bluuebunny/crossref_metadata_2025 huggingface dataset:
The maximum speed of shortening in living and skinned frog muscle fibres.
Authors: Julian F J , Rome L C , Stephenson D G , Striz S
Published: December 2014

This study was performed to determine whether Viso (the maximum speed of shortening extrapolated from force‐velocity curves) equalled Vu (the unloaded speed of shortening determined by the slack test) in both living fibres from Rana temporaria and mechanically skinned fibres from Rana pipiens. In living fibres (R. temporaria) we obtained improved estimates of Viso by performing force clamps (isotonic) and length ramps (isovelocity) down to very low loads (0.005 isometric tension, P0). Force‐velocity characteristics determined by force clamps and length ramps were the same. The hyperbolic Hill curves deviated from the force‐velocity data at both high and low loads and underestimated Viso by varying degrees. A better estimate of Viso was obtained by linear extrapolation of data at loads from 0.005‐0.02 P0 and the mean Viso at 7.5 degrees C was 4.08 muscle lengths/s +/‐ 0.11 (mean +/‐ S.E., n = 14). Improved estimates of Vu in living fibres were obtained by photographically calibrating the slack test. The mean Vu was 4.05 muscle lengths/s +/‐ 0.13 (mean +/‐ S.E., n = 14) and the intercept was 0.0156 fibre lengths (L0) +/‐ 0.0013 (mean +/‐ S.E., n = 14). The step‐ramp photographic method, in which the motor speed is matched to Vu, was developed as an independent way to measure Vu in living fibres. Vu measured in this way agreed well with Vu measured by the slack test. In all living fibres, the improved estimates of Vu agreed well with the improved estimates of Viso. Vu/Viso = 0.99 +/‐ 0.01 (mean +/‐ S.E., n = 14). In mechanically skinned R. pipiens fibres, force clamps were performed down to loads of 0.01 mN. The force‐velocity curve of the skinned fibres differed in shape from that of the living fibres. Although there was significant deviation from the Hill equation at low loads, the data at high loads were well fitted by the Hill curve. Viso determined by extrapolating the Hill equation to zero load was 5.87 muscle lengths/s +/‐ 0.38 (mean +/‐ S.E., n = 9) at 7.5 degrees C. In five fibres, the linear extrapolation of low loads (0.01‐0.05 P0) showed that the Hill equation underestimated the true Viso by 6%. The slack test with mechanically skinned fibres was calibrated by taking a series of photographic exposures of the fibre at various times following each length step. Vu = 6.12 muscle lengths/s +/‐ 0.44 (mean +/‐ S.E., n = 10) and the intercept was 0.0585 L0 +/‐ 0.0069 (mean +/‐ S.E., n = 10).(ABSTRACT TRUNCATED AT 400 WORDS)
Ventilation and cardiac output during the onset of exercise, and during voluntary hyperventilation, in humans.
Authors: Cummin A R , Iyawe V I , Mehta N , Saunders K B
Published: December 2014

Three normal subjects performed rest‐‐exercise transitions on a cycle ergometer, from rest to unloaded pedalling (0 W), 50, 100 and 150 W. Each experiment was performed in triplicate, with randomized work load order, in two sessions. Ventilation was obtained breath‐to‐breath by integration of a pneumotachygraph signal, and cardiac output beat‐to‐beat by a new development of the Doppler technique. Results were bin‐averaged in 4 s bins over the first 20 s, and compared to resting values. Both ventilation and cardiac output increased significantly in the first 2 s. This initial rise in ventilation was due entirely to an increase in rate, the subsequent rise mainly to increase in tidal volume. Cardiac output increased predominantly through change in rate with smaller increases in stroke volume. A striking feature was a tendency for ventilation and cardiac output responses to be biphasic with an initial rise followed by a slight fall at the 14 s mark, and a subsequent rise, at all work loads. Overall correlation between ventilation and cardiac output was therefore high (r = 0.92). Six normal subjects hyperventilated for 45 s voluntarily, (a) at rate 24/min and normal tidal volume; (b) at normal rate and tidal volume of 1.5 l; (c) at rate 24/min and tidal volume of 1.5 l. Cardiac output, averaged over 10‐45 s, rose by 0.4, 0.5, and 1.0 l min‐1 respectively, with falls in end‐tidal PCO2 of 4, 6, and 8 mmHg. Six normal subjects hyperventilated for 60 s with rate 24/min and tidal volume of 1.4 l, and end‐tidal PCO2 maintained at 38 +/‐2 mm Hg. Cardiac output, averaged from 10‐60 s, rose by 1.0 l min‐1. With increased rate and tidal volume, whether isocapnic or hypocapnic, cardiac output responses showed an overshoot with a peak value at about 30 s. The hypothesis of 'cardiodynamic hyperpnoea' considers a possible effect of increasing cardiac output on ventilation. The effects of ventilation on cardiac output must also be considered. We propose an extended hypothesis involving stable positive feed‐back.
Spatial interaction in the domain of disparity signals in human stereoscopic vision.
Authors: Westheimer G
Published: December 2014

When a few isolated features are viewed foveally, changes in the binocular disparity of one introduces apparent depth changes in others. For features a very few minutes of arc apart, the effect is equivalent to a pooling of their disparity signals, even though the features are seen distinctly as separate. When the distance between them is 4‐6 minutes of arc or more, the effect is in the opposite direction: the features act as if they repelled each other in depth. Using a null method, it was possible to characterize this interaction effect numerically. There are some quantitative, but no qualitative, differences between observers, and in any one observer the disparity interaction between vertically separated targets is not necessarily the same as between horizontally separated ones. The disparity interaction effect is seen with presentations both of 50 ms and of 1 s duration. There is a very small temporal after‐effect, seen when the extinction of inducing flanks is synchronous with test target onset.
Changes by acetylcholine of membrane currents in rabbit cardiac Purkinje fibres.
Authors: Carmeliet E , Mubagwa K
Published: December 2014

The ionic mechanisms underlying the effects of acetylcholine (ACh) on electrophysiological properties of rabbit cardiac Purkinje fibres have been analysed using the two‐micro‐electrode voltage‐clamp technique on short preparations. In normal Tyrode solution, ACh shifted the membrane currents in the outward direction at potentials positive to the K+ equilibrium potential, EK, and in the inward direction at potentials negative to EK. When ACh effects were studied in various [K+]o the reversal potential for the ACh‐induced current was changed in a way expected for a pure K+ electrode. The results indicate an increase of an inward‐rectifying K+ conductance by ACh. ACh also decreased the magnitude of the late outward current (ix). The activation curve for this current was not modified, but the fully activated current was decreased. The effect of ACh on ix was more pronounced in the presence of catecholamines. The slow inward current (isi) was not changed by ACh in control conditions. However, the increase produced by beta‐adrenergic stimulation in this current was suppressed by ACh in a concentration‐dependent way.
The action potential and underlying ionic currents in proximal rat middle cerebral arterioles.
Authors: Hirst G D , Silverberg G D , van Helden D F
Published: December 2014

The active and passive electrical properties of isolated segments (length 120‐220 microns, diameter 60‐150 micron) of proximal rat middle cerebral arterioles (less than 1 mm from parent artery) were analysed using a single‐electrode current or voltage clamp. The voltage response to a current step exhibited an exponential time course. The mean resistance and time constant was 102 M omega and 265 ms corresponding to approximate specific resistance and capacitance of 60 k omega/cm and 4 micro F/cm2. Membrane resistance was constant in the range ‐55 to ‐80 mV. At potentials more negative than ‐80 mV there was a decrease in membrane resistance resulting in activation of an inward rectifier. At membrane potentials less negative than ‐50 mV the membrane resistance decreased; larger depolarizations (greater than ‐40 mV) initiated small regenerative responses. External application of tetraethylammonium chloride caused membrane depolarization (10‐15 mV), spontaneous discharge of action potentials and rhythmic arteriolar constriction. Action potentials studied with the membrane held at ‐60 mV had a large rapid depolarizing component, an after‐depolarization and a small slower after‐hyperpolarization. Tetrodotoxin (TTX) had no effect on the action potential. However, both the fast and slow components of the action potential were suppressed by extracellular removal of calcium ions and/or addition of cobalt ions, nifedipine or verapamil. Voltage‐clamp studies demonstrated an inward rectifying current at membrane potentials more negative than ‐80 mV. At depolarized potentials at least four separate currents were activated; two separate calcium currents and two outward currents.
Dose‐response of acetylcholine receptor channels opened by a flash‐activated agonist in voltage‐clamped rat myoballs.
Authors: Chabala L D , Gurney A M , Lester H A
Published: December 2014

Whole‐cell or single‐channel currents through acetylcholine (ACh) receptor channels were studied in voltage‐clamped rat myoballs or in excised membrane patches from myoballs. The recording pipette contained CsCl to suppress outward currents, and tetrodotoxin was used to help suppress Na+ currents. To minimize problems associated with bath applied agonists, myoballs were bathed in a solution containing the inactive (cis) isomer of the photo‐isomerizable azobenzene derivative, Bis‐Q. Calibrated light flashes of varying intensity were presented to produce concentration jumps of agonist, trans‐Bis‐Q. The resulting whole‐cell current relaxations through ACh channels approach a steady state along an exponential time course, then decline as the newly created agonist diffuses away over the next few seconds. The dose‐response relationship was inferred from Hill (double‐log) plots for myoballs bathed in 500 nM‐cis‐Bis‐Q at three membrane potentials. At low agonist concentrations (less than 300 nM‐trans‐Bis‐Q), the slope of the Hill plot averaged 1.62 at ‐150 mV, 1.89 at ‐100 mV, and 2.05 at +80 mV. These results are consistent with an apparent agonist affinity constant that decreases with membrane depolarization and shifts the responses further down on the dose‐response curve. When the myoballs were bathed in higher concentrations of cis‐Bis‐Q (1.5‐20 microM), the slope of the Hill plot was reduced at all membrane potentials, although it was still closer to two at positive potentials. This is expected from the known sigmoid shape of the dose‐response relation. The shallow dependence of the Hill slope on agonist concentration suggests the presence of negative cooperativity in the over‐all binding of agonist molecules. Following treatment of the membrane with dithiothreitol to reduce disulphide groups, the Hill slope for the reversibly bound agonist, trans‐Bis‐Q, remained near two. The kinetics of currents at hyperpolarized membrane potentials became complicated at higher agonist concentrations in a manner that was consistent with open‐channel block by trans‐Bis‐Q; the currents showed a slow secondary increase in conductance. Averaged single‐channel recordings at higher agonist concentrations resemble macroscopic relaxations under comparable conditions. Furthermore, those recordings also suggested that open channels are blocked by trans‐Bis‐Q at concentrations greater than 2 microM; the block depends strongly on membrane potential and increases with hyperpolarization. Currents at positive membrane potentials showed no evidence of open‐channel block.(ABSTRACT TRUNCATED AT 400 WORDS)
Lesions in the cat prepositus complex: effects on the vestibulo‐ocular reflex and saccades.
Authors: Cheron G , Godaux E , Laune J M , Vanderkelen B
Published: December 2014

The effects of bilateral electrolytic lesions within and around the prepositus hypoglossi (p.h.) nucleus on horizontal saccades in the dark and on the horizontal sinusoidal vestibulo‐ocular reflex (v.o.r.) in the dark were studied. After p.h. lesion, including its rostral part between P 7 and P 8, the v.o.r. showed a phase lead as much as about 90 deg at 0.10 Hz. A significant gain reduction paralleled that phase lead at lower frequencies. A large post‐saccadic drift was also observed, the time constant of which ranged from 0.3 to 0.6 s. After p.h. lesion extending from P 8 to P 11 (but sparing the rostral part of the p.h.), no significant gain or phase lead change was observed. Post‐saccadic drift was either missing or weak. A bilateral medial vestibular nucleus (m.v.n.) lesion from P 7 to P 11 produced a marked gain decrease, paralleled by a marked phase advance. A post‐saccadic drift was observed (tau = 0.6 s). A surgical mid‐line lesion from P 7 to P 11 (depth: about 2 mm) was followed by no remarkable change in the gain and in the phase of the v.o.r. No post‐saccadic drift was observed after such lesion. It was concluded that (i) both the horizontal v.o.r. integration processing, and the horizontal saccadic integration processing were destroyed when an electrolytic lesion was made 'in the region of' the rostral part of the p.h. nucleus, and that (ii) the posterior four‐fifths of the p.h. was the location of neither the horizontal v.o.r. integrator nor the horizontal saccadic integrator.
The vestibulo‐ocular reflex during human saccadic eye movements.
Authors: Laurutis V P , Robinson D A
Published: December 2014

Eye and head movements were recorded in normal humans during rapid refixations with the head still (saccades) or moving (gaze saccades) to determine if the vestibulo‐ocular reflex was operating at such times. Subjects made self‐electrooculogram for large saccades and with the eyecoil/magnetic field method for smaller movements. The putative function of the vestibulo‐ocular reflex during a gaze saccade is to adjust the movement of the eye for the movement of the head by adding the saccadic command and the vestibular signal. This action, referred to here as linear summation, would maintain gaze‐saccade accuracy by making gaze velocity (eye in space) independent of head velocity. It would also preserve the duration of the eye saccades of about 200 deg. When a subject increased his head velocity voluntarily, for example, from 420 to 805 deg/s, mean gaze velocity rose from 540 to 820 deg/s and duration dropped from 380 to 250 ms. Linear summation did not occur. By means of a yoke clenched in the teeth, the subject's head could be momentarily and unexpectedly slowed by collision of the yoke with a lead weight during a 180 deg gaze saccade. The perturbation decreased head velocity by about 150‐200 deg/s, decreased gaze velocity by about the same amount and did not change eye velocity (in the head); another indication that the vestibulo‐ocular reflex was not working. Nevertheless, gaze‐saccade duration was automatically increased so that the over‐all accuracy of the movement was not changed. Subjects made saccades between targets at +/‐ 20 deg without attempted head movements. Simultaneously the experimenter struck the yoke, clenched in the subject's teeth, with a rubber hammer. The hammer blow caused a transient head velocity of about 70 deg/s. Gaze velocity transiently rose or fell, depending on the direction of the blow, by similar amounts and a quantitative analysis suggested that the vestibulo‐ocular reflex was essentially absent. Again, duration was automatically altered so that saccade accuracy was not changed. Subjects looked back and forth between targets 20, 40 and 60 deg apart as their head turned through the straight ahead position, actively or passively, at velocities up to 600 deg/s (active) or 300 deg/s (passive).(ABSTRACT TRUNCATED AT 400 WORDS)
The arrhythmogenic current ITI in the absence of electrogenic sodium‐calcium exchange in sheep cardiac Purkinje fibres.
Authors: Cannell M B , Lederer W J
Published: December 2014

Sheep cardiac Purkinje fibres were voltage clamped with a two‐microelectrode technique. Under conditions that are known to elevate intracellular calcium (0 mM‐external potassium), membrane currents were examined. In the above conditions, a brief depolarizing pulse leads to an oscillatory inward current (ITI) which peaks at about 300 ms after the repolarization. An after‐contraction is also observed, the peak of which occurs about 80 ms after the peak of ITI. This result is in accord with the results of Kass, Lederer, Tsien & Weingart (1978a). We replaced external sodium with an isotonic CaCl2 solution to remove the sodium‐calcium exchange mechanism as a possible current carrier for ITI. In the steady state under these conditions an oscillatory membrane current and after‐contraction are seen following repolarization. This current was identified as ITI on the basis of its temporal relation to both the repolarization step and the after‐contraction. In isotonic CaCl2, ITI has a reversal potential of ‐37 mV. Because of this fact ITI cannot be explained by an electrogenic sodium‐calcium exchange mechanism alone. The reversal potential suggests that ITI arises from a channel which is permeable to both potassium and calcium. Fluctuations of membrane current and of tension were recorded in the steady state at different holding potentials. Power spectral analysis showed that the current fluctuations were at a minimum at a holding potential of ‐37 mV. Tension fluctuations were, however, relatively constant over the range of membrane potentials examined (‐17 to ‐70 mV). The peak power of the current fluctuations occurred at about 1.5 Hz (at a holding potential of ‐70 mV). This peak shifted towards higher frequencies with increasing depolarization. A similar shift in frequency was observed for the tension fluctuations. Cross‐correlations between membrane current and tension were calculated for various steady membrane potentials. This analysis shows that the current fluctuations are associated with the tension fluctuations, each with a principal period of about 0.5 s. This analysis also shows that at potentials more negative than the reversal potential of ITI, increasing tension is associated with increasing inward current and that the tension fluctuations follow current fluctuations by about 70 ms. At potentials positive to the reversal potential of ITI, increasing tension was associated with increasing outward current. This analysis therefore indicates that the fluctuations in membrane current reverse at a potential similar to the reversal potential of ITI.(ABSTRACT TRUNCATED AT 400 WORDS)
Non‐cholinergic transmission in a sympathetic ganglion of the guinea‐pig elicited by colon distension.
Authors: Kreulen D L , Peters S
Published: December 2014

Sensory transmission from the colon was studied using a preparation of inferior mesenteric ganglion (i.m.g.) attached to a segment of distal colon in guinea‐pigs, in vitro. Electrical responses to colon distension were recorded intracellularly from neurones of the i.m.g. Distension of the distal colon up to an intraluminal pressure of 20 cmH2O caused an increase in resting asynchronous synaptic activity and a concomitant slow depolarization. The asynchronous synaptic activity, but not the slow depolarization, was abolished by cholinergic antagonists. Distension‐induced non‐cholinergic depolarizations were elicited in 44% of i.m.g. neurons sampled. For distensions of 1 min at 10‐20 cmH2O, depolarizations reached a mean amplitude of 3.4 +/‐ 0.3 mV and lasted 108 +/‐ 7 s. Continuous distension resulted in a tachyphylaxis of the depolarization. Tetrodotoxin (3 X 10(‐7) M) superfused over the i.m.g. reversibly abolished the distension‐induced non‐cholinergic depolarization. Distension‐induced non‐cholinergic depolarizations were accompanied by an increase in input resistance of 21%. Neuronal excitability also increased, as sub‐threshold potentials produced by intracellular current injection reached threshold for firing action potentials during colon distension. The amplitude of non‐cholinergic depolarizations increased with colonic intraluminal pressure between 2 and 20 cmH2O, although the slope of the mean amplitude‐pressure curve decreased progressively at higher pressures. The amplitude of distension‐induced non‐cholinergic depolarizations increased as membrane potential was manually hyperpolarized to approximately ‐80 mV, whereupon further hyperpolarization resulted in a decrease in response amplitude. Non‐cholinergic slow excitatory post‐synaptic potentials (e.p.s.p.s) evoked by repetitive presynaptic nerve stimulation were reversibly attenuated by 19 +/‐ 8% during depolarizations produced by distension. Systemic administration of capsaicin (50‐350 mg/kg) reduced the number of i.m.g. neurones exhibiting the non‐cholinergic mechanosensory response; direct superfusion of capsaicin over the i.m.g. attenuated the response in some neurones but had no effect in others. These results demonstrate the existence of a non‐cholinergic mechanosensory pathway from the colon to the i.m.g., and suggest that non‐cholinergic transmission in the ganglion participates in mediating gastrointestinal reflexes. One transmitter utilized by the non‐cholinergic mechanosensory pathway may be substance P.
Receptive field profiles and integrative properties of spinocervical tract cells in the cat.
Authors: Brown A G , Noble R , Rowe M J
Published: December 2014

The receptive fields of sixteen spinocervical tract (s.c.t.) cells whose responses were recorded extracellularly were mapped using discrete and uniform jets of air given at equally spaced locations on the clipped fur of cats anaesthetized with chloralose. All the cells whose receptive fields were on the thigh or upper hind limb showed approximately unimodal gradients of sensitivity to stimulation within their excitatory receptive fields. The response magnitudes declined steadily as the stimuli were moved sequentially from the centres to the peripheries of the fields and abrupt edges were not found. Spatial summation from within the excitatory receptive field was studied in twelve s.c.t. cells. These cells showed a poor ability to summate the responses to two spatially separated air jets when these stimuli were applied simultaneously within their receptive fields. No significant summation was found in twenty‐five out of thirty‐one trials and in six of these trials (four cells) the responses were significantly reduced. Summation was found in six trials (four cells). Lack of summation or response reduction was more prevalent when the individual response levels were low (less than impulses stimulus‐1). These results are discussed in relation to similar findings for cells of somatosensory relay nuclei and cortex.
Effect of solute concentration on intracellular water volume and hydraulic conductivity of human blood platelets.
Authors: Armitage W J
Published: December 2014

The intracellular water volume of human blood platelets was determined using tritiated water. The cells responded as osmometers over an observed range of solute concentration from 0.292 to 2.180 osmol kg‐1. Only 87% of intracellular water was apparently osmotically active (i.e. Ponder's R was 0.87). Changes in cell volume induced by small step changes in external osmolality were followed photometrically and the time constant for the exponential approach of cell volume to its new equilibrium value was determined. Hydraulic conductivity (LP) was calculated from the time constant and was 1.41 X 10(‐6) cm atm‐1 s‐1 under isotonic conditions at 37 degrees C. LP was inversely dependent on extracellular solute concentration, but it was independent of the direction of movement of water across the plasma membrane.
The effects of anaesthetics and high pressure on the responses of the rat superior cervical ganglion in vitro.
Authors: Little H J , Thomas D L
Published: December 2014

The effects of helium pressure and of general anaesthetics were studied on the responses of the isolated superior cervical ganglion of the rat, to determine how far these reflected the pressure reversal of anaesthesia seen in vivo. The method of Brown & Marsh (1974) for extracellular recording of surface potentials was adapted for use in a high‐pressure chamber. Helium alone, at 130 atm, did not alter the responses of the ganglion to gamma‐aminobutyric acid (GABA) but significantly depressed the depolarizing and hyperpolarizing components of the nicotinic responses, and the muscarinic responses. The potentiation of the responses to GABA caused by pentobarbitone was not altered by the application of helium, at 130 atm. This pressure also decreased further the nicotinic responses which were depressed by pentobarbitone. Nitrogen, at 34 atm (the anaesthetic ED50 in vivo) and at 68 atm, significantly decreased the nicotinic responses of the ganglia, and the addition of helium to a total of 130 atm further increased this depression. At pressures of 3.3‐68 atm, nitrogen caused small decreases in the responses to GABA. Nitrous oxide at 1.5 atm (the ED50 for loss of righting reflex in mice) and at 3 atm, significantly depressed the responses to GABA and to the nicotinic agonist, but did not alter the responses to methylfurmethide. The effects of nitrous oxide were unaltered when helium was added to a total of 130 atm, although this pressure of helium added alone significantly depressed the cholinergic responses. A mixture of 50% nitrous oxide and 50% oxygen, when added to the pressure chamber, at normal atmospheric pressure, caused transient increases in the responses to GABA. The effects of temperature on GABA responses and on nicotinic responses were very different from those of pressure. Preliminary evidence suggested that raising the temperature may decrease the extent of potentiation of GABA responses by pentobarbitone. The results are discussed in relation to the pressure reversal of anaesthesia in vivo. It was concluded that there was no evidence that the basis of this interaction lay in the potentiation of GABA responses by general anaesthetics, or the depression of cholinergic responses, although the changes seen were not in all cases simply additive. It was considered that effects of general anaesthetics such as the potentiation of GABA may contribute to the effects used to measure general anaesthesia in vivo, such as loss of righting reflex, but may not be related to the non‐specific actions which cause anaesthesia.
Facilitation of transmitter action on catecholamine output by cardiac glycoside in perfused adrenal gland of guinea‐pig.
Authors: Nakazato Y , Ohga A , Yamada Y
Published: December 2014

Effects of K+ deprivation and ouabain on catecholamine secretion evoked by splanchnic nerve stimulation (5 Hz), ACh (10(‐5) M) and/or excess K+ (56 mM) were studied in isolated and perfused adrenal glands of guinea‐pig. Exposure to K+‐free Locke solution initially reduced and later enhanced catecholamine secretion sequentially evoked by splanchnic nerve stimulation and ACh. The enhancement attained a maximum, 185% in magnitude of the corresponding control response at 35 min for splanchnic nerve stimulation and 135% at 65 min for ACh after the start of exposure to K+‐free solution. Ouabain (10(‐5) M) caused a larger increase in the evoked catecholamine section than K+ deprivation did. The maximum effect was obtained from 40 to 50 min after the start of exposure to ouabain in which the magnitude of responses to splanchnic nerve stimulation, excess K+ and ACh was about 500, 400 and 300% of each control response, respectively. The effect of ouabain on the evoked catecholamine secretion increased as the concentration of extracellular Na+ was increased from 25 to 154 mM, regardless of the kind of stimuli. The ouabain‐induced enhancement in the evoked responses was reversibly inhibited by removing Ca2+ from, or by adding Mg2+, Co2+ or Ni2+ to the perfusion medium. The ID50 values for Mg2+ were about 9.4 and 7.3 mM and those for Co2+ were 0.8 and 0.4 mM against ouabain on the responses to ACh and excess K+, respectively. The inhibitory effect of Mg2+ and Co2+ on the ouabain action was counteracted by increasing the concentration of Ca2+ from 2.2 to 8.8 mM in the perfusion medium. These results suggest that ouabain enhances catecholamine secretion evoked by splanchnic nerve stimulation, ACh and excess K+ by increasing the rate of Ca2+ influx through the ACh receptor linked Ca2+ channel and/or voltage‐dependent Ca2+ channels on adrenal chromaffin cells of guinea‐pig in a Na+‐dependent manner.
Metabolic consequences of increasing intracellular calcium and force production in perfused ferret hearts.
Authors: Allen D G , Eisner D A , Morris P G , Pirolo J S , Smith G L
Published: December 2014

31P nuclear magnetic resonance was used to measure the relative concentrations of phosphorus‐containing metabolites in Langendorff‐perfused ferret hearts. Intracellular concentrations of inorganic phosphate ([Pi]i), phosphocreatine [( PCr]i), ATP ([ATP]i) and [H+] (pHi) were determined. Exposure of the heart to strophanthidin (10‐40 microM) produced an increase in developed pressure over 5‐10 min. In the presence of strophanthidin, [ATP]i was unchanged, [PCr]i showed a small fall, [Pi]i showed a small rise and there was a small acidosis. Exposure of the heart to a solution in which all the Na had been replaced by K (0 Na(K) solution) produced an increase of resting pressure which then decayed. During this contracture [PCr]i fell transiently and [Pi]i rose transiently with approximately the same time course as the contracture. However, [ATP]i remained constant throughout. The exposure to the 0 Na(K) solution also produced an intracellular acidosis. The changes in [PCr]i and [Pi]i and the intracellular acidosis were all increased during perfusion with 0 Na(K) if the heart had previously been exposed to strophanthidin. The efflux of lactate from the heart was increased during the exposure to the 0 Na(K) solution. The magnitude of this increase was enhanced by prior exposure to strophanthidin. The increase of intracellular lactate (calculated from this efflux) was sufficient to account for the observed intracellular acidification. An increase of lactate efflux could also be measured when an isolated papillary muscle was exposed to the 0 Na(K) solution. The intracellular acidification produced by Na removal was substantially decreased after prevention of glycolysis either by substrate depletion or by the application of iodoacetate. Elevation of the extracellular calcium concentration ([Ca2+]o) produced a large increase of developed pressure which was accompanied by a small transient increase of [Pi]i, a decrease of [PCr]i and a small intracellular acidosis. There was also an increase of lactate efflux. After exposure to strophanthidin the same increase of [Ca2+]o decreased developed pressure. The associated rise in [Pi]i and fall in [PCr]i were increased but there was no significant acidosis under these conditions. In addition to other explanations (Allen, Eisner, Pirolo & Smith, 1985a), it is likely that the fall of force is partly accounted for by the rise of [Pi]i.
Properties of the hyperpolarizing‐activated current (if) in cells isolated from the rabbit sino‐atrial node.
Authors: DiFrancesco D , Ferroni A , Mazzanti M , Tromba C
Published: December 2014

Individual cells were isolated from the sino‐atrial node area of the rabbit heart using an enzyme medium containing collagenase and elastase. After enzymatic treatment the cells were placed in normal Tyrode solution, where beating resumed in a fraction of them. Isolated cells were studied in the whole cell configuration. Action potentials as well as membrane currents under voltage‐clamp conditions were similar to those in multicellular preparations. Pulses to voltages more negative than about ‐50 mV caused activation of the hyperpolarizing‐activated current, if. Investigation of the properties of this current was carried out under conditions that limited the influence of other current systems during voltage clamp. The if current activation range usually extended approximately from ‐50 to ‐100 mV, but varied from cell to cell. In several cases, pulsing to the region of ‐40 mV elicited a sizeable if. Both current activation and deactivation during voltage steps had S‐shaped time courses. A high variability was however observed in the sigmoidal behaviour of if kinetics. Plots of the fully‐activated current‐voltage (I‐V) relation in different extracellular Na and K concentrations showed that both ions carry the current if. While changes in the external Na concentration caused the current I‐V relation to undergo simple shifts along the voltage axis, changes in extracellular K concentration were also associated with changes in its slope. Again, a large variability was observed in the increase of I‐V slope on raising the external K concentration. The current if was strongly depressed by Cs, and the block induced by 5 mM‐Cs was markedly voltage dependent. Adrenaline (1‐5 microM) and noradrenaline (1 microM) increased the current if around the half‐activation voltage range and accelerated its activation at more negative voltages. Often, however, drug application failed to elicit any modification of if. Current run‐down was observed in nearly all cells, although at a highly variable rate. It was accelerated by raising the extracellular K concentration but did not show a marked use dependence. Both the if activation curve and the fully activated I‐V relation were affected by run‐down, the former being shifted to more negative values along the voltage axis and the latter being depressed with no apparent change of the if reversal potential.(ABSTRACT TRUNCATED AT 400 WORDS)
The stiffness of frog skinned muscle fibres at altered lateral filament spacing.
Authors: Goldman Y E , Simmons R M
Published: December 2014

When the surface membrane is removed from a frog muscle fibre the myofibrils swell, so that the spacing between the filaments increases by 10‐30%. In this study, the stiffness of skinned fibres was measured when the lateral spacing of the filament lattice was reduced osmotically using polyvinyl pyrrolidone (PVP), a synthetic linear polymer. In the absence of PVP, the apparent stiffness of relaxed skinned fibres measured during ramp stretches was about 0.05‐0.1 of the stiffness of intact fibres. The stiffness increased when the lattice spacing was decreased. The mechanical characteristics of resting stiffness in the presence of PVP (or bovine serum albumin) were similar to those of the short‐range elastic component of resting intact fibres. However, when the spacing of skinned fibres was reduced osmotically to that of the intact lattice, the stiffness of skinned fibres was about 1.6 times higher. In the absence of PVP, Ca2+‐activated skinned fibres were less stiff than are fully active intact fibres during isometric tetani. The skinned fibre force‐extension relation was markedly curved. As the filament spacing was reduced, the stiffness of the Ca2+‐activated skinned fibres increased, with little change in isometric tension, and the force‐extension curve became more linear. Experiments at varied filament overlap and during feed‐back control of sarcomere length, monitored by laser diffraction, showed that PVP increased the stiffness of the sarcomeres. The increase of active stiffness in the presence of PVP could be partially dissociated from the increase of resting stiffness by inclusion of Mg tripolyphosphate in the bathing solutions. It is concluded that the low stiffness and the non‐linearity of the force‐extension curve observed in fully activated skinned fibres are due primarily to the increase of filament separation that occurs when a fibre is skinned. The mechanism may be related to an increased angle between the subfragment‐2 part of the cross‐bridge and the backbone of the thick filament, perhaps leading to buckling of cross‐bridges under compression.
Inhibition of acid formation by epidermal growth factor in the isolated rabbit gastric glands.
Authors: Dembiński A , Drozdowicz D , Gregory H , Konturek S J , Warzecha Z
Published: December 2014

The effects of epidermal growth factor (EGF) on basal and stimulated (with histamine, dibutyryl cyclic AMP, and high concentrations of K+) acid formation have been studied in isolated glands from the rabbit gastric mucosa. The changes in the accumulation of [14C]aminopyrine [14C]AP have been used as an indirect measurement of acid production in the glands. Unstimulated gastric glands accumulated [14C]AP indicating the existence of basal acid production in these glands, and EGF caused a small but significant reduction in basal [14C]AP uptake. A similar reduction of basal [14C]AP uptake was observed after exposure to omeprazole but not after ranitidine or prostaglandin E2 (PGE2). Histamine, dibutyryl cyclic AMP and K+ caused a strong and dose‐dependent stimulation of acid formation by the glands. EGF, like omeprazole, reduced dose‐dependently the [14C]AP accumulation stimulated by both histamine and dibutyryl cyclic AMP, while ranitidine and PGE2 reduced histamine‐ but not dibutyryl‐cyclic‐AMP‐stimulated accumulation of [14C]AP. In the absence of other external stimuli, an increased K+ concentration enhanced [14C]AP accumulation to levels similar to those produced by histamine and this effect was not changed by EGF, ranitidine or PGE2 but was inhibited by omeprazole. We conclude that EGF interferes with the final steps of acid production between cyclic nucleotides and proton pump of the parietal cells.
Haemodynamic responses to stimulation of the splanchnic and cardiac sympathetic nerves in the anaesthetized cat.
Authors: Barnes R J , Bower E A , Rink T J
Published: December 2014

The changes in cardiac output and mean right atrial pressure (R.A.P.) evoked at different circulating blood volumes by stimulation of the splanchnic sympathetic nerves were investigated in adrenalectomized cats under chloralose anaesthesia, with unopened chests and spontaneous respiration and with active vascular reflexes. The cardiac autonomic nerves were cut or blocked pharmacologically. Stimulation of the distal ends of the splanchnic nerves at 4 Hz caused aortic pressure and R.A.P. to rise to maximum values at 2 min before declining slowly. Cardiac output rose more slowly to a steady state at 3 min; at higher circulating volumes it fell initially. Although the output increments were slower in development they were better sustained than those in total peripheral resistance. The proportionate output increments were largest and the R.A.P. increments least at low circulating volumes whereas at high volumes the R.A.P. increments were large but the output changes were small or negative; the pattern of changes resembled that resulting from infusion of blood. Stimulation of the cardiac sympathetic nerves evoked a rise in output and a fall in R.A.P. related in magnitude to the initial value of R.A.P. On simultaneous stimulation of the splanchnic and cardiac sympathetic nerves the changes in output combined whereas the R.A.P. changes cancelled, to give output increments of 25‐50% with little change in R.A.P. at all circulating volumes. At high circulating volumes infusion of blood did not usually alter output or aortic pressure, but splanchnic nerve stimulation increased peripheral resistance and aortic pressure and commonly evoked a rise in left ventricular stroke work which could not be accounted for by known adrenergic mechanisms or by elevation of left ventricular end‐diastolic pressure. Portal venous pressure was consistently elevated by splanchnic nerve stimulation; it rose more slowly than did aortic pressure or R.A.P. and was independent of a changing central venous pressure provided this did not exceed +5 mmHg. The cardiac output increments were not related to changes in the ratio between the input and output resistances of the portal vein and it is concluded that displacement blood from the peripheral to the central vasculature was induced by contraction capacitance vessels.
Calcium‐dependent chloride currents in isolated cells from rat lacrimal glands.
Authors: Evans M G , Marty A
Published: December 2014

Isolated cells from rat lacrimal glands were studied with the tight‐seal whole‐cell recording technique. Cells were dialysed with K‐free solutions containing a high concentration of Ca2+ buffer in order to record Ca‐dependent Cl‐ currents at a Ca2+ level fixed between 0.1 and 10 microM. HEDTA was preferable to EGTA as a Ca2+ buffer, even under conditions of equivalent equilibrium buffering power. After replacement of all internal K+ with Na+, the cells displayed a small conductance component which could be abolished by removal of external K+ or by external application of 2 mM‐tetraethylammonium. It is suggested that this conductance is due to Ca‐dependent K+ channels. The main part of the cell current was Cl selective. The Cl‐ conductance was negligible at 0.5 microM‐Ca2+, and fully activated at 2 microM‐Ca2+. The dose‐response curve relating Cl‐ currents to the internal Ca2+ concentration, [Ca]i, was steeper than predicted by a simple binding isotherm reaction. Relaxations observed in response to voltage jumps could, in most cases, be fitted with single exponentials. At [Ca]i 0.5 microM, the curve relating the relaxation time constant, tau, to the membrane potential, displayed a maximum near +20 mV and 250 ms. At hyperpolarized potentials, tau varied by an e‐fold factor in 130 mV. At [Ca]i 1 microM, tau decreased from 100 ms at ‐120 mV to 60 ms at +60 mV. Relaxation analysis gave an estimate of the variation of the channel open state probability, Po, with potential. At [Ca]i 0.5 microM, Po varied by an e‐fold factor in 50‐70 mV at hyperpolarized potentials, and saturated above +60 mV. At [Ca]i 1 microM, Po varied e‐fold in 100 to 110 mV at hyperpolarized potentials, and saturated near +20 mV. External Cl‐ was substituted with various anions. From reversal potential measurements, the following permeability sequence was obtained: I‐ greater than NO3‐ greater than Br‐ greater than Cl‐ greater than F‐ greater than isethionate, methanesulphonate greater than glutamate. The corresponding normalized permeability coefficients were 2.7, 2.4, 1.6, 1, 0.2, 0.1, 0.1, 0.05. Replacement of external Cl‐ with Br‐, isethionate, methanesulphonate or glutamate did not alter current kinetics as obtained during or after a depolarizing voltage jump.(ABSTRACT TRUNCATED AT 400 WORDS)
Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre.
Authors: Evans P D , Reale V , Villegas J
Published: December 2014

The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose‐dependent, long‐lasting hyperpolarization of the Schwann‐cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann‐cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]‐enkephalin) blocked the actions of all the above peptides as well as the effects of DL‐octopamine and carbachol. The actions of [Met]‐enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann‐cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL‐octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'‐cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann‐cell membrane. Evidence is presented for the existence of an endogenous VIP‐like component in the normal hyperpolarizing action of giant‐axon activity on the membrane potential of the Schwann cell.
Human ocular vergence movements induced by changing size and disparity.
Authors: Erkelens C J , Regan D
Published: December 2014

Human subjects viewed an electronically generated bright square. Horizontal movements of the two eyes were recorded with the scleral coil method. The dynamic properties of vergence movements induced by movement of the bright square were investigated for the following three kinds of stimulus motion: (a) both the size and the binocular disparity of the square changed together, in such a way as to exactly mimic the retinal image changes produced by a real object's motion in depth; (b) the changing‐size component in (a) was present with no disparity component; (c) the changing‐disparity component in (a) was present with no size component. The gain and phase of the ocular vergence responses to these three stimuli were computed. Ocular vergence movements were induced by changing size in all five subjects. Responses during binocular viewing were higher and less variable than responses during monocular viewing. Size oscillations induced ocular vergence oscillations with a phase lead of up to 65 deg relative to target size for frequencies of stimulation below 1.0 Hz. Vergence oscillation amplitudes were of the order of 10 min of arc and maximal for frequencies of 0.4‐0.7 Hz. Ocular vergence movements were not induced by changes in target size in one dimension nor by flickering a stationary square. Ocular vergence movements induced by size changes were entirely transient with no sustained component: vergence responses to disparity were sustained. When the stimulus combined size change with disparity change in the ratio characteristic of a real moving object, vergence tracking was more accurate and less noisy than when the eyes were stimulated with the disparity component alone. The ocular vergence response induced by the combination of size change with disparity change was accurately predicted by linearly adding the vergence response produced by the size change alone to the vergence response produced by the disparity change alone: combined stimulation produced no evidence of non‐linear interaction between responses to size change and to disparity change. The properties of vergence responses induced by changing size and by changing disparity showed several close correlations with the corresponding data on psychophysical sensitivity for motion‐in‐depth sensation. We suggest that responses to changing size contribute to the accuracy with which ocular vergence tracks real objects moving in depth.