bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric vasodilatation and vasoactive intestinal peptide output in response to vagal stimulation in the dog.
Authors: Ito S , Ohga A , Ohta T
Published: December 2014

1. Gastric vasodilatation, relaxation, and vasoactive intestinal peptide (VIP) output in response to vagal stimulation were studied in anaesthetized dogs. 2. Stimulation of the peripheral end of the vagus nerve (10 Hz, 40 V, 0.5 ms) normally evoked a gastric contraction, but caused relaxation in atropinized dogs. There was no detectable difference between the electrical thresholds for activation of the vagal preganglionic excitatory and inhibitory motor fibres. 3. Vagal stimulation also evoked gastric vasodilatation, which was blocked by hexamethonium but not by combined muscarinic and adrenergic blockade. Vagal fibres evoking vasodilatation had higher thresholds to electrical stimulation than those evoking motor responses. 4. Both gastric motor responses to vagal stimulation increased with increasing frequency up to 10 Hz and a plateau between 10 and 40 Hz, but the vasodilator response was significantly reduced above 20 Hz. Vagal stimulation at 10 Hz caused an increase in gastric venous VIP output which was significantly reduced at 40 Hz. 5. Low‐intensity vagal stimulation (10 Hz, 40 V, 0.05 ms) elicited gastric relaxation (40% of a maximum), with no release of VIP or gastric vasodilatation. 6. It is concluded that release of VIP in response to stimulation of the vagal innervation to the stomach in the dog is primarily vasodilating in action.
Differential actions of pentobarbitone on calcium current components of mouse sensory neurones in culture.
Authors: Gross R A , Macdonald R L
Published: December 2014

1. Using the single‐electrode voltage clamp technique, three calcium current components were recorded at 35 degrees C from mouse dorsal root ganglion (DRG) neurones in culture. A transient low‐threshold calcium current (T current) was recorded at clamp potentials (Vc) positive to ‐60 mV. Holding potentials (Vh) at or negative to ‐90 mV were required to fully remove inactivation. A large transient high‐threshold calcium current component (N current) was recorded at Vc positive to ‐40 mV. Vh at or negative to ‐80 mV removed all steady‐state inactivation. A slowly inactivating high‐threshold calcium current component (L current) was recorded at Vc positive to ‐30 mV. Inactivation was removed by Vh at or negative to ‐60 mV. When currents were evoked at Vc positive to ‐20 mV from Vh negative to ‐60 mV, all three calcium current components were present. 2. Pentobarbitone (500 microM) had no effect on the isolated T current, but reduced the isolated L current 50‐100% when evoked at Vc of ‐20 to 0 mV from Vh of ‐50 mV. Pentobarbitone had voltage‐dependent effects on calcium currents containing all three calcium current components. Pentobarbitone produced small and equal reductions of the peak and late (greater than or equal to 300 ms) calcium currents evoked at ‐20 to 0 mV from Vh at or negative to ‐80 mV, but at more positive Vh there was a greater reduction in the peak current. The rate of current inactivation was increased in the presence of pentobarbitone. 3. Current‐voltage plots were constructed from currents recorded in the absence and presence of 500 microM‐pentobarbitone. Pentobarbitone reduced the magnitude of the calcium current without affecting the voltage dependence of the current‐voltage relation. 4. Calcium current traces were fitted with a multiexponential function to determine the amplitudes and inactivation time constants (tau i) of the three calcium current components. Inactivation time constants decreased with more positive Vc for all three calcium current components. Pentobarbitone reduced only those tau i corresponding to the N current. 5. Recovery from inactivation of the N current was determined using a two‐pulse protocol. In control neurones, recovery from inactivation occurring at 0 mV was slower at Vh = ‐65 mV than at Vh = ‐80 mV. In the presence of pentobarbitone, recovery from inactivation was faster, and occurred at a similar rate at both potentials. 6. Steady‐state inactivation curves for the N current were derived from neurones in the absence and presence of pentobarbitone.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of membrane currents in dissociated adult rat pineal cells.
Authors: Aguayo L G , Weight F F
Published: December 2014

1. Membrane currents, particularly the outward components, were studied in pineal cells acutely dissociated from adult rats using the whole‐cell variant of the patch‐clamp technique. 2. In current clamp, outward constant current elicited a transient graded depolarizing response. A sustained membrane rectification developed within 20 ms; this phenomenon was reduced in cells internally dialysed with 120 mM‐CsCl. 3. Study of the membrane current revealed the existence of a transient and a delayed outward current. These currents were virtually eliminated when the cell was internally dialysed with CsCl. 4. The delayed outward current, isolated from a holding potential of ‐50 mV, activated at potentials near ‐20 mV, reached a steady‐state current amplitude within 60 ms and had little or no decay during steps up to 400 ms in duration. This component was reduced by 80% or more with the addition of 5 mM‐TEA. 5. From ‐100 mV, the transient outward current reached a peak within 15 ms and decayed with a single‐exponential time course. The mean decay time constant was 66 +/‐ 10 ms (at ‐33 mV) and it showed little voltage sensitivity. This current, which activated at potentials positive to ‐60 mV and displayed half‐inactivation at ‐76 +/‐ 8 mV, was reduced by 50% with the addition of 5 mM‐4‐AP (4‐amino‐pyridine). 6. In the presence of external Ca2+, the current‐voltage relationship for the delayed current did not display a region of negative‐slope conductance (N‐shape). Increasing the intracellular ionized Ca2+ concentration by varying the Ca‐EGTA buffer ratio did not alter the dependence of the current on the membrane potential. 7. Block of outward currents with internal Cs+ revealed a small (less than 90 pA) inward Ca2+ current when the external Ca2+ concentration was increased to 10 mM. From a holding potential of ‐50 mV, it had a threshold at ‐30 mV and peaked at +5 mV. Evidence for an inward Na+ current was not obtained. 8. We conclude that acutely dissociated pineal cells display two distinct K+ currents: (i) a slowly activating, sustained current similar to the delayed rectifier (IK); and (ii) a transient A‐current (IA). At normal Ca2+ concentrations, no macroscopic Ca2+‐activated outward current was observed.
Use‐dependent reduction and facilitation of Ca2+ current in guinea‐pig myocytes.
Authors: Fedida D , Noble D , Spindler A J
Published: December 2014

1. Action potentials, calcium currents (iCa) and cell contraction have been recorded from single guinea‐pig myocytes during periods of stimulation from rest. Voltage clamp was carried out using a single microelectrode. Cell contraction was measured optically. All experiments were performed at 18‐22 degrees C. 2. An inverse relationship was observed between cell contraction and action potential duration or iCa. Mixed trains of action potentials and voltage clamp pulses preserved this relationship. Long voltage clamp pulses induced negative 'staircases' of iCa and positive 'staircases' of cell contraction. A facilitation of iCa was observed during repetitive stimulation with clamp pulses of 100 ms duration or less and was accompanied by a decrease in cell contraction. 3. The voltage dependence of inward current staircases was found to depend on Ca2+ entry rather than membrane voltage for long voltage clamp pulses and was not affected by 30 mM‐TEA or 50 microM‐TTX. Current reduction was greatest at 0 mV (P less than 0.05) when iCa was largest. Changes in cell contraction during pulse trains showed a similar voltage dependence. The time constant of current staircases was only mildly voltage dependent. 4. Interference with normal cellular mechanisms for Ca2+ uptake and release by strontium, 1‐5 mM‐caffeine and 1 microM‐ryanodine increased current staircases and could abolish iCa facilitation with short clamp pulses. 5. Variations in the level of Ca2+‐dependent inactivation of iCa can explain many features of the changes in iCa during stimulation after rest. Long clamp pulses (or action potentials) may increase cell Ca2+ loading and inhibit iCa. Short clamp pulses reduce available Ca2+ for cell contraction and this may reflect a lowered myoplasmic Ca2+ level which allows facilitation of iCa.
Mechanism of the use dependence of Ca2+ current in guinea‐pig myocytes.
Authors: Fedida D , Noble D , Spindler A J
Published: December 2014

1. The mechanism of the use‐dependent reduction and facilitation of the calcium current (iCa) in single guinea‐pig myocytes described by Fedida, Noble & Spindler (1988) has been examined by varying [Ca2+]o, [Ca2+]i and iCa. 2. Moderate enhancement of [Ca2+]i and [Ca2+]i changes produced by increasing [Ca2+]o reduces iCa and enhances the use‐dependent reduction. 3. Intracellular calcium overload, produced by reducing [Na+]o, greatly reduces iCa and almost totally eliminates the use‐dependent variations. 4. Use‐dependent reduction of iCa is also smaller after substituting external Ba2+ ions for Ca2+ ions. 5. When [Ca2+]i is buffered by intracellular EGTA sufficient to eliminate other [Ca2+]i‐dependent processes, such as contraction and Na+‐Ca2+ exchange, some use‐dependent reduction of iCa remains, although the effect is smaller. Use‐dependent facilitation of iCa is more prominent in the presence of internal EGTA. 6. The facilitation of iCa is abolished by Ba2+ replacement of Ca2+ and by the beta‐adrenoceptor agonist isoprenaline. This suggests that the facilitation is mediated by Ca2+ entry itself rather than membrane voltage. Facilitation is evident as a delay of current relaxation, even in the presence of internal EGTA.
Na+‐K+ pump activities of high‐ and low‐potassium sheep red cells with internal magnesium and calcium altered by A23187.
Authors: Fujise H , Lauf P K
Published: December 2014

1. Sheep erythrocytes were treated with the divalent metal ionophore A23187 to alter the cellular magnesium (Mgi) and calcium (Cai) composition. Ouabain‐sensitive Na+‐K+ pump fluxes were measured using rubidium as a potassium congener in media where Cl‐ was replaced by NO3‐. 2. A23187, per se, had no effect on ouabain‐sensitive rubidium influx. However, lowering the concentration of cellular magnesium [( Mg]i) and increasing that of calcium [( Ca]i) decreased Na+‐K+ pump flux. 3. Ouabain‐sensitive rubidium influx was found to be a saturating function of [Mg]i in high‐potassium (HK) red cells with a Hill coefficient of about 1.8 and an apparent half‐activation constant (K0.5) of 0.46 mmol/(l original cells). In low‐potassium (LK) cells, in the absence and presence of the Na+‐K+ pump stimulatory L‐antibody, ouabain‐sensitive rubidium influx was also saturated with Mgi yielding Hill coefficients of close to 1.8 and K0.5 values of 0.20 and 0.30 mmol/(l original cells), respectively. 4. When [Ca]i was raised at constant [Mg]i ouabain‐sensitive rubidium influx was inhibited at about 700 mumol/(l cells) in both HK, and in anti‐L‐treated LK red cells. 5. These data exclude the possibility that the Na+‐K+ pump turnover, known to be different in HK red cells, and in LK red cells in the absence and presence of anti‐L (Joiner & Lauf, 1978b), is based on differences in the activation by MgATP, and that Cai interacts with the Na+‐K+ pump cycle differently in the two red cell cation types.
Human eccrine sweat gland epithelial cultures express ductal characteristics.
Authors: Brayden D J , Cuthbert A W , Lee C M
Published: December 2014

1. Isolated human eccrine sweat glands were cultured in vitro. Cells were harvested and plated onto permeable supports to form confluent cell sheets, area 0.2 cm2. These were used to study the electrogenic transepithelial transport of ions by measurement of short‐circuit current (SCC). Epithelial sheets had a basal SCC of 5.89 +/‐ 0.62 microA cm‐2 (n = 33) and a transepithelial resistance of 74.1 +/‐ 5.6 omega cm2 (n = 33). The transepithelial potential difference varied between ‐0.2 and ‐1.8 mV with a mean value of ‐0.71 +/‐ 0.09 mV (n = 33). 2. The basal current was abolished by addition of 10 microM‐amiloride to the apical bathing solution. The concentration of amiloride which inhibited basal SCC by 50% (EC50) was 0.4 microM. Cultures prepared from the secretory coil of sweat glands, rather than from whole glands, were similarly sensitive to amiloride (EC50 = 0.8 microM). 3. Lysylbradykinin (LBK), carbachol, isoprenaline, prostaglandin E2 (PGE2) and A23187 all increased SCC in cultures from whole glands. LBK responses were obtained with basolateral and not with apical application. Furthermore LBK actions were not substantially altered by cyclo‐oxygenase inhibition but showed marked desensitization upon repeated application. Sheet cultures prepared from sweat gland coils also showed SCC responses to both carbachol and LBK. Forskolin, an activator of adenylate cyclase, did not alter SCC in either type of preparation. 4. Replacement of chloride and of chloride and bicarbonate in the bathing solution did not cause attenuation of the responses to LBK or carbachol in whole‐gland sheet cultures. Furthermore responses were unaffected by piretanide or acetazolamide. These results were taken to indicate that anion secretion was not the basis for the SCC responses. 5. Responses to LBK and carbachol were significantly reduced by amiloride (10 microM), this effect being reversible. No responses to LBK or carbachol were seen when N‐methyl‐D‐glucamine (NMDG) was used to replace sodium, whereas reintroduction of sodium ions restored responsiveness to these agents. 6. The SCC responses to the muscarinic agonist carbachol and to LBK appear to be due to stimulation of amiloride‐sensitive, electrogenic sodium absorption in whole‐gland sheet cultures. Further it would appear that, in culture, the pleuripotential capacity of the cells is revealed since both whole‐gland and secretory coil cultures exhibit some properties usually associated in vivo with duct cells. Many mammalian epithelia show electrogenic chloride secretion both in response to carbachol and LBK but also in response to activation of adenylate cyclase with forskolin.(ABSTRACT TRUNCATED AT 400 WORDS)
Ionic basis of receptor potential of frog taste cells induced by acid stimuli.
Authors: Miyamoto T , Okada Y , Sato T
Published: December 2014

1. The ionic mechanism underlying the receptor potential in frog taste cells induced by acid stimuli was studied with single microelectrodes by replacing superficial and interstitial fluids of the tongue with modified saline solutions. 2. The removal of Na+, Ca2+ and Cl‐ from the normal interstitial fluid did not affect the receptor potential induced by acid stimuli. Interstitial 100 mM‐K+ saline did not affect the acid response. 3. The receptor potential was reduced greatly when Ca2+ was removed from the superficial saline, but was increased when the Ca2+ concentration was elevated. The removal of superficial Cl‐ did not affect the receptor potential. The receptor potential elicited by superficial Ca2+‐free saline was partly due to Na+. Li+, K+, NH4+ or choline + substituted for Na+ in producing the receptor potential. The amiloride‐sensitive Na+ channel on the receptor membrane did not contribute to the receptor potential. With pure water adaptation of the tongue surface, the mean magnitude of the acid response was 35% of the control. 4. The receptor potential was unaffected by superficial tetrodotoxin (TTX) but was blocked by superficial Ca2+ antagonists such as Co2+ and Cd2+. Sr2+ substituted for Ca2+ in generating the receptor potential. 5. The receptor potentials observed under various concentrations of superficial Ca2+ became smaller when Na+ was present in the superficial fluid, indicating a competition between Ca2+ and Na+. 6. It is concluded that a large portion of the receptor potential induced by acid stimuli is produced by cations passing through a tastant‐gated Ca2+ channel on the taste receptor membrane. Both divalent (Ca2+, Sr2+) and monovalent (Na+, Li+, K+, NH4+, choline+) cations can pass through the Ca2+ channel. The other mechanism responsible for the remaining part of the receptor potential is discussed.
Taste responses in the nucleus tractus solitarius of sodium‐deprived rats.
Authors: Jacobs K M , Mark G P , Scott T R
Published: December 2014

1. Maintenance of sodium balance is crucial to mammals and is expressed in the innate salt appetite. With depletion, sodium preference is exaggerated, hypertonic solutions accepted and salt balance restored. This compensatory behaviour is thought to result from a centrally induced change in taste responsiveness. This proposal was tested by recording taste activity from ninety‐four single neurones in the nucleus tractus solitarius of sodium‐replete (N = 44) and of deprived (N = 50) rats. Twelve Wistar rats were given a nominally sodium‐free diet for 10‐13 days, and the resulting sodium depletion confirmed by flame photometry of their urine. Nine rats provided control data. Taste stimuli included five concentrations of NaCl (0.003‐0.3 M) plus eight other salts, acids, sugars and alkaloids. 2. Taste responsiveness was generally reduced in sodium‐depleted rats. Spontaneous activity was 33% lower while responses to sodium salts lagged by a mean of 30%, to acids by 25% and to bitter salts and quinine by 17%. Mean activity to sugars was 60% higher in the deprived group. 3. Activity in sugar‐ and salt‐profile neurones was most affected. In deprived animals responses to sodium salts were lower by 80% among salt‐profile cells while among sugar‐profile neurones activity to these stimuli was nearly 10 times greater than in controls. These changes in activity resulted in a dramatic shift in the participation of sodium‐ and sugar‐profile cells in the afferent signal for NaCl. In replete animals 60% of sodium‐induced activity was transmitted through salt‐profile cells while only 1% occurred in sugar‐profile neurones. In deprived subjects this situation was nearly reversed as 7% of the total NaCl response was conveyed through salt‐profile cells while the contribution of neurones with sugar‐profiles rose to 46%. 4. Multidimensional stimulus spaces based on average activity in each of four identifiable neurone subgroups demonstrated a shift in the affiliation of sodium salts away from bitter and acid stimuli and towards sugars. 5. These results confirm earlier findings from the chorda tympani that sodium deprivation suppresses activity evoked by sodium salts. However the application of more recent analytical procedures permits quite a different interpretation of this finding. The overall decrease is merely the net effect of a shift in the major responsibility for encoding sodium from salt‐profile neurones to those whose primary sensitivity is to sugars.(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanism of rate‐dependent pH changes in the sheep cardiac Purkinje fibre.
Authors: Bountra C , Kaila K , Vaughan‐Jones R D
Published: December 2014

1. The mechanism of the rate‐dependent decrease in intracellular pH (pHi) and its recovery were studied in isolated sheep cardiac Purkinje fibres. Intracellular Na+ activity (aiNa) and pHi were measured using ion‐selective microelectrodes. Twitches were elicited by field stimulation or by depolarizing pulses applied using a two‐microelectrode voltage clamp. 2. A 3 Hz train of short (50 ms) depolarizing voltage‐clamp pulses induced a reversible fall in pHi which was accompanied by a reversible increase in aiNa. A train of longer (200 ms) pulses also produced a fall in pHi which was now paralleled by a decrease in aiNa. These observations indicate that the rate‐dependent acidosis is not dependent upon a rise in aiNa. 3. Neither the fall in pHi nor the increase in aiNa seen upon an increase in action potential frequency was inhibited by amiloride (1 mmol l‐1) which indicates that Na+‐H+ exchange is not involved in the generation of the acidosis. Furthermore, the rate‐dependent acidosis was not abolished in Na+‐free solution (Li+ or N‐methyl glucamine substituted) indicating that other Na+‐requiring processes (such as Na+‐Ca2+ exchange) are not a necessary requirement. Rate‐dependent pHi changes were also unaffected by the stilbene compound DIDS indicating no participation by Cl‐‐HCO‐3 exchange. 4. The rate‐dependent acidosis was inhibited by the organic calcium antagonist D600 (20 mumol l‐1) which also inhibited twitch tension. This suggests that the acidosis is related to the activation by Ca2+ of developed tension. D600 also inhibited the rate‐dependent rise in aiNa (field stimulation). 5. The rate‐dependent acidosis was not inhibited by cyanide (2 mmol l‐1) but it was blocked by iodoacetate (0.5 mmol l‐1) and by 2‐deoxyglucose (DOG) (10 mmol l‐1, applied in glucose‐free solution). These results suggest that the acidosis is generated metabolically via stimulation of glycolysis, following an increase in contraction. Contributions from aerobic metabolism are likely to be small. 6. Twitch tension was inhibited by ryanodine (10 mumol l‐1) but the drug had little inhibitory effect on the rate‐dependent acidosis. A tonic component of tension was observed, however, in the presence of ryanodine. The lack of effect of ryanodine upon the rate‐induced acidosis is discussed. 7. The half‐time of pHi recovery from the frequency‐dependent acidosis was consistently shorter than that from an intracellular acid load induced by adding and then removing external NH4Cl (10 mmol l‐1).(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of anions on fluid reabsorption from the proximal convoluted tubule of the rat.
Authors: Green R , Greenwood S L , White S
Published: December 2014

1. Fluid reabsorption from surface proximal tubules of the rat was measured in vivo using stationary microperfusion techniques. Reabsorptive rate (Jv) was measured from droplets containing chloride as the main reabsorbable anion and when chloride was substituted by bromide, iodide, nitrate, acetate, isethionate or methylsulphate in either the tubular lumen alone or in both lumen and peritubular capillaries. 2. In tubules with an intact blood supply, droplet volume decreased in a manner best described by a single exponential and substitution of chloride by nitrate or bromide had no effect on Jv. Substitution by iodide or acetate inhibited Jv by approximately 17% but substitution by methylsulphate or isethionate caused droplets to transiently increase in volume before shrinkage which was itself inhibited by approximately 50%. The inhibitory action of isethionate was found to be concentration dependent. 3. Recollection and analysis of droplets which were initially free of chloride, containing either nitrate or isethionate, showed that chloride entered these droplets, but that the initial rate of chloride entry was greater for nitrate than isethionate droplets. 4. When tubules and capillaries were perfused with chloride solutions containing no bicarbonate, Jv was reduced to about 20% of the value when peritubular capillary blood flow was intact. Substituting chloride in the tubular and capillary perfusion revealed a sequence for supporting fluid reabsorption that was identical to that when chloride was substituted in tubule fluid alone: bromide = nitrate greater than iodide = acetate greater than isethionate. Addition of 2.0 mmol l‐1 NaCN reduced the reabsorptive flux to zero. 5. The results of this study are consistent with transcellular transport of anions across the proximal tubular epithelium. The pathways for anion transport are likely to involve a series of non‐selective mechanisms such as anion exchangers.
Parasympathetic depression of vas deferens contraction in the guinea‐pig involves adenosine receptors.
Authors: Kurokawa M , Tsunoo A
Published: December 2014

1. In the guinea‐pig pelvic plexus‐vas deferens preparation, stimulation of the parasympathetic pelvic nerves contracted the vas deferens then depressed the contractile responses to stimulation of the sympathetic hypogastric nerves. 2. The contraction caused by stimulation of the pelvic nerves was initially phasic then tonic. The contractions were almost abolished by application of hexamethonium to the plexus. The phasic contraction was abolished by alpha,beta‐methylene adenosine triphosphate applied to the vas deferens. 3. Conditioning stimulation of the pelvic nerves preferentially depressed the phasic component of test contractions evoked by hypogastric nerve stimulation but did not affect the compound action potentials in postganglionic nerves evoked by test stimulation. 4. When the pelvic plexus was divided into two parts, one with the pelvic nerves and the other with the hypogastric nerves, conditioning stimulation of the pelvic nerves still depressed test contractions evoked by hypogastric nerve stimulation. 5. In the de‐ganglionated vas deferens preparation, conditioning stimulation of some postganglionic nerves also depressed contractions evoked by test stimulation of the other postganglionic nerves. 6. 8‐Phenyltheophylline (5‐20 microM) applied to the vas deferens antagonized the conditioning stimulation‐induced depression in both the pelvic plexus‐vas deferens and the de‐ganglionated preparations. 7. N6‐Cyclohexyladenosine (CHA) and N6‐(L‐2‐phenylisopropyl)‐adenosine at 0.5 microM preferentially inhibited phasic contractions evoked by the postganglionic nerve stimulation. The effect of CHA was antagonized by 8‐phenyltheophylline (10 microM). 8. The results indicate that the mechanism underlying the conditioning stimulation‐induced depression of phasic contractions operates not in the ganglia, but through activation of adenosine receptors in the vas deferens.
Analysis of the cardiovascular changes induced in the rat by graded levels of systemic hypoxia.
Authors: Marshall J M , Metcalfe J D
Published: December 2014

1. In rats anaesthetized with Saffan, we have further analysed the respiratory, cardiac and regional vascular responses induced by 3 min periods of graded hypoxia (breathing 15, 12, 8 or 6% O2 in N2). 2. Frequently, hypoxia evoked an episode, lasting 1‐1.5 min, of tachycardia, renal and mesenteric vasoconstriction and skeletal muscle vasodilatation. The tachycardia and muscle vasodilatation persisted after vagotomy indicating they were not initiated by pulmonary stretch receptors secondary to hyperventilation. We propose that such episodes represented the cardiovascular components of the alerting‐defence response initiated by activation of the brain stem defence areas by peripheral chemoreceptors. 3. Each of these episodes was superimposed upon gradual hyperventilation, tachycardia, fall in arterial pressure and vasodilatation in renal, mesenteric and muscle circulation the magnitudes of which at 2 min were generally graded with the level of hypoxia. In the 3rd minute, respiration and heart rate tended to wane below control levels. 4. Vagotomy had little effect on the heart rate changes and only slightly reduced the peripheral vasodilatation allowing the conclusion that the gradual tachycardia and peripheral vasodilatation was not a reflex initiated by pulmonary stretch receptors. 5. Guanethidine given after vagotomy abolished the tachycardia indicating it was sympathetically mediated; possible initiating factors are discussed. But the secondary bradycardia persisted indicating it reflected the direct effect of hypoxia on cardiac pacemaker tissue. 6. The peripheral vasodilatation persisted after guanethidine or phentolamine indicating it was mainly attributable to the local vasodilator effects of tissue hypoxia. 7. It is proposed that the components of the alerting response are an integral part of the response to systemic hypoxia. Further, that in the rat this response is superimposed upon, but may be overcome by the direct effects of hypoxia on peripheral vasculature, heart and central nervous system.
Factors affecting the predictability of pseudo‐random motion stimuli in the pursuit reflex of man.
Authors: Barnes G R , Ruddock C J
Published: December 2014

1. Experiments have been performed on human subjects to determine the principal mechanisms underlying the break‐down in performance during ocular pursuit of pseudo‐random target motion stimuli composed of a mixture of two, four or six sinusoids. As observed in a previous experiment there was a reduction in the ratio of eye velocity to target velocity (eye velocity gain) for lower‐frequency components of the stimulus whenever the highest frequency exceeded 0.4 Hz, but the following effects were also observed. 2. Using a combination of four sinusoids in which the three lowest frequencies (0.11, 0.24 and 0.37 Hz) had a constant peak velocity (3 or 6 deg/s) it was shown that an increase in the velocity of the highest frequency (0.78 or 1.56 Hz) caused a progressive decline in gain of the low frequencies and a significant reduction in phase lag for the highest‐frequency component. 3. Using a combination of two sinusoids (0.44 and 1.56 Hz), in which the peak velocity was varied over a wide range (4‐32 deg/s), it was shown that the reduction in low‐frequency gain was dependent on the velocity ratio between the frequency components rather than their absolute velocity. 4. Experiments using a combination of either four or six sinusoids in which the two highest frequencies were very close have revealed a true enhancement in the gain of the highest‐frequency component in relation to other frequency components of the stimulus. 5. In the same experiments the phase relationships in the response were shown to vary according to the frequency range of the stimulus in such a way that phase advance was normally present at the lowest frequency even when this ranged up to 0.89 Hz. 6. When the oculomotor system was passively stimulated by allowing the subject to fixate a tachistoscopically illuminated stationary target, pseudo‐random target motion induced a response which exhibited characteristics similar to those of active pursuit; that is, enhancement of the gain of the highest frequency and phase advance at the lowest frequency. 7. During passive stimulation the changes in gain of the low frequencies with increasing frequency of the highest‐frequency component were not consistent with those of active pursuit. However, increasing the velocity of the highest‐frequency component to simulate the retinal velocity error conditions of normal active pursuit caused a significant decrease in low‐frequency gain and a subjective effect of high‐frequency dominance similar to that observed during active pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)
Rat brain glutamate receptors activate chloride channels in Xenopus oocytes coupled by inositol trisphosphate and Ca2+.
Authors: Oosawa Y , Yamagishi S
Published: December 2014

1. Ionic currents were studied in Xenopus laevis oocytes using the patch‐clamp and the whole‐cell voltage‐clamp techniques. 2. Single‐channel currents were recorded from the cell‐attached patches in oocytes injected with rat brain mRNA when glutamate was applied locally outside the patch. The single‐channel conductance was 3.66 pS, and the extrapolated equilibrium potential was ‐23.0 mV, indicating that the channels were chloride selective. 3. Single‐channel currents with similar characteristics were observed in cell‐attached patches in native oocytes in response to injection of inositol 1,4,5‐trisphosphate (IP3) or Ca2+. 4. Whole‐cell currents were evoked by glutamate in oocytes injected with rat brain mRNA. They usually showed an oscillatory component, and reversed direction at about the chloride equilibrium potential. Injection of IP3 or Ca2+ into a native oocyte evoked a transient whole‐cell current. The reversal potential was near the chloride equilibrium potential, and it changed from negative to positive in low‐chloride solution. 5. The results suggest that the glutamate receptors are not directly coupled with the endogenous chloride channels but indirectly activate these via the messenger system IP3‐Ca2+.
Dual effects of intracellular magnesium on muscarinic potassium channel current in single guinea‐pig atrial cells.
Authors: Horie M , Irisawa H
Published: December 2014

1. The effects of internal Mg2+ ions on the muscarinic acetylcholine (ACh) receptor‐mediated K+ currents were investigated in single atrial cells of guinea‐pigs, using the whole‐cell and inside‐out modes of the patch‐clamp technique. 2. During cell dialysis in the whole‐cell‐clamp condition, the depletion of internal Mg2+ increased outward muscarinic K+ currents but decreased inward currents, thereby reducing the inwardly rectifying property of the channels. 3. When inside‐out patches were prepared, channel availability was abolished and was reactivated by internal application of guanosine 5'‐triphosphate (GTP) or its non‐hydrolysable analogue, 5'‐guanylyl imidodiphosphate (GppNHp), in the presence of Mg2+. GppNHp led to a recovery of the channels also in the nominal absence of Mg2+ (0[Mg2+]i). 4. The activation of single‐channel currents by intracellular GTP and Mg2+ was dose‐dependent. Both concentration‐response curves were fitted by saturation kinetics with Hill coefficients of 1, and the half‐maximum doses were 24 +/‐ 8 microM for GTP and 67 +/‐ 14 microM for Mg2+. The effects of Mg2+ on activation of K+ currents were additive with those of GTP, suggesting the presence of two independent binding sites for GTP and Mg2+. 5. The single‐channel conductance became virtually ohmic when measured at nominally zero [Mg2+]i while GppNHp was used to recover the channel activity. Micromolar [Mg2+]i reduced the unitary amplitude of single open‐channel currents in a dose‐ and voltage‐dependent manner, showing half‐blocking doses of 293 microM at +40 mV and 115 microM at +60 mV. 6. Voltage‐dependent kinetics of Mg2+ block were described using equations based on Eyring rate theory (Woodbury, 1971; Hille, 1984), where the coefficient for voltage dependence (delta) was 0.63. 7. Intracellular Mg2+, at a physiological concentration, has a dual action on the muscarinic K+ channel: first Mg2+ activates the channel in the presence of GTP through GTP‐binding proteins (G proteins), and secondly it blocks outward currents through the channel, thereby causing the inwardly rectifying property.
Responses of electroreceptors in the platypus bill to steady and alternating potentials.
Authors: Gregory J E , Iggo A , McIntyre A K , Proske U
Published: December 2014

1. This is a report of further observations on the response characteristics of electroreceptors in the bill of the platypus, Ornithorhynchus anatinus, first described by Gregory, Iggo, McIntyre & Proske (1987). 2. The main finding is that, with the bill immersed in water, applying a potential difference between large plate electrodes on either side of the bill, produced detectable responses in a population of electroreceptors to field strengths as low as 4 mV cm‐1. Threshold for individual receptors lay between 4 and 25 mV cm‐1. 3. An electric dipole placed in the water close to the receptive field could also elicit responses, threshold being lowest when the cathode was near the centre of the field. On several occasions the most sensitive spot was seen, under the microscope, to correspond to the mouth of a mucous sensory gland (Andres & Von Düring, 1984). Response intensity fell when the dipole was moved further away, the drop being less steep in a direction over the top of the bill towards the mid‐line. 4. For individual receptors the latency of the first impulse initiated by supramaximal voltage pulses was 1.1‐1.8 ms. Latencies tended to be shorter when the site of the receptor lay closer to the recording electrodes. Plotting each latency against conduction path length for eleven receptors gave an approximately linear relation from which was calculated an average axonal conduction velocity of 56 m s‐1. The plot yielded an estimate of impulse initiation time of 0.8 ms. It is argued that this is too short to include a synaptic delay. A peripheral synapse is found in all non‐mammalian electroreceptors. 5. Electroreceptors responded to both steady and rapidly changing potential gradients. For ramp‐shaped gradients of 1‐50 V s‐1 peak firing rate was approximately proportional to log stimulus velocity. In response to sinusoidal potential changes a 1:1 relation between each afferent impulse and the peak of the stimulating waveform could be obtained over the range 12‐300 Hz. Threshold was at its lowest at 50‐100 Hz. Tuning curves measured with the bill immersed in water were little different from those obtained by focal stimulation with the bill in air. 6. It is concluded that platypus electroreceptors, supplied by the trigeminal nerve, and which are therefore not part of the acoustico‐lateralis system as in non‐mammalian electroreceptors, are also unique in not having a peripheral synapse. Furthermore, they are able to respond to both steady and rapidly changing voltage gradients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenal responses to calcitonin gene‐related 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 calcitonin gene‐related peptide (CGRP; 4 micrograms min‐1) have been investigated in the presence and absence of exogenous adrenocorticotrophin ACTH1‐24 (2 or 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 3‐7 days previously. 2. At the higher dose (5 ng min‐1 kg‐1) the I.V. infusion of ACTH raised mean plasma ACTH concentration by about 1000 pg ml‐1 and mean right adrenal cortisol output by about 750 ng min‐1 kg‐1. Under these conditions the intra‐aortic infusion of CGRP had no apparent effect on adrenal cortisol output by about 750 ng min‐1 kg‐1. Under these conditions the intra‐aortic infusion of CGRP had no apparent effect on adrenal function, other than to produce moderate adrenal vasodilatation. In contrast, in the absence of exogenous ACTH, the same dose of CGRP produced a substantial rise in cortisol output, which rose steadily to a peak mean value of 409 +/‐ 31 pg min‐1 kg‐1 at 10 min. It also significantly inhibited the release of free, but not of total, met5‐enkephalin‐like immunoreactivity from the gland (P less than 0.001) together with a significantly greater fall in adrenal vascular resistance (P less than 0.001). 3. At the lower dose of ACTH (2 ng min‐1 kg‐1, I.V.) CGRP raised mean plasma cortisol output from 314 +/‐ 31 to 486 +/‐ 44 ng min‐1 kg‐1 (P less than 0.01) and this effect was not attributable to an increase in the adrenal presentation rate of ACTH. 4. It is concluded that this peptide exerts a steroidogenic action on the adrenal cortex which is manifest in the absence of exogenous ACTH in the functionally hypophysectomized calf.
The effect of extracellular weak acids and bases on the intracellular buffering power of snail neurones.
Authors: Szatkowski M S
Published: December 2014

1. Intracellular pH (pHi) was measured in snail neurones using pH‐sensitive glass microelectrodes. The influence of externally applied weak acids and bases on the total intracellular buffering power (beta T) was investigated by monitoring the pHi changes caused by the intracellular ionophoretic injection of HCl. 2. In the absence of weak acids or bases a reduction in the extracellular HEPES concentration had no effect on pHi or on beta T. It did, however, reduce slightly the rate of pHi recovery following HCl injection. 3. The presence of CO2 greatly increased beta T. However, as predicted for an open buffer system, the contributions to intracellular buffering by CO2 (beta CO2) decreased as pHi decreased. 4. When added to the superfusate, procaine, 4‐aminopyridine, trimethylamine and NH4Cl (1‐10 mM) all increased steady‐state pHi. Procaine was fastest at increasing pHi and 4‐aminopyridine the slowest. All four of these weak bases increased beta T. 5. The intracellular buffering action by these weak bases varied. HCl injection in the presence of procaine usually resulted in steady‐state pHi changes with no pHi transients. In the presence of the other three weak bases HCl injections resulted in intracellular acidifications which were followed by pHi recovery‐like transients. However, these were not blocked by SITS (4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐disulphonic acid) or by CaCl2 and I thus conclude that these transients were as a result of slow or incomplete intracellular buffering by the weak bases. 6. In many cells there was a good correlation between the measured contributions to intracellular buffering by the weak bases (beta base) and those predicted assuming a simple two‐compartment open system. In all cases, as predicted, beta base increased as pHi decreased. 7. I found a clear relationship between the concentration of external buffer (HEPES) and the rate at which weak bases, applied to the superfusate, were able to increase pHi. The greater the extracellular buffer concentration the greater was the speed of intracellular alkalinization. 8. Lowering the extracellular buffer concentration reduced the efficiency of intracellular buffering by weak bases in response to an intracellular acid load. HCl injection in the presence of weak base caused a larger initial intracellular acidification if the extracellular HEPES concentration was reduced. 9. In conclusion, both weak acids and weak bases can make very large, pHi‐dependent contributions to intracellular buffering by way of open buffer systems.(ABSTRACT TRUNCATED AT 400 WORDS)
Synaptic control of excitability in turtle cerebellar Purkinje cells.
Authors: Hounsgaard J , Midtgaard J
Published: December 2014

1. In turtle Purkinje cells in vitro successive climbing fibre responses (CFRs) gradually induced a hyperpolarization that persisted with maintained stimulation and decayed over minutes after climbing fibre stimulation was terminated. 2. The rate of development and the amplitude of this long‐lasting hyperpolarization (LHP) increased with the frequency of CFRs. 3. The LHP was also induced by Ca2+ spikes evoked by current injection but not by Na+ spikes. The LHP was blocked by Co2+ but not by tetrodotoxin and could not be explained solely by an increased K+ conductance. 4. Depolarizing current during a train of CFRs enhanced the regenerative component of CFRs and promoted the LHP. Hyperpolarizing current during the stimulus train reduced the regenerative component of CFRs and attenuated the resulting LHP. 5. In the range of membrane potentials attained at different levels of climbing fibre activity the regenerative component of CFRs varied from being dominant at very low stimulus frequency (0.1 s‐1) to being inconspicuous at high stimulus frequency (10 s‐1). 6. It is concluded that successive CFRs induce a Ca2+‐dependent, long‐lasting hyperpolarization. The magnitude of the hyperpolarization is regulated by the rate of CFRs and by the voltage‐ and frequency‐dependent configuration of each individual CFR. 7. The active, non‐synaptic properties of turtle Purkinje cells make the Ca2+ influx during climbing fibre responses prone to regulation by on‐going synaptic activity and by the after‐effects of synaptic activity on a time scale of minutes. We suggest that this arrangement may enhance the capacity and complexity of spatial and temporal synaptic integration in Purkinje cells.
The properties of calcium‐activated potassium ion channels in guinea‐pig isolated hepatocytes.
Authors: Capiod T , Ogden D C
Published: December 2014

1. Unitary currents due to calcium‐activated potassium ion channels were studied in inside‐out or outside‐out excised membrane patches from guinea‐pig hepatocytes. 2. Potassium ion channels were identified which were activated by internal calcium ions and blocked by external apamin (50 nM) or (+)‐tubocurarine (10 microM). These properties are characteristic of the whole‐cell potassium conductance increase evoked in guinea‐pig hepatocytes by hormonal stimulation. 3. The single‐channel conductance was 20 pS in inside‐out or outside‐out patches with external and internal K+ ion concentrations of 150 and 135 mM respectively and gluconate anion. Reducing external K+ concentration to 5 mM reduced the unitary conductance for outward current to 6 pS. 4. The calcium sensitivity was investigated with buffered internal Ca2+ ion concentrations in the range 0.3‐2.2 microM. Tubocurarine‐sensitive channels had an open probability of less than 0.05 at 0.3 microM‐internal Ca2+. This increased steeply to a maximum of 0.85 at concentrations of 1.1 microM‐Ca2+ or higher. 5. In patches with a single channel active, analysis of open and closed intervals showed that openings occurred in bursts. The increase of open probability at high internal Ca2+ concentration was associated with prolonged bursts of channel opening. 6. Comparison of these results with data from whole‐cell conductance changes and with published levels of intracellular Ca2+ ion concentration (Woods, Cuthbertson & Cobbold, 1987) suggests that a large proportion, more than 40%, of potassium ion channels in guinea‐pig hepatocytes are activated by hormonal stimulation.
The effect of distension of the urinary bladder on activity in efferent renal fibres in anaesthetized dogs.
Authors: Drinkhill M J , Mary D A , Ramadan M R , Vacca G
Published: December 2014

1. To test whether distension of the urinary bladder causes a consistent change in activity in efferent renal nerve fibres, bladder distension was performed in anaesthetized dogs. The carotid sinuses were vascularly isolated and perfused with blood at constant flow. Both ureters were cannulated and the urinary bladder was distended with warm Ringer solution at a steady intravesical pressure. 2. In a first series of experiments all twenty‐six renal nerve fibres in eleven dogs which responded to changes in carotid sinus pressure and changes in the nature of the blood perfusing the carotid sinuses also responded to distension of the bladder. 3. In a second series of experiments, graded bladder distension over a range of pressure of 0‐9.2 kPa led to a graded increase in activity in thirteen efferent renal fibres in six dogs. The magnitude of the renal nerve response was greater at low than at high carotid sinus pressure. Over a range of carotid sinus pressure of 9‐30 kPa, the greatest renal nerve activity was obtained at the lower end of this range in the presence of bladder distension. 4. Thus distension of the urinary bladder resulted in the response of a consistent increase in efferent renal nerve activity, which could be graded according to intravesical pressure. The magnitude of the responses to bladder distension was affected by carotid sinus pressure.