bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary afferent depolarization of central terminals of group II muscle afferents in the cat spinal cord.
Authors: Harrison P J , Jankowska E
Published: December 2014

1. The origin of primary afferent depolarization (PAD) of the central terminals of group II afferent fibres of tibialis anterior and extensor digitorum longus muscles has been investigated in the cat. Changes in the excitability of the terminals to intraspinal stimuli, upon application of conditioning stimuli to muscle nerves (quadriceps, sartorius, gracilis, posterior biceps‐semitendinosus, anterior biceps‐semimembranosus, gastrocnemius‐soleus, deep peroneal), cutaneous nerves (sural, superficial peroneal) and the posterior nerve to the knee joint, were used as a measure of PAD. 2. PAD was most readily evoked by conditioning stimuli which were maximal for group II muscle afferents. However, some PAD was also evoked from group I afferents and evidence is presented that group Ia afferents contributed. Afferents of posterior biceps‐semitendinosus and sartorius muscles appeared to be most effective. PAD was also evoked by stimulation of cutaneous and joint nerves, often in the same fibres which were affected by group Ia afferents. 3. It is concluded that there are several common sources of PAD of group II and group Ia afferent terminals on the one hand, and group Ib afferent terminals on the other. 4. The properties of PAD of group II afferents are discussed in relation to the problem of how PAD affects transmission from fibres with long terminal branches of small diameter.
Voltage‐dependent potassium channels in mouse Schwann cells.
Authors: Konishi T
Published: December 2014

1. Ionic currents in Schwann cells cultured from enzymatically dissociated sciatic nerves of newborn mice were recorded by the whole‐cell variation of the patch‐clamp technique. 2. In these cells only the voltage‐dependent K+ currents were recorded. The K+ current was suppressed by quinine, 4‐aminopyridine (4‐AP) or tetraethylammonium (TEA), their half‐suppression concentrations being 22 microM, 0.3 mM and 15 mM, respectively. 3. The peak amplitudes and density of the K+ currents in these Schwann cells increased rapidly during the first 2 days of the culture. 4. In an investigation of the linkage between K+ channels and Schwann cell proliferation, three different K+ channel blockers (quinine, 4‐AP and TEA) were added to the medium at different stages of the culture. In media containing sublethal doses of quinine or 4‐AP, the start of cell proliferation was delayed when these drugs were added at 12 h or on day 3. The same doses of these drugs applied on day 6, when the Schwann cells were proliferating, did not affect cell proliferation. TEA showed a discrepancy between the dose‐dependent blocking of K+ channels and cell proliferation because of its additional cytotoxic effects. 5. It is concluded that voltage‐dependent K+ channels in mouse Schwann cells are similar to those observed in human and murine T lymphocytes. These K+ channels are suggested to be involved in Schwann cell proliferation at early stages of development.
Calcium channels in isolated rat dorsal horn neurones, including labelled spinothalamic and trigeminothalamic cells.
Authors: Huang L Y
Published: December 2014

1. Single isolated neurones were prepared from the spinal trigeminal nucleus and the dorsal horn of cervical spinal cord of the rat. Spinothalamic and trigeminothalamic neurones were identified using rhodamine‐labelled fluorescent latex microspheres. 2. Calcium currents in these cells were examined by the whole‐cell patch‐clamp technique. Three types of calcium currents, transient (T) and slow inactivating (N and L) types, were identified by their sensitivities to inorganic blockers and rates of inactivation at two different holding potentials (temperature = 21‐25 degrees C). 3. From a holding potential of ‐100 mV, the ICa,T began to activate at ‐60 mV. The current reached its maximum amplitude around ‐30 mV and was inactivated completely when the cell was held more positive than ‐60 mV. The time constant of the inactivation was between 10 and 50 ms. 4. The slow inactivating component of ICa was dissociated into two components by eliciting ICa from two holding potentials of ‐100 and of ‐40 mV. The current (ICa,L) activated from ‐40 mV was characterized by positive activation potentials and a very slow inactivation (time constant, 700‐4000 ms). The current (ICa,N) elicited from a holding potential of ‐100 mV started to activate at ‐30 mV and inactivated slowly with time constants ranging between 400 and 1000 ms. 5. Compared with the ICa,T, the inactivation curve for ICa,N was shifted about 30 mV in the depolarizing direction. ICa,N inactivated over a broader range of potentials, and its inactivation and activation curves overlapped. 6. Cadmium blocked ICa,T at a concentration 24 times higher than that which was needed to block slow inactivating currents. The apparent dissociation constant of nickel for ICa,T is twofold lower than that for the slow inactivating currents. 7. Nimodipine (2 microM) decreased the slow inactivating currents, but had no effect on ICa,T. (‐)‐Bay K 8644 (200 nM) increased both ICa,N and ICa,L and shifted the current activation in the hyperpolarizing direction. This result is different from that obtained in sensory and sympathetic neurones in which ICa,N is insensitive to Bay K 8644.
Electrophysiological evidence for interhemispheric transmission of visual information in man.
Authors: Berardi N , Bodis‐Wollner I , Fiorentini A , Giuffré G , Morelli M
Published: December 2014

1. Electrophysiological evidence is presented of interactions between two stimuli (sinusoidal gratings of equal spatial frequency but different contrast, phase‐reversed sinusoidally at different temporal frequencies) located on opposite side of, and within a few degrees from, the vertical meridian. 2. These interactions are revealed by a depression of the cortical visual evoked potential (VEP) evoked by the grating of lower contrast in the presence of the grating of higher contrast. They are similar to, albeit weaker than, those obtained with superimposed asynchronously modulated gratings. 3. The VEP reduction occurs also if the stimuli are presented dichoptically. 4. It does not occur if the gratings are located one above the other either on the same or on opposite sides of the vertical meridian. 5. The strength of the VEP reduction depends on the relative contrast of the two gratings and vanishes for spatial frequencies beyond 4 cycles/deg and temporal frequencies of the high‐contrast grating beyond 10 Hz. 6. The results are in agreement with data on visual callosal connections in animals and confirm previous psychophysical findings (Berardi & Fiorentini, 1987) indicating the particular properties of the interhemispheric cross‐talk between symmetric regions of the visual field astride the vertical meridian in man.
Depolarization changes the mechanism of accommodation in rat and human motor axons.
Authors: Baker M , Bostock H
Published: December 2014

1. We have previously studied accommodation in rat and human motor axons by testing excitability with combinations of long and short current pulses. We found that normally polarized axons accommodate slowly and partially (over about 50 ms) to subthreshold depolarizing currents, and that the principal mechanism is the activation of slow potassium channels (Bostock & Baker, 1988). To understand the response of human nerves to ischaemia, we have now extended these observations to axons already depolarized before the testing currents were applied. 2. Rat ventral root axons were depolarized by passing continuous currents or by raising the extracellular potassium concentration. Human forearm nerves were depolarized by ischaemia, induced by inflating a sphygmomanometer cuff on the upper arm. Depolarized rat and human motor axons accommodated much more rapidly and completely than normally polarized axons (e.g. accommodation in rat axons was 50% complete within 2 ms at about 15 mV depolarized to rest). 3. The fast component of accommodation in depolarized rat fibres was not blocked by tetraethylammonium ions or 4‐aminopyridine, was not accompanied by a conductance or potential change, and had a time constant of 1.7 ms at 30 degrees C. It was attributed to inactivation of closed sodium channels. 4. In depolarized rat fibres exhibiting fast accommodation, a brief rise in excitability was seen at the break of an anodal current. Our prediction that human motor axons would show anode‐break excitation during ischaemia was readily confirmed. 5. The results are discussed in relation to Hill's (1936) mathematical description of accommodation in nerve, and it is concluded that his description is only applicable to depolarized axons.
2‐Chloroadenosine reduces the N calcium current of cultured mouse sensory neurones in a pertussis toxin‐sensitive manner.
Authors: Gross R A , Macdonald R L , Ryan‐Jastrow T
Published: December 2014

1. The adenosine analogue 2‐chloroadenosine (CADO) reduced the duration of calcium‐dependent action potentials (CAPs) in mouse dorsal root ganglion (DRG) neurones in culture, by reducing voltage‐activated calcium conductance (Macdonald, Skerritt & Werz, 1986). Using the single‐electrode voltage clamp technique, we recorded three calcium current components in these neurones, the transient low‐threshold (T), transient high‐threshold (N) and slowly inactivating high‐threshold (L) currents, as described previously (Nowycky, Fox & Tsien, 1985; Gross & Macdonald, 1987). CADO (100 microM) had no effect on the isolated T and L currents. In contrast, CADO reduced calcium currents evoked at clamp potentials positive to ‐20 mV from holding potentials (Vh) near the resting membrane potential; under these conditions, the calcium current consisted primarily of N and L calcium current components. 2. This effect of CADO was not voltage dependent. CADO reduced the magnitude of the calcium current without affecting the voltage dependence of the calcium current‐voltage relation. In addition, similar reductions of calcium current were observed when currents were evoked from Vh of ‐60 or ‐80 mV. 3. In order to determine if a guanine nucleotide‐binding (G) protein was involved in the CADO effect on calcium current, cultures were pre‐treated with pertussis toxin (PT) for at least four hours. PT (100 ng/ml) reduced or abolished the CADO‐induced reduction of CAP duration and calcium current. 4. Since CADO inhibits adenylate cyclase through the PT‐sensitive G protein, Gi, we compared the effects of CADO and 8‐Br‐adenosine 3',5'‐cyclic‐monophosphate (8‐Br‐cyclic AMP) on calcium current. The effect of 8‐Br‐cyclic AMP was voltage dependent, unlike that of CADO. 8‐Br‐cyclic AMP reduced calcium currents evoked from Vh = ‐65 mV, but had no effect on currents evoked from Vh = ‐85 mV. 5. We conclude that the adenosine agonist CADO reduced CAP duration in mouse DRG neurones by selectively reducing the N current component, and that the coupling between the adenosine receptor and the calcium channel required a PT‐sensitive G protein. The CADO effect was unlikely, however, to be due to modulation of adenylate cyclase activity.
Sodium‐calcium exchange during the action potential in guinea‐pig ventricular cells.
Authors: Egan T M , Noble D , Noble S J , Powell T , Spindler A J , Twist V W
Published: December 2014

1. Slow inward tail currents attributable to electrogenic sodium‐calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea‐pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between ‐65 and ‐88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full ‘repriming’ action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is attributable predominantly to the temperature sensitivity of activation of the delayed potassium current, iK, whose decay can then mask the slow tail current at high temperatures. 5. Studies of the relationship between the tail current and the membrane calcium current, iCa, have been performed using a method of drug application which is capable of perturbing iCa in a very rapid and highly reversible manner. Partial block of iCa with cadmium does not initially alter the size of the associated inward current tail. When iCa is increased by applying isoprenaline, the percentage augmentation of the associated tail current is much greater but occurs more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)
Afferent C fibre innervation of cat tooth pulp: confirmation by electrophysiological methods.
Authors: Jyväsjärvi E , Kniffki K D
Published: December 2014

1. The presence of afferent C fibres innervating the lower canine tooth was investigated in Nembutal‐anaesthetized cats. 2. Twenty‐five single fibres with conduction velocities (CVp) of less than 2.5 m/s, as calculated from the shortest response latency using monopolar electrical stimulation of the tooth, were recorded from the inferior alveolar nerve. In addition, the extradental conduction velocity (CVn) of the fibres was determined by using bipolar electrical stimulation of the trunk of the inferior alveolar nerve. 3. The mean CVp was 1.4 +/‐ 0.4 m/s (n = 25; range, 0.6‐2.4 m/s); the mean CVn was higher, 1.7 +/‐ 0.9 m/s (n = 25; range, 0.6‐4.0 m/s). For 20% of the fibres CVn exceeded 2.5 m/s; these were slowly conducting A delta fibres. For 80% of the fibres, however, the extradental conduction velocity was in the C fibre range. 4. The relationship between CVp (y) and CVn (x) was y = 0.66 + 0.40x, the correlation coefficient being r = 0.85. According to the present results this implies that for a reliable classification of pulpal C fibres (CVn less than or equal to 2.5 m/s) by monopolar tooth stimulation alone, CVp should be less than 1.7 m/s. 5. For twenty‐three of the twenty‐five fibres, one to three discrete shortenings of the response latency occurred when the intensity of the tooth stimulation was increased. When the nerve trunk itself was stimulated, a constant response latency was measured at all stimulus intensities applied. 6. For twelve fibres tested, the mean rate of electrical stimulation of the tooth, which the response followed with a constant latency, was 4.1 +/‐ 2.3 Hz (range, 1.5‐10.0 Hz). With higher rates of stimulation the response latency increased until the fibres failed to follow each stimulus pulse. 7. Fifteen of the nineteen fibres tested responded to radiant heat stimulation of the tooth they were innervating. The mean temperature threshold was 41.4 +/‐ 2.7 degrees C (n = 11; range, 37.4 +/‐ 46.4 degrees C). 8. For eight heat‐sensitive pulpal C fibres the receptive field was determined by mechanical stimulation of the exposed pulp tissue. Four C fibres developed a long‐lasting on‐going discharge after intense mechanical stimulation of the receptive field. 9. The discharge evoked by heat and mechanical stimulation of the tooth occluded the response evoked by simultaneously applied electrical current pulses to the nerve trunk, indicating that the same fibres were activated by both tooth and nerve stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanically evoked responses of afferent fibres innervating the guinea‐pig's ureter: an in vitro study.
Authors: Cervero F , Sann H
Published: December 2014

1. Electrophysiological recordings from ureteric mechanosensitive afferent fibres were performed using an in vitro preparation of the guinea‐pig ureter and associated nerves. Single‐unit recordings were obtained from small ureteric nerves arising from the inferior mesenteric ganglion, the hypogastric nerve or the pelvic plexus. The fibre composition of these ureteric nerves was also examined by electron microscopy. 2. In two ureteric nerve bundles, which were taken as representative of the maximal and minimal size of nerves used in the electrophysiological recordings, the number of nerve fibres was found to be 417 and 48, respectively. In the bigger nerve 12% of the fibres were small myelinated and the rest unmyelinated. The smaller nerve consisted of unmyelinated fibres only. 3. Electrophysiological recordings were made from sixty‐seven mechanosensitive afferent fibres. The conduction velocities (CV) of forty‐two of them were determined and all were found to be in the C fibre range (mean CV, 0.4 m/s). Of 119 additional fibres which were not further characterized 112 were C fibres (mean CV, 0.51 m/s) and seven were A delta fibres (mean CV, 3.78 m/s). 4. Mechanosensitive units were classified into two groups according to their ability to respond to contractions of the ureter: (i) U‐1 units (9% of all mechanosensitive units) responded to contractions of the ureter and did not show on‐going activity or after‐discharges to mechanical stimulation. They had low thresholds to intraluminal distension (mean, 8 mmHg) and responded with a short latency to pressure stimuli. (ii) U‐2 units (91% of all mechanosensitive units) did not respond to contractions of the ureter, had spontaneous activity between 0 and 2.4 Hz and exhibited after‐discharges to mechanical stimuli lasting up to several minutes. They responded after a long latency (greater than 3 s) to distensions in the range of 5‐30 mmHg. 5. The level of spontaneous activity and the pressure thresholds of the U‐2 units were found to be different depending on whether or not the ureter was perfused intraluminally. Thus U‐2 units recorded with intraluminal perfusion had a lower rate of on‐going activity and higher threshold to intraluminal distension than U‐2 units recorded without intraluminal perfusion. 6. Movement of an intraluminal glass bead under the receptive field of the units evoked strong responses in nine of eleven U‐2 units tested as soon as their receptive fields were reached. 7. Our results demonstrate the existence of two classes of mechanosensitive afferent fibres in the guinea‐pig ureter.(ABSTRACT TRUNCATED AT 400 WORDS)
Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses.
Authors: Day B L , Dressler D , Maertens de Noordhout A , Marsden C D , Nakashima K , Rothwell J C , Thompson P D
Published: December 2014

1. The effects of different forms of brain stimulation on the discharge pattern of single motor units were examined using the post‐stimulus time histogram (PSTH) technique and by recording the compound surface electromyographic (EMG) responses in the first dorsal interosseous (FDI) muscle. Electrical and magnetic methods were used to stimulate the brain through the intact scalp of seven normal subjects. Electrical stimuli were applied either with the anode over the lateral central scalp and the cathode at the vertex (anodal stimulation) or with the anode at the vertex and the cathode lateral (cathodal stimulation). Magnetic stimulation used a 9 cm diameter coil centred at the vertex; current in the coil flowed either clockwise or anticlockwise when viewed from above. 2. Supramotor threshold stimuli produced one or more narrow (less than 2 ms) peaks of increased firing in the PSTH of all thirty‐two units studied. Anodal stimulation always produced an early peak. The latencies of the peaks produced by other forms of stimulation, or by high intensities of anodal stimulation, were grouped into four time bands relative to this early peak, at intervals of ‐0.5 to 0.5, 1‐2, 2.5‐3.5 and 4‐5.5 ms later. Peaks occurring within these intervals are referred to as P0 (the earliest anodal), P1, P2 and P3 respectively. 3. At threshold, anodal stimulation evoked only the P0 peak; at higher intensities, the P2 or more commonly the P3 peak also was recruited. The size of the P0 peak appeared to saturate at high intensities. 4. In five of six subjects, cathodal stimulation behaved like anodal stimulation, except that there was a lower threshold for recruitment of the P2 or P3 peak relative to that of the P0 peak. In the other subject, the P3 peak was recruited before the P0 peak. 5. Anticlockwise magnetic [corrected] stimulation, at threshold, often produced several peaks. These always included a P1 peak, and usually a P3 peak. A P0 peak in the PSTH was never produced by an anticlockwise stimulation [corrected] at intensities which we could explore with the technique. 6. Clockwise magnetic [corrected] stimulation never recruited a P1 peak; in most subjects a P3 peak was recruited first and at higher intensities was accompanied by P0 or P2 peaks. 7. On most occasions when more than one peak was observed in a PSTH, the unit fired in only one of the preferred intervals after each shock. However, double firing was seen in five units when high intensities of stimulation were used.(ABSTRACT TRUNCATED AT 400 WORDS)
Triple‐barrel structure of inwardly rectifying K+ channels revealed by Cs+ and Rb+ block in guinea‐pig heart cells.
Authors: Matsuda H , Matsuura H , Noma A
Published: December 2014

1. The hypothesis that the inwardly rectifying K+ channel consists of a triple‐barrel structure was investigated. Inward currents were recorded under the blocking effects of external Cs+ or Rb+ in the cell‐attached configuration of the patch‐clamp technique using single ventricular cells enzymatically isolated from guinea‐pig hearts. 2. Cs+ (10‐100 microM) or Rb+ (20‐100 microM) added to the 150 mM‐K+ pipette solution induced rapid open‐blocked transitions in the inward open‐channel currents. In about 20% of experiments the inward current showed two intermediate current levels equally spaced between the unit amplitude and the zero‐conductance level. The current fluctuated between these four levels. In the remaining experiments no obvious sublevels were observed except spontaneous ones, whose amplitudes were not always equal to one‐third or two‐thirds of the unit amplitude. 3. In experiments showing sublevels, the probability that the open‐channel current stayed at each level was measured at various concentrations of blockers and membrane potentials. In both Cs+ and Rb+ block, the distribution of the current levels showed reasonable agreement with the binomial theorem. This finding suggests that the inwardly rectifying K+ channel is composed of three equally conductive subunits and each subunit is independently blocked by Cs+ or Rb+. 4. The dwell‐time histogram in each substate was well fitted with a single‐exponential function. On the assumption of the binomial model, the blocking (mu) and unblocking (lambda) rate for Cs+ and Rb+ were calculated. The value of mu was linearly proportional to the concentration of the blocking ion at a given membrane potential and increased with hyperpolarization (e‐fold increase with a change of ‐43.5 mV in the Cs+ block). lambda was almost independent of the concentration of the blocking ion and less dependent on the membrane potential than mu. 5. The open and blocked times were calculated in experiments showing no clear sublevels. The mean open time was almost equal to the mean dwell time at the full open level in experiments showing sublevels under the same conditions. On the other hand, the mean blocked time was about two or three times longer than the mean dwell time at the zero‐conductance level measured in experiments with sublevels. These results may suggest that the instant one of the three subunits is plugged by blocking ions, the remaining two subunits are closed by unknown mechanisms. 6. Our results support the hypothesis that the cardiac inwardly rectifying K+ channel is composed of three equally conductive subunits.
Dendrites of cat's spinal motoneurones: relationship between stem diameter and predicted input conductance.
Authors: Kernell D , Zwaagstra B
Published: December 2014

1. The electroanatomy of motoneuronal dendrites was analysed using data from fifty‐two dendritic trees of four completely reconstructed cat spinal motoneurones that had been labelled with intracellularly injected horseradish peroxidase. The cells belonged to m. triceps surae, and their physiological properties covered much of the known range for this muscle. 2. For each dendritic tree, the input conductance, as seen from the soma, was calculated by the method of Rall (1959), using anatomical measurements of the length and diameter of all branches and different assumed values for dendritic membrane resistivity. 3. There was a strong positive correlation between dendritic stem diameter and the calculated dendritic input conductance. Dendritic input conductance was approximately equal to a constant x (stem diameter)3/2 x (dendritic membrane resistivity)‐0.76. 4. The relationship between dendritic stem diameter and computed input conductance was equal to that of Rall's equivalent‐cylinder model of a dendritic tree. However, from a number of other points of view, the properties of the reconstructed dendrites differed from those of the model: (a) at branch points, the sum sigma(daughter diameters 3/2) was, on average, 19% greater than the 3/2 power of the parent diameter; (b) dendritic branches often showed a significant amount of tapering, and the mean overall degree of diameter decrease per branch was about 12%; (c) the termination of dendritic branches occurred at widely different distances from the soma within single dendritic trees (true for anatomical as well as for computed electrotonic distances). 5. When used in conjunction with previously published measurements of motoneuronal input resistance and proximal anatomy (Kernell & Zwaagstra, 1981), the present results gave further support to the conclusion that differences in membrane resistivity are of great importance for differences in motoneuronal input resistance. Furthermore, this conclusion was also confirmed by direct observation of the properties of the present four motoneurones: irrespective of the assumed ratio between somatic and dendritic membrane resistivity, there was a statistically significant positive correlation between the measured neuronal input resistance and the required membrane resistivity of soma and dendrites.
Influence of duodenal digesta composition on abomasal outflow, motility and small intestinal transit time in sheep.
Authors: Gregory P C , Miller S J
Published: December 2014

1. A study was made of the influence of duodenal infusion of some of the components of the digesta on gastrointestinal motility, abomasal outflow and small intestinal transit time in seven sheep fed 1500 g grass pellets/day. Gastrointestinal motility was recorded by electromyography. Abomasal outflow was estimated according to the rate of dilution of CrEDTA injected and sampled via an abomasal catheter. Small intestinal transit time was measured by the passage of Phenol Red from the duodenum to the terminal ileum. 2. Abomasal outflow was inhibited during 3 h infusions (5 ml/min) of 100 mM‐acetic, propionic, butyric and lactic acids, of 50 mM‐HCl, of 0.56 M‐glucose, and of 2 and 4% protein hydrolysate. Abomasal motility was inhibited by these infusions and by infusion of 234 mM‐oleic acid (0.75 ml/min), of a fat emulsion (Intralipid 20% 0.3 ml/min) and of 50 mM‐L‐tryptophan (7.5 ml/min). 3. Abomasal motility and, where tested, abomasal outflow, were not affected by duodenal infusion of 150 mM‐NaHCO3 (5‐10 ml/min), 0.28 M‐NaC1 (5‐7.5 ml/min), distilled water (5‐7.5 ml/min), 25 mM‐L‐tyrosine (5 ml/min), and of 50 mM‐acetic, propionic, butyric and lactic acids (5 ml/min). 4. At concentrations or rates of infusion above the threshold dose needed to inhibit abomasal motility, small intestinal motility was altered and the frequency and amplitude of the reticulo‐ruminal contractions were inhibited. 5. The transit time through the small intestine was increased during infusion of 100 mM‐acetic, propionic, butyric and lactic acids and decreased during infusion of 0.56 M‐glucose and Intralipid. 6. Inhibition of abomasal motility and outflow in sheep receiving 1500 g/day grass pellets was calculated to require increases in the duodenal concentration of volatile fatty acids of about 150% and K+ of about 38%, and to require an increase in the rate of delivery to the duodenum of H+ of about 90%, nitrogen of about 22% glucose of about 2000% and fat of about 84%. 7. These findings are discussed in relation to the composition of abomasal and duodenal digesta in sheep fed different diets. 8. It seems likely that components of duodenal chyme, such as H+, volatile fatty acids, glucose and fat only affect abomasal outflow in sheep fed high‐grain diets (glucose, volatile fatty acids), or diets highly supplemented with fat (fat), for short periods after meal feeding (volatile fatty acids) or under abnormal conditions (H+).(ABSTRACT TRUNCATED AT 400 WORDS)
Autonomic blockade and cardiovascular responses to static exercise in partially curarized man.
Authors: Mitchell J H , Reeves D R , Rogers H B , Secher N H , Victor R G
Published: December 2014

1. The cardiovascular responses, heart rate and mean arterial pressure, were followed in seventeen human subjects who performed static handgrip contractions for 2 min at the same absolute force (15% of the initial maximal voluntary contraction strength) before and during partial curarization. In control contractions the rate of perceived exertion was 10 exertion units, 16 units in contractions with tubocurarine which could be maintained and 20 units in contractions that could not be maintained. Control contractions increased mean arterial pressure by 6 mmHg from 89 mmHg while heart rate was unchanged from the resting value of 68 beats min‐1. With tubocurarine, larger increases in mean arterial pressure of 11 mmHg and for heart rate of 8 beats min‐1 were obtained during maintained contractions, and 15 mmHg and 16 beats min‐1, respectively, during non‐maintained contractions. 2. Atropine increased resting heart rate and blood pressure with tubocurarine to 107 beats min‐1 and 98 mmHg, respectively, in seven subjects. The blood pressure response to exercise with tubocurarine was unaffected by atropine, but the heart rate increase was reduced from 15 to 4 beats min‐1. 3. Propranolol reduced resting heart rate with tubocurarine to 56 beats min‐1 with no effect on blood pressure in seven subjects. The cardiovascular responses to exercise with tubocurarine were unaffected by propranolol. In contrast, phentolamine reduced resting blood pressure with tubocurarine to 80 mmHg without affecting heart rate in seven subjects. Exercise responses with tubocurarine were unaffected by phentolamine. Combinations of atropine and propranolol in fourteen subjects or atropine and phentolamine in five subjects showed similar results during exercise with tubocurarine as with the sole use of the agents used to block autonomic receptors. 4. The results suggest that when partial curarization induces a disproportion between the signal from central command and that from exercising muscles, the larger signal arising from central command determines the magnitude of the cardiovascular responses. The centrally generated heart rate response is in part caused by vagal withdrawal. However, the blood pressure response cannot be attenuated by the sole use of alpha‐ or beta‐receptor adrenergic blockade or combinations of these with atropine. This suggests that there may be greater redundancy in the autonomic control of blood pressure than in the vagal control of heart rate associated with central command during static exercise in man.
Light capture by human cones.
Authors: Chen B , Makous W
Published: December 2014

1. The variation in visual efficiency of light with varying pupillary entry (the Stiles‐Crawford effect) was measured to determine the proportion of light incident on the cones that escapes them without recovery by other cones. 2. The variation in detectability of interference fringes with varying pupillary entry of the interfering beams was measured to determine the proportion of incident light that was recaptured by cones in the dark stripes after escaping cones in the bright stripes of the fringes. 3. By exclusion, these observations determine the variation, with varying pupillary entry, in the proportion of incident light that was captured and absorbed by the first cones it entered. 4. Some 70‐90% of the light absorbed by the cones when it passes through the centre of the pupil, is entirely lost to the visual system if it passes instead through the margin of the (dilated) pupil. 5. Over half the light that cones absorb when the light enters the margin of the pupil is light that has previously passed through other cones. 6. If the spread of recaptured light is assumed to be Gaussian, its standard deviation is at most one minute of visual angle. 7. Such recaptured light makes a previously unknown contribution to the various Stiles‐Crawford effects.
Voltage‐activated membrane currents in rat cerebellar granule neurones.
Authors: Cull‐Candy S G , Marshall C G , Ogden D
Published: December 2014

1. Voltage‐activated currents have been recorded from cerebellar granule neurones in explant cultures from young rats (1‐9 days old). Cells were examined with whole‐cell patch‐clamp methods. Depolarizing pulses from a pre‐pulse potential of ‐100 mV evoked a rapidly activated transient inward current, and an outward current which decayed in two phases. The ionic dependence, kinetics and pharmacological properties of these currents have been studied. 2. Peak inward Na+ currents in cells from 7‐day‐old rats were in the range 350‐450 pA. No evidence was found for the presence of calcium currents. Thus, inward current was unchanged in zero Ca2+, 1 mM‐EGTA solution. No inward current was obtained in medium containing 10 mM‐Ba2+ and tetrodotoxin (TTX). Supplementing the pipette (i.e. intracellular) solution with Mg‐ATP did not reveal any Ca2+ current. 3. Depolarizing steps (from ‐100 mV) in TTX‐containing solution gave an early transient outward current and a late outward current. The transient current resembled IA described in other cells, and reversed close to EK in both normal and elevated potassium concentrations, indicating that K+ is the predominant charge carrier. Depolarizing steps from ‐50 mV failed to give a transient outward current, and gave only a slowly rising current which resembled the late potassium current, IK. 4. Inactivation of the transient current was examined by applying test depolarizations from increasingly negative pre‐pulse potentials (‐50 to ‐120 mV): half‐inactivation occurred at ‐72 mV. Transient outward currents decayed exponentially with time constants, tau, of 7.3‐25.3 ms at 0 mV. The time course of removal of inactivation in cells held at ‐50 mV, and given increasingly long pre‐pulses to ‐100 mV, was exponential with tau = 35 ms. 5. Both transient and late outward currents were reversibly abolished by addition to the bathing medium of 10 mM‐Ba2+ or 1 mM‐quinine. Outward K+ current was not dependent on external calcium. Tetraethylammonium (20 mM) selectively reduced the late outward current; the peak transient current was reduced by less than 20%. 4‐Aminopyridine (2 mM) showed little selectivity between transient and late outward currents. 6. It is concluded that cerebellar granule cells from young rats possess voltage‐activated inward Na+ current as well as two types of K+ current, IA and IK. In terms of neuronal functioning, the properties of the transient outward current may confer a role in regulating excitability and in repolarization, but a definitive statement will require knowledge of the cellular location and relative densities of channels in granule cells in vivo.
Secretion of protein from salivary glands in the ferret in response to vasoactive intestinal peptide.
Authors: Ekström J , Tobin G
Published: December 2014

1. Secretory responses of ferret parotid and submandibular glands were investigated in the presence of muscarinic, alpha‐ and beta‐adrenoceptor blocking agents. 2. In pentobarbitone‐anaesthetized animals I.V. doses of vasoactive intestinal peptide (VIP) failed to elicit overt secretion of saliva from either gland. 3. However, an occult secretion of protein occurred in response to VIP from both types of gland. This was revealed by means of a subsequent I.V. wash‐out injection of substance P, which is a potent secretagogue in ferrets. This effect of VIP was much more marked in the submandibular than in the parotid gland. 4. Electrical stimulation of the chorda‐lingual nerve gave rise to protein secretion in the submandibular gland at subthreshold frequencies for overt non‐cholinergic, non‐adrenergic secretion of saliva, as revealed by subsequent wash‐out I.V. injection of substance P. 5. Protein secretion in response to VIP was also demonstrated in vitro by perifusing small pieces of the two glands. The sensitivity of submandibular tissue to VIP greatly exceeded that of the parotid tissue. 6. It is concluded that VIP, or a structurally related peptide, may be involved in the non‐cholinergic, non‐adrenergic secretory response of ferret salivary glands evoked by parasympathetic nerve stimulation.
Modulation of the delayed rectifier potassium current in frog cardiomyocytes by beta‐adrenergic agonists and magnesium.
Authors: Duchatelle‐Gourdon I , Hartzell H C , Lagrutta A A
Published: December 2014

1. The regulation of IK and ICa were studied in single cells isolated from bull‐frog atrium using the whole‐cell configuration of the patch clamp and a perfused patch pipette. 2. IK was increased approximately 50‐100% and ICa was increased approximately 6‐10 times by 1 microM‐isoprenaline, 5 microM‐forskolin, or internal perfusion with 30 microM‐cyclic AMP. The effects of cyclic AMP and isoprenaline were not additive. The shape of the concentration‐response curves and the EC50 values for the effects of cyclic AMP on ICa and on IK were very similar (2.3 microM for IK and 1.7 microM for ICa). 3. Elevation of intracellular cyclic AMP had a similar effect on IK regardless of whether ICa was blocked with Cd2+ or not. Increasing ICa with dihydropyridine Ca2+ channel agonists had no effect on IK amplitude. 4. Isoprenaline or cyclic AMP caused an increase in the fully‐activated IK and also shifted the activation curves to more negative potentials in most cells. The shift in the activation curve was reversible and was also observed when ICa was blocked with Cd2+. The rate of activation of IK was increased and the rate of deactivation of IK was slowed by isoprenaline. 5. After breaking the membrane patch and initiating whole‐cell recording, IK ran down with time in about 50% of the cells examined when the intracellular solution contained 1 mM [Mg2+]. In contrast, when the solution contained 0.3 mM [Mg2+], rundown was almost never observed. Internal perfusion with increasing concentrations of [Mg2+] caused reversible decreases in the maximum amplitude of IK and shifted the IK activation curve slightly to more negative potentials, but had negligible effects upon the shape or the curvature of the fully activated current‐voltage relationship.
Electrical and synaptic properties of myenteric plexus neurones in the terminal large intestine of the guinea‐pig.
Authors: Tamura K , Wood J D
Published: December 2014

1. Intracellular recording methods were used to investigate the cellular neurophysiology of ganglion cells in the myenteric plexus of the guinea‐pig rectum. The rectum is a region of the gastrointestinal tract with specialized functions that include reflex relaxation of the internal and sphincter during defaecation. Electrical and synaptic properties of myenteric neurones in the rectum had not previously been studied. Therefore, the overall aim of the work was to describe electrical and synaptic behaviour and identify neurophysiological properties of rectal neurones that might be related to specialization of function in this region of the gut. 2. Thirty‐four (58%) of fifty‐nine impaled cells had electrophysiological properties of AH/type 2 enteric neurones. Eighteen (30%) behaved like type 3 neurones and only two (3%) behaved like S/type 1 enteric neurones. Three per cent were presumably glial cells and the remainder were unclassifiable. 3. Nicotinic cholinergic fast EPSPs were recorded in six of thirty‐four (18%) of AH/type 2 neurones and in all eighteen of the type 3 cells. Slow EPSPs occurred in five of thirty‐four (15%) of AH/type 2 neurones and were absent from type 3 neurones. 4. Type 3 neurones received fast synaptic inputs from axons in each of the interganglionic fibre tracts that were connected with the ganglion containing the neurone. 5. AH/type 2 neurones were apparently multipolar neurones with long processes projecting into each of the interganglionic fibre tracts connected with the ganglion. Type 3 neurones did not have processes leaving the ganglion in the fibre tracts. 6. Run‐down in amplitude of the fast EPSPs in type 3 neurones occurred when they were evoked at frequencies of 5 Hz or greater. 7. Presynaptic muscarinic cholinergic receptors behaved like autoreceptors in suppressing the release of acetylcholine at nicotinic synapses on type 3 neurones. 8. Application of 5‐hydroxytryptamine, acetylcholine, substance P and forskolin mimicked the characteristics of slow EPSPs in the AH/type 2 neurones. 9. The principal difference between neuronal behaviour in the rectum and small intestine, colon and stomach was in the relative proportions of AH/type 2, S/type 1 and type 3 neurones. This is discussed in terms of the functional specialization of the rectum.
Modulation of excitatory amino acid receptors by group IIB metal cations in cultured mouse hippocampal neurones.
Authors: Mayer M L , Vyklicky L , Westbrook G L
Published: December 2014

1. Responses to the excitatory amino acids kainate, quisqualate, N‐methyl‐D‐aspartate (NMDA), L‐glutamate and L‐aspartate were recorded in mouse hippocampal neurones in cell culture, using the whole‐cell configuration of the patch clamp technique. Agonists were applied rapidly from an array of flow pipes each of 250 microns diameter, positioned within 100 microns of the nerve cell body. 2. Responses to NMDA, L‐aspartate and to low concentrations of L‐glutamate, recorded with glycine in the extracellular fluid, were strongly antagonized by 50 microM‐zinc. Responses to kainate, quisqualate, and in glycine‐free solution, responses to L‐glutamate, were potentiated by 50 microM‐zinc, but partially antagonized by 1 mM‐zinc. On average, with 50 microM‐zinc, responses to NMDA were reduced to 0.19 times control, while responses to kainate and quisqualate were increased to 1.09 and 1.14 times control. With 1 mM‐zinc responses to kainate and quisqualate were reduced to 0.54 and 0.42 times control. 3. Cadmium had a similar, though less potent action, and at 50 microM antagonized responses to NMDA but potentiated responses to kainate and quisqualate. On average, with 50 microM‐cadmium, responses to NMDA were reduced to 0.39 times control, while responses to kainate and quisqualate were increased to 1.08 and 1.15 times control. With 1 mM‐cadmium responses to NMDA were reduced to 0.04 times control while responses to kainate and quisqualate were reduced to 0.79 and 0.60 times control. Mercury was neurotoxic and increased the leakage current; however, no reduction of the response to NMDA was produced by 5 microM‐mercury. 4. The equilibrium dissociation constant (Kd) for zinc antagonism of responses to NMDA, estimated from fit of a single binding site adsorption isotherm, was 13 microM; cadmium was about 4 times less potent than zinc. These effects of zinc and cadmium were nearly voltage independent. In contrast the antagonism of responses to NMDA by 150 microM‐magnesium was highly voltage dependent, such that the Kd for magnesium increased e‐fold per 17.6 mV depolarization. 5. The potency of zinc as an NMDA antagonist did not vary with the concentration of NMDA, and was not greatly influenced by a 1000‐fold variation in the concentration of the NMDA‐modulator glycine. This suggests that zinc acts as a non‐competitive antagonist, and does not directly interfere with the binding of NMDA to the agonist recognition site nor with the binding of glycine to an allosteric site on the NMDA receptor complex.(ABSTRACT TRUNCATED AT 400 WORDS)
The action of zinc on synaptic transmission and neuronal excitability in cultures of mouse hippocampus.
Authors: Mayer M L , Vyklicky L
Published: December 2014

1. The whole‐cell configuration of the patch clamp method was used to record from hippocampal neurones in cell culture. Synaptic responses were evoked by loose patch stimulation of adjacent presynaptic neurones in low‐density cultures. Agonists and antagonists were applied rapidly, using an array of flow pipes each of diameter 250 microns, positioned within 100 microns of the postsynaptic neurone. 2. Bath application of 50 microM‐zinc produced prolonged periods of synaptic barrage and action potential discharge. Flow pipe application of 50 microM‐zinc, in glycine‐free solution with 1 mM‐Mg2+, produced on average a 75% reduction of IPSP amplitude, but increased the average EPSP amplitude to 171% of control. However, after block of gamma‐aminobutyric acid (GABA) receptors with bicuculline, zinc had no effect on EPSP amplitude, suggesting that potentiation recorded in control solutions reflects block of polysynaptic IPSPs. 3. Consistent with the block of IPSPs postsynaptic responses to flow pipe applications of GABA were blocked by zinc, with fast‐on, fast‐off kinetics. The equilibrium dissociation constant (Kd) for zinc block of GABA responses, estimated from fit of a single binding site adsorption isotherm, was 11 microM and sufficient to explain the degree of reduction of IPSPs by 50 microM‐zinc. Zinc antagonism of responses to GABA was essentially independent of membrane potential over the range ‐60 to +60 mV. 4. With bicuculline methiodide and glycine added to a magnesium‐free extracellular solution, to allow the study of synaptic responses mediated by N‐methyl‐D‐aspartic acid (NMDA) receptors, zinc reduced the amplitude of EPSPs to 50% of control, and decreased the decay time constant of the EPSP, suggesting that zinc blocks synaptic activation of NMDA receptors. 5. Under conditions where synaptic transmission was completely blocked with postsynaptic receptor antagonists (1‐3 mM‐kynurenic acid and 10‐20 microM‐bicuculline methiodide) 50 microM‐zinc decreased the amplitude of the spike after‐hyperpolarization (AHP), but did not produce large changes in action potential amplitude or half‐width. Under these conditions 50 microM‐zinc also decreased the current threshold required to trigger action potential discharge, and blocked accommodation so that repetitive firing replaced single action potential responses to prolonged current pulses.