bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial spread of adaptation within the cone network of turtle retina.
Authors: Copenhagen D R , Green D G
Published: December 2014

1. The spatial characteristics of adaptation were studied in the red‐sensitive cones of the snapping turtle retina using intracellular microelectrodes. Light responses elicited with slit‐shaped test and adapting stimuli revealed that test response amplitudes and adaptation decline similarly with distance from the impaled cone. The spatial spread of adaptation and the light response cannot be accounted for by scattered light and must therefore result from electrical coupling between cones. 2. The reduction in the amplitude of the test response correlated strongly with the magnitude of the sustained hyperpolarization induced by the adapting fields. This dependence of adaptation on membrane potential was independent of the spatial configuration of the adapting field. 3. The time courses of flash responses were monotonically related to the membrane potential induced by adapting stimuli and were also independent of adapting field configuration. 4. Adapting slits imaged on the cone receptive field centres uniformly depressed sensitivity without altering the shape of the field or its exponential fall‐off. Since the membrane potential evoked by the adapting slit falls off exponentially, the invariance of receptive field shape implies that the spread of adaptation cannot be attributed solely to voltage‐dependent desensitization of the transduction apparatus in the cones. Therefore a substantial part of the membrane potential dependency of adaptation probably results from a shunting of signals across the plasma membrane of the cone. 5. Full field backgrounds depressed sensitivity but did not alter the receptive field profiles. On the model of electrical coupling proposed by Lamb & Simon (1976), this suggests that to the extent that the voltage‐dependent desensitization results from an increased conductance and hence an increased shunt of the signals at the plasma membrane, there must be a concomitant increase in the conductance of the electrical pathways linking cones to one another.
Vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin‐releasing factor mRNA stimulation in the rat.
Authors: Lightman S L , Young W S
Published: December 2014

1. Cryostat sections were cut through the hypothalamus of rats which had been given a 2% (w/v) NaCl solution to drink for up to 12 days. 2. In situ hybridization histochemistry was performed on these sections using synthetic oligonucleotide probes against part of the precursor sequence for vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin‐releasing factor (CRF). 3. Drinking 2% NaCl solution resulted in a progressive increase of vasopressin, oxytocin and dynorphin mRNAs hybridized in the magnocellular neurones of the supraoptic (s.o.) and paraventricular (p.v.) nuclei. No enkephalin mRNA was detected in the magnocellular areas of the control animals although small quantities of probe did hybridize after 12 days of salt loading and after the stress of I.P. hypertonic saline. 4. Ten‐day‐lactating female rats were also studied. They had a very marked increase in oxytocin mRNA with smaller increases of vasopressin and dynorphin mRNAs. No detectable enkephalin mRNA was hybridized in the magnocellular s.o. or p.v. nuclei and CRF mRNA was unchanged in both the s.o. nucleus and the p.v. nucleus.
Improvement in human vision under bright light: grain or gain?
Authors: Chen B , MacLeod D I , Stockman A
Published: December 2014

1. The factor by which increment threshold changes with changing background intensity is less if the test flash is small than if it is large. This is commonly attributed to a reduction of the area over which visual signals are integrated as light adaptation increases. 2. We propose and test an alternative hypothesis that the change in slope is the result of purely local processes: if it is assumed that increasing the background intensity increases the exponent of the local response function, but does not alter the extent of spatial integration, then the threshold of the small test flash will rise more slowly than the threshold of the large test flash simply because the small test flash is of a higher intensity than the large and therefore evokes a correspondingly greater local response. 3. We measured small and large test field increment thresholds and dichoptic brightness matches as a function of background intensity. 4. The log‐log slopes of the small and large field increment threshold functions differed by not more than about 20%, suggesting that even under the conventional interpretation of such data, the change of spatial integration is less than is usually supposed. 5. The intensity of a large (2.3 deg) suprathreshold test field matched to a standard in the other eye varies with increasing background intensity with the same shallow slope as the small test (2.6 min) threshold versus intensity function; this is in agreement with the predictions of the local non‐linearity hypothesis and suggests that there is no substantial change in spatial integration during light adaptation.
Kinetic properties of the pentobarbitone‐gated chloride current in frog sensory neurones.
Authors: Akaike N , Maruyama T , Tokutomi N
Published: December 2014

1. The kinetic properties of the activation and inactivation (desensitization) phases of pentobarbitone (PB)‐induced inward Cl‐ current (ICl) were studied in isolated frog sensory neurones, following suppression of Na+, K+ and Ca2+ currents, using the concentration jump technique which combines the internal perfusion and the rapid exchange of the external solutions surrounding a neurone with time constants of 2‐3 ms. The results were compared with those of the gamma‐aminobutyric acid (GABA)‐gated ICl. 2. The PB dose‐response curve was bell‐shaped and the maximum peak value was less than the current induced by 1.7 X 1.5(‐5) M‐GABA, the concentration at which GABA evoked a half‐maximum response. 3. The activation and inactivation phases of PB‐induced ICl consisted of double‐exponential, fast and slow components, respectively. The time constant of the fast component (tau af) of the activation was relatively stable in a concentration range between 3 X 10(‐4) and 6 X 10(‐3) M. The time constant of the slow component (tau as) of the activation decreased with increasing PB concentrations. Both the fast and slow components (tau if and tau is) of the inactivation decreased with increasing PB concentrations. 4. Over a wide range of concentrations the tau af and tau as values of the PB‐induced ICl were 10‐30 times greater than the respective values of GABA‐induced ICl. 5. At concentrations below 10(‐3) M the PB‐induced ICl was voltage dependent at more negative potentials than ‐20 mV. 6. The PB‐induced ICl was blocked by bicuculline and by picrotoxin, but in a different manner. Bicuculline increased the time constants of the activation and inactivation. Picrotoxin had little effect on the activation phase but markedly facilitated the inactivation phase. 7. High concentrations of PB (over 10(‐3) M) led to a decline in both the peak and plateau currents of the PB‐induced ICl. A transient 'hump' current appeared with wash‐out of the external solutions containing high concentrations of PB. This hump current was blocked by bicuculline in a dose‐dependent manner. 8. The results suggest the possibilities that the PB receptor‐ionophore complexes consist of at least two different components having different affinities and kinetics and that the PB and GABA binding sites are closely located.
Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones.
Authors: Fox A P , Nowycky M C , Tsien R W
Published: December 2014

1. Calcium currents in cultured dorsal root ganglion (d.r.g.) cells were studied with the whole‐cell patch‐clamp technique. Using experimental conditions that suppressed Na+ and K+ currents, and 3‐10 mM‐external Ca2+ or Ba2+, we distinguished three distinct types of calcium currents (L, T and N) on the basis of voltage‐dependent kinetics and pharmacology. 2. Component L activates at relatively positive test potentials (t.p. greater than ‐10 mV) and shows little inactivation during a 200 ms depolarization. It is completely reprimed at a holding potential (h.p.) of ‐60 mV, and can be isolated by using a more depolarized h.p. (‐40 mV) to inactivate the other two types of calcium currents. 3. Component T can be seen in isolation with weak test pulses. It begins activating at potentials more positive than ‐70 mV and inactivates quickly and completely during a maintained depolarization (time constant, tau approximately 20‐50 ms). The current amplitude and the rate of decay increase with stronger depolarizations until both reach a maximum at approximately ‐40 mV. Inactivation is complete at h.p. greater than ‐60 mV and is progressively removed between ‐60 and ‐95 mV. 4. Component N activates at relatively strong depolarizations (t.p. greater than ‐20 mV) and decays with time constants ranging from 50 to 110 ms. Inactivation is removed over a very broad range of holding potentials (h.p. between ‐40 and ‐110 mV). 5. With 10 mM‐EGTA in the pipette solution, substitution of Ba2+ for Ca2+ as the charge carrier does not alter the rates of activation or relaxation of any component. However, T‐type channels are approximately equally permeable to Ca2+ and Ba2+, while L‐type and N‐type channels are both much more permeable to Ba2+. 6. Component N cannot be explained by current‐dependent inactivation of L current resulting from recruitment of extra L‐type channels at negative holding potentials: raising the external Ba2+ concentration to 110 mM greatly increases the amplitude of L current evoked from h.p. = ‐30 mV but produces little inactivation. 7. Cadmium ions (20‐50 microM) virtually eliminate both N and L currents (greater than 90% block) but leave T relatively unaffected (less than 50% block). 200 microM‐Cd2+ blocks all three components. 8. Nickel ions (100 microM) strongly reduce T current but leave N and L current little changed. 9. The dihydropyridine antagonist nifedipine (10 microM) inhibits L current (approximately 60% block) at a holding potential that inactivates half the L‐type channels.(ABSTRACT TRUNCATED AT 400 WORDS)
Copper activates a unique inward current in molluscan neurones.
Authors: Weinreich D , Wonderlin W F
Published: December 2014

1. Reidentifiable Aplysia neurones were current and voltage clamped in vitro using standard microelectrode techniques. 2. Bath or focal application of Cu2+ at concentrations of 1‐100 microM produced a rapid and reversible depolarization of the somal, but not the axonal, membrane potential. The depolarization was accompanied by an increased membrane conductance and activation of an inward current (ICu) which could not be activated by intracellular ionophoretic injection of Cu2+. 3. ICu is carried, in part, by Na+ because the reversal potential of ICu was shifted in a Nernstian fashion by decreasing the extracellular Na+ concentration. The reversal potential of ICu was not affected by removal of extracellular Ca2+ or K+. 4. ICu does not result from (1) activation of known chemically or voltage‐gated Na+ conductances, (2) inhibition of the Na+‐K+‐ATPase or (3) a generalized increase in membrane permeability resulting from lipid peroxidation. 5. A similar inward current was activated by AgNO3 (100 microM) and HgCl2 (100 microM).
The inhibition of rabbit skeletal muscle contraction by hydrogen ions and phosphate.
Authors: Cooke R , Franks K , Luciani G B , Pate E
Published: December 2014

1. The effects of phosphate and protons on the mechanics and energetics of muscle contraction have been investigated using glycerinated rabbit psoas muscle. 2. Fibres were fully activated by addition of Ca2+ (pCa 4‐5) at 10 degrees C. The velocities of contraction were measured in isotonic load clamps, and the velocities of unloaded fibres were measured by applying a series of step changes in fibre length. Fibre ATPase activity was monitored using an enzyme system to couple ADP production to reduced nicotinamide‐adenine dinucleotide (NADH) and measuring the depletion of NADH by optical density. 3. At pH 7.0 and 3 mM‐phosphate, isometric tension (P0) was 13.2 +/‐ 0.9 N/cm (mean +/‐ S.E.M., n = 10 observations), the maximum contraction velocity (Vmax) was 1.63 +/‐ 0.05 lengths/s (n = 5) and the ATPase activity was 1.27 +/‐ 0.12 s‐1 myosin head‐1 (n = 35). Increasing phosphate from 3 to 20 mM at pH 7.0 does not affect Vmax, causes a small decrease in the ATPase activity (15‐20%) and decreases P0 by approximately 20%. Changing pH from 7 to 6 at 3 mM‐phosphate decreases P0 by 45% and both Vmax and ATPase activity by 25‐30%. The effects of changing both pH and phosphate were approximately additive for all parameters measured. The inhibition of these parameters by low pH and high concentration of phosphate was reversible. 4. The force‐velocity relation was fitted by the Hill equation using a non‐linear least‐squares method. The value of the parameter which describes the curvature, a/P0, was 0.20. The curvature of the force‐velocity relation was not changed by addition of phosphate or by changes in pH. 5. These data provide information on both the kinetics of the actomyosin interaction and on the process of muscle fatigue. The data are consistent with models of cross‐bridge kinetics in which phosphate is released within the powerstroke in a step involving a rapid equilibrium between states. The inhibition by protons is more complex, and may involve less specific effects on protein structure. 6. During moderate fatigue of living skeletal muscle, MgATP concentration is known to remain approximately constant at 4 mM, phosphate to increase from 3 to 20 mM, and protons from 0.1 to 1 microM. The data suggest that much of the inhibition of P0 observed during moderate fatigue can be explained by the increased levels of phosphate and protons, and that much of the inhibition of fibre Vmax and ATPase activity can be explained by the increase in protons.
Inflammatory changes in permeability and ultrastructure of single vessels in the frog mesenteric microcirculation.
Authors: Clough G , Michel C C , Phillips M E
Published: December 2014

1. In fifteen experiments, single microvessels in the exposed mesenteries of pithed frogs were perfused with Ringer solutions containing bovine serum albumin (40 mg ml‐1). For each vessel, the hydraulic permeability of its walls (Lp) and effective osmotic pressure exerted across them (sigma delta pi) were determined from measurements of fluid filtration rates at two capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974) before and at predetermined times after the tissue temperature had been raised abruptly from approximately 15 degrees C to 30‐35 degrees C. Temperatures greater than 30 degrees C appear to damage the tissues of frogs acclimatized to temperatures of 5‐10 degrees C. 2. In fourteen out of fifteen experiments Lp rose when the temperature was raised to 30‐35 degrees C. In twelve of these experiments the increase in Lp was greater than expected from the fall in water viscosity with temperature, and was progressive. In five vessels where measurements were made 1‐2 min after tissue temperature was raised, Lp increased from an initial mean value (+/‐ S.E.M.) of 3.76 (+/‐ 0.54) x 10(‐3) micron s‐1 cmH2O‐1 to one of 8.72 (+/‐ 1.68) x 10(‐3) micron s‐1 cmH2O‐1. In nine vessels where measurements were made at 10 min after tissue temperature was raised, Lp increased from an initial mean value of 4.03 (+/‐ 0.72) x 10(‐3) micron s‐1 cmH2O‐1 to one of 16.9 (+/‐ 3.5) x 10(‐3) micron s‐1 cmH2O‐1. Further increases in Lp were seen at 15 and 20 min. 3. The changes in the effective osmotic pressure opposing filtration, sigma delta pi, were very variable. Out of the twelve vessels which showed large changes in Lp with tissue heating, four showed no reduction in sigma delta pi after 10 min, though sigma delta pi fell in three of these vessels at 15 min. In the other eight vessels, sigma delta pi fell as Lp rose. A quantitative theory developed in this paper allowed the changes in sigma delta pi to be analysed in terms of a component across the regions of vessel wall of increased permeability (sigma H delta pi H) and a component across regions where Lp was unchanged. In six vessels sigma H delta pi H approximated to zero; in two vessels sigma H delta pi H was 6.2 and 4.5 cmH2O.(ABSTRACT TRUNCATED AT 400 WORDS)
Epithelial transport in guinea‐pig proximal colon: influence of enteric neurones.
Authors: Kuwahara A , Radowicz‐Cooke H J
Published: December 2014

1. The effects of electrical field stimulation and aminophylline on sodium and chloride transport in the guinea‐pig proximal colon were examined. 2. Under basal conditions, both sodium and chloride were actively absorbed and the net fluxes of these ions accounted for the short‐circuit current. 3. Basal short‐circuit current was reduced by furosemide, unchanged by amiloride and increased by aminophylline. The aminophylline‐evoked increase in short‐circuit current resulted from a reduction in net sodium absorption and abolishment of chloride absorption without a significant effect on residual flux. 4. Electrical field stimulation evoked a tetrodotoxin‐sensitive increase in short‐circuit current and total tissue conductance. The stimulus‐evoked response was unaltered by mucosal amiloride, but was reduced by serosal furosemide. Electrical stimulation of submucosal neurones reduced both sodium and chloride absorption without any effect on residual flux. 5. Atropine had no effect on the basal short‐circuit current; however, it reduced, but did not abolish, the neurally evoked response. Carbachol evoked a dose‐dependent increase in short‐circuit current that was reduced by tetrodotoxin. 6. These results suggest that electrical field stimulation activates submucosal neurones that innervate the epithelium. Release of acetylcholine and other neurotransmitters leads to excitation of receptors on epithelial cells, and an increase in short‐circuit current that reflects inhibition of sodium and chloride absorption.
Investigation of mechanism of fade of gastrin‐stimulated gastric acid secretion in the cat.
Authors: Hirst B H
Published: December 2014

1. In conscious cats prepared with gastric fistulae gastric acid secretion in response to pentagastrin was found to reach a maximum after 45 min of stimulation, and to fade thereafter. Over the period 45‐150 min of stimulation the fade was 5.4‐7.8% of the maximum response per 15 min. 2. Once the response to pentagastrin had declined, acid secretion could not be restored by doubling the dose of pentagastrin, although an equisecretory dose of histamine could restore it. 3. Low doses of histamine were additive to the pentagastrin acid secretory response; they tended to prolong the peak response, but did not alter the subsequent fade of acid secretion. The histamine H1‐receptor antagonist mepyramine did not affect maximal acid secretion or the fade of the pentagastrin response. 4. The beta‐adrenoreceptor antagonist propranolol increased the secretory response to pentagastrin, whilst the alpha‐adrenoreceptor antagonist phentolamine was without effect. Neither agent altered the fade of the pentagastrin response. Isoprenaline tended to inhibit pentagastrin‐stimulated acid secretion and increase the rate of fade of the response. 5. The 5‐hydroxytryptamine (5‐HT) receptor antagonist methylsergide slightly enhanced the acid secretory response to pentagastrin, but did not alter the fade of the response. A low dose of 5‐HT did not alter pentagastrin‐stimulated acid secretion, whilst a higher dose of 5‐HT inhibited it. 6. Tetra‐, penta‐ and pentadecagastrin demonstrated tachyphylaxis, i.e. progressively reduced responses upon repeated stimulation, whilst histamine did not. A low dose of histamine did not prevent tachyphylaxis of the pentagastrin response. 7. It is concluded that fade of pentagastrin‐stimulated acid secretion in the conscious cat cannot be satisfactorily explained by the failure of the acid secretory mechanism, depletion of histamine, release of 5‐HT, or activation of histamine H1‐, alpha‐ or beta‐adreno‐, or 5‐HT‐receptors. The similar characteristics of fade and tachyphylaxis of gastrin‐stimulated acid secretion are consistent with a common gastrin receptor inactivation or desensitization mechanism.
Effects of exposure to cold on metabolic characteristics in gastrocnemius muscle of frog (Rana pipiens).
Authors: Ohira M , Ohira Y
Published: December 2014

1. Responses of enzymic characteristics of gastrocnemius muscle were studied when frogs (Rana pipiens) were exposed to cold environment (4 degrees C). 2. The content of adenosine triphosphate (ATP) decreased significantly after cold exposure. This decrease was greater in starved than in fed frogs. 3. Although the glycogen content did not change, lactate levels were lower in cold‐exposed than room‐temperature (control) frogs. No change was observed in glycogen and lactate between fed and unfed frogs kept at 4 degrees C for 2 months. Lactate dehydrogenase activity tended to increase during chronic cold exposure, but not significantly. 4. The activities of citrate synthase, cytochrome oxidase, and beta‐hydroxyacyl CoA dehydrogenase were higher in gastrocnemius of chronically cold‐exposed frogs than in room‐temperature controls. This increase was statistically significant only in the muscles of starved frogs; these muscles had the greatest decrease in ATP. 5. It was suggested that chronic cold exposure decreases skeletal muscle ATP content but may not affect glycolysis. The data also suggested that the decrease in ATP content stimulates mitochondrial biogenesis which increases enzyme activities.
Spatial vision of the achromat: spatial frequency and orientation‐specific adaptation.
Authors: Greenlee M W , Magnussen S , Nordby K
Published: December 2014

1. The psychophysical technique of selective adaptation to stationary sine‐wave gratings of varying spatial frequency and orientation was used to investigate the central processing of spatial information in the visual system of the complete achromat. 2. For adapting spatial frequencies of 1 and 2 cycles/deg, the spatial frequency and orientation selectivity of contrast threshold elevation is similar for achromatic and trichromatic vision. 3. For adapting frequencies below 1 cycle/deg, the achromat shows threshold elevations of normal magnitude with symmetrical spatial frequency and orientation tuning for adapting frequencies as low as 0.09 cycles/deg with 'bandwidth' estimates similar to those found at high frequencies in the trichromat. Below 0.66 cycles/deg no after‐effect could be obtained in the trichromat, and the frequency tuning at 0.66 cycles/deg was skewed towards higher frequencies. 4. The interocular transfer of low‐frequency adaptation in the achromat was 50%, which is the same value obtained at higher frequencies. 5. The time course of the decay of low spatial frequency adaptation in the achromat was similar to that found at higher frequencies. 6. Control experiments show no low‐frequency adaptation in peripheral vision or in central vision in the dark‐adapted trichromat indicating that low spatial frequency adaptation cannot be elicited through the rod system of the trichromat. 7. It is proposed that the observed range shift of adaptable spatial frequency mechanisms in the achromat's visual cortex is the result of an arrest at an early stage of sensory development. The visual cortex of the achromat is comparable, with respect to spatial processing, to that of the young, visually normal human infant.
Calcium and magnesium fluxes across the plasma membrane of the toad rod outer segment.
Authors: Nakatani K , Yau K W
Published: December 2014

1. Membrane current was recorded from an isolated, dark‐adapted toad rod by sucking either its inner segment or outer segment into a tight‐fitting glass pipette containing Ringer solution. The remainder of the cell was exposed to bath solution which could be changed rapidly. 2. In normal Ringer solution the current response of a cell to a saturating flash or step of light showed a small secondary rise at its initial peak. The profile of this secondary rise (i.e. amplitude and time course) was independent of both the intensity and the duration of illumination once the light response had reached a plateau level. 3. This secondary rise disappeared when external Na+ around the outer segment was replaced by Li+ or guanidinium, suggesting that it represented an electrogenic Na+‐dependent Ca2+ efflux which was declining after the onset of light. 4. This Na+‐Ca2+ exchange activity showed a roughly exponential decline, with a time constant of about 0.5 s. Exponential extrapolation of the exchange current to the time at half‐height of the light response gave an initial amplitude of about 2 pA. Using La3+ as a blocker, we did not detect any steady exchange current after the initial exponential decline. 5. An intense flash superposed on a just‐saturating steady background light failed to produce any incremental exchange current transient. 6. Our interpretation of the above results is that in darkness there are counterbalancing levels of Ca2+ influx (through the light‐sensitive conductance) and efflux (through the Na+‐Ca2+ exchange) across the plasma membrane of the rod outer segment. The exchange current transient at the onset of light merely represents the unidirectional Ca2+ efflux which becomes revealed as a result of the stoppage of the Ca2+ influx, rather than a de novo Ca2+ efflux triggered by light. 7. Consistent with this interpretation, a test light delivered soon after a saturating, conditioning light elicited little exchange current, which then gradually recovered to control value with a time course parallel to the restoration of the dark current. Conversely, when the dark current was increased above its physiological level by IBMX (isobutylmethylxanthine) the exchange current transient became larger than control.(ABSTRACT TRUNCATED AT 400 WORDS)
Guanosine 3',5'‐cyclic monophosphate‐activated conductance studied in a truncated rod outer segment of the toad.
Authors: Nakatani K , Yau K W
Published: December 2014

1. In darkness, a single rod outer segment isolated from the toad retina was sucked partially, tip first, into a tight‐fitting, Ringer solution‐filled glass pipette for recording membrane current. The basal end of the outer segment outside the pipette was sheared off with a probe to allow internal dialysis. The potential between the inside and the outside of the pipette was held at 0 mV. 2. With cyclic GMP and IBMX (isobutylmethylxanthine) in the dialysis solution, a large inward current appeared across the plasma membrane of the outer segment; this current saturated at around 1 mM‐cyclic GMP. IBMX by itself was ineffective. 3. The saturated cyclic GMP‐induced current recorded varied in size with the length of outer segment (L) within the suction pipette. For L less than 25 micron, the relation was linear, with a current density of 4‐20 pA micron‐1. 4. At short L (less than 25 micron), the dose‐response relation between current magnitude and cyclic GMP concentration was sigmoidal, with a Hill coefficient (n) of 1.8‐3.1 and a half‐saturating cyclic GMP concentration (K1/2) of 30‐85 microM. 5. In the presence of IBMX and the absence of GTP, the dose‐response relation was the same in continuous bleaching light as in darkness. This indicates that both the characteristics of cyclic GMP binding and the intrinsic conduction properties of the open conductance are not affected by light. 6. Removing IBMX from the dialysing solution had little effect on the saturated current, but substantially reduced the current induced at low concentrations of cyclic GMP. When the analogue 8‐bromo cyclic GMP was used instead, however, the presence of IBMX was relatively unimportant even at low agonist concentrations. These observations indicated that significant phosphodiesterase activity was present within the truncated outer segment. 7. In the absence of IBMX and the presence of GTP, the cyclic GMP‐induced current could be suppressed by light. When ATP was also present in the dialysing solution, the effect of light was significantly reduced and the suppression also became more transient. 8. We conclude from the above results that the cyclic GMP‐gated conductance is indeed present in the plasma membrane of the rod outer segment, and that this conductance and the light‐sensitive conductance are one and the same entity. 9. From the results, we estimate that only about 1% of the conductance is normally open in darkness. This fraction of open conductance corresponds to a free cyclic GMP concentration of a few micromolar.
Limitations of facial immersion as a test of parasympathetic activity in man.
Authors: Gallo L , Maciel B C , Manço J C , Marin Neto J A
Published: December 2014

1. The heart rate response to immersion of the face in water, as an isolated manoeuvre or in combination with apnoea, was studied in eight normal volunteers to establish the conditions under which it could be used as a standardized, simple, non‐invasive and reproducible test of parasympathetic activity. 2. The following procedures were evaluated: (a) 10 s apnoea in air at different lung volumes; (b) facial immersion in water for 2 min at various temperatures (5, 15 and 25 degrees C), with respiration maintained through a closed circuit; (c) combination of immersion and apnoea at different lung volumes. Three volunteers were re‐evaluated after pharmacological blockade with atropine sulphate (0.04 mg/kg body weight). 3. The results showed that: (a) apnoea in air triggered lung volume‐dependent heart rate responses; (b) facial immersion in water induced transient bradycardia which was maximum between 20 and 30 s of immersion; (c) there was no appreciable difference in the bradycardia evoked by immersion at different temperatures; (d) the combination of immersion and apnoea caused heterogeneous heart rate responses with no potentiation of bradycardia in relation to each manoeuvre as performed separately; (e) atropine did not reduce the magnitude of bradycardia induced by immersion in two of the subjects studied. 4. The variability of responses observed in the present study was probably due to the multiple receptors and afferent pathways that are simultaneously excited during these manoeuvres. As a consequence, the autonomic efferent response will depend on the unpredictable net effect of interaction of these mechanisms. This is a limiting factor for the standardization of this test as a simple and reproducible method for the assessment of parasympathetic activity. 5. Furthermore, the results obtained under pharmacological blockade indicate that the vagal efferent mechanism is not the only factor responsible for the bradycardia caused by facial immersion without apnoea.
Effect of intracellular pH on force and heat production in isometric contraction of frog muscle fibres.
Authors: Curtin N A , Kometani K , Woledge R C
Published: December 2014

1. The intracellular pH (pHi) of live fibres from the anterior tibialis of the frog Rana temporaria was measured at 10 degrees C (using pH‐sensitive microelectrodes) in Ringer solutions containing a fixed bicarbonate concentration (20 mM) and varying PCO2 concentrations of 0.5‐54%. As extracellular pH was changed from 7.99 to 6.00, mean pHi changed from 7.24 to 5.97. Similar results were obtained at 20 degrees C. 2. In parallel experiments force and rate of heat production in 4 s isometric tetani at 10 degrees C were measured, and compared to control observations (5% CO2, pHi 6.80). 3. As the fibres became more acid (to pHi 5.95), force and heat rate were progressively reduced (to 0.75 and 0.71 of the control values, respectively). 4. As the fibres became more alkaline (to pHi 7.26), force increased slightly (by a maximum of 0.03 of the control value) but heat rate did not increase. 5. When the dependence on pH of the molar enthalpy change for phosphocreatine splitting is taken into account, these results indicate that the force‐time integral per cross‐bridge cycle increases with pHi over this range.
The formation of topographical maps in developing rat gastrocnemius muscle during synapse elimination.
Authors: Bennett M R , Ho S
Published: December 2014

1. The rat lateral gastrocnemius muscle (LG) is a complex of four muscle compartments, each defined in terms of its unique innervation by a single primary nerve branch of the muscle nerve. A study has been made of the topographical distribution of motor units in the medial compartment of the LG (LGM) both before and after the loss of polyneuronal innervation that accompanies development. 2. Glycogen depletion methods showed that the distribution of single motor units depended on the rostro‐caudal origins of their axons in the spinal cord: rostral axons possessed motor units almost exclusively confined to the medial half of the LGM; intermediate axons possessed motor units primarily in the intermediate and lateral part of the LGM; caudal axons possessed motor units that were not restricted to any particular part of the LGM. 3. Myosin ATPase staining showed that about 80% of the LGM consists of type II A fibres, whilst the remainder are type II B. Physiological determination of the contractile properties of motor units indicated two classes of units: those that were relatively fatigue resistant and did not show a sag property (like fast‐twitch, fatigue‐resistant fibres or FR) and those that were relatively fatigable and did show a sag property (like fast‐twitch, fatigable fibres or FF). 4. Glycogen depletion was also used to determine the distribution of motor units in the LGM at 7 days post‐natal, when most fibres still receive a polyneuronal innervation. The LGM primary nerve branch innervated a confined sub‐volume of muscle fibres which is similar to the mature pattern. However, rostral axons possessed motor units that extended into the lateral half of the LGM, a position from which they are excluded in the adult. 5. These observations suggest that the axons of rostral and intermediate units form a topographical map within adult FR motor units (type II A fibres) in the LGM. The results suggest that competition between axon terminals for synaptic sites plays a role in the elimination of inappropriately positioned terminals and subsequent emergence of the topographical map.
Regulation of intraganglionic synapses among rabbit parasympathetic neurones.
Authors: Johnson D A
Published: December 2014

1. The response of parasympathetic neurones to the removal of preganglionic innervation was studied in the ciliary ganglia of adult rabbits. After section of the preganglionic oculomotor nerve, individual ciliary neurones were characterized electrophysiologically by intracellular recording, and morphologically by intracellular injection of horseradish peroxidase. 2. Within the first 24‐48 h after nerve section, only two of fifty‐nine neurones responded to antidromic stimulation of the postganglionic ciliary nerve with synaptic potentials. This result indicates that synaptic connections between principal neurones are rare in normal ganglia. 3. One week after denervation, however, excitatory postsynaptic potentials were recorded in thirty‐nine out of fifty‐three cells examined. Thus there is a rapid and extensive formation of intraganglionic connections after denervation. Morphological analysis of these ganglion cells showed numerous fine processes arising from the cell bodies and dendrites; such neurites were not present among control neurones. Many of these newly formed processes appeared to form synapses on neighbouring cells. 4. A similar proportion of neurones (about two‐thirds of the cells) showed antidromically evoked excitatory postsynaptic potentials 2 weeks after denervation. Dendrites were still longer and more complex than controls at this time. After several months the morphology and prevalence of intraganglionic connections returned to normal as the ganglion became reinnervated. 5. Thus, denervation of rabbit ciliary ganglion cells induces the rapid formation of large numbers of functional synaptic connections among ganglion cells. It is postulated that local regulatory factors govern connections between parasympathetic ganglion cells. After denervation, these trophic signals are no longer modulated by presynaptic axons and they exert a stimulus for sprouting and synapse formation among this population of cholinergic neurones.
Inositol 1,4,5‐trisphosphate and diacylglycerol mimic bradykinin effects on mouse neuroblastoma x rat glioma hybrid cells.
Authors: Brown D A , Higashida H
Published: December 2014

1. The role of inositol 1,4,5‐trisphosphate (InsP3) and diacylglycerol (DAG) as possible mediators of the membrane current responses of NG108‐15 neuroblastoma x glioma hybrid cells to bradykinin (BK, Brown & Higashida, 1988b) has been tested using intracellular ionophoresis of InsP3 and external application of phorbol dibutyrate (PDBu) and 1‐oleoyl‐2‐acetylglycerol (OAG). 2. Intracellular ionophoresis of InsP3 into cells clamped at ‐30 to ‐50 mV produced (i) a transient outward current, (ii) a transient outward current followed by an inward current, or (iii) an inward current. All currents were accompanied by an increased input conductance. 3. The transient outward current reversed at between ‐80 and ‐90 mV. The reversal potential was shifted to more positive potentials on raising extracellular [K+], suggesting that it resulted from an increased K+ conductance. 4. The outward current was inhibited by apamin (0.4 microM) or d‐tubocurarine (0.2‐0.5 mM); these drugs also inhibit the outward current produced by BK or by intracellular Ca2+ injections (Brown & Higashida, 1988 a, b). The outward current was also slowly reduced in 0 mM [Ca2+] or 0.5 mM [Cd2+] plus 2 mM [Co2+] solution. 5. Ionophoretic injection of inositol 1,3,4‐trisphosphate and inositol 1,3,4,5‐tetrakisphosphate, guanosine trisphosphate or inorganic phosphate did not evoke an outward current but produced only an inward current with an increased conductance, reversing at between ‐10 and ‐20 mV. 6. Bath application of PDBu (10 nM‐1 microM) or OAG (1‐10 microM) produced an inward current with a fall in input conductance. The inward current was voltage dependent and was accompanied by an inhibition of the time‐dependent current relaxations associated with activation or deactivation of the voltage‐dependent K+ current, IM. 7. PDBu did not clearly reduce the Ca2+ current or the Ca2+‐dependent K+ current recorded in these cells. During superfusion with PDBu, the outward current produced by intracellular ionophoresis of InsP3 was greatly enhanced. 8. The results support the view that the two membrane current responses to BK might both result from accelerated membrane phosphatidylinositide hydrolysis. One product, InsP3, releases Ca2+ and activates an apamin‐curare‐sensitive outward K+ current; this effect is imitated by intracellular InsP3 ionophoresis. The second product, DAG; activates protein kinase C to inhibit the voltage‐dependent K+ current IM and generate an inward current; this effect is imitated by external application of PDBu or OAG.
Is the central arachidonic acid cascade system involved in the development of acute‐phase response in rabbits?
Authors: Morimoto A , Murakami N , Watanabe T
Published: December 2014

1. In the present study, endogenous pyrogen (EP), prostaglandin E2 or arachidonic acid was injected into the cerebral ventricle to investigate whether central arachidonic acid metabolites are involved in the development of the acute‐phase response. The central effects of a cyclo‐oxygenase inhibitor, indomethacin, and of a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on the acute‐phase response induced by an intracerebroventricular injection of EP were also examined. 2. The ventricular injection of EP decreased the plasma concentrations of iron and zinc, while increasing those of copper and fibrinogen and the circulating leucocyte count. However, ventricular injection of prostaglandin E2 affected neither of them, indicating that prostaglandin E2 does not contribute to the acute‐phase response production by itself. 3. Both the ventricular injections of indomethacin and NDGA had no effect on the changes in the plasma concentrations of iron, copper and fibrinogen which were induced by ventricular injection of EP. In addition, when arachidonic acid was administered into the cerebral ventricle, the changes in the plasma levels of iron, copper and fibrinogen were not induced. 4. In contrast, EP‐induced hypozincaemia was observed upon pre‐treatment with NDGA, but not upon pre‐treatment with indomethacin. However, plasma zinc increased after the ventricular injection of arachidonic acid. Ventricular injection of EP alone and of EP with NDGA increased the number of circulating leucocytes 8 and 24 h after the ventricular injection, while ventricular injections of arachidonic acid, and of EP with administration of indomethacin induced leucocytosis 8 h after injections. 5. These results suggest that arachidonic acid metabolites do not participate in the genesis of the acute‐phase response.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism of depolarization in the ischaemic dog heart: discrepancy between T‐Q potentials and potassium accumulation.
Authors: Blake K , Clusin W T , Franz M R , Smith N A
Published: December 2014

1. To study the origin of ischaemic myocardial depolarization, the diastolic surface potential ‐ T‐Q depression‐was correlated with subepicardial extracellular K+ accumulation during serial episodes of widespread ischaemia in open‐chest dogs, and in isolated, blood‐perfused canine hearts. Placement of the reference electrode on a small island of non‐ischaemic myocardium simplified the interpretation of the T‐Q potentials. 2. In some experiments, changes in resting potential in the ischaemic zone were recorded using a 'contact' monophasic action potential (MAP) electrode. The change in MAP resting potential was linearly related to T‐Q depression for a wide range of experimental conditions (R greater than 0.98). T‐Q depression is therefore a linear index of depolarization in superficial myocardial cells. 3. The validity of T‐Q depression as a 'measure' of local cellular depolarization was further tested by infiltration of isotonic KCl into the superficial myocardium subjacent to the ischaemic zone electrode. Resulting T‐Q depression was 2‐ to 3‐fold larger than the maximum values obtained in ischaemia; and the ratio of T‐Q depression to the amplitude of the accompanying monophasic potential was consistent with the assumption that KCl had fully depolarized the underlying myocardium (delta Vm = 89 mV). KCl prevented (i.e. occluded) further changes in the T‐Q potential during ischaemia. KCl did not have these effects if it was introduced at sites more remote from the electrode (greater than 4 mm). 4. Ischaemic T‐Q depression was drastically accelerated by increasing the heart rate from 90 to 180 beats/min and was further accelerated by arterial infusion of CaCl2. These effects were most striking during the first minute of ischaemia. 5. In contrast, the above manoeuvres produced little acceleration of subepicardial K+ accumulation. After CaCl2 infusion, large ischaemic potentials, severe conduction impairment, and arrhythmias could be observed when K+ activity was almost normal (aK = 4.0‐4.5 mM). 6. T‐Q depression was larger in vivo than in isolated hearts, both absolutely and relative to K+ accumulation. 7. Based on the reproducible amplitude of ischaemic epicardial potential‐estimates of cellular depolarization (delta Vm) could be obtained, which were compared with the concurrent change in K+ electrode potential (delta EK) for each experimental condition. 8. Estimated depolarization was nearly identical to delta EK in isolated hearts under basal conditions. However, depolarization significantly exceeded delta EK during rapid pacing, CaCl2 infusion, or during paced occlusions performed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
Transient calcium‐dependent potassium current in magnocellular neurosecretory cells of the rat supraoptic nucleus.
Authors: Bourque C W
Published: December 2014

1. Magnocellular neurosecretory neurones were impaled in the supraoptic nucleus of perfused explants of rat hypothalamus. Membrane currents were studied at 35 degrees C using the single‐microelectrode voltage‐clamp technique. 2. Depolarizing voltage steps applied from ‐100 mV evoked a transient outward current (TOC) from a threshold of ‐75 mV. From this potential, the amplitude of the current increased non‐linearly with voltage. 3. Following its activation TOC reached a peak within 7 ms and subsequently decayed monotonically with a time constant of 30 ms. This time constant did not vary significantly with voltage between ‐75 and ‐55 mV. 4. The TOC showed complete steady‐state inactivation at potentials positive to ‐55 mV. Inactivation was removed by hyperpolarization, with a mid‐point near ‐80 mV. The removal of inactivation followed a complex time course with distinct fast (tens of milliseconds) and slow (hundreds of milliseconds) components. 5. Tail current measurements revealed that the TOC equilibrium potential (ETOC) lies near ‐97 mV in the presence of 3 mM [K+]o. Increasing [K+]o caused a decrease of TOC amplitude and a shift in ETOC of 57 mV/log [K+]o. The TOC is therefore predominantly a K+ current. 6. The TOC was unaffected by tetraethylammonium (up to 12 mM) but was reversibly reduced by 4‐aminopyridine (ca. 50% block at 1.0 mM) and dendrotoxin (ca. 50% block at 4 nM). 7. The TOC was strongly inhibited (greater than 70%) by adding Co2+ or Mn2+ (1‐3 mM) or Cd2+ (50‐400 microM) to Ca‐containing solutions, or by removal of Ca2+ from the perfusate. These effects were not accompanied by detectable changes in threshold voltage. The amplitude of TOC was also depressed by the organic Ca2+ channel blocker methoxyverapamil (D600). Finally replacement of Ca2+ by Ba2+ in the perfusate completely and reversibly abolished the TOC. 8. These findings suggest that neurosecretory neurones of the rat supraoptic nucleus display a transient K+ current which is strongly dependent on the presence of external Ca2+. The possible role of this current is briefly discussed.