bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions of guanidinium ions with sodium channels in frog myelinated nerve fibre.
Authors: Benoit E , Dubois J M
Published: December 2014

1. The effects of external guanidinium ions on fast and slow inactivating currents flowing through sodium channels of the frog myelinated nerve fibre (Benoit, Corbier & Dubois, 1985) were analysed under voltage‐clamp conditions. 2. When external sodium ions were partially replaced by guanidinium ions, the fast inactivating current was preferentially reduced and was absent in a solution containing guanidinium ions as the only external permeant cations. The inactivation time constants of both fast and slow currents were not significantly modified by the replacement of sodium ions by guanidinium ions. 3. Substitution of guanidinium ions for all sodium ions shifted the steady‐state inactivation curve of the slow inactivating current towards positive voltages. 4. The voltage dependence of the activation of fast and slow inactivating currents was shifted towards positive voltages by guanidinium ions. Moreover, the activation‐voltage curve of the slow inactivating current, which was biphasic under control conditions, was monophasic when guanidinium ions were substituted for all sodium ions. 5. Whereas the slow inactivating current could be carried by guanidinium ions, these cations were not only impermeant through the sodium channels which give rise to the fast inactivating current but also blocked this type of channel with an apparent dissociation constant of 49 mM. 6. It is concluded that guanidinium appears to be an efficient tool for further separating the two types of inactivating current and studying the properties of the slow inactivating current. These results are consistent with the suggestion that there are two types of sodium channels, fast and slow, with guanidinium ions being permeant only through the slow ones.
Release of substance P from the cat spinal cord.
Authors: Go V L , Yaksh T L
Published: December 2014

1. The present experiments examine the physiology and pharmacology of the release of substance P‐like immunoreactivity (SP‐l.i.), from the spinal cord in the halothane‐anaesthetized, artificially ventilated cat. 2. Resting release of SP‐l.i. was 36 +/‐ 4 fmol/30 min (mean +/‐ S.E.; n = 106). Bilateral stimulation of the sciatic nerves at intensities which evoked activity in fibres conducting at A beta conduction velocities (greater than 40 m/s), resulted in no change in blood pressure, pupil diameter or release of SP‐l.i. Stimulation intensities which activate fibres conducting at velocities less than 2 m/s resulted in increased blood pressure, miosis and elevated release of SP‐l.i. (278 +/‐ 16% of control). 3. The relationship between nerve‐stimulation frequency and release was monotonic up to approximately 20 Hz. Higher stimulation frequencies did not increase the amounts of SP‐l.i. released. At 200 Hz there was a reduction. 4. Capsaicin (0.1 mM) increased the release of SP‐l.i. from the spinal cord and resulted in an acute desensitization to subsequent nerve stimulation. This acute effect was not accompanied by a reduction in spinal levels of SP‐l.i. measured 2 h after stimulation. 5. Cold block of the cervical spinal cord resulted in an increase in the amounts of SP‐l.i. released by nerve stimulation. 6. Pre‐treatment with intrathecal 5,6‐dihydroxytryptamine (300 micrograms) 7 days prior to the experiment caused a reduction in the dorsal and ventral horn stores of SP‐l.i., but had no effect on the release of SP‐l.i. evoked by nerve stimulation. Similar pre‐treatment with intrathecal capsaicin (300 micrograms) resulted in depletion of SP‐l.i. in the dorsal but not in the ventral horn of the spinal cord and diminished the release of SP‐l.i. evoked by nerve stimulation. 7. Intense thermal stimulation of the flank resulted in small (20‐35%), but reliable increases in the release of SP‐l.i. above control. 8. Putative agonists for the opioid mu‐receptor (morphine, 10‐100 microM; sufentanil, 1 microM), and for the delta‐receptor (D‐Ala2‐D‐Leu5‐enkephalin, 1‐10 microM; D‐Pen2‐D‐Pen5‐enkephalin, 10 microM), but not the kappa‐receptor (U50488H, 100‐1000 microM), produced a dose‐dependent, naloxone‐reversible reduction of the evoked, but not of the resting release of SP‐l.i. (‐)‐Naloxone, but not (+)‐naloxone, resulted in a significant increase in evoked but not resting SP‐l.i. release.(ABSTRACT TRUNCATED AT 400 WORDS)
Contribution of chloride shifts to the fade of gamma‐aminobutyric acid‐gated currents in frog dorsal root ganglion cells.
Authors: Akaike N , Inomata N , Tokutomi N
Published: December 2014

1. The contribution of Cl‐ redistribution to the decay phase of the GABA (gamma‐aminobutyric acid) response was investigated in isolated frog sensory neurones, using a suction‐pipette technique which allows for internal perfusion under conditions of voltage clamp. 2. In neurones perfused with 120 mM [Cl‐]i and [Cl‐]o at driving forces (delta VH) of less than 15 mV, no shift of GABA equilibrium potential (EGABA) occurred during a continuous application of GABA, at various concentrations. However, increases of delta VH towards negative or positive potentials over 15 mV induced EGABA shifts. 3. The degree of EGABA shift was governed by the total amount of Cl‐ flux across the soma membrane, an event which depends upon delta VH, GABA concentration and drug application time. 4. The time‐dependent EGABA shift due to Cl‐ redistribution during GABA application induced a current run‐down resulting from a decreased Cl‐ gradient and a diminished Cl‐ conductance (gCl), the latter brought about by a drop in the intracellular ionic density of Cl‐. 5. The EGABA shift during a continuous GABA application was also affected by [Cl‐]i; e.g. the shift more readily occurred at lower [Cl‐]i. 6. In neurones perfused with internal and external solutions containing 120 mM‐Cl‐ at a delta VH of less than 10 mV, the change of gCl occurred with no shift of EGABA during the continuous application of GABA at concentrations over 6 x 10(‐5) M, thereby indicating a 'real' GABA receptor desensitization. The desensitization depended solely upon the agonist concentrations but not upon the amount of ICl. Under these conditions, the time course of recovery from GABA desensitization was estimated. The decrease of gCl at the desensitization phase was a single exponential. 7. At a delta VH greater than 15 mV, therefore, the decay of ICl induced by GABA concentrations over 6 x 10(‐6) M consists of the sum of both the 'real' GABA receptor desensitization and the current run‐down brought about by Cl‐ shifts. The gCl at the current decay phase consisted of a double exponential. In the present experiments we chose experimental conditions with which Cl‐ shift become negligible. 8. The 'pure' GABA receptor desensitization during a continuous application of GABA developed rapidly at GABA concentrations over 10(‐5) M. The speed of desensitization was facilitated by increasing the magnitude of desensitization.
Human thermal responses during leg‐only exercise in cold water.
Authors: Golden F S , Tipton M J
Published: December 2014

1. Exercise during immersion in cold water has been reported by several authors to accelerate the rate of fall of core temperature when compared with rates seen during static immersion. The nature of the exercise performed, however, has always been whole‐body in nature. 2. In the present investigation fifteen subjects performed leg exercise throughout a 40 min head‐out immersion in water at 15 degrees C. The responses obtained were compared with those seen when the subjects performed an identical static immersion. 3. Aural and rectal temperatures were found to fall by greater amounts during static immersion. 4. It is concluded that 'the type of exercise performed' should be included in the list of factors which affect core temperature during cold water immersion.
Adrenal cortical responses to vasoactive intestinal peptide in conscious hypophysectomized calves.
Authors: Bloom S R , Edwards A V , Jones C T
Published: December 2014

1. Right adrenal and various cardiovascular responses to an intra‐aortic infusion of vasoactive intestinal polypeptide (VIP; 4 micrograms min‐1 kg‐1) have been investigated in the presence and absence of exogenous adrenocorticotrophin, (ACTH1‐24; 5 ng min‐1 kg‐1, i.v.). The adrenal clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3‐4 days previously. 2. The i.v. infusion of ACTH1‐24 increased mean plasma ACTH concentration by between 1000 and 1100 pg ml‐1 and mean right cortisol output by about 700 ng min‐1 kg‐1. Under these conditions the intra‐aortic infusion of VIP produced a further rise in mean adrenal cortisol output, together with a consequential rise in mean arterial plasma cortisol concentration, without affecting the concentration of ACTH in the arterial plasma significantly. In the absence of ACTH the same infusion of VIP had no detectable effect on adrenal cortisol output. 3. In each of the above respects this intra‐aortic infusion of VIP closely mimicked the effect of stimulation of the peripheral end of the right splanchnic nerve in these animals, as it also did by causing a substantial fall in adrenal vascular resistance in the absence, but not in the presence, of ACTH. 4. It is concluded that release of this peptide from splanchnic nerve terminals in the adrenal gland most probably accounts, at least in part, for the powerful adrenocortical steroidogenic response to splanchnic nerve stimulation, that occurs in the presence of submaximal doses of ACTH.
Rat jejunal disaccharidase activity increases biphasically during early post‐natal development.
Authors: Lund E K , Smith M W
Published: December 2014

1. Injection of hydrocortisone into 9‐day‐old rats induces the early appearance of sucrase in jejunal homogenates, the time course of the subsequent increase and magnitude of the final effect being similar to that seen to start on day 16 during normal development. 2. Cytochemical comparison of the effect of hydrocortisone and normal development on the appearance of a mixture of sucrase, maltase, isomaltase and trehalase disaccharidases (alpha‐glucosidase activity) shows this enzyme to appear first in enterocytes at the base of the villus. Enzyme activity then increases and spreads along the whole villus during the next 96 h. 3. The rate at which enterocytes migrate along the villus after hydrocortisone injection is not significantly different from that measured during the early phase of normal development. The later phase of normal development is associated with a threefold increase in cell migration rate and a twofold increase in crypt depth. 4. The rate at which alpha‐glucosidase activity increases in enterocytes at the base of the villus during early normal development is similar to that determined after hydrocortisone injection into younger animals. This rate of appearance increases eight to tenfold during normal development, shortly after the appearance of solid food in the stomach of normal control animals. 5. Injection of steroid hormones into young rats is generally supposed to mimic events taking place normally at weaning. Present results show alpha‐glucosidase induction during normal development to be under more complicated control than had been previously suspected.
The effects of magnesium upon adenosine triphosphate‐sensitive potassium channels in a rat insulin‐secreting cell line.
Authors: Findlay I
Published: December 2014

1. The patch‐clamp method of single‐channel recording was applied to K+ channels which are inhibited by intracellular adenosine 5'‐triphosphate (ATP: K+‐ATP channels) in membrane patches obtained from the insulin‐secreting cloned cell line RINm5F. 2. The magnitude of K+ currents flowing outwards through these K+‐ATP channels was reduced by internal Mg2+ ions in a dose‐dependent manner. Currents flowing inwards through the channels were not affected by Mg2+. Internal Na+ ions had similar effects. 3. Divalent cations (Mg2+, Sr2+ and Ca2+) applied to the internal surface of the patch membrane inhibited the opening of K+‐ATP channels in a dose‐dependent manner. Internal Na+ ions had no effect. 4. K+‐ATP channel activity was stimulated by adenosine 5'‐diphosphate (ADP), guanosine 5'‐triphosphate (GTP), guanosine 5'‐diphosphate (GDP), guanosine 5'‐o‐(3‐thiotriphosphate) (GTP gamma S) and guanosine 5'‐o‐(2‐thiodiphosphate) (GDP beta S) when millimolar Mg2+ bathed the internal surface of the patch membrane. In the virtual absence of internal Mg2+ ions ADP, GTP, and GTP gamma S inhibited K+‐ATP channels and GDP and GDP beta S were without effect. Adenosine 5'‐o‐(2‐thiodiphosphate) (ADP beta S) inhibited K+‐ATP channel activity in the presence and absence of Mg2+. 5. K+‐ATP channel openings could be evoked by either ADP or GDP in the presence of an inhibitory concentration of ATP. These openings were abolished in the absence of internal Mg2+. 6. Run‐down K+‐ATP channels could be reactivated by ATP in the presence of internal Mg2+, but not in its absence. Analogues of ATP were unable to reactivate K+‐ATP channels even in the presence of Mg2+. 7. It is concluded that internal Mg2+ ions (i) cause the rectification of the K+‐ATP channel current‐voltage relationship, (ii) are required for K+‐ATP channel activity to be maintained by a phosphorylation process and (iii) are required for K+‐ATP channel activity evoked by ADP, GTP and GDP.
Myogenic electrical control activity in longitudinal muscle of human and dog colon.
Authors: Chow E , Huizinga J D
Published: December 2014

1. The myogenic electrical activities of longitudinal muscle cells of the dog and human colon were investigated using intracellular microelectrodes. 2. The resting membrane potentials of dog and human longitudinal muscle cells at the serosal side of the muscle layer were ‐49.4 +/‐ 0.9 and ‐44.8 +/‐ 1.3 mV respectively. 3. Spontaneous electrical activity consisted of electrical oscillations of 13.7 +/‐ 1.1 mV and 8.6 +/‐ 2.1 mV amplitude, and 19.8 +/‐ 1.0 cycles/min and 26.1 +/‐ 1.6 cycles/min frequency for dog and human cells respectively. 4. Spiking activity only occurred superimposed on the electrical oscillations; the mean rate of rise of spikes was approximately 150 mV/s in the dog and approximately 260 mV/s in human cells and that of the oscillations was approximately 18 mV/s in the dog and approximately 16 mV in human cells. 5. Spiking activity was abolished by calcium influx blockers and 0.01 mM‐calcium Krebs solution. The amplitude of the electrical oscillations was reduced to 0.2‐1.0 mV 30 min after calcium influx blockade or 30 min in 0.01 mM‐calcium Krebs solution. 6. Because of the high frequency of the oscillation‐spike complexes, there was summation of associated contractile events in such a way that contraction frequency corresponded to frequency of bursts of oscillations and not to the frequency of the individual oscillations. 7. The resting membrane potential of the longitudinal muscle cells at the myenteric plexus side of the layer was ‐44.9 +/‐ 1.0 mV, significantly lower than at the serosal side. 8. A gradient in membrane potential and slow‐wave amplitude exists in circular muscle of dog colon, with the highest value at the mucosal side (‐68.4 and 28.1 mV respectively) and the lowest at the myenteric side (‐62.5 and 8.6 mV) of the muscle layer. 9. Differences between resting membrane potential and electrical activity of longitudinal and circular muscle cells of the dog colon measured at the myenteric side of both muscle layers suggests absence of electrotonic coupling between the two types of cells. 10. Similarity of resting membrane potentials of longitudinal and circular muscle of the human colon suggests possible electronic coupling. 11. Since the electrical oscillations in longitudinal muscle control occurrence of spiking activity and type of contraction, they may be called 'electrical control activity'.
Two types of 'slow waves' in intestinal smooth muscle of cat.
Authors: Dahms V , Prosser C L , Suzuki N
Published: December 2014

1. Smooth muscle from cat small intestine shows two types of spontaneous slow electrical waves in the frequency range of 10‐15 min‐1. One type of slow wave is a ouabain‐sensitive, atropine‐insensitive spontaneous oscillation. The other type of wave can be induced by acetylcholine (ACh), is blocked by atropine, and is not blocked by ouabain. 2. Ouabain‐sensitive slow waves rise directly from the baseline, are near sinusoidal and may or may not have spikes. ACh‐induced waves have pre‐potentials, are usually topped by spikes and show after‐hyperpolarization. 3. The two types of rhythmic wave differ in ionic and metabolic requirements and drug sensitivity. Ouabain‐sensitive waves occur only in intestinal muscle attached to a boundary layer containing interstitial cells; ACh‐induced waves can occur in strips of muscle lacking boundary cells. 4. Na+ pump inhibitors ouabain, cold and K+‐free solution, reduce amplitude but not frequency of ouabain‐sensitive slow waves. 5. The ACh‐induced waves require higher extracellular concentrations of Na+ and Ca2+ and can occur in preparations in Li+‐Krebs solution; the ouabain‐sensitive rhythm persists in lower concentrations of Na+ and Ca2+ and is not supported by Li+. The ouabain‐sensitive waves are more sensitive to cyanide and less sensitive to cooling than the ACh‐induced waves. 6. Guinea‐pig intestine shows only one type of rhythmic wave, which is atropine sensitive and resembles in shape the ACh‐induced wave of other species. Ouabain increases the frequency of the guinea‐pig rhythm. 7. It is concluded that intestinal muscle of most mammals, but not of guinea‐pig, is capable of two types of slow electrical rhythms.
The effects of stimulating carotid chemoreceptors on renal haemodynamics and function in dogs.
Authors: Karim F , Poucher S M , Summerill R A
Published: December 2014

1. Dogs were anaesthetized with chloralose and artificially ventilated. The carotid chemoreceptors were stimulated by changing the perfusion of vascularly isolated carotid sinus regions from arterial to venous blood. The mean carotid sinus pressure and the mean arterial blood pressure were held constant at 124 +/‐ 3 and 122 +/‐ 3 mmHg, respectively. Both vagosympathetic trunks were sectioned in the neck and propranolol (17 micrograms kg‐1 min‐1 I.V.) and gallamine triethiodide (0.2‐2.0 mg kg‐1 30 min‐1 I.V.) were infused. Renal blood flow was measured by an electromagnetic flow probe, glomerular filtration rate by creatinine clearance, sodium excretion by flame photometry and solute excretion by osmometry. 2. In sixteen tests in thirteen dogs perfusion of the carotid sinus regions with venous blood resulted in significant decreases in renal blood flow from 271 +/‐ 24 to 198 +/‐ 21 ml min‐1 100 g‐1 renal mass; glomerular filtration rate from 41.0 +/‐ 4.8 to 22.1 +/‐ 3.1 ml min‐1 100 g‐1; filtration fraction from 0.25 +/‐ 0.02 to 0.19 +/‐ 0.02; urine flow from 0.48 +/‐ 1.0 to 0.21 +/‐ 0.03 ml min‐1 100 g‐1; sodium excretion from 18.1 +/‐ 4.1 to 12.9 +/‐ 4.2 mumol min‐1 100 g‐1; and osmolar excretion 327 +/‐ 42 to 171 +/‐ 26 mu osmol min‐1 100 g‐1. The right atrial pressure did not change significantly from 4.6 +/‐ 1.2 cmH2O. 3. In seven dogs, tying renal sympathetic nerves abolished all the responses except that of sodium excretion which was now reversed; sodium excretion increased from 68 +/‐ 19 to 116 +/‐ 38 mumol min‐1 100 g‐1 without significant change in right atrial pressure from 7.4 +/‐ 1.9 cmH2O. Crushing the carotid bodies, however, abolished all the responses. 4. The results show that carotid chemoreceptor stimulation can cause significant reflex effects on renal haemodynamics and function which are mediated via renal sympathetic nerves. They also show that the chemoreceptor stimulation can cause natriuresis in the absence of haemodynamic changes, in the denervated kidney, presumably via a humoral factor.
The effect of noradrenaline on the ion permeability of isolated mammalian hepatocytes, studied by intracellular recording.
Authors: Field A C , Jenkinson D H
Published: December 2014

1. The influence of noradrenaline on the membrane potential and conductance of isolated guinea‐pig and rabbit hepatocytes in short‐term (2‐8 h) tissue culture has been studied by intracellular recording. 2. Resting hepatocytes had linear current‐voltage relationships, with input resistances of 166 and 216 M omega in guinea‐pig and rabbit cells respectively. The recorded membrane potential was ‐18 mV in each species, though the true resting potential is likely to have been up to 10 mV greater. 3. The hepatocytes sometimes slowly hyperpolarized during intracellular recording, and this was associated with a fall in membrane resistance, and an increase followed by a decrease in membrane potential noise. These effects were abolished by quinine (200 microM) but not by apamin (50 nM), and are attributable to a K+ conductance activated by cell swelling. 4. Noradrenaline (2 microM, in the presence of propranolol at 1 microM) was applied to individual hepatocytes by pressure ejection (puffer pipette technique). After a short latency, the cells hyperpolarized by a mean of 18 mV in both guinea‐pig and rabbit preparations. This was associated with a large rise in membrane conductance (50 nS in guinea‐pig, 54 nS in rabbit cells). The reversal potential for this action was ‐38 mV. 5. The experiments were repeated in the presence of apamin (50 nM) to block the Ca2+‐dependent K+ permeability which noradrenaline activates in these cells. Noradrenaline still caused some hyperpolarization and a substantial increase (approximately 40 nS) in conductance, with a reversal potential (Er) of ‐31 mV. This can be attributed to an increase in Cl‐ conductance. 6. In keeping with this interpretation, noradrenaline applied in the absence of Cl‐ (replaced by isethionate or gluconate) caused a much greater hyperpolarization (58 mV in guinea‐pig, 40 mV in rabbit cells) associated with a smaller rise in conductance (approximately 12 nS). Er for this action was ‐95 mV (guinea‐pig) and ‐68 mV rabbit), suggesting that the conductance increase was now mainly to K+. 7. The magnitudes of the conductance changes produced by noradrenaline under the various experimental conditions suggest that the increase in the conductance to Cl‐ (delta GCl) is 3‐fold greater than that to K+ (delta GK). 8. The activation of delta GCl occurs either at the same time as delta GK, or (in ca. one cell in ten) a few seconds later.(ABSTRACT TRUNCATED AT 400 WORDS)
Difference in the amplitude of the human soleus H reflex during walking and running.
Authors: Capaday C , Stein R B
Published: December 2014

1. The Hoffman reflex, or H reflex, was strongly modulated in the human soleus muscle during both walking (4 km/h) and running (8 km/h). It was relatively low at the time of heel contact, increased progressively during the stance phase, and reached its maximum amplitude late in the stance phase. During ankle dorsiflexion the H reflex was absent. 2. During running the peak e.m.g. level of the soleus was on average 2.4 times higher than during walking but the maximum amplitude of the H reflex was never larger than during walking. In fact, the H reflex was on average significantly (P less than 0.05 for one‐tailed t test) smaller during running than during walking. Furthermore, the slope of the least‐squares line fitted to the relation between the H reflex amplitude and the background e.m.g. was always steeper for the walking data than for the running data. 3. The difference in the H reflex in the two tasks is evidence that the size of the H reflex is not simply a passive consequence of the alpha‐motoneurone excitation level, as indicated by the e.m.g., but is also influenced by other central neural mechanisms. We suggest that presynaptic inhibition is the most likely mechanism accounting for the change in the slope. 4. The modulation of the reflexes during walking and running can be interpreted in terms of the idea of automatic gain compensation. The decreased gain during running may be appropriate to reduce saturation of motor output and potential instability of the stretch reflex feed‐back loop.
Regulation of cell calcium and contractility in mammalian arterial smooth muscle: the role of sodium‐calcium exchange.
Authors: Ashida T , Blaustein M P
Published: December 2014

1. The contraction and relaxation of rings of rat thoracic aorta and bovine tail artery were examined as a function of changes in the Na+ electrochemical gradient in order to determine the role of Na‐Ca exchange in the control of contractility. 2. Inhibition of the Na+ pump in rat aorta by K+‐free media or a low concentration (5 x 10(‐5) M) of strophanthidin reversibly increased the contractile responses to caffeine and noradrenaline. These effects were dependent upon external Ca2+ and were observed even in the presence of a Ca2+ channel blocker (10 microM‐verapamil or 10 microM‐diltiazem) and an alpha‐receptor blocker (10 microM‐phentolamine). 3. Reduction of external Na+ concentration, [Na+]o (replaced by N‐methylglucamine, tetramethylammonium or Tris), also caused an external Ca2+‐dependent increase in tonic tension and, in rat aorta, an increase in the response to caffeine. These effects were also observed in the presence of verapamil and phentolamine. 4. Caffeine relaxed the bovine tail artery, but increased the sensitivity of the rat aorta to reduced [Na+]o. The latter effect was presumably due to block of Ca2+ sequestration in the sarcoplasmic reticulum, so that entering Ca2+ was more effective in raising the intracellular free Ca2+ level, [Ca2+]i. 5. Relaxation from K+‐free or low‐Na+ contractions, in Ca2+‐free media, depended upon [Na+]o. Reduction of [Na+]o to 1.2 or 7.5 mM slowed the relaxation of rat aorta (5 mM‐caffeine present) 3‐ to 5‐fold, and the relaxation of bovine tail artery (without caffeine) 5‐ to 10‐fold. These effects were seen in the presence of verapamil and phentolamine. 6. These observations are all consistent with an Na‐Ca exchange transport system that can move Ca2+ either into or out of the arterial smooth muscle cells. Ca2+ entry is enhanced by raising [Na+]i (by Na+ pump inhibition) and/or lowering [Na+]o. Ca2+ extrusion from the contracted muscles is largely dependent upon external Na+. The latter observation implies that, when [Ca2+] exceeds the contraction threshold, Ca2+ efflux is mediated primarily by the Na‐Ca exchanger, rather than by the sarcolemmal ATP‐driven Ca2+ pump. 7. When bovine tail artery was treated with verapamil and phentolamine, and [Na+]o was reduced from 139.2 to 43.9 mM, substitution of K+ for Na+ induced a larger external Ca2+‐dependent contraction than did substitution of Tris for Na+. The amplitudes of these contractions were greatly increased when the Na+ pump was inhibited by 5 x 10(‐5) M‐strophanthidin, presumably because of the rise in [Na+]i.(ABSTRACT TRUNCATED AT 400 WORDS)
Iodide transport in rat small intestine: dependence on calcium.
Authors: Ilundain A , Larralde J , Toval M
Published: December 2014

1. The involvement of calcium in the regulation of iodide secretion was investigated in stripped sheets of rat small intestine. 2. In the absence of exogenous modifiers a net iodide absorption was observed in the rat proximal intestine, whereas the mid‐intestine secreted iodide. 3. Removal of Ca2+ from the bathing solutions abolished net I‐ secretion in the mid‐intestine. The calcium channel blocker verapamil produced similar effects on net I‐ secretion. 4. Theophylline increased net I‐ secretion both in the absence and in the presence of verapamil, but the effects of theophylline were less in the presence of verapamil or in Ca2+‐free media. 5. Trifluoperazine inhibited basal iodide secretion and attenuated theophylline‐induced I‐ secretion. 6. All the modifiers which prevented net I‐ secretion reduced iodide fluxes across the mucosal border and increased serosal iodide exit. The opposite was observed with theophylline. 7. It is suggested that I‐ secretion might result from changes in both mucosal and serosal I‐ permeabilities, and that both processes appear to be regulated by calmodulin.
[3H]noradrenaline release from rabbit pulmonary artery: sodium‐pump‐dependent sodium‐calcium exchange.
Authors: Magyar K , Nguyen T T , Török T L , Tóth P T
Published: December 2014

1. The release of [3H]noradrenaline ([3H]NA) from the isolated main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 X 10(‐5) M) and extraneuronal (corticosterone, 5 X 10(‐5) M) uptake blockers. 2. K+ removal from the external medium increased the release of [3H]NA, an action transiently inhibited by Ca2+‐free (+1 mM‐EGTA) solution, i.e. after Ca2+ removal transmitter release was first abolished and then started to increase again after a delay lasting about 90‐120 min. 3. Ca2+ readmission to arteries which had been kept in Ca2+‐ and 'K+‐free' solution, markedly increased the [3H]NA release. The rate of transmitter release was dependent on the preceding perfusion period with 'K+‐free' solution, being greater for longer exposure times. 4. When Ca2+ and K+ were readmitted together to K+‐depleted and Na+‐enriched preparations, the release of [3H]NA transiently increased. 5. If K+ was readmitted first, the subsequently applied Ca2+ was ineffective in producing transmitter release. 6. Different alkali metal ions (Rb+, Cs+ or Li+) were also readmitted as K+ substitutes together with Ca2+. In all cases the release of neurotransmitter transiently increased; however, the rate of release was dependent on the monovalent cation used. Thus, Rb+ ions were as effective as, Cs+ about one‐third as effective as, and Li+ about one‐fifth as effective as K+ in activating the Na+ pump. 7. It is concluded that in the absence of external Ca2+, and in response to Na+‐pump inhibition, the release of Ca2+ from internal stores is responsible for the NA release observed. On readmission of Ca2+ the rate of transmitter release is dependent on the Na+ previously gained inside. Furthermore, the activity of the Na+ pump determines the rate of transmitter release through the Na‐Ca exchange mechanism.
Effects of beta‐adrenergic blockade on the ventilatory responses to hypoxic and hyperoxic exercise in man.
Authors: Conway M A , Petersen E S
Published: December 2014

1. The ventilatory responses to step changes from rest to 100 W cycling exercise were studied in five healthy human subjects. Exercise was performed in hypoxia (end‐tidal O2 pressure, PET,O2, 50‐55 mmHg), a condition characterized by a marked enhancement of arterial chemoreceptor activity, and in hyperoxia (PET,O2 greater than 250 mmHg), a condition in which arterial chemoreceptor activity is largely suppressed. The subjects were studied at each O2 level after placebo and after an oral dose of 120 mg propranolol. 2. The magnitude of phase 1, the immediate, rapid ventilatory response at the onset of work, was unaffected by hypoxia and at both oxygen levels it was also unaffected by propranolol. 3. Phase 2, analysed from 20 to 120 s after the onset of exercise, was significantly affected by both O2 level and beta‐blockade. The kinetics of the ventilatory changes in this phase were well described in all four conditions by a simple exponential function. The overall mean time constants after placebo were shorter in hypoxia (31.0 s) than in hyperoxia (40.2 s), and at each O2 level longer after propranolol, in hypoxia 61.3 s and in hyperoxia 106.0 s. 4. Continuous analysis of gas sampled at the mouth with a mass spectrometer showed constancy of end‐tidal PCO2 throughout the step change in hypoxia both with and without beta‐blockade. In contrast, in both hyperoxic conditions PET,CO2 rose, mainly in phase 2, to a value 5‐6 mmHg higher than the starting value. 5. The steady‐state ventilation was higher in hypoxia than in hyperoxia, and end‐tidal CO2 pressure, PET,CO2, correspondingly lower. Neither ventilation nor PCO2 were, however, affected by propranolol in either condition. 6. It is concluded that the arterial chemoreceptors are important for both the rate of adaptation of ventilation to a new rate of metabolism during a step change of work rate, and for the matching of ventilation to CO2 flow which normally ensures isocapnia. The further slowing of the dynamics of the ventilatory response in hyperoxia as well as the preserved isocapnia in hypoxia after beta‐blockade argue against any major role of beta‐adrenergic mechanisms for these functions of the arterial chemoreceptors. The observed effects are considered to be secondary to the reduced cardiac output and an increased CO2 storage initially during exercise following beta‐adrenergic blockade.
The effect of electrical stimulation of the sympathetic chain on peripheral lymph flow in the anaesthetized sheep.
Authors: McGeown J G , McHale N G , Thornbury K D
Published: December 2014

1. Pressure fluctuations and lymph flow were measured in cannulated popliteal efferent and metatarsal afferent lymphatics in anaesthetized sheep. 2. Stimulation of the lumbar sympathetic chain at 1.4 and 10 Hz increased lymph flow and lymphatic contraction frequency. These effects were most marked during 10 Hz stimulation where, in some efferent preparations, greater than 5‐fold increases in lymph flow and contraction frequency were observed. 3. Strain‐gauge plethysmograph recordings in the lymphatic's drainage area indicated that during stimulation blood flow was reduced. There was also a slow continuous fall in tissue volume throughout the periods of stimulation, presumably due to a net uptake of fluid by the blood vessels. 4. Intra‐arterial infusion of phentolamine at a rate of 10 micrograms kg‐1 min‐1 blocked the increases in lymph flow and contraction frequency. 5. These results suggest that the observed increases in lymph flow were due to direct neurogenic stimulation of lymphatic pumping.
Properties of motor units in the transversus abdominis muscle of the garter snake.
Authors: Lichtman J W , Wilkinson R S
Published: December 2014

1. The organization of motor units in the single‐fibre‐thick transversus abdominis muscle of the garter snake has been studied. This small segmental muscle (60‐100 fibres) contains three distinct fibre types (faster twitch, F; slower twitch, S; and tonic, T) which are predominantly arranged in the repeating pattern F, T, S, T, F, T, etc. 2. Motor‐unit maps were obtained by activating an individual motor axon and identifying all of the muscle fibres innervated by that axon, using either the activity‐induced uptake of extracellular marker molecules to label presynaptic terminals of the stimulated axon, or systematic intracellular recording to identify muscle fibres activated by the axon. 3. Each muscle contained three types of motor units (F, T and S) that corresponded to the three types of fibres. All of the muscle fibres in a motor unit were of the same type. Each segmental muscle contained approximately the same number of motor units: one to two faster twitch, three to four slower twitch, and three tonic. 4. Each motor unit was dispersed widely throughout the muscle. Fibres within a motor unit were neither clustered nor anticlustered. This suggests that despite the fact that axons are constrained to innervate fibres of the appropriate type, the distribution of each motor unit does not generate the alternating pattern of fibre types. 5. In several experiments, all of the twitch motor units in one segmental component of the muscle were mapped. The projection of any one axon appeared random not only with respect to the muscle's fibre type pattern, but also with respect to the innervation supplied by other axons. 6. Twitch motor units were arranged according to a hierarchy of sizes. In each muscle examined, the largest motor unit was faster twitch; a single faster twitch motor axon usually innervated all of the faster twitch fibres in the muscle (fourteen to twenty‐four fibres). This was followed by three to four slower twitch motor units which varied in size from eight to ten fibres to very small motor units containing only four to five fibres. 7. Each tonic motor axon innervated an average of ninety‐three end‐plates per segmental muscle. The relatively large size of tonic motor units compared to twitch motor units is related to the ability of tonic muscle fibres to retain polyneuronal innervation into adulthood, both by providing five to seven end‐plate sites per fibre, and by allowing terminal boutons from different tonic motor axons to co‐innervate the same end‐plate.(ABSTRACT TRUNCATED AT 400 WORDS)
Stable maintenance heat rate and contractile properties of different single muscle fibres from Xenopus laevis at 20 degrees C.
Authors: Elzinga G , Lännergren J , Stienen G J
Published: December 2014

1. Different types of fibres were isolated from the iliofibularis muscle of Xenopus laevis. Resting length was adjusted to obtain a sarcomere length of 2.3 microns as judged by laser diffraction. Heat production was measured during tetanic contractions lasting 0.3‐2 s at 20 degrees C. From twenty fibres the force‐velocity relationship was determined as well. 2. After correcting the records for heat loss, and taking the relevant heat capacities into account, stable maintenance heat rate was determined by fitting the corrected heat records from 0.35 s after the onset of contraction onwards by a straight line. The value obtained was then normalized on the dry weight of the fibre. The force‐velocity relationships were fitted according to Hill's equation, yielding values for a and Vmax (Hill, 1938). 3. Stable maintenance heat rate (hb) depended on fibre type and ranged from 0.05 to 0.86 W g‐1 dry wt. Isometric tetanic force per cross‐sectional area (P0) varied between 190 and 427 kN m‐2. Therefore the variations in hb were not proportional to the variations in P0. 4. The maximum velocity of shortening (Vmax) differed considerably from fibre to fibre (4.6‐10.3 lengths s‐1). Between Vmax and hb a non‐linear relationship was found. The curvature of this relationship was such that its slope (delta hb/delta Vmax) increased with Vmax. 5. A proportional relationship was found between the rate of force redevelopment, following a period of rapid shortening, and hb. 6. Maximum power output during loaded shortening as derived from the force‐velocity (P‐V) relationships was on average 2.2 times higher than hb. 7. The curvature of the force‐velocity relationship, as reflected by the value of a/P0, varied between fibres from 0.18 to 0.53. A larger value of a/P0 i.e. a less curved relationship, corresponded with a larger value of hb. 8. Since hb reflects the rate at which ATP is hydrolysed during contraction, the results suggest that the maximum velocity of shortening and the in vivo actomyosin ATPase under isometric conditions are non‐linearly related. This would imply that these two variables are not dominated by the same rate‐limiting step of the cross‐bridge cycle.
Activation of the primary kinetic modes of large‐ and small‐conductance cholinergic ion channels in Xenopus myocytes.
Authors: Auerbach A , Lingle C J
Published: December 2014

1. The kinetic properties of single acetylcholine (ACh)‐activated ion channels in tissue‐cultured Xenopus myocytes have been examined in cell‐attached patches. The rates of agonist binding and channel gating were inferred from the durations of open and closed intervals from channels exposed to 40 nM‐200 microM‐ACh. The predominant kinetic forms of large‐ (gamma 60) and small‐conductance (gamma 40) cholinergic channels were compared. 2. At high [ACh], bursts were defined so that they primarily reflect sojourns in activatable states. The probability that a channel is open within a burst (Po) increases between 2 and 200 microM‐ACh. Po is half‐maximal at approximately 5 microM for gamma 40 channels and at approximately 25 microM for gamma 60 channels. 3. Open interval durations for gamma 40 channels are distributed as the sum of two exponentials, with the slow component (tau approximately 2.8 ms) accounting for greater than 80% of the total. Open interval durations for gamma 60 channels are often distributed as a single exponential with an apparent time constant of approximately 0.8 ms. For both conductance forms of channel, open interval durations show no significant dependence on [ACh] in the range 0.04‐10 microM, but decrease at higher [ACh] in a manner consistent with channel block by agonist molecules. 4. Closed interval durations within bursts (2‐100 microM‐ACh) for gamma 60 or gamma 40 channels are described by the sum of two or three exponentials. For both conductance forms of channel the apparent time constant of the fastest component is approximately 40 microseconds and does not change significantly with [ACh], and the time constant of the predominant, slowest component (tau slow) decreases with increasing [ACh]. 5. For gamma 40 channels, at high [ACh] tau slow saturates at approximately 0.17 ms, while no saturation is apparent for gamma 60 channel tau slow values up to 200 microM‐ACh. Below 50 microM‐ACh, gamma 40 tau slow values are approximately 1.5 times shorter than gamma 60 values. 6. Estimates of rate constants for agonist binding and channel gating were obtained by fitting closed interval durations in the range 2‐100 microM‐ACh. Gamma 60 channels have a greater than 5‐fold faster opening rate, approximately 10‐fold faster closing rate, and approximately 3‐fold lower affinity than do gamma 40 channels. There is some indication of positive co‐operativity of ACh binding to gamma 40 channels.
Respiratory modulation of left ventricular stroke volume in man measured using pulsed Doppler ultrasound.
Authors: Guz A , Innes J A , Murphy K
Published: December 2014

1. Beat‐by‐beat changes in left ventricular stroke volume (l.v.s.v.) with breathing were recorded in four normal subjects using pulsed Doppler ultrasound. The l.v.s.v. fell during inspiration and rose during expiration; these changes were exaggerated at high tidal volumes. 2. Respiratory changes in l.v.s.v. persisted when respiratory rate was increased to 25 breaths/min despite an associated reduction in the degree of sinus arrhythmia. 3. During relaxed breath‐holding, respiratory variations in l.v.s.v. ceased immediately, and on resumption of breathing a significant fall in l.v.s.v. occurred with the first inspiratory effort. 4. Inspiratory efforts against an occluded mouthpiece were accompanied by significant variations in l.v.s.v., although the magnitude of these changes was smaller than during unoccluded breathing with similar pleural pressure changes. 5. A resistive inspiratory load increased the respiratory variations in l.v.s.v. in the three subjects studied. 6. In three patients with implanted dual‐chamber pacemakers set to constant heart rates, breathing was associated with larger variations in l.v.s.v. 7. In two patients who had undergone pericardectomy, the magnitude of respiratory changes in l.v.s.v. was less than in the normal subjects. 8. We conclude that inspiration directly lowers l.v.s.v. in man by a direct mechanism which is largely independent of lung volume changes, is dependent on changes in pleural pressure, and persists in the absence of sinus arrhythmia. All these results, particularly those in pericardectomy patients, are compatible with previous animal work on the anatomical and functional interdependence of right and left ventricles during breathing.
Epidermal growth factor selectively increases maltase and sucrase activities in neonatal piglet intestine.
Authors: James P S , Smith M W , Tivey D R , Wilson T J
Published: December 2014

1. Pig intestinal sucrase and maltase activities increase markedly, and lactase activity decreases, during the second week of post‐natal life. Correlations noted between the time course describing these changes and that found previously to describe a decline in the ability of the pig intestine to take up macromolecules suggest that both events are subject to the same type of developmental control. 2. Injection of epidermal growth factor (EGF) into 3‐day‐old piglets increase sucrase and maltase activities measured 3 days later. These increases, which are not seen when measuring other hydrolase enzymes, are confined to the mid and distal regions of the small intestine. 3. Dexamethasone injected into 3‐day‐old piglets inhibits lactase and, on occasion, sucrase activities without affecting other intestinal hydrolases. Significant increases in sucrase and maltase activities also occur in distal intestine following injection of EGF plus dexamethasone into 3‐day‐old pigs. 4. Cytochemical analysis shows EGF effects on sucrase and maltase activities to be exerted in crypt and basal villus enterocytes produced post‐natally. Dexamethasone inhibits lactase activity mainly by acting on mid and upper villus enterocytes produced before birth. 5. EGF appears to increase sucrase and maltase activities by extending the time during which young enterocytes continue to accumulate these enzymes in their brush‐border membranes. Dexamethasone appears to cause a more fundamental change in the biochemistry of older enterocytes. accompanied by an increasing ability of these cells to transport neutral amino acids through a sodium‐dependent mechanism (see James, Smith, Tivey & Wilson, 1987a).
Baclofen and velocity storage: a model of the effects of the drug on the vestibulo‐ocular reflex in the rhesus monkey.
Authors: Cohen B , Helwig D , Raphan T
Published: December 2014

1. Baclofen had a characteristic effect on vestibular and optokinetic nystagmus in rhesus monkeys. Each aspect of nystagmus that is dependent on the velocity‐storage mechanism in the vestibulo‐ocular reflex (v.o.r.) was altered by the drug: (a) Baclofen reduced the dominant time constant of the v.o.r. in a dose‐dependent manner up to 5 mg/kg, the highest dosage used. The alteration in v.o.r. time constant began within 15 min of injection, was maximal between 1 and 4 h, and lasted for 14‐18 h. This effect mirrors changes in plasma levels of baclofen after oral doses in humans (Faigle, Keberle & Agen, 1980). (b) Slow‐phase velocities of steady‐state nystagmus induced by rotation about axes tilted from the vertical (off‐vertical axis rotation, o.v.a.r.) were reduced after baclofen and could not be maintained at previous levels. (c) There was a dose‐dependent decline in the steady‐state gain of optokinetic nystagmus (o.k.n.), and at the highest dosages little o.k.n. was induced. In parallel, the peak velocity and falling time constant of optokinetic after‐nystagmus (o.k.a.n.) were reduced. Since baclofen is a GABA agonist, systems utilizing GABA and acting on GABAB receptors appear to produce inhibitory control of velocity storage. 2. The step gain of the v.o.r., measured at the beginning and end of constant‐velocity rotation in darkness, was unaffected by baclofen, as were saccades, quick phases of nystagmus, and the ability to hold positions of fixation or to generate linear slow phases of nystagmus. This indicates that it is possible to use baclofen to manipulate the dominant time constant of the v.o.r. and of o.k.a.n. in relative isolation from effects on other oculomotor components. 3. Baclofen caused a dose‐dependent reduction in the initial jump in eye velocity at the onset of o.k.n., suggesting that the initial jump is also under inhibitory control of GABAB receptors. However, there were still occasional slow phases with velocities up to 30‐40 deg/s after baclofen, and animals were capable of visually suppressing the v.o.r. This indicates that pathways responsible for causing rapid changes in slowphase velocity were capable of functioning, at least intermittently, in the presence of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)