heart. In quiescent preparations, cells at the distal end had resting potentials which averaged 66 mV compared with 71 mV at proximal sites. Action potentials were also smaller and shorter in duration in cells at the distal end. 4. In spontaneously active preparations, pace‐making potentials were observed in cells at the distal end while cells close to the heart showed a stable diastolic potential between action potentials. The spontaneous activity of the pulmonary vein was influenced by both inhibitory and excitatory nerves. 5. The interaction between the pulmonary vein and atrial activities was studied in spontaneously active atrial‐pulmonary vein preparations. Action potentials recorded from the pulmonary vein always followed those from the right atrium. Electrical stimulation at the pulmonary vein generated action potentials that propagated back into the right atrium. 6. This study demonstrated that isolated pulmonary veins were capable of independent pace‐making activity. However the activity of the pulmonary vein was dominated by the SA node in atrial‐pulmonary vein preparations under normal conditions.
The effect of knee joint afferent discharge on transmission in flexion reflex pathways in decerebrate cats.
Authors: Baxendale R H , Ferrell W R
Published: December 2014

1. Changes in excitability of reflex arcs mediating flexion withdrawal ad crossed extensor reflexes have been examined in decerebrate cats. 2. The excitability of flexion withdrawal and crossed extensor reflexes was shown to be modulated by knee joint position. Flexion withdrawal reflexes were most easily elicited when the knee was extended and crossed extensor reflexes were most easily elicited when the knee was flexed. 3. The modulation of transmission was not confined to reflex pathways to muscles acting at the knee but also included pathways to muscles acting at the hip and ankle, as well as pathways to muscles in the contralateral limb. 4. The changing excitability of reflex pathways caused by movement of the knee joint was unrelated to the stretch applied to muscles acting at the knee and to cutaneous afferent discharge. Modulation of reflex excitability by joint movement was totally abolished by local anaesthesia of the knee joint in an otherwise intact limb. 5. The results of the present experiments indicate that transmission in flexion reflex pathways can be inhibited by knee joint afferent discharge.
Mechanics of competition walking.
Authors: Cavagna G A , Franzetti P
Published: December 2014

1. The work done at each step to lift and accelerate the centre of mass of the body has been measured in competition walkers during locomotion from 2 to 20 km/hr. 2. Three distinct phases characterize the mechanics of walking. From 2 to 6 km/hr the vertical displacement during each step, Sv, increases to a maximum (3.5 vs. 6 cm in normal walking) due to an increase in the amplitude of the rotation over the supporting leg. 3. The transfer, R, between potential energy of vertical displacement and kinetic energy of forward motion during this rotation, reaches a maximum at 4‐5 km/hr (R = 65%). From 6 to 10 km/hr R decreases more steeply than in normal walking, indicating a smaller utilization of the pendulum‐like mechanism characteristic of walking. 4. Above 10 km/hr potential and kinetic energies vary during each step because both are simultaneously taken up and released by the muscles with almost no transfer between them (R = 2‐10%). Above 13‐14 km/hr an aerial phase (25‐60 msec) takes place during the step. 5. Speeds considerably greater than in normal walking are attained thanks to a greater efficiency of doing positive work. This is made possible by a mechanism of locomotion allowing an important storage and recovery of mechanical energy by the muscles.
Development of sodium, calcium and potassium channels in the cleavage‐arrested embryo of an ascidian.
Authors: Takahashi K , Yoshii M
Published: December 2014

1. The cleavage of the embryos of an ascidian, Halocynthia roretzi, was arrested with cytochalasin B (1 microgram/ml.) at the 16‐ or 64‐cell stage. These cleavage‐arrested embryos were still able to develop membrane excitability. 2. In the cleavage‐arrested 64‐cell embryos at the time when control embryos became hatched larvae, Ca spikes were evoked in the presumptive muscle blastomeres, and Na‐ and Ca‐dependent action potentials were induced in some ectodermal blastomeres. 3. Membrane currents of the cleavage‐arrested 16‐cell embryos were recorded with the voltage‐clamp technique and analysed as a function of developmental time at 15 degrees C. For this purpose, intact eggs, 4‐ and 8‐cell embryos were also used. The cleavage‐arrested embryos behaved electrically like single cells, due to tight electrical coupling between blastomeres. After the 25‐hr stage decoupling occurred. 4. Both Na and Ca currents decreased during the initial 10 hr. Na current became less than one third and Ca current almost disappeared. At 17 hr both Na and Ca currents increased again. 5. The potential‐dependence of the Na and Ca currents after 17 hr was similar to that in the egg, although substantial parallel shifts in the current‐voltage relations were observed: a 5 mV positive shift for the Na current and a 15‐20 mV negative shift for the Ca current. 6. Delayed (outward) K current developed gradually until 20 hr and then increased abruptly. The activation level for the delayed rectification was markedly negative (around ‐10 mV) in comparison with that of the egg (around + 100 mV). Anomalous (inward) K current, on the other hand, increased gradually without changes in the potential‐dependence throughout development. 7. The results suggest that the differentiation of excitable membranes in the ascidian embryo does not involve changes in the properties of the individual channels, but rather changes in the numbers of various kinds of ion channels.
Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro.
Authors: Llinás R , Yarom Y
Published: December 2014

The electrophysiological properties of the high‐ and low‐threshold Ca spikes described in inferior olivary neurones were analysed in detail. 1. During hyperpolarization the low‐ and high‐threshold Ca action potentials can coexist as two distinct spikes, demonstrating non‐mutual exclusion. 2. The high‐threshold Ca spike shows a lack of refractoriness, is generated remotely from the site of recording and is composed of several all‐or‐none components, the last two properties suggesting a dendritic origin. 3. Hyperpolarization of the neurones allows the activation of the low‐threshold Ca spike, which has activation properties resembling those of the early K conductance described in invertebrates. This low‐threshold Ca spike shows refractoriness. 4. The relation between membrane polarization and low‐threshold Ca spike is S‐shaped. Low‐threshold Ca spikes become apparent at ‐70 mV and have a maximum rate of rise (saturation) at polarization levels more negative than ‐85 mV. Thus, hyperpolarization removes a voltage‐dependent Ca inactivation which is present at normal resting membrane potential (‐65 mV). 5. Replacement of extracellular Ca by Ba or addition of tetraethylammonium to the bath corroborates the lack of fast inactivation for the high‐threshold Ca spike and the inactivation properties of the low‐threshold Ca conductance. It also demonstrates that the duration of the after‐depolarization is determined by an interplay between inward Ca current and both voltage‐dependent and Ca‐dependent K currents. 6. Extracellular recordings from single cells indicate that the Na‐dependent spike and the low‐threshold Ca action potential are somatic in origin, while the high‐threshold Ca spike (after‐depolarization) and the hyperpolarization that follows are apparently located in the dendrites. 7. The ionic conductances comprise the main components of the oscillatory behaviour of these cells. The sequence of events leading to oscillation entails initially a low‐threshold Ca spike or Na spike, followed by an after‐depolarization/after‐hyperpolarization sequence and then a post‐anodal exaltation product by a rebound low‐threshold Ca spike.
A comparison of the effects of sympathomimetic agents on gastric acid secretion by the rat stomach in vivo and in vitro.
Authors: Canfield S P , Price C A
Published: December 2014

1. The action of isoprenaline on gastric acid secretion in rats with Heidenhain pouches has been compared with its action in a rat isolated stomach preparation. 2. Isoprenaline (40 micrograms kg‐1 h‐1) inhibited the acid secretion in response to pentagastrin (20 micrograms kg‐1 h‐1) in conscious rate with Heidenhain pouches. 3. This inhibition could be abolished by propranolol (2 mg kg‐1) and butoxamine (8 mg kg‐1) and partially reversed by practolol (8 mg kg‐1). 4. Propranolol (2 mg kg‐1) significantly increased the response to pentagastrin (20 micrograms kt‐1 h‐1) but butoxamine and practolol (both at 8 mg kg‐1) and the inactive isomer (+)‐propranolol (2 mg kg‐1) were without any effect on the pentagastrin response in the rats with pouches. 5. In the rat isolated stomach preparation isoprenaline stimulated acid secretion over the range 10(‐7) M‐10(‐3) M whereas phenylephrine and methoxamine were without effect. 6. Propranolol (2 X 10(‐5) M) inhibited this stimulatory effect of isoprenaline in vitro but (+)‐propranolol (2 X 10(‐5) M), practolol and butoxamine (both at 10(‐4) M) had no effect on the response. 7. Propranolol (2 X 10(‐5) M) did not have any effect on the response of the isolated stomach to pentagastrin (5 X 10(‐7) M) or bethanechol (1.7 X 10(‐5) M). 8. Phenylephrine (2 X 10(‐5) M) did not affect the in vitro responses to pentagastrin (2.17 X 10(‐7) M), bethanechol (1.7 X 10(‐5) M) or histamine (5.4 X 10(‐5) M). 9. It is concluded that isoprenaline has a direct stimulatory effect and an indirect inhibitory effect on gastric acid secretion in the rat. Both effects involve stimulation of beta‐adrenoceptors. The relative predominance of one or other of these two opposing effects may help to explain the contradictory results in the literature regarding the actions of beta‐adrenoceptor agonists on gastric acid secretion.
The action of beta‐adrenoceptor agonists on acid secretion by the rat isolated stomach.
Authors: Canfield S P , Hughes A D , Price C A , Spencer J E
Published: December 2014

1. The action of beta‐adrenoceptor agonists on acid secretion by an immature rat isolated stomach preparation has been studied. 2. Isoprenaline, salbutamol, salmefamol, adrenaline and noradrenaline all stimulated acid output over a concentration range of 2 X 10(‐7) M‐‐10(‐5) M. 3. These responses were antagonized by propranolol (2 X 10(‐5) M), pindolol and timolol (10(‐6) M). 4. The antagonism of isoprenaline and salmefamol by propranolol was consistent with competitive inhibition. 5. Selective beta‐adrenoceptor antagonists (practolol, atenolol, butoxamine and ICI 118 551) caused significant inhibition of noradrenaline‐stimulated secretion but not of that due to the other agonists. 6. An adult rat isolated mucosa preparation responded to adrenaline in a similar manner to the immature stomach preparation. 7. Acid secretion stimulated by beta‐adrenoceptor agonists was not antagonized by atropine (10(‐5) M), metiamide (10(‐4) M) or prostaglandin E2 (10(‐5) M). The concentrations of these three antagonists caused marked inhibition of the responses to submaximal concentrations of bethanechol, histamine and pentagastrin respectively. 8. The results are discussed in relation to the possible mechanisms of action of beta‐adrenoceptor stimulation of acid secretion: it is concluded that the response is probably mediated by beta‐receptors on the parietal cell.
The effect of tetraethylammonium chloride on potassium permeability in the smooth muscle cell membrane of canine trachea.
Authors: Imaizumi Y , Watanabe M
Published: December 2014

1. The effect of tetraethylammonium ions (TEA) on potassium or rubidium permeability was studied in canine tracheal smooth muscle. 2. TEA (15‐30 mM) markedly increased the rate of 42K‐ and 86Rb‐efflux in normal Krebs solution. This increase is probably due mainly to the occurrence of electrical activity such as spike potentials and only partially to depolarization. 3. The rate coefficients of 42K‐ and 86Rb‐efflux from depolarized tracheal smooth muscle bathed in a medium with elevated potassium (50‐100 mM) were so large that the coefficients did not remain constant. When chloride ions in the medium were replaced with larger anions such as acetate, propionate or benzoate, the rate of 86Rb‐efflux remained constant even in high‐potassium solution (70 mM). 4. TEA caused a remarkable blockade of 86Rb‐efflux in depolarized tracheal smooth muscle. The maximum decrease in the rate coefficient by TEA was approximately 52.5% of the control value in high‐potassium‐acetate solution. The dissociation constant for the interaction between TEA and its sites of action on the cell membrane was about 0.93 mM. 5. Spontaneous activity was, however, elicited only when TEA was added at a concentration of 10‐30 mM and the membrane was depolarized more than 15‐20 mV. It is assumed that TEA blocks not only the voltage‐sensitive potassium conductance but also the conductance in the resting state, and that the latter may be possibly less sensitive to TEA.
The effect of the red cell membrane and a diffusion boundary layer on the rate of oxygen uptake by human erythrocytes
Authors: Huxley Virginia H. , Kutchai Howard
Published: December 2014

1. This paper deals with the contributions of the red cell membrane and an external diffusion boundary layer (‘unstirred layer’) to the resistance to O2 entry into the red cell. Bovine serum albumin (BSA) was added to the extracellular fluid to enhance the effect of the diffusion boundary layer by diminishing both the solubility and the diffusivity of O2. The rate of O2 uptake by human red cells at various extracellular BSA concentrations was determined with a stopped‐flow rapid‐reaction apparatus.

2. The initial rate of O2 uptake by the red cells was directly proportional to the diffusion coefficient of O2 in the extracellular fluid.

3. If the diffusion boundary layer and the plasma membrane are considered as resistors in series, we estimate that 82‐100% of the total resistance to O2 entering the cell is due to the diffusion boundary layer. Our best estimate is that 95% of the resistance resides in the diffusion boundary layer.

4. Our best estimate of the O2 permeability of the red cell membrane is 3·15 × 10−6 m‐mole/(cm2 sec mmHg). With this permeability the membrane would account for only 5% of the total resistance to O2 entering the cell. Partly because the membrane O2 diffusion resistance is a small fraction of the total resistance our estimate of the membrane resistance has a large standard deviation. Taking our estimate of the membrane resistance plus and minus its standard deviation we find that the membrane may account for 0‐18% of the total resistance to O2 entering the cell.

5. The effective thickness of the diffusion boundary layer immediately after mixing is about 1·93 μm according to our analysis.
Applicability of models for carrier‐mediated serotonin transport to pools of serotonin in intact human platelets.
Authors: Costa J L , Murphy D L , Stark H
Published: December 2014

Intact human platelets can accumulate serotonin (5HT) in compartments which are vesicular (thrombin‐releasable) or extra‐vesicular (non‐thrombin‐releasable). 1. The net accumulation of extracellular 5HT in either compartment is not coupled in a reciprocal fashion to the presence of appropriate sodium gradients across the cell plasma membrane, and 5HT already present in either compartment is not removed when trans‐membrane sodium gradients are abolished or reversed. 2. Net counter‐transport of 5HT in either compartment is not detectable. 3. The data are not consistent with transport models such as that for glucose in which appropriate sodium gradients produce gradients of a co‐transported molecule, or with models in which counter‐transport can occur.
A study of desensitization of acetylcholine receptors using nerve‐released transmitter in the frog
Authors: Magleby K. L. , Pallotta B. S.
Published: December 2014

1. Desensitization of acetylcholine (ACh) receptors was studied at the frog neuromuscular junction under voltage clamp.

2. ACh was applied directly to junctional receptors by stimulating the motor nerve with trains of impulses. End‐plate currents (e.p.c.s) were used to estimate the total number of channel openings by the junctional ACh receptors, and miniature end‐plate currents (m.e.p.c.s) were used to measure changes in post‐synaptic sensitivity. Under the conditions of these experiments the changes in m.e.p.c. amplitudes were shown to be post‐synaptic in origin and thus provided a measure of desensitization.

3. When the acetylcholinesterase was inhibited with diisopropylfluorophosphate, neostigmine, or collagenase treatment to prolong the duration of the nerve‐released ACh in the synaptic cleft, desensitization developed during repetitive stimulation of 1000 impulses at 5‐33 impulses/sec and then recovered after the conditioning trains, with a time constant of about 25 sec.

4. When the acetylcholinesterase was active so that the duration of ACh in the synaptic cleft resulting from each nerve impulse was brief (< 300 μsec), desensitization developed in response to 300‐500 pairs of nerve stimuli if the interval between the impulses of each pair was 25 msec or less. When the interval was 30 msec or greater, however, measurable desensitization did not occur, even if the total number of channel openings was many times greater than in the experiments with shorter intervals or inhibited esterase where desensitization readily occurred.

5. The desensitization observed to pairs of impulses was enhanced by chlorpromazine and decreased when the post‐synaptic membrane was depolarized, properties similar to those described previously for desensitization to bath and ionophoretic application of ACh.

6. These results indicate that desensitization to nerve‐released transmitter is not a simple consequence of receptor activation, is not due to blockade of the open receptor channels by ACh, and does not result from ACh binding directly to desensitized receptors with a resulting shift in the receptor population towards the desensitized state.

7. We suggest that the desensitization observed to nerve‐released transmitter is a two‐step process with both steps initiated by ACh. In the first step ACh converts some receptors into a desensitizable state which has an apparent lifetime of less than 30 msec; in the second step ACh desensitizes the desensitizable state.
pH and temperature dependence of glutamine uptake, carbon dioxide and ammonia production in kidney slices from acidotic rats.
Authors: George J P , Solomon S
Published: December 2014

1. The effects of medium pH and temperature on glutamine uptake, NH3 production and CO2 production were examined using kidney cortex slices from normal and acidotic rats. 2. Uptake of glutamine by kidney slices from normal rats shows a pH optimum of 7.5 at 25 degrees C and 7.3 at 37 degrees C. Uptake is optimal, however, at a constant OH‐/H+ ratio of 10. 3. In slices from acidotic rats greatest uptake was at pH 6.8 at 25 degrees C and 6.6 at 37 degrees C. Optimal OH‐/H+ ratio was 0.4 and constant at both temperatures. 4. CO2 production from glutamine was greatest at pH 7.0 at 37 degrees C in slices from control rats. No pH optimum was detected at 25 degrees C. With slices from acidotic animals, optimal pH for CO2 production became identical with that for uptake. 5. Both basal and glutamine‐stimulated NH3 production showed no optimal pH but were significantly higher in slices from acidotic rats compared with those from controls. 6. Dependence of glutamine penetration on optimal OH‐/H+ ratio is considered to reflect a general membrane phenomenon which is produced by either an increase in carrier‐substrate complexes or an increase in the number of carriers at this ratio. 7. Cellular penetration of glutamine does not appear to be a limiting factor in production of NH3 in vitro.
The neuromuscular junction of the mouse after black widow spider venom.
Authors: Duchen L W , Gomez S , Queiroz L S
Published: December 2014

1. A sublethal quantity of black widow spider venom was injected into the calf muscles of mice. After 30 min to 6 weeks soleus muscles were examined by light and electron microscopy and by electrophysiological techniques. 2. Within 30 min motor nerve terminals were swollen and depleted for synaptic vesicles and by 6 h were disrupted and engulfed by Schwann cells. By 24 h every end‐plate examined was denervated. Some preterminal myelinated axons also showed degenerative changes. 3. Re‐innervation was first seen at 2 days. By 3 days axon terminals were present at most end‐plates and by 8 days their morphology was nearly normal. The normal pattern of innervation of the muscle was re‐established in that axons re‐innervated their original end‐plates and very few ultraterminal axonal sprouts were found. 4. Physiological study showed complete failure of transmission and absence of miniature end‐plate potentials (m.e.p.p.s) and end‐plate potentials (e.p.p.s) until day 3, when muscles responded weakly to indirect stimulation and m.e.p.p.s were recorded at 30% and e.p.p.s at 40% of fibres. The mean quantal content of e.p.p.s was low and there was rapid fatigue on repetitive stimulation. Extrajunctional sensitivity to acetylcholine developed within 1 day, was maximal at 3 days and declined to normal at 12‐14 days. 5. The proportion of fibres at which m.e.p.p.s and e.p.p.s were recorded returned to normal by day 6 and mean quantal content was normal by day 9. 6. These findings show that the re‐innervation of original end‐plates is of importance in facilitating the rapid return of transmission to normal levels and limiting the extent of axonal growth.
Initiation of the migrating myoelectric complex in dogs.
Authors: Bueno L , Rayner V , Ruckebusch Y
Published: December 2014

1. Contractile and spike activity in the conscious dog were recorded from strain gauge force transducers and electrodes chronically implanted on the antrum, duodenum and jejunum. The pattern of activity was related to the time elapsed after feeding a daily meal, both in intact dogs and in dogs with antro‐jejunal or oesophago‐duodenal anastomoses. 2. From 8 to 10 h after feeding, transient reductions of the continuous antral spiking activity were recorded while phases of regular spiking activity (RSA) and contractions developed on the proximal intestine. 3. About 18 h after feeding, the post‐prandial antral activity became intermittent, each period of contractions being accompanied by the duodenal development of a RSA phase. 4. The RSA phases were still initiated on the duodenum after an antro‐jejunal anastomosis and after gastrectomy. 5. It is concluded that phases of RSA of the migrating myoelectric complex are initiated in the proximal part of the small intestine rather than in the stomach. It is suggested that the RSA phase exerts an inhibitory effect on the antrum which may serve to reduce the flow of digesta through the pylorus when the ability of the duodenum to receive chyme is restricted.
Gastric pH changes associated with duodenal motility in fasted dogs.
Authors: Bueno L , Fioramonti J , Ruckebusch Y
Published: December 2014

1. The electrical activity of the antrum and duodenum was recorded from chronically implanted electrodes in six conscious dogs fitted with gastric and/or duodenal cannulae. Antral and duodenal pH were concomitantly registered using glass electrodes inserted through the respective cannula. 2. In dogs fasted for 18‐24 h an alkalinization of the antrum of about 5 pH units lasting 15‐30 min occurred regularly at 90‐120 min intervals at the cessation of a period of antral spiking activity. This antral alkaline period was accompanied by the reflex of intestinal juice into the stomach, as determined by the presence of bile salts in gastric samples. 3. The antral pH rise was related to the development of a phase of regular spiking activity (RSA), or activity front, on the proximal duodenum concomitant with the motor quiescence of the antrum. The rise in pH disappeared after occlusion of the pylorus, which prevented the passage of duodenal contents into the antrum. 4. It is concluded that the mean antral pH value is 5.8 for half the recording time in fasted dogs, the causative factor of this alkalinization being the regurgitation of duodenal contents into the antrum while quiescent. Accordingly, more alkaline duodenal contents were observed during the occurrence of the RSA phase and the following gastro‐duodenal quiescence; then the progressive acidification of the gastric and duodenal contents when the motility reappeared may be an inducing factor of a new RSA phase.
Pattern of ‘non‐reciprocal’ inhibition of motoneurones by impulses in group Ia muscle spindle afferents in the cat
Authors: Jankowska Elżbieta , McCrea David , Mackel Robert
Published: December 2014

1. Inhibitory post‐synaptic potentials (i.p.s.p.s) evoked by adequate stimulation of group Ia muscle spindle afferents of triceps surae and plantaris and by near‐threshold electrical stimulation of quadriceps and hamstring nerves were recorded in a number of motoneurone species. The aim of the study was to compare the pattern of non‐reciprocal Ia inhibitory actions on hind‐limb motoneurones with the pattern of inhibition evoked from group Ib tendon organ afferents.

2. In all the motoneurone species analysed in which i.p.s.p.s were evoked by electrical stimulation maximal for both group Ia and Ib afferents of triceps surae and plantaris, they were also evoked when these muscles were stretched and the amplitude of the stretch (10‐35 μm) was below threshold for Ib afferents; 70‐100% of motoneurones with Ib i.p.s.p.s showed stretch‐evoked i.p.s.p.s. The stretch‐evoked i.p.s.p.s appeared with latencies compatible with disynaptic and trisynaptic linkage. Since these latencies were too short to allow their mediation by group II afferents the i.p.s.p.s are attributed to a selective action of Ia afferents. The i.p.s.p.s did not appear after the nerves to triceps surae and plantaris had been cut.

3. Electrical stimulation of quadriceps and hamstring nerves which was near threshold for Ia afferents and well below threshold for either the Ib component of the incoming volley or group II afferents, similarly evoked non‐reciprocal i.p.s.p.s. They were found in those motoneurones in which inhibition was evoked by stimulation maximal for group I afferents. Such Ia i.p.s.p.s were evoked both in homonymous motoneurones and in motoneurones of four other hind‐limb muscles. Their latencies corresponded to di‐ and trisynaptic coupling.

4. In some motoneurones of the pretibial flexors (anterior tibial, extensor digitorum longus and peroneus longus), disynaptic i.p.s.p.s evoked from triceps surae and/or plantaris which were depressed by a conditioning ventral root stimulation (i.e. Ia reciprocal i.p.s.p.s) were followed by trisynaptic i.p.s.p.s which were not depressed in this way (Ia ‘non‐reciprocal’ i.p.s.p.s). It thus appears that the same motoneurones may be inhibited by impulses in group Ia afferents via different spinal pathways.

5. The study leads to the conclusion that the non‐reciprocal inhibition from group Ia muscle spindle afferents operates in parallel with the inhibition from group Ib tendon organ afferents in all motoneurone species tested.
Electrical current‐induced contraction in the smooth muscle of the rabbit aorta.
Authors: Mekata F
Published: December 2014

1. In the smooth muscle of rabbit aorta, the relationship between the change in membrane potential and the concentration evoked by current application was studied. 2. In normal Krebs solution, outward current produced contraction when the membrane was depolarized to about ‐45 mV and the membrane resistance was decreased. Further increase in the outward current intensity produced an increase in tension development with very small additional depolarization but with a marked decrease in membrane resistance. 3. With arteries depolarized to about ‐20 mV, in excess K solution of concentration more than 60 mM, outward current failed to produce further contraction. However, contraction was produced when the inward current was switched off. This may be due to removal of an inactivation process by hyperpolarization of the membrane. 4. In excess K solution, no relaxation was observed with inward current application. However, when artificial stretch was applied to the preparation immersed in 98 mM‐K solution, a prolonged hyperpolarizing current of more than 3 sec could cause relaxation. 5. Ca‐free solution and Mn ion (0.5 mM) blocked the concentration induced by outward current. Phentolamine and tetrodotoxin had not effect. 6. It is suggested that increased membrane conductance associated with depolarization by outward current increased the Ca influx which causes contraction.
The effects of rubidium ions and membrane potentials on the intracellular sodium activity of sheep Purkinje fibres.
Authors: Eisner D A , Lederer W J , Vaughan‐Jones R D
Published: December 2014

1. Intracellular Na activity, aiNa, was measured in voltage‐clamped sheep cardiac Purkinke fibres. 2. Increasing [Rb]0 from 0 to 4 mM in K‐free solutions (at a fixed membrane potential) decreased aiNa. Further increases of [Rb]0 (up to 20 mM) had little or no effect. 3. Following exposure to Rb‐free, K‐free solution, the addition of a test concentration of Rb produced an exponential decrease of aiNa. The rate constant of decay of aiNa increased with increasing [Rb]0 over the measured range (0‐20 mM). 4. The accompanying electrogenic Na pump current transient decayed with the same rate constant as aiNa over the range of [Rb]0 examined. During this decay the electrogenic Na pump current was a linear function of aiNa. Increasing [Rb]0 increased the steepness of the dependence of the electrogenic current on aiNa. 5. A constant fraction of the net Na efflux was electrogenic. This fraction was not affected by varying [Rb]0 over the range 0‐20 mM. 6. Using a simple model, it is shown that the dependence of steady‐state aiNa on [Rb]0 is half‐saturated by less than 1 mM‐[Rb]0. The rate constant of decay of aiNa and the slope of the relationship between electrogenic Na pump current and aiNa are, however, better fitted with a lower affinity for Rb (K0.5 = 4 mM‐[Rb]0). 7. Depolarizing the membrane potential with the voltage clamp decreased aiNa; hyperpolarization increased it. These effects persisted in the presence of 10(‐5) M‐strophanthidin. An effect of membrane potential on the net passive Na influx can account for the observations. 8. The effects of membrane potential on the net passive Na influx were examined by measuring the maximum rate of rise of aiNa at different holding potentials after inhibiting the Na‐K pump in a K‐free, Rb‐free solution. Depolarization decreased the Na influx. 9. Using the constant field equation, the net passive Na influx was used to estimate the apparent Na permeability coefficient, PNa. This was between 0.8 x 10(‐8) and 1.5 x 10(‐8) cm sec‐1.
Force‐velocity relation in deuterium oxide‐treated frog single muscle fibres during the rise of tension in an isometric tetanus.
Authors: Cecchi G , Colomo F , Lombardi V
Published: December 2014

1. The force‐velocity (P‐V) relation from a single fibres isolated from the semitendinosus muscle of the frog was determined at pre‐set times during the rise of tension and the plateau of isometric tetani. The controlled‐velocity release method was used. Experiments were performed at about 2.25 micrometers sarcomere length and at 3‐4 degrees C or at 19‐21 degrees C. 2. Replacing H2O with D2O resulted in a rapid large reduction of the peak twitch tension and of the speed of development of twitch and tetanic tensions. The tetanic tension (P0) was usually reduced, in certain fibres to as low as 5% of the value in H2O‐Ringer solution. 3. The depression of twitch and tetanus characteristics was followed by a recovery, the duration of which varied greatly in different fibres. During the recovery period previous conditioning activity potentiated the tetanus characteristics. 4. After the end of the recovery period in D2O‐Ringer solution both the peak twitch tension and the speed of development of tetanic tension was still greatly depressed, whereas the value of P0 was slightly greater than in H2O‐Ringer. The speed of rise of isometric tension after a quick release imposed at the tetanus plateau was reduced in D2O‐Ringer, usually to about 50% of the value in H2O‐Ringer. 5. D2O increased the development time of the P‐V relation and produced a conspicuous increase in the degree of its curvature. The value of V0 (the velocity of shortening at zero load) was not significantly depressed by D2O and it was the same independent both of the time after the beginning of stimulation and of the isometric tension at which the measurement was made. The P‐V relation attained its final characteristics before the isometric tension reached the plateau. During the recovery period in D2O‐Ringer, at the plateau of isometric tetani of different size, the relative force exerted at a given velocity of shortening was constant. 6. In D2O‐treated fibres, NO3‐ and caffeine (i) potentiated the peak twitch tension and the speed of development of tetanic tension without affecting significantly the speed of the redevelopment of tension after a quick release imposed at the tetanus plateau and (ii) reduced the development time of the P‐V relation, but did not affect either the degree of its curvature or the value of V0 and P0. 7. The results are discussed by assuming that the release of Ca2+ from the sarcoplasmic reticulum is a rate‐limiting process for the development of activation and in turn for the development of isometric tension. In terms of the cross‐bridge model of Huxley (1957), the time or Ca2+‐dependent factor of activation appears to be the recruitment of actin sites for cross‐bridge formation, whereas the value of the rate constants regulating the cross‐bridge kinetics appears to be time and Ca2+‐independent.
Effect of pH on the formation and decay of the metarhodopsins of the frog.
Authors: Baumann C , Zeppenfeld W
Published: December 2014

1. Suspensions of membrane vesicles were prepared by sonication of dark‐adapted frog rod outer segments. The pH was adjusted to one of twelve values between 5.0 and 9.8; the temperature was 15 degrees C. Each preparation was exposed to a single yellow flash of 120 microseconds duration, and rapid slow changes of absorbance were measured at 475 nm wavelength. 2. Rapid changes consist of a transient rise followed by a diphasic decay to a new level of absorbance which is lower than that before the light exposure. The level of absorbance reached at the end of the rapid changes is lower at lower pH. 3. Kinetic analysis reveals that three reactants take part in the rapid reactions, viz. metarhodopsin I and two isochromic forms of metarhodopsin II named metarhodopsin II' and metarhodopsin II". The kinetics of the reversible transition from metarhodopsin I to metarhodopsin II' are not measurably influenced by the pH of the medium. However, the reversible reaction of metarhodopsin II' with metarhodopsin II" is dependent on pH because metarhodopsin II" is encountered either as a protonated or as a deprotonated compound. 4. Slow reactions are due to metarhodopsin I and to metarhodopsin III. A combined quantitative analysis of both rapid and slow reactions involves a reversible reaction between metarhodopsin II' and metarhodopsin III and a hydrolysis of metarhodopsin II' to retinal and opsin. The scheme employed accounts for the pH dependence of all equilibria although only one of the metarhodopsins reacts directly with protons.
Adrenergic transmissions in the guinea‐pig mesenteric artery and their cholinergic modulations.
Authors: Kuriyama H , Suzuki H
Published: December 2014

1. Neuromuscular transmission in the guinea‐pig mesenteric artery and the effect of acetylcholine (ACh) on transmission were investigated by the micro‐electrode method. 2. The membrane potential, length and time constant of the smooth muscle of the mesenteric artery were found to be ‐69.6 +/‐ 1.9 mV, 0.81 +/‐ 0.15 mm and 129 +/‐ 42 msec, respectively. 3. Perivascular nerve stimulation produced an excitatory junction potential (e.j.p.) and repetitive stimulation produced facilitation. When the amplitude of an e.j.p. reached threshold, a spike was evoked. 4. Very rarely, miniature e.j.p.s. were recorded. The amplitude histogram showed a skew distribution. Increases in the stimulus intensity enlarged the amplitude of e.j.p.s. as a stepwise manner. These results indicate multiple innervation to the muscle cells. 5. The time constant of the falling phase of an e.j.p. was consistently larger than that of the muscle membrane. 6. ACh, in concentrations of less than 10(‐8) M, suppressed the e.j.p. amplitude without change in the membrane potential and resistance of the muscle membrane, but accelerated facilitation. These ACh actions were suppressed by pre‐treatment with atropine. 7. ACh suppressed neither the conduction velocity of excitation of adrenergic nerves nor the number of nerves contributing to the generation of an e.j.p. 8. These results suggest that pre‐ and post‐junctional muscarinic receptors possess different sensitivities to ACh, and a low concentration of ACh (less than 10(‐8)M solely suppressed the release of noradrenaline by activating the pre‐junctional muscarinic receptors.
Pre‐ and post‐synaptic actions of botulinum toxin at the rat neuromuscular junction.
Authors: Sellin L C , Thesleff S
Published: December 2014

1. Extensor digitorum longus muscles of rats were paralysed with local, non‐lethal doses of botulinum toxin Type A (BoTx). At 2 and 7 days after toxin injection, the nerve‐muscle preparations were excised and end‐plate currents analysed at 23 degrees C by dual‐micro‐electrode voltage clamp. 2. At 2 days after BoTx injection, the growth time of miniature end‐plate currents (m.e.p.c.s) increased from a rather narrow range with a mean of 0.59 to a mean of 1.35 ms with a large variability between m.e.p.c.s. End‐plate currents (e.p.c.s) were reduced compared to unpoisoned muscle. The decay phase of m.e.p.c.s and e.p.c.s, the growth phase of e.p.c.s and the voltage sensitivity of m.e.p.c.s were unchanged. 3. At 7 days after BoTx injection, the findings were similar to 2 days except that the time constant of the decay phase of m.e.p.c.s. and e.p.c.s. was about twice a long as normal and that the voltage sensitivity of m.e.p.c.s was increased. 4. The acetylcholine null potential (about 0 mV) was unchanged after treatment with BoTx. 5. The increase in the growth time of m.e.p.c.s compared to e.p.c.s following the injection of BoTx suggests that the poisoning, besides blocking quantal release, affects the time course of spontaneous but not that of evoked release. After BoTx poisoning the trans‐synaptic diffusion of a majority of spontaneously released transmitter quanta seems to occur more slowly or from areas more distant from the highest concentration of the post‐synaptic receptor than that of evoked release. 6. The increase in the decay phase of m.e.p.c.s and e.p.c.s and its increased voltage sensitivity observed in muscles poisoned for 7 days with BoTx suggest that appearance at the end‐plate of a population of new receptors with a prolonged ion channel opening time similar to that previously described for extrajunctional receptors after denervation and for junctional receptors during development.
Modulation of vagal efferent fibre discharge by mechanoreceptors in the stomach, duodenum and colon of the ferret.
Authors: Grundy D , Salih A A , Scratcherd T
Published: December 2014

1. A single‐fibre‐dissection technique was used to investigate the reflex modulation of vagal efferent fibre discharge by afferent fibres from various parts of the gastrointestinal tract of the urethane‐anaesthetized ferret. 2. All but four of the 168 efferent fibres isolated in this study were spontaneously active. The majority of these had discharge frequencies of less than 6 spikes/sec. 3. All the efferent units received an afferent input from mechanoreceptors in the stomach. Two main types of response to gastric distension were seen: (i) an increase in efferent discharge and (ii) a decrease or complete suppression of efferent discharge. 4. The vagal efferent discharge was also modulated by duodenal and colonic distension, with the major effect being one of inhibition. 5. Bilateral vagotomy completely abolished the response to gastric distension in 68% of the units tested. The response to colonic and duodenal distension, however, was relatively unaffected by vagotomy. Thus the vagus provides the major afferent pathway from the stomach to these vagal efferent fibres, whilst the major input from the duodenum and colon is via a non‐vagal pathway. Both vagal and splanchnic afferents therefore converge on to the vagal nucleus. 6. The destinations of these vagal efferent fibres and their possible functions are discussed.
The release of rat intestinal cholecystokinin after oral trypsin inhibitor measured by bio‐assay.
Authors: Brand S J , Morgan R G
Published: December 2014

The distribution, molecular form and release of cholecystokinin (CCK)‐like activity in extracts of rat small intestine was studied with an in vitro gall‐bladder bio‐assay. In contrast to the reported heterogeneity of CCK‐like immunoreactivity in the intestine, only a single molecular form of CCK‐like activity was detected using the bio‐assay. 2. The CCK‐like activity eluted from Sephadex G50 with a Kav of 0.69, after the triacontriapeptide of cholecystokinin (CCK33) and before cholecystokinin octapeptide 2500, may represent the 22 amino acid peptide of CCK (CCK22). The bio‐assay peak of CCK‐like activity had pancreozymin activity and CCK/gastrin C terminal immunoreactivity. The CCK‐like activity weas readily extracted from the small intestine at neutral pH, but subsequent treatment with cold 0.5 M‐acetic acid extracted further CCK‐like activity of the same molecular form as that recovered under neutral conditions. 3. The bio‐assay detected no CCK‐like activity, nor was pancreozymin‐like activity found in fractions corresponding to CCK33 or CCK8 after Sephadex G50 chromatography of rat intestinal extracts. 4. Oral trypsin inhibitor was a potent stimulus for the release of CCK‐like activity from the upper small intestine of the rat. After oral trypsin inhibitor release, CCK‐like activity was rapidly resynthesized.
Control of canine renin release: macula densa requires prostaglandin synthesis.
Authors: Gerber J G , Nies A S , Olsen R D
Published: December 2014

1. The macula densa mechanism of renin release was functionally isolated in uninephrectomized, anaesthetized dogs by producing renal denervation, beta‐adrenoceptor blockade, and maximum renal vasodilation with an infusion of papaverine into the renal artery. 2. A suprarenal aortic clamp was adjusted to reduce renal perfusion pressure by 50% which resulted in a 90% reduction in urinary sodium excretion and a two to threefold increase in plasma renin activity within 10 min. 3. Indomethacin (8 mg/kg) or meclofenamic acid (10 mg/kg) inhibited the rise plasma renin activity produced by the decrease in renal perfusion pressure in this model, although a comparable decrease in urinary sodium excretion was achieved. 4. We conclude that the macula densa mechanism of renin release is blocked by inhibition of prostaglandin synthesis.