bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in renal haemodynamics and kidney weight during pregnancy in the unanaesthetized rat
Authors: Davison J. M. , Lindheimer M. D.
Published: December 2014

1. Glomerular filtration rate ([3H]inulin clearance) and renal plasma flow (PAH clearance) were measured in unanaesthetized Sprague‐Dawley rats early in pregnancy (8‐10 days) and near term (18‐20 days); the results were compared with studies in virgin litter‐mates. Evidence of kidney growth was sought by analysing renal dry weights as well as [14C]choline incorporation into membrane phospholipids of renal cortical slices.

2. Inulin clearances were similar early in pregnancy (pregnant 2·36 ± 0·12 (
S.E. of mean) vs. non‐pregnant 2·33 ± 0·10 ml./min) but near term values were significantly increased (pregnant 2·80 ± 0·05 vs. non‐pregnant 2·39 ± 0·05 ml./min, P < 0·001). PAH clearances were similar in pregnant and litter‐mate control animals at each stage of the study.

3. Total renal weight increased significantly both early and late in pregnancy, but renal dry weights as well as [14C]choline incorporation were similar in pregnant and non‐pregnant animals both at 8‐10 days gestation and near term.

4. Data confirm our previous findings on renal haemodynamics in anaesthetized rats. Observations that renal dry weight and [14C]choline incorporation into phospholipids are similar in litter‐mate pregnant and control animals suggests that renal enlargement in this species is due to increments in water content and not to accelerated growth.
Mechanical activation in slow and twitch skeletal muscle fibres of the frog.
Authors: Gilly W F , Hui C S
Published: December 2014

1. Slow and twitch muscle fibres of the frog were studied with a two‐micro‐electrode point voltage‐clamp method. Slow fibres were identified in pyriformis and cruralis muscles by their appearance in the light microscope, electrical characteristics, and rate of sarcomere shortening or of tension development. 2. The relation between the amplitude and duration of threshold depolarizing pulses was determined in sartorius twitch and pyriformis slow fibres. Strength‐duration relations for contractile activation are very similar in the two fibre types. 3. The effect of a brief subthreshold pulse on the threshold voltage level decays with a half‐time of 1‐2 msec at 9 degrees C in both slow and twitch fibres. This fast decay, thought to reflect voltage‐dependent deactivation of Ca2+ release following repolarization, is followed by a slower decay of greatly different rates in the two fibre types. the slower components of decay might reflect the rate of background Ca2+ removal by the sarcoplasmic reticulum. 4. Reducing external Ca2+ levels to about about 0.1 microM with 2.5 mM‐EGTA has no effect on the shapes of strength‐duration curves for both slow and twitch fibres, suggesting that activator Ca2+ in both fibre types originates entirely from intracellular stores. 5. "Tonic' contractions were studied using voltage‐clamped short cruralis slow fibres at 20 degrees C. Reducing external Ca2+ to about 0.1 microM had no effect on the steepness of the steady‐state tension‐voltage relation or on the ability of slow fibres to maintain maximal tension during long (200 sec) depolarizations to membrane potentials of up to +50 mV. 6. Functional similarities in activation kinetics of slow and twitch fibres are discussed in relation to the sensing of tubular membrane potential by the sarcoplasmic reticulum, to Ca2+ release from it, and to possible mechanisms involved in these processes. Processes leading to the rapid turning on and off of Ca2+ release in response to changes in tubular membrane potential are probably similar in slow and twitch fibres. However, the apparent lack of voltage‐and time‐dependent inactivation of Ca2+ release in slow fibre points to a major difference in the two types of muscle.
The elimination of redundant preganglionic innervation to hamster sympathetic ganglion cells in early post‐natal life.
Authors: Lichtman J W , Purves D
Published: December 2014

The superior cervical ganglion of adult and neonated hamsters has been studied with intracellular recording. 1. Neurones in adult hamster ganglia are innervated by an average of 6‐7 preganglionic axons. During the first week of post‐natal life, however, these cells are innervated by at least eleven to twelve axons. Ganglion cells in animals 2‐3 weeks old are innervated to an intermediate degree, indicating that these neurones lose a substantial portion of their initial synaptic contacts during the first weeks after birth. 2. The over‐all innervation of the superior cervical ganglion in adult hamsters arises from thoracic segments T1‐T5; no additional segments contribute significantly to the innervation of neonatal ganglia. 3. The average number of segments innervating each adult ganglion cell is 2 . 8 compared to 3 . 7 segments innervating neonatal neurones. Throughout post‐natal development the innervation of individual neurones arises from a contiguous subset of the spinal segments that innervate the ganglion as a whole. 4. We conclude that the elimination of redundant innervatin in early life is not limited to those nerve and muscle cells contacted by a sigle axon in maturity, but also occurs in sympathetic ganglia where adult neurones remain multiply innervated. Moreover, the loss of some synaptic contacts during development refines the selective innervation of individual neurones.
Levels of high‐energy phosphates in crayfish nerve during prolonged repetitive impulse activity.
Authors: Smith D O
Published: December 2014

1. Levels of ATP and arginine phosphate (ArgP) in the mixed nerve bundle of the crayfish walking leg were assayed in fresh tissue and after prolonged repetitive stimulation. 2. In fresh tissue, ATP and ArgP levels were estimated to be about 34 n‐mole/mg protein and 157 n‐mole/mg protein, respectively, corresponding to concentrations of 3 . 0 and 13 . 9 mM. 3. Following 5 min of repetitive stimulation at 30 impulses/sec, the ATP concentration in the nerve increased by 0 . 52 mM; after 10 and 20 min of stimulation, the concentrations returned to values similar to those of fresh tissue. 4. The ArgP concentrations were similar to those of fresh tissue after 5 min of stimulation at 30 impulses/sec but dropped to about 85% of those values after 10 and 20 min of stimulation. 5. Increased K+ in the physiological saline reduced [ATP] following stimulation; decreased Na+ in the saline increased the content of ATP in unstimulated nerves. 6. It is concluded that repetitive action potential activity may be associated with relatively constant and perhaps increased production of ATP.
Parallel secretion of enzymes by the rabbit pancreas.
Authors: Gilliland E L , Glazer G
Published: December 2014

1. The purpose of this study was to determine whether or not the secretion of pancreatic enzymes by the rabbit remained proportional (parallel) after acute stimulation. 2. Hourly samples of pancreatic juice were collected from anaesthetized rabbits, each sample being analysed for volume, protein, amylase, trypsinogen and chymotrypsinogen. 3. Four groups of animals were studied for 2 hr before and 2 hr after stimulation with either saline (controls), methacholine, sincalide (C‐terminal active octa‐peptide of CCK‐PZ) or CCK‐PZ. 4. Despite a rise in protein output of more than 100% in the hour after stimulation in all experimental groups, there was no change in the specific activity (u./mg protein) of the three enzymes monitored, and the ratios of these enzymes to each other remained constant. 5. These results in the in vivo rabbit confirm our previous observation of parallel secretion in the in vitro rabbit pancreas; they are at variance with other studies in the rabbit (predominantly in vitro but also in vivo) which showed non‐parallel secretion after CCK‐PZ stimulation. 6. Our results tend to support the theory of mass transport and parallel secretion of pancreatic enzymes though no firm deductions on intracellular events can be made from juice analysis alone.
Pancreatic acinar cells: electrophysiological evidence for stimulant‐evoked increase in membrane calcium permeability in the mouse.
Authors: Laugier R , Petersen O H
Published: December 2014

1. Membrane potential and resistance were measured in acini from superfused isolated segments of mouse pancreas using two micro‐electrodes inserted into neighbouring acinar cells. Stimulation was carried out exposing segments to 5 x 10(‐7) M‐acetylcholine (ACh) or 3 x 10(‐7) M‐pentagastrin. 2. Sustained stimulation with ACh or pentagastrin caused sustained membrane depolarization and resistance reduction. For periods of stimulation up to 15 min there was no sign of desensitization. 3. Sustaind stimulation during exposure of the tissue to a Ca‐free solution containing EGTA (ethylene glycol bis‐(beta‐aminoethyl ether)‐N,N'‐tetraacetic acid) resulted only in a transient depolarization and resistance reduction. 4. Removal of external Ca during sustained stimulation resulted in immediate hyperpolarization and increase in resistance. Readmission of Ca, still during exposure to ACh or pentagastrin, depolarized the membrane and reduced the resistance. Mn could not mimic this effect of Ca. 5. Removal of external Ca in the absence of stimulation evoked depolarization and membrane resistance reduction. 6. It is concluded that sustained stimulation of pancreatic acinar cells with cholinergic agents or peptides of the cholecystokinin‐gastrin group evokes an increase in the Ca permeability of the plasma membrane. Ca entering the cells from the outside is important in maintaining ion channels in their open state, thus sustaining the stimulant‐evoked depolarization and resistance reduction. The initial stimulant‐evoked membrane response, however, seems to be triggered by release of Ca from internal stores and is independent of external Ca.
The reflex responses of single motor units in human hand muscles following muscle afferent stimulation.
Authors: Buller N P , Garnett R , Stephens J A
Published: December 2014

1. Changes in the probability of firing of motor units active during voluntary muscle contraction have been studied in human first and second dorsal interosseous muscles in response to muscle afferent stimulation. 2. Short latency, possibly monosynaptic, excitatory responses were found in both first and second dorsal interosseous muscles following brief mechanical pulses applied to the belly of first dorsal interosseous. A second longer latency excitatory response followed the first with a mean latency of 25 msec. 3. All units in both muscles showed qualitatively the same responses but units recruited at low levels of voluntary contraction strength were more responsive to muscle afferent input than units recruited at high contraction strengths. The excitatory effect of muscle afferent input within the two motoneurone pools appears to be weighted in the same way as the more complicated input associated with a gradually increasing voluntary contraction. 4. These findings are discussed in relation to the relative importance of short and long latency reflex effects of muscle afferent input in the control of hand movements.
Release of prostaglandins from the isolated frog ventricle and associated changes in endogenous cyclic nucleotide levels.
Authors: Flitney F W , Singh J
Published: December 2014

1. A study has been made of the decline in contractility and some associated metabolic changes which occur in the isolated frog ventricle during the development of hypodynamic depression. 2. The release of two identified prostaglandins (PG), E1 and E2, together with several as yet unknown prostaglandin‐related substances (PRS), accompanies the development of hypodynamic depression. There is a close correlation between the extent to which the isometric twitch is depressed and the quantity of prostaglandin released into the superfusate. 3. Fractionation of extracts of ‘used’ superfusates, using preparative‐scale thin‐layer chromatography, revealed the presence of six major components, four of which (PGE1 and PGE2 and two unidentified components) were found to be cardioactive and potentiated contraction when tested subsequently on hypodynamic preparations. 4. Two agents which influence prostaglandin biosynthesis, arachidonic acid and indomethacin, are found to affect both the rate at which the hypodynamic state develops and the extent to which the ‘steady‐state’ twitch tension is depressed, in a dose‐dependent manner. Indomethacin, a PG‐synthetase inhibitor, accelerates the decay and depresses the final ‘steady‐state’ tension attained, whereas arachidonic acid, the principal precursor for prostaglandin biosynthesis, has the converse effects. 5. Measurements of endogenous 3'5'‐cyclic nucleotide levels reveal a time‐dependent decrease in intracellular adenosine 3'5'‐cyclic monophosphate (3'5'‐cyclic AMP) and a concomitant increase in guanosine 3'5’ cyclic monophosphate (3'5'‐cyclic GMP). The decline in isometric twitch tension is paralleled almost exactly by an equivalent reduction in the ratio 3'5'‐cyclic AMP: 3'5'‐cyclic GMP. 6. Superfusion of isolated ventricles with Ringer solution containing exogenous, lipid‐soluble derivatives of 3'5'‐cyclic AMP and 3'5'‐cyclic GMP affects both the rate of decline of the isometric twitch and the steady‐state tension ultimately reached: thus, 8‐bromo‐3'5'‐cyclic GMP accelerates the decline in contractility and depresses the steady‐state level, whereas dibutyryl 3'5'‐cyclic AMP delays the development of hypodynamic depression, and elevates the final twitch tension. The effects of both 3'5’ cyclic nucleotide derivatives are dose‐dependent. 7. The possible involvement of prostaglandins and 3'5'‐cyclic nucleotides as causal agents in the mechanism of hypodynamic depression is discussed. The biochemical basis for the implied antangonistic effects of 3'5'‐cyclic AMP and 3'5'‐cyclic GMP in regulating ventricular contractility is considered in the following paper (Flitney & Singh, 1980).
Body mass and sex as determining factors in the development of fever in rats.
Authors: Ford D M , Klugman K P
Published: December 2014

1. We have investigated the effect of a single I.P. injection (20 microgram/kg) of bacterial endotoxin on rectal temperature in rats of both sexes and from a wide range of body mass. 2. In male rats, endotoxin produced a monophasic or a biphasic rise in temperature, or a monophasic fall. 3. The extent of the rise in rectal temperature in male rats is related to body mass. There is a statistically significant correlation between body mass and the mean change in temperature measured over 100 min after injection of endotoxin. 4. In the female rats, endotoxin produced a monophasic fall in rectal temperature. The extent of the fall was not significantly correlated with body mass. 5. We suggest that the effect of endotoxin in male rats is determined by the physical relationship between body mass and surface area, because larger animals developed greater fevers. 6. The difference between the effect of endotoxin in male and female rats may have a physiological explanation and may involve differences in susceptibility to cutaneous vasodilation occurring immediately after injection of endotoxin.
Observations on the mechanism for the active extrusion of lithium in mammalian non‐myelinated nerve fibres.
Authors: Ritchie J M , Straub R W
Published: December 2014

1. A study has been made of the O2 consumption, and the corresponding efflux of labelled phosphate, from the non‐myelinated fibres of the desheathed rabbit vagus nerve at 37 degrees C in Locke solutions in which various ions were substituted for Na, and also in the presence of ouabain. 2. Switching from Na‐Locke solution to Li‐Locke solution produced a small transient decrease in the resting O2 consumption (of 14%), which rapidly recovered to its original value. This was accompanied by an initial brief rise followed by a maintained fall in the resting phosphate efflux. 3. In Li‐Locke solution, ouabain (100 microM) produced a fall in the resting O2 consumption of 40%, i.e. similar to that produced in Na‐Locke solution. Any depression of the resting phosphate efflux was absent or small. 4. In choline‐Locke solution, in Tris‐Locke solution, in K‐Locke solution or in sucrose‐Locke solution the resting O2 consumption, which fell by 30‐40%, was insensitive to the addition of ouabain (100 microM). 5. Addition of either Na ions or of Li ions partially restored respiration in choline‐Locke solution, Li being an order of magnitude less effective than Na. 6. In choline‐Locke solution the internal K content was not affected by ouabain. However, if Li (77 mM) was present in the bathing solution ouabain (100 microM) produced a 30% fall in the internal K content. 7. It is concluded that these effects of Li, and their alteration by ouabain, reflect the activity of a mechanism for the active extrusion of Li ions. It is suggested that the mechanism for the active extrusion of Li is the same as that for Na. 8. There also seems to be a site for Li that controls the phosphate efflux and which is half‐maximally activated with external Li concentrations of about 2‐4 mM.
Rate‐limiting step of inhibitory post‐synaptic current decay in Aplysia buccal ganglia.
Authors: Gardner D , Stevens C F
Published: December 2014

1. In neurones BL and BR 3, 6, 8, 9, 10 and 11 of Aplysia buccal ganglia, cholinergic inhibitory post‐synaptic potentials are produced by activity in either of two presynaptic cells. In order to analyse the synaptic conductance change, neurones were voltage‐clamped inhibitory post‐synaptic currents (i.p.s.c.) recorded. 2. The synaptic conductance change rises to an average peak value of 0.65 micromho and decays exponentially with single time constant tau of 19 msec. 3. We have attempted to identify the rate‐limiting step responsible for i.p.s.c. decay from among the following possibilities: (1) acetylcholine (ACh) supply, (2) ACh removal by diffusion, (3) ACh removal by hydrolysis or (4) a slow unbinding or conformational change closing open synaptic current channels. 4. Cooling prolongs tau, with Q10 of 5.2. Cooling and eserine treatment together produce greatly prolonged, exponentially decaying i.p.s.c.s with tau > 150 msec. These results suggest that ACh removal, either by diffusion or hydrolysis, is not the rate‐limiting step. 5. Prolonging synaptic action potential time course with intracellular injection of tetraethylammonium broadens the i.p.s.c. peak but does not affect the decay tail, suggesting that the rate‐limiting step is not ACh release. 6. The spectrum of ACh‐induced current fluctuations is fitted by a double Lorentzian with cut‐off frequencies of 7.8 and 47 Hz. The frequency of the slower component corresponds to the macroscopic i.p.s.c. decay tau. 7. We conclude that a slow conformational change closing open synaptic current channels is likely to determine i.p.s.c. decay. We cannot, however, exclude either delayed diffusion or a late tail of slow ACh release as possibilities.
Time integral of synaptic conductance.
Authors: Gardner D
Published: December 2014

1. Inhibitory post‐synaptic currents (i.p.s.c.s) were recorded under voltage clamp from neurones of Aplysia buccal ganglia. 2. The synaptic charge, Q, transferred by each i.p.s.c. was calculated as the time integral of the synaptic current, approximated by numerical integration. For typical i.p.s.c.s recorded at or near resting potential, Q = ‐100 to ‐500 pC. The majority of the charge is transferred during the interval between the peak and a time one time constant later. 3. In order to characterize an alternative measurement of synaptic efficacy, the slope of the Q vs. membrane potential curve was calculated and defined as the time integral of conductance, b. Values of b ranged from 2.6 to 51 pC/mV, averaging 14 pC/mV. For i.p.s.c.s recorded in thirty‐one cells at room temperature, b was well correlated with Gpeak, the peak synaptic conductance (r = 0.86). 4. In most synapses, the time integral of conductance, which incorporates both amplitude and duration, may be a more revealing measure of synaptic efficacy than peak conductance. 5. Size of synaptic response was determined as a function of temperature, T. While Gpeak decreases with decreasing temperature over the range 9‐22 degrees C, b peaks at 12‐18 degrees C and decreases at higher and lower values of T. The data permit the speculation that lengthening average channel lifetime, and therefore time constant of decay, with decreasing temperature, may have adaptive significance in maintaining synaptic efficacy.
Effects of monocular deprivation in the lateral geniculate nucleus of the cat: an analysis of evoked potentials.
Authors: Mitzdorf U , Neumann G
Published: December 2014

The effects of monocular deprivation on excitatory post‐synaptic activity in the lateral geniculate nucleus and on the afferent activity to the geniculate in the cat were examined. Field potentials elicited by electrical stimulation of the optic nerves were recorded and analysed. This approach revealed that the most severe effects of deprivation originate at the input stage to the lateral geniculate nucleus. 1. The membrane currents resulting from excitatory post‐synaptic activity in the geniculate are at least a factor of two smaller in amplitude in the deprived than in the non‐deprived laminae, indicating a severe reduction of synaptic strength. This effect is equally pronounced for activity mediated by the X‐ and the Y‐system and has to be considered as the major origin of the imbalance of activity from the deprived and non‐deprived eye apparent in cortex. 2. Judged from amplitudes and latencies of compound action potentials in the optic tract, afferent Y‐activity is not affected by deprivation. This indicates that the number of afferents from the retina of the deprived eye to the geniculates is not significantly reduced by deprivation. 3. During several periods of recording conduction block in the afferents from both eyes was observed.
Voltage‐sensitive outward currents in cat motoneurones.
Authors: Barrett E F , Barrett J N , Crill W E
Published: December 2014

1. The soma membrane of cat motoneurones was voltage‐clamped in vivo using intracellular current and voltage electrodes whose tips were separated by at least 5 micrometer. 2. Depolarization activates two separate, non‐interacting K conductance systems whose rates of activation and decay differ by a factor of about 10. These conductances have a similar reversal potential, in the range of ‐6 to ‐21 mV (these and all subsequent voltages are expressed relative to the resting potential). Both conductances show linear ‘instantaneous’ current‐voltage relationships. The steady‐state magnitudes of both conductances increase with increasing depolarization. Neither conductance inactivates substantially during prolonged depolarizations. 3. The faster K conductance is similar to that described for squid axons and frog node. Activation begins at about +30 mV and is more than 90% complete within 5 msec of a depolarizing voltage step to +50 mV. Activation kinetics appear to be nonlinear. This fast K conductance contributes to the fast falling phase of the action potential. Following repolarization, this conductance decays with a time constant of 2‐4 msec. 4. The slower K conductance activates during depolarizations of 10 mV or greater. The activation and decay of this conductance can be described by first‐order exponential functions with time constants ranging from 20 to 50 msec. The slow K conductance underlies the prolonged hyperpolarization that follows motoneurone action potentials. Evidence from other studies suggests that this slow K conductance is regulated by intracellular Ca ions. 5. In addition to the two K conductance systems activated by depolarization, motoneurones exhibit another distinct conductance system that is activated by hyperpolarization. This third system has a reversal potential near the resting potential. Activation of this conductance during a hyperpolarizing voltage step can be fitted by a single exponential function with a time constant of 50‐60 msec over the range ‐20 to ‐50 mV. This hyperpolarization‐activated conductance accounts for some aspects of the anomalous rectification reported in cat motoneurones. 6. When the clamp circuit was turned off and the motoneurones were stimulated to discharge repetitively by depolarizing current steps, the apparent soma threshold voltage increased as the applied current (and discharge frequency) increased. 7. The basic features of the motoneurone action potential were reconstructed by simulations based on voltage clamp measurements of the voltage dependent conductance systems and previous measurements of passive membrane properties. These simulations assumed that the kinetics of the fast Na and K conductance systems in motoneurones can be described by equations of the same form as the Hodgkin‐Huxley equations. These action potential reconstructions indicated that a major portion of the delayed depolarization following the action potential is attributable to capacitative currents from the dendrites...
Effects of metabolic intermediates on sugar and amino acid uptake in rabbit renal tubules and brush border membranes.
Authors: Kippen I , Klinenberg J R , Wright E M
Published: December 2014

1. The effects of tricarboxylic acid cycle intermediates on the renal transport of alpha‐methyl‐D‐glucoside and alpha‐amino‐isobutyric acid were examined using separated renal tubules of the rabbit. 2. The effect of citrate on alpha‐methyl‐D‐glucoside and alpha‐amino‐isobutyric acid uptake was markedly biphasic with maximum stimulation of transport occurring at a citrate concentration of 0.64 mM. Biphasic effects were also apparent for L‐malate, succinate, fumarate, alpha‐ketoglutarate and oxaloacetate. 3. The route of uptake of alpha‐methyl‐D‐glucoside into separated renal tubules is primarily across the brush border (luminal) membrane. 4. Tricarboxylic acid cycle intermediates produced significant stimulation of renal O2 consumption; however, the effects on O2 consumption were not biphasic suggesting that reduced stimulation of transport at high substrate concentration was not caused by a reduction in the supply of metabolic energy. 5. In purified renal cortical brush border membrane vesicles, citrate and alpha‐ketoglutarate inhibited the uptake of alpha‐methyl‐D‐glucoside and alpha‐amino‐isobutyric acid indicating that inhibition of their transport in respiring renal tubules by high concentrations of tricarboxylic acid cycle intermediates occurs via an effect at the membrane level.
Cellular synthesis and axonal transport of gamma‐aminobutyric acid in a photoreceptor cell of the barnacle.
Authors: Koike H , Tsuda K
Published: December 2014

1. [3H]glutamate or [3H]gamma‐aminobutyric acid (GABA) was injected into the photoreceptor cell of the lateral ocellus of Balanus eburneus, in order to study the transmitter substance of the cell. 2. The photoreceptor cell synthesized [3H]GABA from injected [3H]glutamate. 3. The newly formed [3H]GABA moved inside the photoreceptor axon towards the axon terminal with a velocity of about 0.9 mm/hr. Injected [3H]GABA moved at 0.9 mm/hr and also at 0.4 mm/hr. 4. Axonally transported [3H]GABA reached the axon terminal within several hours following the injection. It did not accumulate at the terminal, but gradually disappeared. 5. Light‐microscope and electron‐microscope autoradiography following the injection of [3H]GABA revealed that [3H]‐reacted silver grains were present in a certain type of axon terminal. The terminal thus identified as that of a photoreceptor cell contains many clear, polymorphic synaptic vesicles about 300‐500 A in diameter, some dense‐cored vesicles 700‐1300 A in diameter, and glycogen granules. The terminal forms many synapses, and each synapse has a synaptic dense body. The terminal always faces two post‐synaptic elements at the synapse, forming a triad with a gap distance of about 160‐200 A. 6. A GABA analogue, [3H]di‐aminobutyric acid, was selectively taken up into the terminals previously identified as those of photoreceptors. 7. These results support the notion that the transmitter substance of the photoreceptor cell of the barnacle is GABA.
Mechanisms of gastric acid secretion after pylorus and oesophagus ligation in the rat.
Authors: Håkanson R , Hedenbro J , Liedberg G , Sundler F , Vallgren S
Published: December 2014

1. The effect of vagotomy on gastric acid secretion was studied in chronic gastric fistula rats at various times after denervation. In these rats basal and pentagastrin‐induced acid output was permanently reduced. Thus, the magnitude of the acid response to pentagastrin in the conscious fistula rat is dependent upon an intact vagus. 2. The acid response to pylorus ligation in vagally intact rats was unaffected by drainage of the stomach and therefore not caused by distension. Bilateral vagotomy, performed simultaneously with the ligation, completely abolished acid secretion, while unilateral vagotomy reduced the acid output by half. Hence, in innervated rats, an intact vagal impulse flow appears to be essential for the acid response to pylorus ligation. When the pylorus ligation was performed 2‐8 weeks after truncal vagotomy, the acid output showed a progressive return towards pre‐denervation values. In the denervated rats the acid response to pylorus ligation was blocked by drainage of the stomach and therefore probably caused by distension, a mechanism which is independent of the vagal impulse flow. 3. The response to pylorus ligation in innervated rats was blocked by atropine and chlorisondamine but not by metiamide. In the denervated rats, the response to pylorus ligation was blocked by all three drugs. 4. Following ligation of both the pylorus and the oesophagus the acid response was poor. With drainage of the oesophagus the acid response was much enhanced, suggesting that oesophageal distension inhibits acid secretion. In the vagotomized rat the poor acid response to oesophageal + pyloric ligation could not be overcome by drainage of the oesophagus. In the innervated rat gastric distension could overcome the inhibition induced by oesophageal ligation. Also in chronically, but not in acutely vagotomized rats, gastric distension brought about a good acid response. Conceivably, gastric reflex mechanisms can activate acid secretion through vagal and/or intramural pathways. Both in innervated and denervated rats the response to gastric distension was inhibited by atropine, chlorisondamine and metiamide. 5. The results suggest that in the innervated rat vago‐vagal reflexes are important for the gastric hypersecretion following ligation of the pylorus, and for the acid response to gastric distension following ligation of the pylorus and oesophagus. In the chronically vagotomized rat local intramural reflexes elicited by gastric distension are responsible for the acid response.
Re‐evaluation of the ‘contralateral’ effects of sodium and potassium on sodium transport through toad skin.
Authors: Isaacson L C
Published: December 2014

1. Changes in the concentration of Na in the outer bathing solution, [Na]o, or of K in the inner bathing solution, [K]i, alter the electrical responses of the isolated toad skin to changes in ionic concentrations in the contralateral solutions. The mechanism(s) of these apparently contralateral effects remain(s) unknown. 2. The phenomenon has been investigated here in the isolated abdominal skin of Xenopus laevis. Each skin was exposed to multiple levels of [Na]o and [K]i, of between 5 and 112 m‐mole 1.(‐1) The p.d. and short‐circuit current (s.c.c.) responses were analysed both in terms of kinetics and in terms of changes in the equivalent electrical circuit of the Na transport mechanism. 3. Kinetic analysis revealed that the relationship between [Na]o and s.c.c., at any level of [K]i, followed Michaelis‐Menten kinetics. Increasing levels of [K]i reduced the s.c.c. response to changes in [Na]o, conforming with the algebraic descriptions of ‘slope‐parabolic competitive inhibition'. High levels of [Na]o (of 60‐112 m‐mole 1.(‐1)) occasionally reduced the s.c.c. in a manner reminiscent of ‘substrate inhibition'; this effect was independent of the level of [K]i. At high [K]i and low [Na]o, s.c.c was again often less than that predicted by Michaelis‐Menten kinetics. 4. In terms of the equivalent electrical circuit, increasing [Na]o produced a fall in Rseries; in the presence of ‘substrate inhibition', however, Rseries rose on increasing [Na]o; in either case, ENa and Rsh remained unchanged. Increasing [K]i lowered both ENa and Rsh; Rseries fell with modest increments in [K]i, but increased at higher levels of [K]i. 5. These results can be interpreted without invoking unknown contralateral effects. Thus the changes in s.c.c., as induced by changes in [Na]o or [K]i, are consistent with homolaterally mediated effects on an enzymic mechanism of transepithelial Na transport; the changes in p.d., given the [K]i‐dependent changes in Rsh, are similarly explicable.
Relationship between hydrogen ion concentration and flow of gastric juice during inhibition of gastric secretion in the cat.
Authors: Hirst B H , Labib L A , Reed J D , Stephen J G
Published: December 2014

1. The normal relationship between the [H+] and rate of flow of gastric juice was determined in conscious cats prepared with cannulated gastric fistulae. Gastric secretion was monitored during stimulation with pentagastrin, insulin and histamine. 2. [H+] rose asymptotically with the flow of gastric juice. This relationship was quantified by applying the data to the integrated form of the Fick equation for diffusion, a graphical plot of log [H+] vs. 1/flow. The calculated relationships were similar for gastric secretion stimulated by pentagastrin, insulin and histamine, and were used to define the normal relationship between gastric [H+] and flow. 3. Significant inhibition of pentagastrin‐stimulated gastric secretion with the histamine H2‐receptor antagonists, metiamide and cimetidine, atropine or somatostatin did not alter the normal relationship between [H+] and flow; the [H+] observed fell within the normal range observed at that flow rate in the presence of pentagastrin alone. Similarly, inhibition of insulin‐stimulated secretion with metiamide, did not alter the normal relationship between [H+] and flow of gastric juice. 4. These data provide evidence that histamine H2‐receptor antagonists, atropine and somatostatin all act to reduce the primary rate of acid secretion and do not influence the [H+] per se, either by interfering with back‐diffusion of H+, or by changing the proportions of a non‐parietal component of gastric secretion added to the parietal H+ component.
The contribution of potassium accumulation to outward currents in frog atrium.
Authors: Brown H , DiFrancesco D , Noble D , Noble S
Published: December 2014

1. Voltage‐clamp experiments on frog atrial muscle were designed to distinguish effects due to K accumulation in extracellular spaces from those due to activation of K conductance mechanisms in the membrane. 2. The set of instantaneous current‐voltage relations obtained at various external K concentrations following depolarization to about ‐10 mV for several seconds was found to be quite different from that obtained before the depolarization. Hence the process of increasing the extracellular K concentration cannot account for all the time‐dependent changes in outward current during depolarization. 3. Although the instantaneous current‐voltage relations obtained at different values of external K concentration before prolonged depolarization show the cross‐over phenomenon (Noble, 1965), those obtained at the end of the depolarization did not show this feature. It is concluded that the current‐voltage relations for the channels conducting the time‐dependent K current do not show cross‐over. 4. These results were used to construct a model involving both K activation and K accumulation. This model successfully reproduces the appearance of a very slow component in outward current decay tails which, when subtracted by semi‐exponential curve‐stripping leaves a component with the real time constant of conductance change. The model does not however reproduce the appearance of a fast decaying component without adding a second conductance mechanism, or assuming non‐exponential decay of a single conductance mechanism. 5. It is therefore suggested that i chi, fast is not a perturbation of i chi, slow or of iK1 by the process of K accumulation. This conclusion is reinforced by the results of experiments showing that the relative magnitude of i chi, fast is not greatly changed by substantially increasing the external K concentration in order to reduce the proportionate effect of K accumulation on the K concentration.
Calcium efflux from Myxicola giant axons: effects of extracellular calcium and intracellular EGTA
Authors: Abercrombie Ronald F. , Sjodin Raymond A.
Published: December 2014

1. 45Ca efflux was examined in Myxicola giant axons injected with 45CaCl2 or various concentrations of 45Ca/EGTA buffers. In axons injected with 45CaCl2, the Cao‐dependent Ca efflux in 1 m
M‐Cao was about half that in 10 m
M‐Cao.

2. Axons injected with 45Ca/EGTA buffers consistently showed two types of results: in one type (B type), K½ for Cao activation was less than 1 m
M‐Cao. In the other type of result (A type), there was an additional Ca activation of Ca efflux. This additional efflux exhibited a linear dependence on Cao when the Cao values ranged between 1 m
M‐Cao and 10 m
M‐Cao.

3. The B‐type result remained unchanged when the injected Ca/EGTA concentrations were varied. The A type result, however, changed as a function of Ca/EGTAi in the following way: (a) at a constant ratio of Ca/EGTAi = 8/10, the megnitude of the linear component of the Cao‐activated Ca efflux was reduced by increasing the intracellular concentration of (Ca/EGTA) buffer; and (b) at a ratio Ca/EGTA = 1/10, the linear component of the Cao‐activated Ca efflux appeared to acquire a slower time response to changes in Cao.

4. Nao acts synergistically with Cao to produce the linear component of the Ca‐activated Ca efflux seen in the A type result.

5. With axons containing 45Ca/EGTA buffers (total EGTAi = 1 m
M), changing the Ca/EGTA ratio by repetitive injections of CaCl2 did not increase 45Ca efflux by as great an amount as would be predicted if Cai2+ were controlled by the EGTA buffer alone.

6. Cai2+ (measured by arsenazo III absorbance) is influenced by Cao irrespective of the presence of 1 m
M‐EGTA buffer inside the axon. There was a variability in the sensitivity of Cai to Cao that resembled the variability found in 45Ca efflux measurements.

7. 45Ca influx is not affected by the concentration of Ca/EGTA buffer injected into the cell and appears to be only slightly, if at all, affected by increasing ionized Cai2+ from 0·016 to 0·56 μ
M in the injection medium.

8. These results are consistent with the interpretation that the Ca efflux system of the Myxicola giant axon, or something controlling it, can exist in more than one state. One of these states, which exhibited a large Cao‐dependent Ca efflux, may represent axons in which Cai is poorly controlled by the natural endogenous Ca buffers.
Enhancement of synaptic function in cat motoneurones during peripheral sensory regeneration
Authors: Gallego R. , Kuno M. , Núñez R. , Snider W. D.
Published: December 2014

1. Monosynaptic excitatory post‐synaptic potentials (e.p.s.p.s) were recorded from medial (m.g.) and lateral gastrocnemius (l.g.) motoneurones in the cat 2‐30 weeks after crushing the m.g. nerve.

2. The mean amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were initially depressed (2‐3 weeks after injury) and subsequently reached levels greater than normal for a period (8‐12 weeks) before slowly declining to about 70% of the normal values (by week 30).

3. Monosynaptic e.p.s.p.s evoked in m.g. motoneurones from the intact l.g. nerve showed neither initial depression nor subsequent alterations following crush of the m.g. nerve.

4. By the eighth week after nerve crush, about 70% of Group I and Group II sensory fibres in the m.g. nerve responded to muscle stretch, about 15% had regenerated into the muscle but did not respond to muscle stretch, and the remainder failed to regenerate across the neuroma formed by the nerve crush.

5. Homonymous, monosynaptic e.p.s.p.s produced by impulses in single sensory fibres responding to stretch of the m.g. muscle were recorded 8 weeks after crush of the m.g. nerve. Their amplitude distribution was indistinguishable from that obtained in normal, unoperated cats. Thus, there was no evidence that functionally reinnervated sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s observed during peripheral regeneration.

6. When the m.g. nerve had been sectioned and prevented from regenerating into the muscle for 8 weeks, the amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were significantly smaller than those observed in control animals. Thus, there was no evidence that non‐regenerating sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s after nerve crush.

7. It is suggested that the sensory fibres responsible for abnormally large composite e.p.s.p.s following nerve crush are those that regenerate into the muscle but do not achieve functional reinnervation. This possibility is discussed in relation to the increase in central synaptic efficacy observed after prolonged disuse of the sensory pathway.
End‐plate channel opening and the kinetics of quinacrine (mepacrine) block.
Authors: Adams P R , Feltz A
Published: December 2014

1. The effects of quinacrine on the relaxation of the agonist‐induced currents in response to a voltage step were investigated at voltage clamped frog end‐plates. A fast perfusion technique allowed the application of known concentrations of the agonist acetylcholine (ACh) or carbachol to end‐plate viewed with Nomarski optics. 2. In the presence of quinacrine, and in response to a hyperpolarizing voltage jump, an agonist‐induced current shows a fast initial relaxational increase and then relaxes slowly back to a new equilibrium level. 3. The slow relaxation can be described by a single exponential with a time constant tau s . tau s gets smaller at increasing quinacrine concentrations (0‐‐2 microM) and the decay rate constant, 1/tau s, increases linearly with quinacrine concentration. Increasing agonist concentration reduces tau s, in a manner dependent on the nature of the agonist. Tau s is markedly lengthened at more hyperpolarized potential, but this voltage effect gets less at higher concentrations of agonist. 4. These data suggest a slow voltage dependent blockage of open end‐plate channels by quinacrine. The binding rate constant of quinacrine is estimated as 10(8) M‐1 s‐1, and the voltage dependent, backward rate constant, as 5 s‐1 at ‐60 mV and 1 s‐1 at ‐140 mV. These values are in fair agreement with those obtained from the analysis presented in the preceding paper. 5. The agonist concentration dependence of the blocking kinetics is compatible with a simple model for channel opening. In this model, independent sequential binding of two agonist molecules leads to an isomerization of the receptor. The intrinsic binding constant of ACh is estimated to be around 20 microM, and for carbachol around 200 microM. Distinct isomerization constants could lead to a maximal activation of 70% of the available channels by ACh, and only 40% by carbachol. 6. An example of a possible interaction in between quinacrine block and desensitization is shown. At the break of an hyperpolarizing jump which has increased quinacrine blockade, a transient increase in the synaptic current is observed with apparently a temporary reduction of the desensitization.
Effect of glucagon on digestive enzyme synthesis, transport and secretion in mouse pancreatic acinar cells.
Authors: Singh M
Published: December 2014

1. Effect of glucagon on amylase secretion and lactic dehydrogenase (LDH) release from functionally intact dissociated pancreatic acinar cells and acini was studied. 2. In dissociated rat pancreatic acinar cells, the rate of amylase secretion was increased by 70% with bethanechol (maximally effective concentration, 10(‐4) M) and 125% with A23187 (10(‐5) M), but the response to cholecystokinin‐pancreozymin (CCK‐PZ) was inconsistent. In dissociated cells from mouse pancreas, the increases amounted to 78% with bethanechol (10(‐4) M), 134% with A23187 (10(‐5) M) and 82% with CCK‐PZ (maximally effective concentration, 0 . 01 u. ml.‐1). Glucagon in concentrations ranging from 10(‐7) to 10(‐4) M increased amylase secretion by 3, 26, 67 and 80%, whereas secretin (10(‐8)‐‐10(‐5) M) increased amylase secretion by 8, 39, 88 and 138%. LDH release was increased with A23187 in concentrations greater than 10(‐6) M. 3. CCK‐PZ, bethanechol and A23187 used in maximal concentrations potentiated the effect of a submaximal dose of glucagon whereas secretin did not have an additive or a potentiating effect. 4. Pancreatic acini were approximately 3 times more responsive to secretagogues than cells. The dose‐‐response curves to bethanechol, glucagon and CCK‐PZ for increase in amylase secretion were similar. LDH release was not increased by these agents. Cytochalasin B (5 microgram ml.‐1) which is known to disrupt the integrity of luminal membrane inhibited the amylase secretion stimulated by glucagon, bethanechol and CCK‐PZ. 5. Glucagon inhibited incorporation of a mixture of fifteen 14C‐labelled amino acids (algal profile, Schwarz Mann) into perchloric acid precipitable proteins in dissociated mouse pancreatic acini within 30 min. 6. In ‘pulse‐chase’ experiments, glucagon decreased the specific activity of zymogen granules isolated by differential centrifugation, from pancreatic lobules (120 min) and increased the specific activity of radiolabelled proteins in the medium (60 and 120 min). 7. It is concluded that glucagon increased digestive enzyme secretion from pancreatic acinar cells by a direct action (in contrast to its reported indirect effect in vivo) and decreased digestive enzyme synthesis. The data on transport and secretion do not support the suggested role of glucagon as an inhibitor in the intact animal.
Insulin secretion in sheep exposed to cold.
Authors: Sasaki Y , Takahashi H
Published: December 2014

1. Cold exposure caused a marked decrease in insulin response to intravenous injection of glucose, with a sharply declining response over the first 4 days of cold exposure followed by a constant low response up to 13 days of the experimental cold period. 2. The glucose‐induced insulin response was unaffected by concomitant infusion of phentolamine in the warm environment. In contrast, the low response of insulin secretion to glucose during cold exposure was so augmented by concomitant infusion of phentolamine as to exceed the response observed in the warm environment. 3. Intravenous infusion of phentolamine caused an increase in the concentration of plasma insulin in the cold but not in the warm environment. 4. Adrenaline completely abolished the insulin response to glucose in the warm environment. 5. Exposure to cold environment brought about an increase in urinary excretion of adrenaline and noradrenaline and in heart rate, but rectal temperature was unchanged. 6. It is concluded that cold exposure insufficient to cause hypothermia produces a marked decrease in insulin secretion by the pancreas of sheep, mediated through adrenergic alpha‐receptors stimulated by augmented sympatho‐adrenomedullary activity.