bluuebunny/crossref_metadata_2025 huggingface dataset:
The importance of renal vascular tone in determining the severity of renal artery stenosis in dogs.
Authors: Anderson W P , Korner P I
Published: December 2014

1. The effects of the state of renal vascular tone during induction of renal artery stenosis on the subsequent systemic blood pressure and renin responses have been studied in chronically instrumented, conscious dogs. 2. In one group of dogs, renal vascular tone was altered by brief (2‐3 min) renal artery infusions of ACh, saline, methoxamine or angiotensin II during narrowing of the renal artery to reduce distal pressure to 40 mmHg. The infusions were turned off 1 min later. 3. The more vasoconstricted the kidney at the time of stenosis, the slower was the restoration of distal renal artery pressure and the greater the rises in systemic blood pressure, plasma renin activity (PRA) and effective stenosis resistance. At the end of 1 hr of stenosis, the rises in systemic blood pressure were 4.3 +/‐ 3.3, 11.3 +/‐ 3.3, 28.9 +/‐ 3.3 and 26.3 +/‐ 2.8 mmHg for the ACh, saline, methoxamine and angiotensin II‐infused dogs respectively; rises in PRA were 0.3 +/‐ 0.24, 1.18 +/‐ 0.42, 5.09 +/‐ 1.38 and 4.02 +/‐ 0.74 ng/ml. per hr respectively. 4. In another group of dogs a given aortic‐renal artery pressure gradient was produced on two occasions: (i) with the animal conscious; (ii) under brief sodium pentobarbitone anaesthesia and preparation for surgery. After 24 hr systemic blood pressure had risen by 15.7 +/‐ 3.6 mmHg above initial values when stenosis was induced under anaesthesia (P < 0.05) and only by 1.2 +/‐ 3.6 mmHg (N.S.) when it was induced with the animal conscious. Corresponding rises in PRA were 1.29 +/‐ 0.42 (P < 0.05) and 0.25 +/‐ 0.11 (N.S.) ng/ml. per hr. Establishment of a given gradient in the high vascular resistance kidney of the anaesthetized dog thus requires greater narrowing of the renal artery than in the lower resistance renal bed of the conscious animal. 5. The tone of the renal vascular bed is a major determinant of the severity of renal artery stenosis.
Effects of tetraethylammonium chloride on sympathetic neuromuscular transmission in saphenous artery of young rabbits.
Authors: Holman M E , Surprenant A
Published: December 2014

1. Excitatory junction potentials and electrotonic potentials were recorded from the smooth muscle of the rabbit saphenous artery using intracellular electrodes. 2. Tetraethylammonium chloride (TEA) in concentrations greater than 3.5 mM caused depolarization. Concentrations greater than 5 mM caused spontaneous electrical activity in the form of excitatory junction potentials (e.j.p.s) and all‐or‐nothing action potentials which were associated with spontaneous mechanical activity. 3. Concentrations of TEA less than 2.5 mM did not alter the resting potential nor the passive membrane properties of the smooth muscle over a range of +/‐ 15 mV. 4. The following effects were observed in 2.0 mM‐TEA. (a) The minimum stimulus strength required for the initiation of an e.j.p. fell by three to fivefold. (b) Single stimuli that elicited only a small e.j.p. in normal solution evoked an all‐or‐nothing action potential of up to 70 mV amplitude. (c) Whereas in normal solution e.j.p.s could only be recorded up to 7 mm away from the perivascular stimulating electrode e.j.p.s could be recorded at distances of up to 13 mm. (d) The duration of the e.j.p. was prolonged. 5. Based on these results and the effects of TEA reported for other synapses it is proposed that TEA may act to increase the amount of transmitter released per axon, to increase the duration of release and to cause an increased invasion throughout the autonomic ground plexus by nerve impulses. This would imply that in normal solution, in vitro, the action potential may not propagate throughout the whole length of the terminal axon and its many branches due to failure of conduction at one or more points along the terminal portion of the axon.
Calcium‐mediated inactivation of calcium current in Paramecium
Authors: Brehm Paul , Eckert Roger , Tillotson Douglas
Published: December 2014

1. The Ca current seen in response to depolarization was investigated in Paramecium caudatum under voltage clamp. Inactivation of the current was measured with the double pulse method; a fixed test pulse of an amplitude sufficient to evoke maximal inward current was preceded by a conditioning pulse of variable amplitude (0‐120 mV).

2. The amplitude of the current recorded during the test pulse was related to the potential of the conditioning pulse. Reduction of test pulse current was taken as an index of Ca current inactivation. The current recorded during a test pulse showed a progressive decrease to a minimum as the potential of the conditioning pulse approached +10 to +30 mV. Further increase in conditioning pulse amplitude was accompanied by a progressive restoration of the test pulse current. Conditioning pulses near the calcium equilibrium potential had only a slight inactivating effect on the test pulse current.

3. Injection of a mixture of Cs and TEA which blocked late outward current had essentially no effect on the inward current or its inactivation.

4. Elevation of external Ca from 0·5 to 5 m
M was accompanied by increased inactivation of the test pulse current. The enhanced inactivation of the test pulse current was approximately proportional to the increase in current recorded during the conditioning pulse.

5. Following injection of the Ca chelating agent, EGTA, the inactivation of the test pulse current was diminished; in addition, the transient inward current relaxed slightly more slowly, and the transient was followed by a steady net inward current.

6. The time course of recovery from inactivation in the double pulse experiment approximated a single exponential having a time constant of 80‐110 msec. Injection of EGTA shortened the time constant by as much as 50%.

7. It is concluded that interference with the entry of Ca or enhanced removal of intracellular free Ca2+ interferes with the process of Ca current inactivation, while enhanced entry of Ca promotes the process of inactivation. While the mechanism of inactivation is unknown, arguments are presented that the accumulation of intracellular Ca influences the Ca channel conductance.
Quinacrine (mepacrine) action at frog end‐plate.
Authors: Adams P R , Feltz A
Published: December 2014

1. The effects of quinacrine on end‐plate currents (e.p.c.s.), miniature end‐plate currents (m.e.p.c.s.) and ionophoretic responses at voltage clamped frog end‐plates were investigated. 2. A quinacrine concentration (2 microM) that by itself has little effect on m.p.e.c.s. will considerably attenuate responses to bath applied carbachol. The combined effect of the two drugs causes the m.e.p.c.s. to disappear. 3. The depressant effect of quinacrine on ionophoretic responses to carbachol or acetylcholine is increased in acid solutions and decreased in alkaline solutions, suggesting that quinacrine is active as an acridinium ion. 4. Quinacrine (2‐10 microM) causes a use‐dependent block of end‐plate channels which manifests as an inhibitory effect of an ionophoretic prepulse on the response to a test pulse. The inhibitory interaction decays exponentially with a time constant tau s that depends on the nature of the agonist used for the prepulse, on the quinacrine concentration, and on the membrane potential. 5. Quinacrine (5‐20 microM) reduces the amplitude of e.p.c.s. and m.e.p.c.s. It also increases the rate of decay of the e.p.c. or m.e.p.c. tails, which remain exponential. The decay rate constant 1/tau f increases linearly with quinacrine concentration both in the presence and absence of 3 microM‐neostigmine. The slope of this linear relation increases slightly with membrane hyperpolarization. 6. These data suggest that quinacrine's main action is a slow, voltage dependent blockade of open end‐plate channels, though there are probably additional effects on acetylcholinesterase and channel opening. In accordance with the open channel blocking model, 1/tau s and 1/tau f both increase linearly with quinacrine concentration. However, the slopes of these lines lead to rather different estimates of the forward blocking rate constant (8 X 10(7) and 4 X 10(8) M‐1 S‐1 respectively). 7. The unblocking rate constant is about 5 S‐1 at ‐80 mV. It is much more voltage dependent than the forward rate constant.
Alterations in perceived heaviness during digital anaesthesia.
Authors: Gandevia S C , McCloskey D I , Potter E K
Published: December 2014

1. It was shown by Gandevia & McCloskey (1977) that anaesthesia of the thumb causes weights lifted by thumb flexion to feel heavier, and weights lifted by thumb extension to feel lighter. This was confirmed by Marsden, Rothwell & Traub (1979). Gandevia & McCloskey explained the effects in terms of altered motor command (and so, altered ‘sense of muscular force, or heaviness') required when sources of peripheral reflex facilitation or inhibition were removed by anaesthesia. Marsden et al. proposed, instead, that co‐contraction of antagonists altered in anaesthesia. They said that increases in heaviness occurred for flexion because anaesthesia was associated with increased activity in the thumb extensor and, similarly, that decreases in heaviness occurred for extension because anaesthesia reduced activity in the thumb flexor. 2. The apparent heaviness of weights lifted by flexion of the thumb is not systematically altered by paralysis of the extensor of the thumb (radial nerve block at the elbow). Heaviness is increased by local anaesthetization of the thumb (digital nerve block). If paralysis of the thumb extensor is induced after digital nerve block, no further alteration in apparent heaviness occurs. 3. If extensor co‐contraction is encouraged for stabilization of the wrist, as by having subjects perform an isometric contraction with the index‐finger while lifting weights by thumb flexion, the apparent heaviness of the weights is increased. If co‐contraction of the extensors is prevented by radial nerve block the manoeuvre of simultaneous contraction of the index finger then fails to alter the heaviness of weights lifted by thumb flexion. 4. The middle finger can be postured in such a way that active extension but not active flexion of its distal joint is impossible. When co‐contraction of the extensor cannot act at the distal joint, anaesthetization of the middle finger causes an increase in apparent heaviness of weights lifted by flexion of this joint. 5. The effects of digital anaesthesia on the apparent heaviness of objects lifted by digital flexion are not caused by co‐contraction of the extensors of the digits, as proposed by Marsden et al. Where extensor co‐contraction occurs unrelated to the digital flexion task, as in stabilization of the wrist during simultaneous flexion of more than one digit, it may affect the apparent heaviness of objects borne by individual digits.
Thermoregulatory characteristics of neurogenic hyperthermia in the rat.
Authors: Ackerman D , Rudy T A
Published: December 2014

1. The thermoregulatory characteristics of the neurogenic hyperthermia produced in rats by unilateral mechanical destruction of the rostral hypothalamic/preoptic region were studied. 2. The investigational methods employed included (a) observing the thermoregulatory effector activities which were responsible for generation of hyperthermia, (b) observing the thermoregulatory reactions elicited by forcefully elevating or lowering core temperature during neurogenic hyperthermia and (c) observing the effect of ambient temperature on hyperthermia magnitude. 3. At 26 degrees C, hyperthermia was effected by a transient increase in shivering thermogenesis and a concomitant minimization of heat loss through the tail. 4. At 26 degrees C, perturbations of core temperature during the plateau phase of hyperthermia were induced by internal or external heating and cooling. The disturbances elicited compensatory changes in shivering activity and in tail vasomotor tonus, and core temperature was rapidly and precisely returned to its pre‐perturbation level. 5. The magnitudes of hyperthermias experienced by rats lesioned at 10, 15, 26 and 32 degrees C, as measured by the change in colonic temperature and by the area under the fever curve, were not significantly different. At 36 degrees C, rats were hyperthermic prior to lesioning, and the magnitude of the lesion‐induced hyperthermia was significantly attenuated. 6. The results indicate that the neurogenic hyperthermia produced by unilateral hypothalamic puncture in the rat is generated by a coordinated modulation of thermogenic and heat retentive effectors and that the plateau level of hyperthermia is well regulated. These characteristics are compatible with the hypothesis that neurogenic hyperthermia is mediated by prostaglandins released from injured tissue and acting on surviving rostral hypothalamic tissue.
Physiological regulation of synaptic effectiveness at frog neuromuscular junctions.
Authors: Grinnell A D , Herrera A A
Published: December 2014

1. Nerve terminals in two different muscles of the frog, the sartorius and cutaneous pectoris (c.p.), have been found to differ sharply in safety factor. This difference is shown to be attributable to corresponding disparities in the amount of transmitter released, without evident correlated morphological differences. 2. In Ringer containing 0.3 mM‐Ca2+ and 1 mM‐Mg2+, quantal content of c.p. junctions exceeded that of sartorius junctions by 3‐4 times. 3. When quantal content was corrected for nerve terminal size, c.p. terminals still released 2‐4 times more transmitter per unit terminal length. 4. Light and electron microscopic examination of junctional morphology in the two muscles revealed no significant difference in the spacing of presynaptic active zones, the width of synaptic contact, or the density of presynaptic vesicles and mitochondria. It seems likely, therefore, that the greater release at c.p. junctions is due to a ‘physiological’ difference between the two populations of terminals. 5. No evidence could be found that action potential invasion of the terminal was less complete in the sartorius than in the c.p. 6. The dependence of evoked and spontaneous release on Ca2+ concentration was of similar slope for terminals in the two muscles, but of different absolute value, consistent with the observed difference in release.
Mechanism by which renin secretion from perfused rat kidneys is stimulated by isoprenaline and inhibited by high perfusion pressure.
Authors: Fray J C
Published: December 2014

1. Rat kidneys were completely isolated and perfused to determine the ionic mechanism whereby isoprenaline stimulates and high perfusion pressure inhibits renin secretion. 2. Isoprenaline (2.43 microM) stimulated renin secretion, but K‐free medium and ouabain also reduced perfusate flow. 3. Removing Ca from the perfusion medium increased renin secretion threefold when perfusion pressure was 100 mmHg and fourfold when pressure was raised to 150 mmHg. Simultaneously raising the perfusion pressure to 150 mmHg and the Ca concentration to 5 mM inhibited renin secretion. Verapamil (50 microM) prevented this inhibition. Raising Ca also caused vasoconstriction at a pressure of 150 mmHg, but verapamil partially prevented the vasoconstriction. 4. High concentration of K (50 mM) in the perfusion medium also stimulated renin secretion when Ca was removed and inhibited secretion when Ca concentration was raised to 5 mM. Verapamil (50 microM) prevented this inhibition. High K induced vasoconstriction in the presence of high Ca, but verapamil partially prevented the constriction. 5. High concentration of K (50 mM) and high perfusion pressure (150 mmHg) stimulated renin secretion in the absence of Ca and 20 mM‐Mg potentiated this effect. This suggests that both sets of stimuli activate renin secretion by different cellular mechanisms, but that both act to lower cytoplasmic Ca in the juxtaglomerular cell. This is discussed. 6. High perfusion pressure inhibited renin secretion and reduced perfusate flow when Na was lowered from 145 to 14.5 or 0 mM whether or not Ca was present. 7. K‐free medium and ouabain blocked the elevated renin secretion and reduced the high flow stimulated by high perfusion pressure when Ca was removed from the perfusion medium. 8. These observations suggest that isoprenaline stimulates renin secretion by a mechanism coupled to the Na‐K pump. These observations are also consistent with the hypothesis that high renal perfusion pressure inhibits renin secretion by promoting Ca movement into the juxtaglomerular cell and stimulates secretion by a mechanism coupled to the Na‐K pump. High perfusion pressure also causes renal vasoconstriction by increasing the Ca permeability of the smooth muscle cells in the afferent arteriole.
Filtration coefficients and osmotic reflexion coefficients of the walls of single frog mesenteric capillaries.
Authors: Michel C C
Published: December 2014

1. Single capillaries in the mesentery of pithed frogs were perfused with frog Ringer solutions containing various concentrations of bovine serum albumin and myoglobin. Filtration coefficients (Lp) of the capillary wall were determined from measurements of fluid filtration rate at a series of different capillary pressures (Michel, Mason, Curry & Tooke, 1974). The osmotic reflexion coefficients (sigma) to albumin and myoglobin were determined by comparing the effective osmotic pressure exerted by these solutes across the capillary walls with their osmotic pressures in a membrane osmometer. 2. Lp and sigma to albumin were measured in eighteen vessels at different sites in the capillary bed with the tissue temperature in the range of 20‐24 degrees C. Lp varied from 1.5 x 10(‐3) to 15 x 10(‐3) micrometer sec‐1 cm H2O‐1 having a higher mean value in nine venous capillaries (11.33 x 10(‐3) micrometer sec‐1 cm H2O‐1) than in nine arterial and mid‐capillaries (4.83 x 10(‐3) micrometer sec‐1 cm H2O‐1). For all eighteen vessels sigma to albumin had a mean value of 0.816 (S.E. of mean +/‐ 0.027). There was no correlation between Lp and sigma. The mean value of sigma for the venous capillaries was 0.841 (S.E. of mean +/‐ 0.04) and the other nine vessels 0.802 (S.E. of mean +/‐ 0.034). 3. The osmotic reflexion coefficient to myoglobin was measured in seven different capillaries and found to have a mean value of 0.348 (S.E. of mean +/‐ 0.012) at 20‐24 degrees C. The Lp of the capillaries varied from 3.0 x 10(‐3) to 10.5 x 10(‐3) micrometer sec‐1 cm H2O‐1. There was no correlation between sigma for myoglobin and Lp. 4. The method of Curry, Mason & Michel (1976) was used to measure sigma for urea in eight capillaries at 20‐24 degrees C (sigma for albumin was also measured in two of these vessels). The mean value of sigma for urea was 0.061 (S.E. of mean +/‐ 0.012). The exclusive water channel (Curry et al. 1976) was calculated to have a value of 0.209 x 10(‐3) micrometer sec‐1 H2O‐1. 5. The effects of temperature on Lp were investigated in a further seven capillaries. It was found that when tissue temperature changed slowly (less than 2 degrees C min‐1) the changes of Lp were similar to the reciprocal changes in the viscosity of water. 6. The estimates of Lp and sigma for myoglobin and serum albumin are discussed in terms of the classical pore theory and in terms of a theory that the molecular sieving properties of the capillary wall reside in a matrix of molecular fibres which covers the endothelial cells and fills the channels through or between them. A quantitative theory of a fibre matrix membrane is given in the Appendix.
Role of calcium and albumin in the autoregulation of renal perfusate flow
Authors: Baker S. , Cohen A. J. , Fray J. C. S. , Laurens N. J.
Published: December 2014

1. We investigated the role of calcium and albumin on the perfusate flow in isolated perfused rat kidneys. The initial perfusion medium was Krebs‐Henseleit bicarbonate solution with 1.82 m
m‐calcium without albumin. Perfusate flow autoregulation occurred above 100 mmHg.

2. Raising albumin concentration to 20 and 60 g/l. abolished autoregulation and increased perfusate flow.

3. Keeping ionized calcium at 1.82 m
m restored autoregulation in medium containing 20 and 60 g albumin/l. However, in 60 g albumin/l. autoregulation occurred at a significantly higher flow.

4. 1.82 m
m‐ionized calcium appears to be a critical level for autoregulation of flow in these experiments, for autoregulation was not obtained in 60 g albumin/l. medium containing 1.80 m
m‐ionized calcium. On the other hand, autoregulation occurred in medium containing 1.83 m
m‐ionized calcium, but at a lower perfusate flow.

5. Raising albumin concentration to 120 g/l. increased perfusate flow from 14.6±0.8 to 20.8±0.7 ml./min.g (n = 5, P < 0.01) in the presence of 1.82 m
m‐total calcium, and from 11.6±1.0 to 15.8±0.7 ml./min.g (n = 5, P < 0.01) in 1.82 m
m‐ionized calcium. The effect of raising albumin concentration was reversible.

6. Removing the capsule from the kidneys abolished the increased flow in response to raising albumin concentration.

7. We conclude that (a) the mechanism for the autoregulation of renal perfusate flow in isolated perfused kidneys is critically dependent on an extremely narrow range of ionized calcium concentration in the perfusion medium, below this range, autoregulation is not achieved; above it, however, autoregulation is achieved, but during intense vasoconstriction; (b) raising albumin concentration in the perfusion medium increases perfusate flow and abolishes autoregulation by lowering extracellular ionized calcium and by raising intrarenal tissue pressure.
The effect of (+)‐tubocurarine on neuromuscular transmission during repetitive stimulation in the rat, mouse, and frog.
Authors: Magleby K L , Pallotta B S , Terrar D A
Published: December 2014

1. The effect of tubocurarine on amplitudes of end‐plate currents in response to trains of repetitive stimulation (50‐150/sec) was investigated in voltage‐clamped muscle fibres of the rat, mouse and frog. 2. In rat and mouse muscle, the presence of tubocurarine led to a more rapid decline (rundown) in the amplitudes of successive end‐plate currents during trains of impulses. In frog, tubocurarine caused an increase in apparent facilitation of end‐plate current amplitudes during the first few impulses of repetitive stimulation; this increase was followed by a more rapid rundown of end‐plate current amplitude. 3. These effects of tubocurarine appear not to be an artifact resulting from inadequate control of membrane potential in voltage‐clamped fibres. 4. The more rapid rundown during trains of end‐plate currents in the presence of tubocurarine showed little variation with membrane potential indicating that voltage‐sensitive channel blockade by tubocurarine was not a major factor contributing to the rundown. 5. The effect of tubocurarine on the apparent facilitation and rundown of end‐plate current amplitudes was typically decreased by reducing the frequency of stimulation. 6. These results suggest that tubocurarine affects transmitter release at neuromuscular junctions during repetitive stimulation.
The mechanism of transfer for L‐leucine into the vascular bed of the Anuran small intestine.
Authors: Cheeseman C I
Published: December 2014

1. The vascularly perfused small intestine of Rana pipiens was used to investigate the movement of the amino acid L‐leucine from the epithelium into the vascular bed. It was found that only a few amino acids when present in the lumen inhibited the wash‐out leucine into the vascular bed. The series of amino acids which had this effect belonged to the group previously shown to be transported by ‘L‐type’ carrier systems. 2. Nearly all amino acids when present in the lumen accelerated the flux of leucine from the vascular bed to the lumen and there was little correlation between the amino acids which caused this effect and those which inhibited leucine wash‐out into the vascular bed. Replacement of luminal sodium also promoted serosal‐to‐mucosal leucine flux. 3. The effect of the presence of amino acids in the lumen on the uptake of leucine from the vascular bed was measured using a fractional extraction technique; sucrose was the extracellular marker. There was complete correlation between the amino acids which promoted the extraction of leucine from the vascular bed and those which inhibited leucine wash‐out into the vascular bed. 4. In contrast, the wash‐out of leucine into the vascular bed was not accelerated by the addition of amino acids to the vascular perfusate, and the presence of 10 mM‐leucine in the vascular bed had very little effect upon the mucosal‐to‐serosal flux of leucine. 5. These results are discussed with regard to the specificity of an exit system for leucine, in the intestinal epithelium, which appears to have an energy requirement.
Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones.
Authors: Dunlap K , Fischbach G D
Published: December 2014

Several neurotransmitters including noradrenaline (NA), gamma‐aminobutyric acid (GABA) and serotonin (5‐HT), and also certain peptides, decrease the duration of the Na+‐Ca2+ action potential recorded in cell bodies of embryonic chick dorsal root ganglion neurones maintained in cell culture. To determine if these agents decreased action potential duration by affecting Ca2+ channels (inward current) or K+ channels (outward current) membrane currents were recorded in voltage‐clamped sensory neurone somata. 1. Depolarization produced a prominent inward Na+ current and a smaller and slower inward Ca2+ current (ICa). The inactivation of ICa was not simply dependent on membrane potential but apparently required prior entry of Ca2+. Two components of outward current, voltage‐activated and Ca2+‐activated, were evident in most cells. 2. The effect of NA, and also of GABA and 5‐HT, was shown to result from a direct effect on ICa because: NA decreased the TTX‐resistant tail current recorded at EK and also the inward current recorded in the presence of 125 mM‐TEA and TTX (in which Na+ and K+ currents were blocked). 3. The decrease in ICa is most likely due to an effect on the number of available Ca2+ channels and/or the single Ca2+ channel conductance rather than to a shift in either the kinetics of channel activation or the Ca2+ equilibrium potential. 4. No effect of the several transmitters on the voltage‐dependent Na+ and K+ currents was observed. 5. Implications of ICa modulation for the phenomenon of presynaptic inhibition are discussed.
Receptive fields of frog retinal ganglion cells: response formation and light‐dark‐adaptation.
Authors: Donner K
Published: December 2014

1. The excitatory and inhibitory receptive field mechanisms of retinal ganglion cells were studied by extracellular recording from the eyecup of Rana temporaria in order to elucidate the nature of adaptational changes in the functioning of the receptive field. 2. The responses to large stimuli were always strongly depressed relative to responses evoked by smaller spots. This was true even in the fully dark‐adapted state and at the very lowest stimuli intensities. 3. Threshold measurements confirmed earlier findings, usually revealing the surround only in light‐adapted states. However, in more than 10% of fully dark‐adapted cells thresholds to large stimuli were significantly elevated. 4. The central summation area of the receptive field was found to shrink with light‐adaptation. There was a gradual decrease in diameters, amounting to some 20‐30%, from the dark‐adapted, rod‐determined receptive fields to the cone‐determined ones. 5. Adaptation by bleaching and adaptation by backgrounds changed the effects of the surround in different ways. After a rhodopsin bleach the transition from a light‐adapted to a dark‐adapted situation was seen as an abrupt drop of large‐stimulus thresholds at some time during adaptation. Steady backgrounds produced no such dramatic changes, but the increment threshold lines were somewhat steeper with test spots stimulated the surround than with smaller spots. 6. Although the discharge patterns generally show the strength of the surround influence, they underwent no qualitative change at the time of the drop of large‐stimulus thresholds after a bleach. 7. It is suggested that the drop does not reflect a sudden reorganization of the receptive field, but is the consequence of the different ways the response to large stimuli are formed in different ranges of stimulus intensity (pre‐inhibitory at high intensities, post‐inhibitory at low intensities), and of gradual changes in signal dynamics.
Effects of pregnancy on glucose reabsorption by the proximal convoluted tubule in the rat.
Authors: Bishop J H , Green R
Published: December 2014

1. Free‐flow micropuncture techniques were used to investigate glucose, sodium and water reabsorption along the proximal convoluted tubule in 7‐8 day pregnant rats undergoing saline or glucose infusion and in virgin controls. 2. Absolute proximal tubular reabsorption of glucose was greater in pregnant animals than virgins during both saline and glucose infusion; and fractional reabsorption of glucose was higher in pregnant than in virgin animals during glucose infusion. 3. During glucose loading, less glucose escaped reabsorption in the proximal tubule in pregnant than in virgin animals. It is concluded that the increased excretion of glucose observed in pregnant rats cannot be due to failure to proximal tubular mechanisms. 4. During saline infusion pregnant animals had a higher single nephron glomerular filtration rate (S.N.G.F.R.) when compared with virgin animals and a corresponding increase in reabsorption of sodium and water. The small increases in S.N.G.F.R. and sodium reabsorption in pregnant animals (compared with virgin animals) during glucose infusion were not statistically significant. 5. Fractional reabsorption of sodium (and water) along the proximal convoluted tubule was not significantly different in the four series. It is concluded that glomerulo‐tubular balance operates during pregnancy.
Action of 5‐hydroxytryptamine on intestinal ion transport in the rat.
Authors: Hardcastle J , Hardcastle P T , Redfern J S
Published: December 2014

1. 5‐HT increased the electrical activity of rat jejunum both in vivo and in vitro. The increased potential difference and short‐circuit current resulted from a stimulation of electrogenic chloride secretion. NaCl absorption may also have been inhibited. 2. 5‐HT did not alter cyclic AMP levels in isolated enterocytes. 3. The 5‐HT response in vivo was unaffected by atropine, cyproheptadine, propranolol and hexamethonium. Phenoxybenzamine reduced the maximum response without affecting the dose required to produce a 50% maximum response. Methysergide, at a dose of 40 mg/kg, had a similar effect while a lower dose of 2 mg/kg produced no change. Mianserin competitively antagonized the response to 5‐HT, a dose of 2 mg/kg producing a fourfold increase in the amount of 5‐HT required to produce a 50% maximum response. 4. Acetylcholine and 5‐HT seem to act independently in inducing intestinal secretion since atropine did not block the response to 5‐HT and Mianserin did not alter the response to acetylcholine. 5. Experiments in which the intestinal villi or crypts were subjected to preferential damage suggested that 5‐HT primarily produced its response at the crypt cell level.
The release of biologically active secretin‐like immunoreactivity into duodenal lumen of dogs.
Authors: Chang T M , Chey W Y , Kim M S , Lee K Y
Published: December 2014

1. Immunoreactive secretin in the duodenal contents was determined in four conscious and four anaesthetized dogs in which hydrochloric acid (0.1 N) was infused into the duodenum at 2.2 ml./min. In the conscious dogs, immunoreactive secretin concentration in duodenal juice increased from 5‐7 to 40‐60 ng/ml. after infusion of HCl. In anaesthetized dogs, luminal immunoreactive secretin concentration increased from 2‐3 to 12‐16 ng/ml. after acid infusion. In both groups of dogs, a 20‐ to 30‐fold increase in the total output of luminal immunoreactive secretin was observed. 2. Duodenal juice collected from anaesthetized dogs after diversion of both bile and exocrine pancreatic secretion was found to be the only source of luminal immunoreactive secretin. No immunoreactive secretin was found in either bile or pancreatic juice. 3. Gel filtration of the duodenal juice on a Sephadex G‐50 column indicated that the immunoreactive secretin‐like material in the duodenal juice possesses a molecular size similar to that of natural porcine secretin. 4. Immunoreactive secretin was partially purified from dog duodenal juice by chromatography on a SP‐Sephadex column and found to be capable of stimulating pancreatic bicarbonate and water secretion in dogs.
Calcium and potassium currents in muscle fibres of an insect (Carausius morosus).
Authors: Ashcroft F M , Stanfield P R
Published: December 2014

1. A three electrode voltage‐clamp was used to investigate membrane currents in the skeletal muscle fibres of the stick insect, Carausius morosus. Contraction was blocked by hypertonic solutions. 2. Membrane currents elicited by step depolarizations consisted of an inward current, an early outward current and a delayed outward current. 3. The reversal potential of the delayed outward current did not change when SO4(2‐) was substituted for Cl‐, but shifted by 14.1 mV when [K]0 was increased from 20 mM to 40 mM in SO4(2‐) solution, suggesting that the delayed current is carried by K+. Both early and delayed outward currents were substantially reduced by 120 mM‐tetraethylammonium (TEA) ions. 4. The small size of the shift in the reversal potential of the delayed outward current with increased pulse duration suggests that the delayed current measured flows mainly across the surface membrane. 5. Increasing [Ca]o made the apparent reversal potential for the inward current (120 mM‐TEA Ringer) more positive and increased the size of the maximum inward current. However, Ca‐currents showed saturation with increasing [Ca]o, indicating that there is a site to which Ca ions bind during their passage through the membrane. The dissociation constant of this site was 7.3 mM at 0 mV and was voltage‐dependent. 6. Inward currents were blocked by 1 mM‐La3+ or Cd2+, or by substitution of Co2+ or Ni2+ for Mg2+. Strontium and barium were able to permeate the channel but Na+ and Mg2+ appear impermeant. 7. As expected from the low intracellular Ca concentration, the instantaneous current‐voltage relation of the Ca current rectified strongly in the inward direction. 8. Both constant field theory and the simplest, single site, Eyring rate theory model predict the rectification of the instantaneous current‐voltage relation. The rate theory model also predicts saturation of the Ca current with [Ca]o.
Conduction block in rat myelinated fibres following acute exposure to antigalactocerebroside serum
Authors: Lafontaine Serge , Rasminsky Michael , Saida Takahiko , Sumner Austin J.
Published: December 2014

1. We have observed conduction in single rat spinal ventral root nerve fibres following acute topical application of anti‐galactocerebroside serum.

2. Conduction of nerve impulses was initially slowed and subsequently blocked at the site of serum exposure.

3. Conduction block occurred within as little as 1 hr in more slowly conducting (20‐30 m/sec) myelinated fibres but occurred later in fibres conducting more rapidly.

4. Conduction block was preceded by a rise in internodal conduction time from the normal 20 μsec to about 200 μsec.

5. At nodes exposed to serum, conduction block was invariably associated with greatly decreased depolarization; this was contrasted with nodes exposed to local anaesthetic or tetrodotoxin where conduction block occurred despite nodal depolarization well beyond threshold potential.

6. Nodal capacitance and resistance were estimated from simultaneous recordings of membrane current and extracellular potential at blocked nodes exposed to local anaesthetic or tetrodotoxin (normal nodes) and at blocked nodes exposed to anti‐galactocerebroside serum.

7. For normal fibres of internodal length 0·8‐1·1 mm, an upper limit estimate for average nodal capacitance was 2·6 ± 0·3 pF and a lower limit estimate for average nodal resistance was 55 ± 10 MΩ. There was an order of magnitude increase in the capacitance of nodes at which conduction block occurred following exposure to anti‐galactocerebroside serum.

8. We conclude that the early conduction block caused by anti‐galactocerebroside serum is due to paranodal demyelination and that acute paranodal demyelination is sufficient to cause conduction block.
Renal blood‐flow changes during renal nerve stimulation in rats treated with alpha‐adrenergic and dopaminergic blockers.
Authors: Chapman B J , Horn N M , Robertson M J
Published: December 2014

1. Blood flow through the inner cortex and outer medulla of the rat kidney was measured by the hydrogen wash‐out technique. 2. Renal nerve stimulation caused vasoconstriction in both cortex and medulla. This constriction was abolished or reduced by phenoxybenzamine (9 mumole/kg I.V.), phentolamine (100 n‐mole/kg) or prazosin (1.5 mumole/kg). 3. After prazosin (6 mumole/kg I.V.), renal nerve stimulation caused small but significant renal cortical vasodilatation. This vasodilatation was reversed by sulpiride (0.7 mumole kg‐1 min‐1), but was unaffected by propranolol (10 mumole/kg) or atropine (4.3 mumole/kg). 4. These results indicate the existence of dopaminergic vasodilator nerves to the renal cortex of the rat.
Inhibition of the sodium pump by inorganic phosphate in resealed red cell ghosts.
Authors: Eisner D A , Richards D E
Published: December 2014

1. Ouabain‐sensitive Rb influx was measured into K‐free resealed red cell ghosts. The effects of inorganic phosphate (Pi) were examined. 2. Phosphate decreased the magnitude of the influx. Increasing Pi lowered the apparent affinity for both ATP and external rubidium ions. The effects of Pi on the affinity for external Rb were greatest at low ATP concentrations. 3. In the nominal absence of phosphate, increasing ATP from 1 to 100 microM had little effect on the Rb influx from solutions of low (1 microM) rubidium concentrations. In the presence of Pi, ATP increased Rb uptake markedly, even from solutions of low Rb concentration. 4. The above interactions between Pi, ATP and external Rb are consistent with a consecutive scheme for the Na pump in which phosphate is released after potassium binds at the external surface and before ATP binds to release potassium ions to the internal solution. 5. Previous failures to find an effect of phosphate on either the affinity for ATP or that for external potassium (rubidium) ions are shown to be equally consistent with the model. The lack of change of apparent affinity is shown to result from the restricted range of concentrations used in these previous experiments.
Reinnervation of denervated parasympathetic neurones in cardiac ganglia from Rana pipiens.
Authors: Roper S , Taylor B
Published: December 2014

1. The sequence of events during reinnervation of the cardiac ganglion in the frog following interruption of the vagosympathetic nerve supply was studied with both electrophysiological and morphological techniques. 2. When cardiac ganglia were denervated by crushing the vagosympathetic nerve supply to the heart all synaptic endings on parasympathetic ganglion cells degenerated. Vacated post‐synaptic densities were detected on denervated neurones for periods of at least 7 weeks. 3. The earliest signs of reinnervation were subthreshold responses evoked by stimulating the regenerating vagosympathetic trunks 2 1/2‐3 weeks after crushing the cardiac branches of the vagus nerves. Analysis of the reversal potentials of these responses indicated that these synapses were distant from the cell body. 4. At slightly longer times (4‐5 weeks), regenerating synapses could be recognized on post‐ganglionic axons; no synapses were detected on the neuronal perikarya at these times. 5. By 6‐7 weeks following denervation, vagal synapses reinnervated neuronal perikarya as well as post‐ganglionic axons. At the same time, vacated post‐synaptic densities declined in number. Furthermore, vagal stimulation at this stage evoked large, suprathreshold post‐synaptic potentials. 6. These studies indicate that post‐ganglionic axons are the initial sites for reinnervation of parasympathetic neurones in the heart. Only some time later are neuronal perikarya reinnervated and ganglionic transmission completely restored.
Competitive elimination of foreign motor innervation on autonomic neurones in the frog heart.
Authors: Proctor W , Roper S
Published: December 2014

1. Somatic motoneurones are capable of forming functional synapses when redirected to vagotomized autonomic neurones in the frog heart. We tested if regenerating vagus nerves could reinnervate ganglion cells in the presence of foreign hypoglossal innervation and, furthermore, whether hypoglossal innervation persisted when vagal axons regenerated to the heart. 2. Simulating the redirected hypoglossus nerve produced a parasympathetic‐like cardiac inhibition in the absence of vagal regeneration. However, when the vagus nerve was allowed to regenerate to the heart, vagal cardio‐inhibition was restored and hypoglossal inhibition disappeared. 3. Intracellular recordings showed that 71% of the cardiac ganglion cells were innervated by hypoglossal axons before vagal regeneration, but that this value fell to less than 9% over a period of 40 weeks during vagal regeneration. 4. If the vagus nerve was prevented from regenerating to the heart, hypoglossal innervation did not decline, indicating that elimination of the foreign motor innervation was dependent upon vagal reinnervation. 5. Although hypoglossal terminals formed synapses only on the axons of parasympathetic ganglion cells, regenerating vagal fibres re‐established synaptic contact both on axons as well as on neuronal perikarya. 6. The data indicate that in the frog parasympathetic cardiac ganglion, extensive synaptic remodelling can take place during reinnervation and that previously established, inappropriate inputs can be functionally eliminated by regeneration of the native nerve supply.
Active and inactive renin release from rabbit kidney cortex slices: effect of sodium concentration and of furosemide.
Authors: Munday K A , Noble A R , Richards H K
Published: December 2014

1. Active and inactive renin release by rabbit kidney cortex slices was investigated. Inactive renin was estimated as the increase in renin activity after acidification (pH 2 . 8) of slice supernatant solutions. 2. Active renin release was increased when incubation medium [Na+] was reduced. This relationship was linear (r2 = 0 . 96) over the range [Na+] = 23‐133 mM. 3. For the same range of [Na+] inactive renin secretion decreased when medium [Na+] was reduced (r2 = 0 . 92). Therefore, the proportion of total renin which was in the inactive form decreased linearly as [Na+] was reduced (r2 = 0 . 97). 4. Chloride ions did not appear to be important in altering the secretion of either active or inactive renin. 5. Adding furosemide to the incubation medium in concentrations up to 40 micrograms/ml. did not change secretion of either form of renin. The action of furosemide on secretion of active and inactive renin in vivo is therefore secondary to altered renal function. 6. Regulation of the relative amount of active and inactive renin in plasma could be entirely an intrarenal event. It is not essential to invoke a plasma activating enzyme for inactive renin in order to explain changes in plasma levels of the two forms of renin. 7. This paper supports the hypothesis that release of inactive renin by the kidney is controlled by a sodium‐sensitive mechanism.
Is action potential duration of the intact dog heart related to contractility or stimulus rate?
Authors: Drake Angela J. , Noble Mark I. M. , Schouten Vincent , Seed Anthony , Keurs Henk E. D. J. Ter , Wohlfart Bjorn
Published: December 2014

1. The contractility (maximum rate of rise of left ventricular pressure) and action potential duration were measured in intact closed‐chest anaesthetized dogs with complete atrioventricular dissociation and β‐adrenergic blockade.

2. Measurements were confined to test beats following a 1 sec interval. Prior to the test interval (priming period) a variety of potentiating stimulus trains were introduced.

3. When the frequency of stimulation was increased in the priming period (frequency potentiation), there was an inverse relationship between action potential duration and contractility of the test beat.

4. When the test beat was potentiated by a single beat terminating the priming period with one short interval (post‐extrasystolic potentiation), there was no relationship between the action potential duration and contractility of the test beat.

5. Paired pulse stimulation was used for any given frequency to vary contractility by short interval potentiation. For any given frequency of stimulation there was no relationship between action potential duration and contractility of the test beat. For any given value of contractility, action potential duration decreased with increased frequency of stimulation.

6. The introduction of a high frequency train caused a step decrease in action potential duration on the first beat of the train. This was followed by a further slow decline in action potential duration with a time course of over 3 min. These two changes could be dissociated by the introduction during the train of one second interval test pulses, which only showed the slow shortening.

7. The lack of a consistent relationship between action potential duration and contractility of the test beat disagrees with the hypothesis that repolarization is controlled by the activator calcium responsible for the contractility. The action potential shortening associated with increased frequency is related to the frequency change per se.

8. The slow time course of change in action potential duration following an increase in stimulation frequency suggests that these changes are caused by the accumulation of an ion or metabolite, or possibly by changes of activity of the electrogenic Na+—K+ pump.
Injection of guanosine and adenosine nucleotides into Limulus ventral photoreceptor cells
Authors: Bolsover S. R. , Brown J. E.
Published: December 2014

1. Several nucleotide and nucleotide analogues had striking effects when pressure‐injected into Limulus ventral photoreceptor cells. The poorly hydrolysable GTP analogues guanosine 5′‐0‐(3‐thiotriphosphate) (GTPγS), guanylyl imidodiphosphate (Gpp[NH]p) and guanylyl (β, γ methylene) diphosphonate (Gpp[CH2]p) produced large increases in the frequency of ‘discrete events’ that were recorded from photoreceptors in darkness. This effect was only observed after the injected cell was exposed to light. Injection of the ATP analogue ATPγS had effects similar to those of the GTP analogues.

2. We conclude that GTPγS, Gpp[NH]p, Gpp[CH2]p and ATPγS act at a common site to cause a light‐dependent, long‐term activation of the excitation mechanism of the photoreceptor.

3. Injection of GTP or GDP at pH 4.8 was followed by a smooth, transient depolarization that was observed neither when GTP at pH 7.5 was injected nor when ATP, 5′GMP or 2‐[N‐morpholino] ethane sulphonic acid (MES) were injected at pH 4.8. The reversal potential of the current induced by GTP injection was significantly more positive than the reversal potential of the light‐induced current.

4. We conclude that GTP injection induces changes of membrane conductance either in addition to, or different from, the light‐induced change of membrane conductance.

5. Injection of the ATP analogue adenylyl imidodiphosphate (App[NH]p), and the pyrophosphate analogue imidodiphosphate (p[NH]p) produced a drastic decrease in the sensitivity of photoreceptors to light. This decrease in sensitivity was partially reversed when the concentration of calcium ions in the bathing medium was reduced.

6. We suggest that App[NH]p and p[NH]p injections act by increasing the cytoplasmic concentration of calcium ions.