bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control.
Authors: Rojas E , Taylor R E
Published: December 2014

1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca‐28Mg or 45Ca‐22Na. Resting influxes and extra influxes during voltage‐clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM‐CaCl2 the resting influx of calcium was 0‐016 +/‐ 0‐007 p‐mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84‐7 mM‐CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM‐CaCl2 was 0‐017 +/‐ 0‐013 p‐mole/cm2 sec for Loligo axons. 3. With 55 mM‐MgCl2 outside the average resting magnesium influx was 0‐124 +/‐ 0‐080 p‐mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0‐105 +/‐ 0‐046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM‐CaCl2, given as 0‐094 p‐mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM‐NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27‐7 +/‐ 4‐5 to 25‐1 +/‐ 6‐2 p‐mole/cm2 sec and for Loligo fibres in 460 mM‐NaCl from 50‐5 +/‐ 4 to 20 +/‐ 8 p‐mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before the sodium or is involved in the activation of the sodium system. 7. These measurements confirm for Loligo, as previously shown for Dosidicus axons, that the magnitude and time course of the sodium entry during a depolarizing pulse deduced from electrical measurements is the same as that measured with 22Na. 8. Using 28Mg, or mixtures of 45Ca and 28Mg, we observed a single phase of magnesium entry which was insensitive to external tetrodotoxin or internal tetraethyl ammonium. The magnitude of the magnesium influx was considerably greater than the calcium extra entry and large enough to have been detected in the experiments of Meves & Vogel (1973) if it represented current. 9. We suggest the possibility that the calcium and magnesium extra influxes, after external treatment with tetrodotoxin, during a depolarizing pulse, do not contribute to the measured current.
Extracellular potassium activity, intracellular and extracellular potential responses in the spinal cord.
Authors: Lothman E W , Somjen G G
Published: December 2014

1. Microcapillary electrode assemblies of two or three channels were used to record extracellular and intracellular potentials together with the extracellular activity of potassium ions, from essentially single locations within the substance of the decapitate spinal cord of cats. A liquid ion exchanger filled the tip of the potassium sensing microprobe. Activity was evoked by electrical stimulation of afferent peripheral nerves (ventral roots were cut). 2. Within the substance of the spinal grey matter increments of extracellular potassium activity evoked by repetitive afferent volleys were precisely correlated with magnitudes of sustained shifts of extracellular electric potential. Raising [K+]o from 3 to 4 mM was associated with a negative shift of potential of 2‐5 +/‐ 0‐5 mV, regardless of the position of the electrode in the tissue, and regardless of treatment by convulsant or depressant drugs. 3. The spatial distribution of the responses of potassium activity was mapped by the spatial distribution of the negative sustained potential shifts. 4. Depolarization shifts of potential recorded from within neuroglia cells ran parallel with changes of extracellular potassium potential. Even though the magnitude of extracellular sustained potential shifts was precisely correlated with the responses of both extracellular potassium and intracellular glial potentials, the trajectory of sustained potential shifts did not exactly mirror the two other variables. Onset and offset of sustained potential shifts were faster than those of glial potentials or of extracellular potassium. 5. The responses of the true transmembrane potential (intracellular less extracellular potential shifts) of neuroglia cells in the spinal grey matter can fully be described by the Nernst equation. 6. Membrane potentials of neurones, potentials recorded from dorsal root filaments, or from white matter, appeared unrelated to the activity of potassium ions in extracellular fluid. 7. The results are compatible with the suggestions that changes of the membrane potential of spinal neuroglia cells are fully determined by the change of the activity of extracellular potassium, and that glia cells supply most of the current which generates sustained shifts of the extracellular potential of spinal grey matter. The results are hard to reconcile with suggestions that under conditions of moderate excitation (i.e. in the absence of convulsive neuronal activity) changes of extracellular potassium would significantly influence the membrane potential of spinal neurones, or of primary afferent nerve fibres.
The actions of volatile anaesthetics on synaptic transmission in the dentate gyrus.
Authors: Richards C D , White A E
Published: December 2014

1. The action of four volatile anaesthetics on the evoked synaptic potentials of in vitro preparations of the hippocampus were examined. 2. All four anaesthetics (ether, halothane, methoxyflurane and trichloroethylene) depressed the synaptic transmission between the perforant path and the granule cells at concentrations lower than those required to maintain anaesthesia in intact animals. 3. The population excitatory post‐synaptic potential (e.p.s.p.) and massed discharge of the cortical cells (population spike) were depressed at concentrations of the anaesthetics lower than those required to depress the compound action potential of the perforant path nerve fibres. None of the anaesthetics studied increased the threshold depolarization required for granule cell discharge. Furthermore, frequency potentiation of the evoked cortical e.p.s.p.s was not impaired by any of the anaesthetics studied. 4. It is concluded that all four anaesthetics depress synaptic transmission in the dentate gyrus either by reducing the amount of transmitter released from each nerve terminal in response to an afferent volley, or by decreasing the sensitivity of the post‐synaptic membrane to released transmitted or by both effects together.
Inhibition of thermal tachypnoea in rabbits following exposure to cold and water deprivation.
Authors: Maskrey M , Nicol S C
Published: December 2014

1. Rabbits were clipped and exposed in turn to four environmental conditions: control (C), cold exposure (CE), water deprivation (WD) and water deprivation and cold exposure together (WD/CE). 2. Following each type of treatment, the rabbits were exposed for 1 hr to an ambient temperature (Ta) of 35 degrees C. During this time, respiratory frequency (RF), rectal temperature (Tre), activity and oxygen consumption (V02) were recorded. 3. It was found that under both cold exposure and water deprivation conditions, the mean respiratory frequency during the first 30 min of heat exposure was reduced when compared with controls. This was associated with a delay in the onset of thermal tachypnoea. Under conditions of water deprivation and cold exposure together, the mean respiratory frequency was further reduced and the length of the delay was increased. 4. Previous cold exposure led to an increase in the V02 measured at 35 degrees C, whereas the V02, after water deprivation and water deprivation and cold exposure together were not significantly different from the control. 5. Neither the initial Tre nor the change in the Tre during the course of the heat exposure were significantly different from the controls under any of the experimental conditions. 6. It is concluded that both water deprivation and previous cold exposure cause a block to panting in the heat and that the blocking mechanisms involved are closely interrelated. It is also concluded that neither the metabolic rate of the animal nor its initial or final Tre are important factors in determing the degree to which thermal tachypnoea is inhibited.
Discrete and discontinuous action of brown widow spider venom on the presynaptic nerve terminals of frog muscle.
Authors: Castillo J D , Pumplin D W
Published: December 2014

1. A study was made of the effects of the venom of the brown widow spider (Latrodectus geometricus) on end‐plates of the frog sartorius muscle. 2. The increase in the frequency of the minature end‐plate potentials (m.e.p.p.s), elicited by the venom in normal‐"Ca2+" Ringer solution, occurs in discrete volleys having a sharp onset and end. The frequency of the m.e.p.p.s is high (up to 300 sec‐1) and relatively constant during the volley. 3. The volleys recur at intervals during a period from 5 to 10 min after addition of the venom until the onset of electrical silence, up to 4 hr later. The activity occurs in groups containing volleys of loing and short duration. 4. Simultaneous intracellular and extracellular recording from single end‐plates indicates that the volleys originate at highly localized areas of the nerve terminals. The high‐frequency release of m.e.p.p.s in hypertonic sol solutions, which was studied for comparison purposes, occurs randomly over the entire end‐plate. Volleys originating simultaneously at different sites are often superimposed in the intracellular recordings. 5. In high‐"Ca2+" Ringer solution, the initial frequency of the m.e.p.p.s in a volley is comparatively higher. However, the frequency drops to one half its value in a few seconds. The volley then terminates or else the frequency of m.e.p.p.s remains high for some time and the volley has no sharp end. Activity occurs in groups containing both long and short volleys. Many more short (less than 5 sec) and long (greater than 30 sec) volleys occur in high‐"Ca2+" solution than in normal‐"Ca2+" solutions. 6. In low‐"Ca2+", high‐"Mg2+" Ringer solution, the volleys of m.e.p.p.s are fewer in number and much longer in duration. Intra‐ and extra‐cellular recording of uninterruped activity during long periods suggests that in this solution the m.e.p.p.s originate diffusely rather than at discrete areas of the nerve terminals. 7. Implications of the above data on possible modes of action of the venom are discussed.
An alkyl etherase in rat liver.
Authors: Peters R A , Shorthouse M
Published: December 2014

1. Diethyl ether, which is known to be partly metabolized in vivo, has been found to show an O2 uptake with the rat liver microsomal membranes; a similar reaction is given with other short chain aliphatic ethers, isoproply and n‐butyl ether. 2. The "etherase" reaction is optimal at pH 7.2‐7.4 and is not accompanied by an increased formation of malondialdehyde. 3. When CoA is added to the microsomes together with a source of oxaloacetate and the consensing enzyme synthase, the etherase present forms citrate from diethyl ether, indicating an acetylation of CoA, which then enters the citric acid cycle. 4. Similarly to 3, fluorocitrate is formed from methyl fluoroethyl ether. 5. Differing from plasmalogens, a tetrahydropteridine does not have to be added as a co‐factor.
Two mechanisms for the meperidine block of action potential production in frog's skeletal muscle; non‐specific and opiate drug receptor mediated blockade.
Authors: Frank G B
Published: December 2014

The effects of meperidine and naloxone, and their interaction effects on action potential production in frog's sartorius muscle fibres, were studied with intracellular micro‐electrode techniques. 1. Meperidine, a narcotic analgesic drug, depressed the rate of rise, the rate of fall and the amplitude of the action potentials. 2. At a meperidine concentration of 0‐35 mM, the depression in the action potential maximum rate of rise followed a diphasic time course. At first there was a rapid reduction in the maximum rate of rise which was levelling off at about 60% of control 60‐90 min after drug application. This was followed by the second phase during which there was an initial rapid decrease in the maximum rate of rise and all surface fibres were inexcitable by 180 min. 3. The addition of naloxone, a narcotic antagonist, in low concentrations (3 X 10(‐5) to 3 X 10(‐4) mM) at 70‐90 min blocked the second phase of the meperidine‐induced depression. 4. With lower concentrations of meperidine (0‐18 and 0‐07 mM) the depression usually developed more slowly (up to 6 hr with the latter dose) and the addition of low naloxone concentrations partially antagonized the effects of meperidine. However, under no conditions was it possible to completely antagonize the effects of meperidine by the addition of naloxone. 5. A linear relation was found between action potential amplitude and the action potential maximum rate of fall. 6. Meperidine caused a shift in the relation of rate of fall against amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductivity (gK) associated with the falling phase of the action potential. 7. When low naloxone concentrations antagonized the effects of meperidine on the rate of rise and restored action potential amplitudes to control levels, the effect of meperidine on the maximum rate of fall was not antagonized. 8. Larger naloxone concentrations (1‐5 X 10(‐2) mM or more) depressed the action potential rate of rise but did not alter the relation between action potential amplitude and the maximum rate of fall. 9. It is proposed that meperidine blocks action potential production by two mechanisms: (i) a non‐specific mechanism in which the increases in both gNa and gK ar depressed and (ii) an opiate drug receptor mediated mechanism causing a specific depression of gNa. 10. The impression gained from the results is that there are opiate drug receptors located on the inner surface of the muscle membrane associated with the 'sodium channels' and that drug activation of these receptors by either meperidine or high naloxone concentrations interferes with the opening of the 'sodium channels' normally produced by membrane depolarization.
Further studies on the control of ACh sensitivity by muscle activity in the rat.
Authors: Lomo T , Westgaard R H
Published: December 2014

1. Denervated rat soleus muscles were stimulated directly through chronically implanted electrodes and the influence of different amounts and patterns of stimuli on the acetylcholine (ACh) sensitivity of the muscle was studied. The number of stimuli was varied by giving similar trains of stimuli (10 Hz for 10 sec) at different intervals (0 to 12 hr). The pattern of stimulation was varied by giving different trains of stimuli (100 Hz for 1 sec, 10 Hz for 10 sec and 1 Hz continuously) as the same average frequency of stimulation (1 Hz). 2. Stimulation usually started 5 days after the denervation when ACh hypersensitivity was fully developed. Most stimulation procedures reduced extrajunctional ACh sensitivity to normal or below normal values within 5‐21 days, and these levels were maintained on prolonged stimulation. 3. The rate at which ACh hypersensitivity disappeared increased with increasing amount and frequency of stimulation. However, as few as 100 stimuli given every 5‐5 hr for 3 weeks caused a tenfold reduction of sensitivity. 4. The stimulation had little or no effect on the ACh sensitivity at the end plate. Along the rest of the fibre the sensitivity was reduced at approximately the same rate except near the tendons where it appeared to fall more slowly in some fibres. 5. The stimulation restored the resting membrane potential of the denervated fibres to normal.
The mechanisms of action of chloromercuribenzene‐p‐sulphonic acid as insulin secretagogue: fluxes of calcium, sodium and rubidium in islets exposed to mercurial and a membrane‐active antagonist.
Authors: Hellman B , Sehlin J , Söderberg M , Täljedal I B
Published: December 2014

Chloromercuribenzene‐p‐sulphonic acid (CMBS) is known to markedly stimulate insulin release and to enhance formation of adenosine 3':5'‐cyclic monophosphate (cyclic AMP) and monovalent cation permeability in the pancreatic islet cells. The effects on insulin release and cyclic AMP can be inhibited with 4‐acetamido‐4'‐isothiocyanostilbene‐2,2'‐disulphonic acid (SITS). To elucidate the role of cationic fluxes in CMBS‐ induced insulin release, uptake of 22Na+ and 45Ca2+ as well as efflux of 86Rb+ were studied in islets exposed to 0‐1 mM CMBS or 1‐0 mM SITS or both. 2. The enhancing effect of CMBS on Na+ permeability, and probably also that on Rb+ permeability, was inhibited by SITS. 3. CMBS stimulated the rate of 45Ca2+ uptakes when the islets were incubated in a poly‐anionic bicarbonate buffer but not when they were incubated in Tris buffer containing only Cl‐ as anion. In bicarbonate buffer, the enhancement of 45Ca2+ flux was observed both with the lanthanum method for measuring intracellular 45Ca2+ uptake and with a method estimating the total islet uptake. SITS had no significant effect on the CMBS‐induced 45Ca2+ uptake. 4. Chromatography on Sephadex G‐15 did not reveal any significant chemical interaction between 0‐1 mM CMBS and 1 mM SITS. 5. The following hypothesis for the recognition of CMBS as insulin secretagogue is suggested: by increasing Na+ permeability more than K+ permeability, CMBS depolarizes the beta‐cell, leading to initiation of insulin release by an ionic mechanism which may or may not involve a change in transmembrane Ca2+ fluxes. The marked intensity of the secretory response is due to the fact that CMBS also enhances cyclic AMP formation, potentiating the effect of the ionic mechanisms on the insulin discharge apparatus.
The effects of fusimotor stimulation during small amplitude stretching on the frequency‐response of the primary ending of the mammalian muscle spindle.
Authors: Goodwin G M , Hulliger M , Matthews P B
Published: December 2014

Single fusimotor fibres to the de‐efferented soleus of the anaesthetized cat were stimulated repetitively while recording the response of single primary afferents to small amplitude sinusoidal stretching at frequencies of 0‐5‐‐500 HZ. The response of the ending was determined by averaging its firing for many cycles to construct a 'cycle histogram'. When small enough, the stretching modulated the firing sinusoidally; as the frequency increased the requisite amplitude fell to a fraction of a micron. The amplitude of the modulation (in impulses/sec) divided by be amplitude of stretchin (in mm) gave the sensitivity of the ending for the particular frequency in question. 2. The passive frequency‐‐response curve obtained in the absence of fusimotor stimulation agreed with those obtained before...
Absorption of amino acids and peptides from a complex mixture in the isolated small intestine of the rat.
Authors: Gardner M L
Published: December 2014

Amino acid and peptide absorption from a pancreatic digest of casein at low concentration by an isolated preparation of perfused rat small intestine has been measured. 2. The rate of absorption of each amino acid (free or peptide‐bound) is closely proportional to its concentration in the perfusate; this implies a constant Vmax/Km ration for all amino acids in the mixture. 3. There is a high correlation between the compositions of luminal perfusate and secretion into the tissue fluid (apart from the content of glutamic and aspartic acids and alanine). 4. The concentrations of each free amino acid are, on average, 9 times as great in secretion as in lumen; the total peptide‐N concentration in secretion is approximately 4 times that in the lumen. 5. The rate of absorption of each free amino acid is highly negatively dependent on the rate of absorption of that amino acid in peptide‐bound form, in addition to being positively dependent on the perfusate concentration of free amino acid. 6. While peptide‐bound proline appears to be well absorbed, free proline liberated by hydrolysis appears to pass back into the lumen as well as into the tissue fluid. Substantial back flux of hydrolysis products may occur for all amino acids. 7. About one‐third of the amino acids appearing in the secretion on the serosal surface are peptide‐bound. 8. The rate of absorption of peptides appears to determine the rate of their hydrolysis which probably occurs mainly after entry into the mucosal cells.
Vibration‐induced discharge patterns of single motor units in the masseter muscle in man.
Authors: Desmedt J E , Godaux E
Published: December 2014

Single motor unit potentials were recorded with small bipolar wires from intact masseter muscles in the adult man and a detailed parametric analysis of the effects of muscle vibration on motor unit discharges was carried out. 2. When the vibration amplitude was kept constant, each unit started firing at a definite threshold of vibration frequency. With higher frequencies the rate of firing rapidly reached a maximum. Units recruited at higher frequencies presented a lower maximum rate of firing. 3. When the vibration frequency was kept constant, each masseter unit discharged at a definite threshold of vibration amplitude. With higher amplitudes the unit quickly reached a maximum rate of discharge. Units with a higher frequency threshold tended to also present a higher amplitude threshold. Motor unit "excitability" curves could be plotted using the combined threshold conditions for frequency and amplitude of applied vibrations. 4. With a given parametric set of vibration, the units only started firing at a given delay after the onset of vibration. The delay was quite different for different units and it increased considerably, sometimes by several seconds, when the vibration amplitude was made smaller. 5. In all the experimental conditions tested, and even when the unit discharge did not start until several seconds after vibration onset, the unit potential presented a close and highly consistent temporal relation to the vibration cycles. The slow recruitment process is thought to involve a polysynaptic excitatory mechanism which progressively depolarizes the masseter motoneurones close to their threshold, the actual firing being triggered by monosynaptic excitatory post‐synaptic potentials from I(a) afferents, hence the small latency jitter recorded. This special pattern of tonic vibration reflex in jaw‐closing muscles in man may result from the lack of reciprocal inhibition from the jaw‐opening muscles.
Some central mechanisms of thirst in the dog.
Authors: Ramsay D J , Reid I A
Published: December 2014

Measurements of water intake were made on a population of trained conscious dogs of both sexes prepared with chronic third ventricle cannulae. 2. Injection of 100 ng angiotensin II into the third ventricle lead to a prompt stimulation of drinking, the mean water intake over a 5 min period being 503 +/‐ 89 ml. (n=6) compared with controls. This dipsogenic effect of angiotensin II was abolished by prior central administration of 10 mug saralasin acetate or 100 ng atropine. 3. Injection of 1 mug carbachol into the third ventricle produced a small, variable increase in drinking. 4. Injection of 0‐2 ml. 5% NaCl into the third ventricle stimulated drinking, a response that was not affected by prior administration of 10 mug saralasin acetate or 100 ng atropine. 5. Following a 24 hr period of water deprivation there was an increase in plasma osmolality and plasma‐renin activity. The drinking following this period of water deprivation was not affected by prior control administration of either 10 mug saralasin acetate or 100 ng atropine. 6. In two acute dogs, intracarotid infusion of 125I angiotensin II was not followed by significant appearance of radioactivity in the third ventricle or cisterna magna c.s.f. 7. The relevance of these results to the control of water intake is discussed.
Aerobic recovery metabolism following a single isometric tetanus in frog sartorius muscle at 0 degrees C.
Authors: Kushmerick M J , Paul R J
Published: December 2014

1. Basal and recovery O2 consumption, delatO2, in frog sartorius muscles at 0 degrees C were measured with a polarographic electrode. Reproducible observations were made with the same muscle over many hours. 2. The experimental records had an exponential form except for the early phases of recovery following a single isometric tetanus. Diffusion of O2 within the muscle was adequate to account for this deviation from an exponential time course of recovery. The time constant of the recovery O2 consumption increased with the duration of tetanic stimulation from 5 to 20 sec. 3. Lactate synthesis was measureable in unstimulated aerobic muscles and increased in proportion to total O2 consumption as long as the muscle did not lack O2. The contribution of glycolysis to the total chemical energy production during recovery was 6‐9%; for hypoxic muscles it was greater. 4. The resynthesis of phosphorylcreatine and the decrease in inorganic phosphate and free creatine following a tetanus showed an exponential time course similar to recovery O2. Initial concentrations were re‐attained within 60 min following a 20 sec tetanus. 5. We conclude that recovery O2 consumpation is a useful and accurate measure of the net chemical energy utilization for a single contraction.
Alterations in resting membrane properties during neural plate stages of development of the nervous system.
Authors: Blackshaw S E , Warner A E
Published: December 2014

1. The mean resting membrane potential of cells in the neural plate of axolotl embryos increases from ‐25 to ‐45 mV (maximum values from ‐35 to ‐60 mV) when the embryos move from early to mid‐neural plate stages of development. 2. Increasing the extracellular [K] to 20 mM shortly before the spontaneous increase in resting potential occurs causes neural plate cells to hyperpolarize. 3. A moderate increase in [K]omicron does not hyperpolarize the membrane of neural plate cells at earlier stages or at late neural fold stages. 4. Both the hyperpolarization produced by K and the normal increase in resting potential are blocked by cardiac glycosides. 5. Cells of the ventral ectoderm do not display an increase in resting potential during the neural fold stages of development and do not hyperpolarize in response to a moderate increase in [K]omicron. 6. The results suggest that activation of the Na pump may be an early consequence of neural induction. They are discussed in the light of this suggestion.
Intercellular coupling in the atrioventricular node and other tissues of the rabbit heart.
Authors: Pollack G H
Published: December 2014

1. A fluorescent tracer dye, sodium fluorescein (mol.wt. 332), was used to assess the relative degree of intercellular coupling in various tissues of the rabbit heart. 2. Dye was injected intracellularly by micro‐iontophoresis. Subsequent movement into contiguous cells was monitored by video microscopy. From these data the permeability of the intercellular boundaries was computed. 3. The values of boundary permeability were consistent with those expected from previous studies with tracers whose molecular weights bracketed that of fluorescein. 4. In the atrium, ventricle, Purkinje strands and His bundle, the relative magnitude of the boundary permeability correlated reasonably well with the relative profusity of gap junctional area on the intercalated disk, the latter estimated from published data. 5. The rate of passage of dye between N cells of the atrioventricular, AV, node was at least three orders of magnitude lower than between cells of the other tissues studied; this result is consistent with published reports indicating few gap junctions between cells within the region of slow conduction. 6. Quantitative considerations based on these data indicate that N cells may not be sufficiently well coupled to permit impulse propagation through the AV node by intercellular current flow, alone.
Lactate metabolism in the isolated perfused rat kidney: relations to renal function and gluconeogenesis.
Authors: Cohen J J , Little J R
Published: December 2014

In the intact dog, decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. 2. In order to determine whether, in the absence of other added substrates, the metabolism of lactate supports only the 'basal' renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney have been quantified in relation to renal function and one measure of renal basal metabolism, glucose production. 3. The perfusate was Krebs‐Ringer bicarbonate (pH 7‐35‐7‐48) with Fraction V bovine serum albumin, 6g/100 ml. L‐(+)‐lactate was added to raise the lactate concentration from endogenous levels to 2‐5, 5‐0 or 10 mM. 4. We determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L‐(+)‐[U‐14C]lactate), net glucose production rate, and net re‐absorptive rate of Na+. 5. The apparent Km and Vmax for lactate oxidation were 2‐1 mM and 1‐29 mumole.g‐1.min‐1 respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At ca. 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant since glucose production increases as lactate concentration is raised. 6. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from ca. 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Therefore, addition of lactate increased both the basal mebabolism and tubular function. However, these observations do not permit us to conclude whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate.
Evidence for carrier‐mediated uptake and efflux of sugars at the serosal side of the rat intestinal mucosa in vitro.
Authors: Bronk J R , Ingham P A
Published: December 2014

A modification of the everted sac technique is described which allows several sacs to be prepared rapidly and simultaneously from the same segment of rat intestine. 2. A method has been developed for comparing the transport of two sugars by measuring changes in the ratios of their concentrations as they pass across the intestinal wall. 3. With this method significant differences were observed between the D‐[3H]galactose and L‐[14C]glucose ratios in the mucosal epithelium, the serosal tissue and the serosal compartment. These results indicate that both the efflux of galactose from the serosal side of the mucosal epithelium and the uptake of the sugar into the mucosa are carrier‐mediated processes. 4. The mediated efflux of galactose at the serosal side of the epithelial layer is inhibited by the presence of phlorizin on the mucosal side and to some extent by any reduction in the mucosal Na+ concentration. Both of these treatments inhibited galactose uptake at the brush border. Serosal efflux of the sugar appeared to be saturated at high concentrations of D‐galactose. 5. Pre‐treatment of the sacs with mercuric chloride considerably reduced D‐galactose uptake from the luminal side, but did not affect its efflux relative to L‐glucose at the serosal side of the mucosal epithelium. 6. Carrier‐mediated sugar uptake into the mucosal epithelium from the serosal side was also examined. The role of the bidirectional, carrier‐mediated sugar transport processes at the serosal pole of the mucosal epithelial cell in transintestinal transport is discussed.
Haemodynamic responses and renin release during stimulation of afferent renal nerves in the cat.
Authors: Calaresu F R , Stella A , Zanchetti A
Published: December 2014

1. Experiments were done on anaesthetized cats to study the effect of electrical stimulation of afferent renal nerves on the circulatory system and on the release of renin from the kidney. 2. Stimulation of afferent renal nerves over a wide range of parameters consistently elicited an increase in arterial pressure and heart rate. This response was still present in paralysed animals and was not accompanied by changes in respiration or in sympathetic autonomic activity usually associated with painful stimulation. Mesenteric and iliac vasoconstriction was observed concomitantly with the increase in arterial pressure. 3. Release of renin from the contralateral innervated kidney was not significantly changed by stimulation of afferent renal nerves. 4. The existence of renal vascular mechanoreceptors was investigated by altering renal circulation. Stenosis of the renal artery or a marked reduction in renal perfusion pressure elicited an increase in arterial pressure while stenosis of the renal vein elicited a decrease in arterial pressure. These responses, however, were not affected by denervation of the kidney and were therefore interpreted as not being due to neural mechanisms. 5. The precise nature, location and physiological role of renal receptors involved in the cardiovascular responses observed during electrical stimulation of afferent renal nerves remain to be determined.
The utilization of glucose and production of lactate by in vitro preparations of rat small intestine: effects of vascular perfusion.
Authors: Hanson P J , Parsons D S
Published: December 2014

1. The rate of metabolism of glucose to lactate has been measured in a number of non‐vascularly perfused preparations of rat jejunum in vitro. The glucose and lactate metabolism was measured simultaneously and under conditions such that the uptake of glucose and the appearance of lactate were linearly related to time. 2. It is found that there is no difference between the rates at which rings of rat jejunum utilize glucose during the first 45 min of anaerobic or aerobic incubation. During the first 15 min of incubation between 60‐70% of the metabolized glucose was converted to lactate under aerobic conditions; this value increased to 80‐90% during the subsequent 30 min. During the period 0‐15 min of incubation, lactate production was found to be higher under anaerobic than under aerobic conditions but after this initial period the rate of lactate production was the same under aerobic and anaerobic conditions. 3. For segments of rat jejunum, maintained in vitro by the recirculation of nutrient fluid through the intestinal lumen, neither the rate of production of lactate, nor the utilization of glucose, was stimulated if the preparation was maintained under anaerobic rather than aerobic conditions. The direct delivery of gas into the intestinal lumen in the form of a stream of bubbles (segmented circulation) reduced both the utilization of glucose and the production of lactate under aerobic conditions. However, not effect on glucose metabolism was observed under anaerobic conditions. The finding of a Pasteur effect with the segmented‐circulated preparation, but not with the simple recirculated preparation, is associated with lower rate of aerobic lactate production in the former preparation. Reasons are given for supposing that under conditions of segmented circulation, the luminal compartment is better stirred, thereby increasing access of O2 to the tissue. 4. A preparation of rat small intestine perfused through the vascular bed is described. With this preparation the rate of glucose utilization is significantly lower than that for recirculated preparations and the rate of lactate production is substantially less than that of the other preparations studied. 5. With the preparation perfused through the vascular bed, and with glucose, 10 mM, present only in the vascular medium the addition of erythrocytes to the vascular infusate causes a significant reduction in both glucose utilization and in the rate of lactate production. The addition of erythrocytes to produce an haematocrit of 40% (v/v) causes a greater reduction in glucose utilization and lactate production than is found for an haematrocrit of 15%. About 10% of the lactate produced appears in the luminal contents. With an haematocrit of 15%, the O2 consumption of the whole wall of the jejunum was found to be 6‐4 mumole O2 g dry wt.‐1 min‐1, equivalent of a value for the Q02 of 8‐6 mul. O2 mg druwy wt.‐1 hr‐1. The uptake of O2 was almost entirely from the vascular infusate. 6...
The effect of a meal of meat on glomerular filtration rate in dogs at normal urine flows.
Authors: O'Connor W J , Summerill R A
Published: December 2014

1. The exogenous creatinine clearance of conscious dogs has been measured by a method in which no loading doses of water or saline were given. The urine volume was thus in the normal range, 0‐1‐0‐3ml./min. 2. Under these conditions, the exogenous creatine clearance of fourteen dogs, measured 17 hr after a meal, was 2‐74 ml./min kg‐1+/‐0‐54 (s.d.). This is about 40% lower than values usually regarded as "normal." 3. A meal of meat, 10g/kg, increased exogenous creatinine clearance reflects an increase in glomerular filtration rate. Since this occurs with small doses of meat, increase in glomerular filtration may be important in normal renal function of dogs.
Voltage gradients across the receptor layer of the isolated rat retina
Authors: Arden G. B.
Published: December 2014

1. The electroretinogram (e.r.g.) of the isolated rat retina has been investigated by recording potential differences developed between two micropipettes.

2. In the uniformly illuminated receptor layer, voltage gradients at 90° to the long axes of the receptors are negligible in comparison with the radial voltage gradients.

3. When all transsynaptic neural activity has been abolished, the photoresponse recorded across the receptor layer is very different from the photoresponse recorded across the inner retinal layer.

4. The photoresponse developed across the inner retinal layers, slow P III, develops slowly and the peak voltage is approximately proportional to log. flash energy.

5. The photovoltage across the receptor layer rises rapidly to its peak, before a significant fraction of slow P III has developed.

6. The faster photovoltage (receptor potential) increases with flash intensity according to the hyperbolic function characteristic of photo‐receptors.

7. The faster photovoltage can be split into two components. Between the tips of the outer limbs and the bases of the inner limbs, it has a simple wave form. In the region between the bases of the inner limbs and the receptor synapses, there is an additional peak (nose) to the photovoltage.

8. In the scleral portion of the receptor layer, the photovoltage approximately equals the dark voltage. In the remaining, vitreal portion of the receptor layer the photovoltage exceeds the dark voltage.

9. Photocurrent divergence has been measured and the results indicate that the source of photocurrent extends further vitreally than the base of the outer limb.

10. The results suggest that the photoresponse generated in the outer limb is modified by an active process which occurs in portions of the rods which are nearer the synapse.
Chloride distribution in Aplysia neurones
Authors: Ascher P. , Kunze Diana , Neild T. O.
Published: December 2014

1. The intracellular Cl− concentration (Cli) and the membrane potential (Em) were measured in the medial pleural neurones of Aplysia under various experimental conditions designed to determine the Cl− conductance of the neurones and investigate the possibility of an active Cl− transport.

2. The magnitude of the Cl− conductance of the cell depends on the experimental conditions.

3. In normal sea water, large changes of Em produced by passing current across the cell membrane caused no change of Cli, suggesting that the Cl− conductance was low. Similarly, moderate changes of ECl produced by decreasing Clo or increasing Cli had little or no effect on Em.

4. A high Cl− conductance was observed in high Ko or very low Clo. It was greatly reduced if the external Ca2+ was replaced by Co2+, or in the presence of tubocurarine, or if the experiment was performed on an isolated cell soma. The high Cl− conductance is therefore attributed to the release of ACh and perhaps other transmitters from synaptic terminals.

5. High concentrations of tetraethylammonium ions or procaine induced a depolarization of the cell, but a decrease of Cli. The rate of fall of Cli was increased by lowering external K+ or raising external Ca2+, and was decreased by replacing external Ca2+ by Co2+.

6. NH4+ ions applied externally had effects similar to those of K+ ions. In situations in which intracellular NH4+ might be increased a fall in Cli was observed.

7. The changes of Cli caused by TEA, procaine, or internal NH4+ occur against the driving force for passive Cl− movements. They are still observed in isolated cell bodies, and cannot be attributed to the activation of synaptic channels.

8. Some interpretations of these anomalous Cl− movements are discussed which could also account for the difference between ECl and Em observed under normal conditions.
Permeability of the sheep placenta to unmetabolized polar non‐electrolytes.
Authors: Boyd R D , Haworth C , Stacey T E , Ward H T
Published: December 2014

1. The rate of appearance in uterine venous blood of radioactively labelled, polar, non‐electrolytes has been measured following their injection into the foetal circulation in the chronically catheterized sheep near term. Uterine blood flow was measured by an antipyrine technique. 2. Estimates of a placental permeability constant not corrected for area were 61‐2 +/‐ 5‐5 ml. min‐1 (mean +/‐ S.E. of mean) for [14C] urea, 1‐85 +/‐ 0‐16 for [14C]erythritol and 0‐21 +/‐ 0‐03 for [3H]mannitol. Results are also presented for [14C]ethylene glycol, [14C]L‐glucose, [14C]mannitol, [51Cr] EDTA and [3H] and [14C]sucrose. 3. In four sheep, permeability measurements for several solutes were made and the results were analysed in terms of restricted diffusion via cylindrical, water‐filled pores. Calculation of pore radius was made by a minimum variance method and values ranging from 0‐43 to 0‐45 nm were obtained. 4. Stability and absence of protein binding of probe molecules was investigated by gel permeation on Sephadex columns.
Inhibition by efferent nerve fibres: action on hair cells and afferent synaptic transmission in the lateral line canal organ of the burbot Lota lota.
Authors: Flock A , Russell I
Published: December 2014

1. Intracellular recordings were made from morphologically identified hair cells in the lateral line canal organs of the burbot Lota lota. 2. I.p.s.p.s were recorded from hair cells when the efferent fibres were excited by electrical stimulation of the lateral line nerve. The i.p.s.p.s were abolished when the fish was injected with immobilizing concentration of Flaxedil which is known to block the efferent synapses. 3. The i.p.s.p.s are accompanied by a decrease in the resistance of the hair cell membrane and an increase in the intracellular receptor potential. 4. Spontaneous and mechanically evoked e.p.s.p.s which were recorded intracellularly from the post‐synaptic afferent nerve terminals were reduced in amplitude for the duration of the i.p.s.p.
The effect of A23187 ionophore on calcium movements and contraction processes in single barnacle muscle fibres.
Authors: Desmedt J E , Hainaut K
Published: December 2014

1. Ca movements were studied in single giant muscle fibres of the barnacle before and after exposure to the Ca ionophore A23187. 2. In fibres micro‐injected with the photoprotein aequorin, the resting rate of light emission (resting glow) reversibly increased when the external Ca was augmented in the presence of A23187. This resulted from an increased Ca influx through the outer membrane. In zero external Ca, A23187 induced a delayed increase of the resting glow which was related to Ca leakage from intracellular storage sites. 3. When the experiment was carried out at 5 degrees C instead of 22 degrees C, the resting glow about doubled (temperature‐sensitive mechanisms for maintaining a low myoplasmic Ca2+ were thus depressed) but A23187 was much less effective in increasing Ca influx in high external Ca. 4. In 45Ca efflux experiments, A23187 increased both the Ca‐Ca exchange diffusion and the net Ca outflux at the outer membrane of the fibre. The Na‐Ca exchange process was not affected to a significant extent. 5. The Ca2+ transient and the force of the contraction elicited by imposed membrane depolarizations (below the threshold of the propagated action potential) were markedly increased by A23187, but the electromechanical threshold was not significantly modified. The linear relation between membrane depolarizations and the area of the Ca transient became much steeper in the presence of A23187. However the relation between the area of the Ca transient and the force output was not affected which suggests that A23187 specifically involved the Ca2+ intracellular release, but not the subsequent Ca‐troponin reaction. 6. A23187 potentiates by ionophoretic action the Ca movements at the outer membrane, and it also acts inside the intact muscle fibre to intensify the intracellular release of Ca.
The regulation of cellular volume in renal cortical slices incubated in hyposmotic medium.
Authors: Hughes P M , Macknight D C
Published: December 2014

1. Changes in water and ion contents of renal cortical slices from rat, rabbit and guinea‐pig incubated in medium of a half normal osmolarity were followed over 60 min incubation at 25 degrees C.2. Metabolizing slices gained water and lost sodium and chloride but not potassium. These changes reflected in part changes in cellular composition, and were complete within 5 min. A new steady‐state was then maintained for a further 55 min.3. Slices initially incubated for 60 min with ouabain, also lost sodium and chloride when transferred to the hyposmotic medium but did not, in the first minutes, lose any further potassium. Ouabain, in concentrations sufficient to produce maximal inhibition of the Na‐K ATPase, did not cause additional cellular swelling in the hyposmotic medium.4. The results offer no support for the claim that cellular volume in metabolizing renal cortical cells exposed to hyposmotic media is regulated by loss of cellular potassium. They suggest that under such conditions the regulation of volume involves the same ouabain‐insensitive mechanism as is seen in cells incubated in isosmotic medium.