bluuebunny/crossref_metadata_2025 huggingface dataset:
Paraventricular and supraoptic bursting oxytocin cells in rat are locally regulated by oxytocin and functionally related.
Authors: Moos F , Richard P
Published: December 2014

1. Oxytocin was pressure injected through a glass micropipette into a supraoptic (SON) or paraventricular nucleus (PVN) while recording the electrical activities of oxytocin cells in a contralateral nucleus, to see whether oxytocin acts locally in the magnocellular nuclei to control their bursting activity and whether the oxytocin cells of the four magnocellular nuclei were functionally interconnected during suckling. To test the rapidity of these relations, similar intranuclear injections were realized with acetylcholine, known to rapidly increase the background activity of oxytocin cells. The effects of intranuclear injections of oxytocin and acetylcholine were tested before and after interhemisphere sections of various dimensions. 2. Injecting oxytocin (1 ng in 100 nl) into a magnocellular nucleus (5 times into the PVN and 15 times into the SON) facilitated the occurrence and increased the amplitude of bursts of the oxytocin cells in both the contralateral PVN and SON. This facilitatory effect was similar to that induced by intraventricular injection of the same dose of oxytocin, though slightly delayed and lower. 3. Injecting acetylcholine (0.6 microgram in 100 nl) into the SON (7 times) induced a rapid and sustained increase in the background activity of oxytocin cells in both the contralateral PVN (2 times) and SON (5 times) within the same delay (less than 15 s). This excitatory effect was similar to that induced by an intraventricular injection of 5 micrograms acetylcholine. The effects on bursting activity were not considered in this study. 4. Neither the injections of oxytocin or acetylcholine outside but near the magnocellular nuclei (200‐500 microns), nor the intranuclear injection of 100‐200 nl of cerebrospinal fluid‐like medium, modified the background activity, the frequency and amplitude of bursts of the oxytocin cells in the nucleus contralateral to the injection site. 5. After interhemisphere sections most oxytocin cells were silent, bursts occurred in an erratic manner, and their amplitude was attenuated and irregular (more than the 20% variation normally recorded in non‐operated rats). Moreover, the amplitudes of successive bursts of pair‐recorded supraoptic‐supraoptic (SO‐SO) oxytocin cells, highly related in control conditions (correlation coefficient, r = 0.68 to 0.98) were no longer correlated after interhemisphere section (r = 0.24 to ‐0.61), but all bursts remained synchronized.(ABSTRACT TRUNCATED AT 400 WORDS)
Measurement of renal function in unrestrained conscious rats.
Authors: Shirley D G , Walter S J , Zewde T
Published: December 2014

1. Inulin clearance and lithium clearance (used as a marker of end‐proximal fluid delivery) were measured in unrestrained conscious rats without the use of catheters. Lithium was added to the food and [14C]inulin was administered via an osmotic minipump implanted in the peritoneal cavity; blood was sampled from the tail. 2. Urinary excretion rates and body weight fell during the 24 h after implantation of the minipump. Within 4 days, however, excretion rates and the rate of gain of body weight were indistinguishable from pre‐implantation values. 3. During the rats' active period (i.e. the hours of darkness) urinary excretion rates of sodium, potassium and water were greater than during the inactive period. Inulin clearance, lithium clearance and fractional lithium excretion were also greater during the active period. Fractional distal reabsorptive rates of sodium and water (calculated using lithium clearance) did not differ significantly between the two phases of the light‐dark cycle. 4. The experimental procedures used in this study provide an assessment of renal function which involves minimal disturbance to the animal. The results suggest that circadian variations in urinary excretion are caused largely by variations in glomerular filtration rate, accompanied by minor changes in fractional proximal fluid reabsorption.
Effect of pulmonary venous congestion on respiratory rate in dogs.
Authors: Kappagoda C T , Ravi K , Teo K K
Published: December 2014

1. The effect of pulmonary venous congestion on the respiratory rate was examined in dogs anaesthetized with alpha‐chloralose. The study was done on both spontaneously breathing and artificially ventilated animals. Pulmonary venous congestion was produced by partial obstruction of the mitral valve sufficient to raise the left atrial pressure by 5 mmHg. 2. In artificially ventilated dogs, pulmonary venous congestion increased significantly the activity in phrenic nerves. Both the number of bursts/min and the total number of impulses/min increased. However, there was no significant change in the number of impulses/burst. 3. In spontaneously breathing dogs, pulmonary venous congestion produced a significant increase in the frequency of breathing with a significant shortening of the inspiratory and expiratory durations. 4. Cooling of the cervical vagi to 8‐9 degrees C abolished both the above responses. 5. Pulmonary venous congestion (left atrial pressure +5 mmHg) stimulated the rapidly adapting receptors of the airways. This effect was abolished by cooling the ipsilateral vagus proximally to 8‐9 degrees C. 6. It is concluded that pulmonary venous congestion increases the respiratory rate reflexly in dogs. The afferent pathway for this reflex response resides in the vagus and the rapidly adapting receptors are likely to be the receptors involved in this response.
Descending influences on the cutaneous receptive fields of postsynaptic dorsal column neurones in the cat.
Authors: Noble R , Riddell J S
Published: December 2014

1. The influence of activity in descending systems on the cutaneous receptive field properties of postsynaptic dorsal column (PSDC) neurones has been investigated in chloralose‐anaesthetized cats. The main aim of the study was to determine whether the receptive field boundaries of PSDC neurones are under the control of systems descending from the brain. 2. Single‐unit recordings were made from the ascending axons of PSDC units in the dorsal columns. Receptive fields were analysed using light tactile and noxious mechanical and thermal stimuli, both before and during a reversible block of spinal conduction produced by cooling the cord rostral of the recording site. 3. The light tactile excitatory fields of PSDC neurones were largely unaffected by the cold‐block procedure. 4. In contrast, both the sensitivity of PSDC neurones to noxious stimuli and the area of skin from which they could be effectively excited by such stimuli were found to be profoundly modified by interruption of descending activity. Two‐thirds of the units excited by noxious pinch responded more vigorously in the cold‐blocked state and one‐half from an expanded area of skin. Responses to noxious radiant heat were similarly modified. 5. Inhibition evoked in PSDC neurones, whether by light tactile or noxious stimuli, involved predominantly segmental mechanisms since it remained effective in the cold‐blocked state. 6. It is concluded that neurones of the PSDC system are amongst those dorsal horn neurones with receptive field geometries which may be modified by activity in descending systems.
Fatigability of rat hindlimb muscle: associations between electromyogram and force during a fatigue test.
Authors: Enoka R M , Rankin L L , Stuart D G , Volz K A
Published: December 2014

1. An experimental protocol designed to assess fatigability in motor units (Burke, Levine, Tsairis & Zajac, 1973) has been applied to the whole muscles of anaesthetized adult rats, and the association between the electromyogram (EMG) and force was monitored over the course of the test. 2. Both test muscles (soleus and extensor digitorum longus) exhibited a wide range of fatigability, which was defined as the decline in isometric peak force at 6 min, such that the data could be separated into five levels of fatigability. Fatigue indices for each test muscle were distributed across three levels. 3. The EMG was quantified with four measures of amplitude, four of duration, and one interaction term (area). Correlation analyses indicated that the EMG was adequately represented by one measure of amplitude (absolute amplitude), one of duration (peak‐to‐peak duration) and area. The best single measure was area. 4. The EMG‐force associations for soleus varied markedly among its three fatigability groups. In contrast, over the course of the test, all three extensor digitorum longus groups displayed qualitatively similar EMG‐force associations. 5. Multiple regression analyses indicated that the EMG parameters were able to predict peak force better for extensor digitorum longus than for soleus. Furthermore, for both test muscle, the prediction was best for the most fatigable group. 6. The associations between EMG and force exhibited three patterns for the two test muscles and three levels of fatigability. These differences suggested variation in the mechanisms, related to both fibre‐type composition and susceptibility to fatigue, that dictate the performance elicited by this particular stimulus regimen. The mechanisms seem to include both intracellular and transmission processes.
Specificities of afferents reinnervating cat muscle spindles after nerve section.
Authors: Banks R W , Barker D
Published: December 2014

1. We have made quantitative assessments of the sensory reinnervation and recovery of peroneus brevis muscle spindles following section and epineurial repair of the common peroneal nerve. After 6‐50 weeks recovery, single‐unit, dorsal‐root recordings were made of the responses to ramp‐and‐hold or sinusoidal stretch of the reinnervated spindles, which were subsequently examined in teased, silver preparations. 2. Assessments of recovery used data obtained from cross‐union experiments in which foreign afferents (including Ib) were given the opportunity of reinnervating spindles in the absence of their native (Ia, spindle II) afferents; and from an examination of tenuissimus spindles reinnervated by Ia and spindle II afferents in the absence of Ib afferents. These studies revealed: (i) that regenerating Ib afferents can terminate in sites originally occupied by the endings of Ia or spindle II afferents, and respond to stretch like normal Ia and spindle II afferents; (ii) that Ib and spindle II afferents reinnervating spindles are histologically identical apart from diameter range; and (iii) that some cutaneous afferents can reinnervate spindles and give highly abnormal, phasic stretch responses. 3. Recovery of afferents reinnervating spindles was marked by increases in conduction velocity and proportions firing tonically, but their firing rates at the three phases of ramp‐and‐hold stretch were considerably lower than normal and showed no tendency to increase. 4. Some relatively fast afferents that gave spindle II‐type responses were identified as Ib afferents reinnervating secondary‐ending sites; conversely, some relatively slow afferents that gave Ia‐type responses were identified as spindle II afferents reinnervating primary‐ending sites. 5. The estimated loss of spindle afferents from tenuissimus after nerve section (52% Ia, 49% spindle II) was considerably less than the estimated loss of these afferents from peroneus brevis after section of the common peroneal nerve (79% Ia, 86% spindle II). The proportion of spindles in tenuissimus reinnervated by free‐ending afferents was also much lower (22%) than in peroneus brevis (73%). These differences are partly attributed to the greater size and degree of afferent complexity of the common peroneal nerve. 6. Similar proportions of spindles in peroneus brevis were reinnervated by Ia and Ib afferents after both partial (27% Ia, 20% Ib) and complete (21% Ia, 20% Ib) section of the common peroneal nerve.(ABSTRACT TRUNCATED AT 400 WORDS)
The specificity of pyrimidine nucleoside transport and metabolism by rat jejunum in vitro.
Authors: Bronk J R , Hastewell J G
Published: December 2014

1. 5‐Methyluridine perfused through the lumen of isolated loops of rat jejunum gave rise to serosal thymine as the major species transported across the epithelial layer; no serosal 5‐methyluridine was detected. 2. At 0.1 mM‐luminal 5‐methyluridine there was enhanced transmural transport of thymine (P less than 0.001) when compared with either 0.1 mM‐thymine or 0.1 mM‐thymidine as the luminal substrate for thymine transport. 3. At low luminal concentrations (0.025 mM) thymine was a significantly better substrate (P less than 0.001) for the transport of the free pyrimidine than either of the two nucleosides (thymidine or 5‐methyluridine). 4. Luminal deoxyuridine gave rise to uracil as the major species appearing in the serosal secretion. High luminal concentrations of deoxyuridine (0.5 and 1.0 mM) gave rise to low levels of the nucleoside in the serosal fluid. 5. As a consequence of the specificity of the mucosal phosphorolysis the ribonucleosides are favoured over the deoxyribonucleosides as substrates for transmural pyrimidine transport.
The transport of albumin across the ferret in vitro whole trachea.
Authors: Webber S E , Widdicombe J G
Published: December 2014

1. The whole trachea of the ferret has been isolated in vitro in an organ bath and used to study the transport of bovine serum albumin (BSA) and two dextrans (70,000 and 9000 Da) from external buffer solution to air‐filled lumen, assessed by fluorescent‐labelled tracers. 2. In control conditions, when mucus secretion was not stimulated by drugs, the concentration of albumin in the lumen was over half that in the buffer, and about six times greater than those of the two dextrans. 3. Methacholine and phenylephrine caused large increases in mucus secretion and albumin output and decreases in albumin concentration. The responses were proportional to drug concentration. We concluded that albumin output is increased but diluted with submucosal gland secretion. 4. Salbutamol caused a small increase in mucus secretion and large increases in output and concentration of albumin. The concentration of albumin became greater than that in the external buffer medium. The responses were proportional to concentration of salbutamol. 5. Histamine increased mucus secretion and albumin output and concentration. 6. None of the four drugs increased the output of dextran‐70,000. Methacholine and phenylephrine increased the output of dextran‐9000, but to a far less extent than for albumin. 7. Cooling the trachea and buffer to 4 degrees C almost abolished the stimulation of mucus and albumin outputs due to methacholine. 8. Increasing the concentration of albumin external to the trachea did not proportionally increase albumin secretion, the logarithmic relationship suggesting saturation of an active transport system. 9. We conclude that albumin is secreted by active transport into the tracheal lumen, and that the rate of transport can be augmented by salbutamol to build up a higher concentration in the lumen than in the external buffer.
Pulmonary glucose transport in the fetal sheep.
Authors: Barker P M , Boyd C A , Ramsden C A , Strang L B , Walters D V
Published: December 2014

1. In the chronically catheterized sheep fetus between 122 and 143 days gestation the concentration of D‐glucose in lung liquid was very low (usually less than 0.01 mM, the lower limit of detection of the analytical method) whereas the mean plasma concentration was 0.19 mM (S.E.M. 0.4, n = 13). 2. When the lung liquid concentration of D‐glucose was raised to 1.67‐5.00 mM, rapid uptake was observed until the concentration had fallen to its preceding low level. The uptake showed saturation kinetics (Vmax = 2.29‐8.78 mumol/min, increasing with gestation; mean Km = 0.14 +/‐ 0.02 mM, n = 11, no change with gestation). This active uptake of glucose was blocked by phloridzin (10(‐4) M). It was associated with a decrease in lung liquid secretion rate from which a change in net sodium flux could be inferred of an order suggesting one‐to‐one glucose‐sodium co‐transport. 3. Radiolabelled 3‐O‐methyl‐D‐glucose (3‐O‐meG) ‐ a monosaccharide which is transported but not metabolized ‐ was taken up rapidly from lung liquid and this rapid uptake was inhibited by D‐glucose with 50% inhibition at 0.35 mM (+/‐ 0.08, n = 9). It was also inhibited by phloridzin (10(‐4) M). 4. Radiolabelled 2‐deoxy‐D‐glucose ‐ a monosaccharide which is not a substrate for sodium‐coupled transport ‐ was taken up only very slowly from lung liquid; the rate of uptake was appropriate for passive diffusional transport and it was unaffected by the addition of D‐glucose or phloridzin to lung liquid. 5. Intravenous infusion of D‐glucose caused no detectable increase in the concentration of glucose in lung liquid unless phloridzin was added, when a slow increase was observed. 6. In two experiments with active transport blocked by phloridzin in lung liquid (10(‐4) M), the rate of entry of labelled 3‐O‐meG from plasma to lung liquid was measured during intravenous infusion of this tracer for 29 and 23 h. The rates of entry were similar to the rate of efflux of the tracer from lung liquid when uptake was blocked by phloridzin or D‐glucose, and similar to the rate expected for a metabolically inert tracer (i.e. it was some two orders of magnitude less than efflux from lung liquid in the absence of an inhibitor).(ABSTRACT TRUNCATED AT 400 WORDS)
The intrinsic intracellular H+ buffering power of snail neurones.
Authors: Szatkowski M S , Thomas R C
Published: December 2014

1. We measured intracellular pH (pHi) in snail neurones using pH‐sensitive glass microelectrodes. We then calculated the intracellular buffering power (beta i) from the pHi changes associated with the influx or efflux of a variety of weak acids or bases. 2. The weak acid anions butyrate and propionate (20 mM) gave similar values for beta i but those measured using 20 mM‐acetate were on average twice as great. 3. Although solutions were nominally CO2‐free, blockage of pHi regulation with SITS (4‐acetamido‐4'‐isothiocyanatostilbene‐2,2'‐disulphonic acid) increased the sizes of the pHi changes upon weak acid addition and removal. The corresponding measured values of beta i were on average 26% lower with SITS than without. 4. With pHi regulation blocked, the use of 2.7% CO2 to measure beta i gave beta i values similar to those measured with butyrate or propionate. These values were about 50% less than those previously measured in snail neurones using CO2. 5. beta i values calculated from the pHi changes due to the removal of 5 mM of the weak bases trimethylamine, procaine and NH4Cl were all similar and comparable to those measured using butyrate or propionate. Removing the influence of pHi regulation on the undershoots after NH4Cl removal was found to decrease the apparent measured values of beta i by 10%. 6. Combining all the data (except the values obtained using CO2 and acetate), and adjusting for the errors due to pHi regulation reducing the sizes of the pHi changes, we found that the mean value for beta i was 10.4 +/‐ 0.6 mM (+/‐ S.E.M.) at a mean pHi of 7.36 +/‐ 0.05. 7. We also investigated the relationship between beta i and pHi using ionophoretic acid injection. By means of step‐wise injections, with pHi regulation blocked, we found that at normal pHi levels beta i remained relatively constant. However, at a pHi of less than about 6.8 beta i increased with decreasing pHi.
Potentiation and suppression by eserine of muscarinic synaptic transmission in the guinea‐pig hippocampal slice.
Authors: Misgeld U , Müller W , Polder H R
Published: December 2014

1. The effects of the anticholinesterase eserine on CA3 pyramidal cells and dentate gyrus granule cells in guinea‐pig hippocampal slices were investigated with single‐electrode current‐clamp and voltage‐clamp recording. 2. In the majority of cells superfused with eserine (0.5‐10 microM) for 3‐10 min, tetanic stimulation near the cell layers elicited a delayed depolarization (slow EPSP; duration up to 60 s) at a pre‐stimulation membrane potential of ‐60 mV. The slow EPSP was blocked by atropine (1 microM). 3. Under voltage clamp at ‐60 mV holding potential, an apparent inward current (slow EPSC) with a similar time course to the slow EPSP was observed. 4. The amplitude of the delayed inward current was about 50 pA. The amplitude increased at holding potentials more positive than ‐60 mV. At holding potentials negative to ‐60 mV, the delayed inward current was too small to allow reliable analysis. In the absence of eserine, there was a delayed inward current, which was rather small, however, due to a superimposed outward current. 5. Eserine reduced the after‐hyperpolarization following a train of action potentials. This effect was antagonized by atropine, but not to pirenzepine. In voltage‐clamp recording, eserine reduced a current termed IAHP. 6. CA3 neurones treated with eserine exhibited a region of negative slope conductance (in tetrodotoxin). The slow inward current which developed at clamp potentials between ‐50 and ‐40 mV was reduced by Ni2+ (50 microM). The effect of eserine on slope conductance increased with time of exposure. In all neurones superfused with eserine for more than 60 min, burst discharges were observed. Burst discharges were blocked by atropine and Ni2+, but not by pirenzepine. 7. In cells superfused with eserine for more than 1 h, tetanic stimulation failed to elicit a slow EPSP or EPSC. Currents induced by focal acetylcholine (ACh) application were first enhanced by eserine, but blocked after exposure to eserine for more than 1 h. Blockade of ACh‐induced currents was also observed after bath application of carbachol (CCh) in a concentration (0.2 microM) in which it did not induce an inward current at ‐60 mV holding potential. Further, the slow EPSP faded when elicited by repeated tetanic stimulation. 8. While the observed effects of eserine on hippocampal neurones can be explained by eserine's well‐known ability to block acetylcholinesterase activity, our data indicate that the effects of eserine involve more than one muscarinic receptor site, i.e. desensitizing and non‐desensitizing postsynaptic receptor sites.
Somatostatin blocks a calcium current in rat sympathetic ganglion neurones.
Authors: Ikeda S R , Schofield G G
Published: December 2014

1. The effects of somatostatin and somatostatin analogues on a Ca2+ current from acutely isolated and short‐term (24‐48 h) cultured adult rat superior cervical ganglion (SCG) neurones were studied using the whole‐cell variant of the patch‐clamp technique. 2. [D‐Trp8]Somatostatin (SOM) produced a rapid, reversible and concentration‐dependent reduction of the Ca2+ current. Ca2+ current amplitude was reduced over the voltage range ‐15 to +40 mV with the greatest reduction occurring where the amplitude was maximal (ca +10 mV). In the presence of SOM, the Ca2+ current rising phase was slower and biphasic at potentials between 0 and +40 mV. 3. Application of 0.1 microM‐SOM for greater than 10 s resulted in a desensitization of the response. During a 4 min application of 0.1 microM‐SOM, Ca2+ current amplitude returned to about 90% of control. A second application of 0.1 microM‐SOM produced less block than the initial application. 4. Concentration‐response curves for SOM, somatostatin‐14 (SOM‐14) and somatostatin‐28 (SOM‐28) were fitted to a single‐site binding isotherm. The concentrations producing half‐maximal block and the maximal attainable blocks of the Ca2+ current for SOM, SOM‐14 and SOM‐28 were 3.3, 5.4 and 35 nM, respectively and 55, 51 and 54%, respectively. SOM‐14 and SOM‐28 slowed the Ca2+ current rising phase in a manner similar to that of SOM. Somatostatin‐28 had no effect on the Ca2+ current at 1 microM. 5. The magnitude of the Ca2+ current block produced by 0.1 microM‐SOM was not significantly altered in the presence of 1 microM‐idazoxan, atropine, naloxone or the somatostatin antagonist aminoheptanoyl‐Phe‐D‐Trp‐Lys‐O‐benzyl‐Thr. 6. Internal dialysis with solutions containing 500 microM‐guanylyl‐imidodiphosphate (Gpp(NH)p) or guanosine‐5'‐O‐(3‐thiotriphosphate)(GTP‐gamma‐S) decreased the Ca2+ current amplitude by 36 and 41%, respectively, and induced a biphasic rising phase in the Ca2+ current. Under these conditions, application of 0.1 microM‐SOM produced significantly less block of Ca2+ current amplitude (7.1 and 14.7%, respectively) when compared with controls. 7. Internal dialysis with solutions containing 500 microM‐guanosine‐5'‐O‐(2‐thiodiphosphate)(GDP‐beta‐S) had no significant effect on either the Ca2+ current amplitude or block produced by 0.1 microM‐SOM. 8. Internal dialysis with solutions containing 500 microM‐cyclic adenosine 3',5'‐monophosphate (cyclic AMP) and 3‐isobutyl‐1‐methylxanthine had no significant effect on either the Ca2+ current block produced by 0.1 microM‐SOM or the Ca2+ current amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)
Endogenous histamine excites neurones in the guinea‐pig superior cervical ganglion in vitro.
Authors: Christian E P , Undem B J , Weinreich D
Published: December 2014

1. Intracellular recordings were obtained from neurones in the guinea‐pig superior cervical ganglion (SCG) in vitro to study the electrophysiological effects of endogenously released histamine. 2. Guinea‐pigs were actively sensitized to the specific antigen, ovalbumin. SCG removed from these animals rapidly released a significant proportion of their endogenous histamine stores into the extracellular space upon exposure to the sensitizing antigen. Several observations indicated that the released histamine was derived from ganglionic mast cells. 3. The electrophysiological effects produced by antigen challenge in a neurone mimicked qualitatively and quantitatively those effects produced by exogenously applied histamine in the same neurone. Under current clamp the membrane effects of antigen and histamine included a transient depolarization, an increase in input resistance and transient blockade of a long‐duration component of the spike after‐hyperpolarization. In voltage clamp histamine and antigen produced an inward current and decreased membrane conductance. 4. Histamine H1, but not H2 or H3 receptor antagonists prevented the membrane depolarization to both histamine and antigen treatments. 5. These convergent biochemical, physiological and pharmacological data demonstrate that a sufficient quantity of endogenous histamine is released by an antigenic stimulus in SCG from sensitized guinea‐pigs to affect specific electrophysiological characteristics of neurones. Histamine may thus be involved in mediating interactions between the mammalian immune system and the peripheral sympathetic nervous system.
Deactivation kinetics of different components of calcium inward current in the membrane of mice sensory neurones.
Authors: Kostyuk P G , Shirokov R E
Published: December 2014

1. Deactivation kinetics of different components of calcium inward current were analysed by measuring ‘tail currents’ in intracellularly perfused sensory neurones isolated from dorsal root ganglia of newborn mice. 2. Deactivation of a low‐threshold inactivating component had a mono‐exponential time course with time constants that decreased as the potential was made more negative, and reached a limiting value of 1.0‐1.2 ms at extreme hyperpolarizations. Replacement of Ca2+ by Ba2+ as a charge carrier decreased this value almost twofold. 3. Deactivation of the high‐threshold component of calcium current contained two exponential components with time constants of similar potential dependence. The fast time constant became practically constant (0.1‐1.2 ms) during repolarizations beyond ‐50 mV, and the slow time constant became constant (0.80‐0.85 ms) at repolarization beyond ‐70 mV. 4. Replacement of intracellular aspartate with phosphate, or a depolarized holding potential of ‐40 mV, abolished reversibly the slow component of the tail current; in parallel, the peak current‐voltage relation of the current became shifted by 15‐20 mV in the depolarizing direction. 5. Extracellular application of the calcium channel agonist Bay K 8644 (2.5‐5 mumol/l) did not change deactivation kinetics of the low‐threshold current; however, it increased considerably the slow exponential component of high‐threshold current deactivation or induced such a component in conditions when the latter was absent before application (Vh = ‐40 mV; cell perfusion with Tris phosphate). 6. The data obtained are analysed on the basis of the presence of three types of calcium channels in the neuronal membrane which possess similar kinetic mechanisms of activation and deactivation but differ in the activation thresholds and the time constants of transitions between open and closed states. The three calcium channels differ also in interaction with different permeant ions and calcium channel agonists.
Convergence during human vertical saccades: probable causes and perceptual consequences.
Authors: Enright J T
Published: December 2014

1. When a downward saccade is made between equidistant targets, convergence consistently occurs during the saccade: about 1 deg overconvergence after an 8 deg saccade, with either binocular or monocular viewing, with either far (3 m) or near (30 cm) viewing distance. 2. During binocular viewing, this unnecessary convergence is corrected by divergence movement with a half‐time of about 200 ms. During monocular viewing of far targets, similar post‐saccadic divergence occurs, but for monocularly‐seen near targets, recovery is considerably slower. 3. Vergence changes associated with upward saccades are much smaller and typically more variable among subjects. 4. The up‐down asymmetry of intrasaccadic vergence changes can be accounted for by superposition of two plausible adventitious processes: co‐contraction of the vertical recti, and tension increase (upward saccades) or tension release (downward saccades) in the superior oblique muscles. 5. During the 1000 ms after an upward saccade, constriction of the pupil consistently occurs; it apparently represents a near‐triad response, for which concurrent convergence is masked. Such near‐triad activation during upward gaze would presumably be necessary to counterbalance residual steady‐state torques from the superior oblique muscles. 6. The up‐down asymmetry of intrasaccadic vergence changes also arises when targets require both a vergence change and a vertical shift of gaze, thereby accelerating refixation for the typical natural spatial configuration, in which nearer objects are lower in the visual field. 7. During binocular viewing of equidistant targets, the convergence resulting from downward saccades produces large transient disparities, which can be expected to lead to biased evaluations of relative distances to targets. Several up‐down illusions involving apparent distance may well be due to these disparities, including (a) backward tilt of the apparent vertical and of the vertical horopter, (b) the 'soup‐bowl sky’ illusion, and (c) the ‘diverging sunbeams’ illusion.
Inhibitory postsynaptic potentials in neonatal rat sympathetic preganglionic neurones in vitro.
Authors: Dun N J , Mo N
Published: December 2014

1. Intracellular recordings were made from antidromically identified sympathetic preganglionic neurones (SPNs) in transverse sections of thoraco‐lumbar spinal cord from neonatal (12‐22 day) rats. 2. Two types of hyperpolarizing (inhibitory) postsynaptic potentials (IPSPs) were recorded in the SPNs. The first type, which we have termed unitary IPSPs, were small, discrete IPSPs that occurred spontaneously and also following chemical or electrical stimulation applied to the spinal cord slices. The second type IPSP was a hyperpolarizing response evoked by either dorsal or ventral root stimulation. 3. Spontaneously occurring unitary IPSPs had an amplitude of 1 to 5 mV, and reversal potential of ‐60 to ‐75 mV; they were reversibly abolished by low Ca2+, tetrodotoxin (TTX) or strychnine but not by bicuculline and picrotoxin. 4. Pressure application of N‐methyl‐D‐aspartate (NMDA), an excitatory amino SPNs; these were abolished by either strychnine or by the NMDA receptor antagonist D‐2‐amino‐5‐phosphonovalerate. Furthermore, electrical stimulation of dorsal rootlets elicited in several SPNs the discharge of strychnine‐sensitive unitary IPSPs. 5. Electrical stimulation applied to dorsal or ventral rootlets elicited in nineteen and eight SPNs, respectively, an IPSP of larger amplitude (5 to 15 mV). The IPSP exhibited a reversal potential of ‐60 to 75 mV; it was changed to a depolarizing response in a low [Cl‐]o solution, but was not significantly affected in a low [K+]o. Strychnine but not bicuculline or picrotoxin reversibly blocked the IPSPs in nearly all the SPNs. Additionally, hexamethonium and d‐tubocurarine antagonized the IPSPs evoked by ventral but not by dorsal root stimulations. 6. Our results suggest that unitary and evoked IPSPs recorded in SPNs are due primarily to an increase of Cl‐ conductance by glycine or a glycine‐like substance, released from interneurones, that can be activated by NMDA. Furthermore, IPSPs evoked by ventral root stimulation appear to represent a disynaptic event whereby nicotinic activation of a glycine‐releasing interneurone results in a release of the inhibitory transmitter; this is then analogous to the Renshaw cell circuitry of the spinal motoneurones.
An inwardly directed electrogenic sodium‐bicarbonate co‐transport in leech glial cells.
Authors: Deitmer J W , Schlue W R
Published: December 2014

1. We have used double‐barrelled ion‐sensitive microelectrodes to measure the intracellular pH, pHi, the intracellular Na+ activity, aiNa, and the membrane potential in identified glial cells of the central nervous system of the leech Hirudo medicinalis to study the effect of CO2‐HCO3‐. 2. When a HEPES‐buffered saline was exchanged for a saline buffered with 2% CO2 + 11 mM‐HCO3‐, keeping the pH constant at 7.4, the mean steady‐state pHi of the glial cells increased from 6.85 +/‐ 0.06 to 7.18 +/‐ 0.13 (mean +/‐ S.D., n = 25). 3. This CO2‐HCO3‐ ‐dependent alkalinization was inhibited in the absence of external Na+ (exchanged by N‐methyl‐D‐glucamine), but was unaffected by the inhibitor of Na+‐H+ exchange, amiloride (2 mM). 4. The aiNa of the glial cells increased by 2‐4 mM from a mean steady state of 7.2 +/‐ 2 mM (mean +/‐ S.D., n = 6) upon introduction of CO2‐HCO3‐ ‐buffered saline. This CO2‐HCO3‐ ‐dependent rise in aiNa increased to about double when the pHi had been decreased by acid loading the cells (addition and subsequent removal of NH4+). 5. The CO2‐HCO3‐ ‐dependent increases of pHi and aiNa were inhibited by the stilbene 4,4‐diisothiocyanostilbene‐2,2'‐disulphonic acid (DIDS, 0.5‐1.0 mM). 6. Removal of external Cl‐ and depletion of intracellular Cl‐ did not inhibit the CO2‐HCO3‐ ‐dependent alkalinization. 7. The CO2‐HCO3‐ ‐dependent alkalinization was unaffected by inhibitors of the carbonic anhydrase, acetazolamide (0.2 mM) or ethoxzolamide (2 microM). 8. The membrane potential became more negative by 3‐20 mV upon addition of CO2‐HCO3‐. This hyperpolarization was even further enlarged in the presence of Ba2+ (which reduces the K+ permeability) or at increased external K+ concentration (which depolarizes the membrane and brings the membrane potential to the K+ equilibrium potential). The CO2‐HCO3‐ ‐induced membrane hyperpolarization was inhibited in Na+‐free saline and in the presence of DIDS. Ouabain (0.5 mM) sometimes reduced, but never abolished, the hyperpolarization. 9. The stoichiometry of the co‐transport is suggested to be 2 HCO3‐:1 Na+ with an equilibrium potential of ‐90 mV calculated for this coupling ratio in the steady state. 10. It is concluded that in the presence of CO2‐HCO3‐ an inwardly directed electrogenic Na+‐HCO3‐ co‐transport is stimulated across the glial membrane, which greatly determines the pHi and thereby affects the intracellular buffering power of the glial cells.
Central neurotensin nerves modulate colo‐colonic reflex activity in the guinea‐pig inferior mesenteric ganglion.
Authors: Stapelfeldt W H , Szurszewski J H
Published: December 2014

1. The effects of neurotensin and of stimulation of preganglionic nerves on peripheral afferent synaptic input from segments of distal colon to neurones in the inferior mesenteric ganglia of guinea‐pigs were studied using intracellular recording techniques in vitro. 2. Electrical stimulation of colonic afferent nerve fibres evoked fast, nicotinic synaptic responses (fast EPSPs or action potentials) followed by a slow depolarizing response (slow EPSP). 3. Neurotensin (1 microM) increased the amplitude and duration of slow EPSPs evoked by stimulation of colonic afferents. 4. Distention of a segment of distal colon left attached to an inferior mesenteric ganglion evoked a slow depolarization. Neurotensin (1 microM) increased the amplitude and duration of distention‐induced depolarizations. 5. Electrical stimulation of central preganglionic nerve fibres present in the third and fourth lumbar ventral roots increased the amplitude and duration of slow EPSPs evoked by electrical stimulation of colonic afferent nerves. This facilitatory effect was abolished after desensitization to neurotensin. 6. Slow depolarizations evoked by neurotensin and by stimulation of central preganglionic nerves converted subthreshold fast EPSPs due to mechanosensory synaptic input from an attached segment of distal colon to action potentials. This increase in firing rate of sympathetic ganglion cells led to a decrease in colonic intraluminal pressure. 7. Taken together these data support the hypothesis that neurotensin or a closely related substance contained in central preganglionic nerves facilitated release of a non‐cholinergic excitatory transmitter from colonic mechanosensory nerves. The slow depolarization evoked by the non‐cholinergic transmitter converted on‐going subthreshold fast EPSPs to action potentials thereby increasing sympathetic output to the colon. 8. It is suggested that under normal in vivo conditions, central preganglionic fibres containing neurotensin or a closely related peptide modulate peripheral reflex activity through prevertebral ganglia in guinea‐pigs.
The effects of metabolic inhibition on intracellular calcium and pH in isolated rat ventricular cells.
Authors: Eisner D A , Nichols C G , O'Neill S C , Smith G L , Valdeolmillos M
Published: December 2014

1. Intracellular calcium concentration [( Ca2+]i) and pH (pHi) were measured in single, isolated rat ventricular myocytes using, respectively, the fluorescent indicators Fura‐2 and BCECF (2',7'‐bis(carboxyethyl‐5(6)‐carboxyfluorescein). Contraction was measured simultaneously. The intracellular calibration of BCECF is demonstrated. In a HEPES‐buffered bathing solution of pH 7.4, pHi had a mean value of 7.16 +/‐ 0.05 (mean +/‐ S.E.M.). 2. Addition of NH4Cl (5‐20 mM) produced an intracellular alkalosis that was associated with an increase of contraction amplitude. Removal of NH4Cl produced an acidosis and decrease of contraction. 3. The addition of 2 mM‐cyanide (CN‐) to inhibit oxidative phosphorylation had variable effects on contraction amplitude. Changes of contraction amplitude could largely be accounted for by changes in the systolic Ca2+ transient. 4. CN‐ addition increased lactic acid production. However, in the majority of experiments, this was not accompanied by an intracellular acidosis. 5. Anaerobic glycolysis was inhibited by either removal of glucose, addition of deoxyglucose, or addition of iodoacetate. Under these conditions the application of CN‐ decreased systolic [Ca2+]i and contraction amplitude. This was sometimes preceded by a transient increase of systolic [Ca2+]i and contraction amplitude. 6. When glycolysis was inhibited, the subsequent addition of CN‐ always increased diastolic [Ca2+]i and produced a contracture. The increase of [Ca2+]i occurred before the contracture. However, once the contracture had developed, decreasing [Ca2+]i (by removal of external Ca2+) did not cause relaxation. 7. With glycolysis inhibited, addition of CN‐ resulted in a large (0.51 +/‐ 0.05 pH unit) acidosis that was sometimes preceded by an alkalosis. This acidosis was unaffected by removal of external Ca2+ or external alkalinization. Calculations show that some of this acidosis may result from protons released by ATP hydrolysis. 8. If the acidosis produced by metabolic blockade was partly reversed by adding NH4Cl then a contracture immediately developed. This suggests that the acidosis delays the onset of the contracture. 9. We conclude that metabolic inhibition increases diastolic [Ca2+]i. The accompanying acidosis prevents contraction. Once the contracture has developed it is maintained by factors other than increased [Ca2+]i, possibly by a fall of [ATP].
Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle.
Authors: Aickin C C , Betz W J , Harris G L
Published: December 2014

1. Double‐barrelled Cl(‐)‐sensitive microelectrodes have been used to measure the intracellular Cl‐ activity (aCli) and membrane potential (Em) in rat lumbrical muscles. The mean Cl‐ equilibrium potential (ECl), calculated from the measured aCli in sixty fibres, was 2.9 +/‐ 2.5 mV (S.D. of an observation) less negative than Em. The value of aCli was higher than would be expected for a passive distribution, by a mean 1.4 +/‐ 1.2 mM. The mean Em was ‐59.5 +/‐ 8.2 mV. 2. Removal of external Cl‐ (Cl‐(o)) resulted in a rapid fall in aCli and a transient depolarization. aCli stabilized at an apparent level of 1.7 +/‐ 1.0 mM (n = 24) while Em became substantially more negative than in normal Krebs solution (mean, ‐80.1 +/‐ 12.4 mV). Readdition of Cl‐(o) caused a rapid rise in aCli and transient hyperpolarization. ECl quickly became less negative than Em and both then fell in parallel towards the levels previously recorded in normal Krebs solution. 3. If lack of selectivity of the Cl(‐)‐sensitive ion exchanger and the intracellular presence of interfering anions, assumed to be responsible for the apparent aCli recorded in Cl(‐)‐depleted fibres, were also responsible for the apparently non‐passive Cl‐ distribution recorded under normal conditions, the difference between the calculated ECl and Em would increase at more negative potentials. This was not observed over a range of Em values between ‐46 and ‐84 mV. 4. Inhibition of the Cl‐ permeability by application of 9‐anthracene carboxylic acid (9‐AC) resulted in an immediate rise in aCli and hyperpolarization. An aCli up to 40 mM higher, or eleven times higher, than that predicted by a passive distribution was recorded. Application of 9‐AC after depletion of intracellular Cl‐ in Cl(‐)‐free solution had no effect on either the apparent aCli or Em. 5. It is concluded that Cl‐ ions are actively accumulated by the skeletal muscle fibre and that the Cl‐ distribution therefore normally exerts a depolarizing influence. 6. In the presence of 9‐AC and nominal absence of CO2 and HCO3‐, readdition of Cl‐(o) to Cl(‐)‐depleted fibres resulted in a substantial rise in aCli and a small, maintained depolarization. This clear demonstration of active accumulation was used to investigate the mechanism responsible for inward transport of Cl‐ ions. 7. Neither application of CO2 and HCO3‐ nor application of DIDS (4,4'‐diisothiocyanostilbene‐2,2'‐disulphonic acid) had any effect on the accumulation of Cl‐ ions. This suggests that Cl(‐)‐HCO3‐ exchange is not involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Rubidium ions and the gating of delayed rectifier potassium channels of frog skeletal muscle.
Authors: Spruce A E , Standen N B , Stanfield P R
Published: December 2014

1. Unitary currents were measured through delayed rectifier potassium channels of frog skeletal muscle, under conditions where either potassium or rubidium ions carried current. 2. Unitary currents were reduced in amplitude when Rb+ was the charge carrier, indicating that Rb+ permeated the channel less readily than did K+. On the other hand permeability ratios (PRb/PK) measured from the change in reversal potential upon ionic substitution were 0.92 for the external and 0.67 for the internal mouth of the channel. 3. Ensemble‐averaged currents activated under depolarization along a similarly S‐shaped time course whether K+ or Rb+ carried current, though slightly more slowly in Rb+. However, under repolarization to a negative level, tail currents were prolonged about tenfold in Rb+. 4. The duration of channel opening was substantially prolonged in Rb+. The distribution of open times was fitted by a single exponential whether K+ or Rb+ was the charge carrier, indicating a single open state. But the mean open time, averaged over all voltages investigated, was 2.65 times greater in Rb+. 5. The prolongation in Rb+ of tail currents under repolarization was associated with increases in the number of openings per burst and in the number of bursts during each tail. 6. The implications of these results for channel gating are discussed. It is argued that an early step in channel activation is more voltage dependent than later steps.
Contractile characteristics and innervation ratio of rat soleus motor units.
Authors: Chamberlain S , Lewis D M
Published: December 2014

1. Physiological properties of motor units in the soleus muscle were studied in anaesthetized rats using ventral root splitting to isolate single units. 2. Motor unit types were classified by the same criteria used to classify cat hindlimb motor units into types FR (fast‐twitch, fatigue‐resistant) and type S (slow‐twitch, fatigue‐resistant). Type FR units were estimated to generate 10% of whole‐muscle tension and type S 90%. All FR units showed sag in the unfused tetanus at frequencies with interpulse intervals greater than 175% of twitch time to peak, but not at 125% (Burke, Levine, Tsairis & Zajac, 1973). 3. The muscle fibres belonging to twelve single motor units were depleted of glycogen by prolonged stimulation, permitting analysis of their histochemical profiles. Type FR units were found to consist of type IIA muscle fibres and type S units of type I muscle fibres. 4. Direct determinations were made of fibre area, innervation ratio (number of muscle fibres supplied by one motoneurone) and hence specific tension (tetanic tension generated per unit cross‐sectional area) of individually identified motor units. Motoneurons were found to innervate between 84 and 178 muscle fibres (mean 110) in type S units and between 126 and 161 fibres in type FR units (mean 142). Fibre areas were larger for type FR units and there was a significant difference in specific tension of the two unit types (type S lower). 5. Indirect estimates of innervation ratio and specific tension were obtained from counts of muscle fibre types, and relative frequencies of motor unit types in the soleus unit pool. Observations agreed well with results of direct measurements. 6. The evidence provided suggests that differences in tension generated by type FR and S units in rat soleus muscle are primarily due to differences in innervation ratio and fibre area, with a small contribution from differences in specific tension.