bluuebunny/crossref_metadata_2025 huggingface dataset:
Chloride and bicarbonate transport in chick embryonic red blood cells.
Authors: Sieger U , Brahm J , Baumann R
Published: December 2014

1. Unidirectional efflux of 36Cl‐ and H14CO3‐ from erythrocytes of 4‐ to 16‐day‐old chick embryos was measured under steady‐state conditions at 37 degrees C and pH 7.7. The efflux rates were high, > 3 s‐1, and were, therefore, measured by means of the continuous flow tube method. 2. At day 4 of development the range of permeability coefficients for bicarbonate and chloride (PHCO3 and PCl was 1‐30 x 10(‐4) cm s‐1, with average values of respectively 10 x 10(‐4) and 8 x 10(‐4) cm s‐1. However, the results can be divided into two groups, one with PHCO3 and PCl above 12 x 10(‐4) cm s‐1, and one with values below 5 x 10(‐4) cm s‐1. The same range of values was also obtained for day 6 erythrocytes, but the overlap is more conspicuous. At day 16, PHCO3 and PCl were respectively 9 x 10(‐4) and 6 x 10(‐4) cm s‐1 (37 degrees C, pH 7.7). In adult chicken red blood cells PHCO3 and PCl were respectively 7 x 10(‐4) and 4 x 10(‐4) cm s‐1, and in human red blood cells the respective values were 5.6 x 10(‐4) and 4 x 10(‐4) cm s‐1. 3. Chloride self‐exchange, measured at 0 degrees C, was almost completely inhibited by addition of 1 mM 4,4'‐diisothiocyanostilbene‐2,2'‐disulphonate (DIDS) at both days 6 and 16 of embryonic development, supporting the finding that the embryonic chick erythrocytes also have a transmembrane anion exchanger similar to that of other red cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of hypercapnia on membrane potential and intracellular calcium in rat carotid body type I cells.
Authors: Buckler K J , Vaughan-Jones R D
Published: December 2014

1. An acid‐induced rise in the intracellular calcium concentration ([Ca2+]i) of type I cells is thought to play a vital role in pH/PCO2 chemoreception by the carotid body. In this present study we have investigated the cause of this rise in [Ca2+]i in enzymatically isolated, neonatal rat type I cells. 2. The rise in [Ca2+]i induced by a hypercapnic acidosis was inhibited in Ca(2+)‐free media, and by 2 mM Ni2+. Acidosis also increased Mn2+ permeability. The rise in [Ca2+]i is dependent, therefore, upon a Ca2+ influx from the external medium. 3. The acid‐induced rise in [Ca2+]i was attenuated by both nicardipine and methoxyverapamil (D600), suggesting a role for L‐type Ca2+ channels. 4. Acidosis depolarized type I cells and often (approximately 50% of cells) induced action potentials. These effects coincided with a rise in [Ca2+]i. When membrane depolarization was prevented by a voltage clamp, acidosis failed to evoke a rise in [Ca2+]i. The acid‐induced rise in [Ca2+]i is a consequence, therefore, of membrane depolarization. 5. Acidosis decreased the resting membrane conductance of type I cells. The reversal potential of the acid‐sensitive current was about ‐75 mV. 6. A depolarization (30 mM [K+]o)‐induced rise in [Ca2+]i was blocked by either the removal of extracellular Ca2+ or the presence of 2 mM Ni2+, and was also substantially inhibited by nicardipine. Under voltage‐clamp conditions, [Ca2+]i displayed a bell‐shaped dependence on membrane potential. Depolarization raises [Ca2+]i, therefore, through voltage‐operated Ca2+ channels. 7. Caffeine (10 mM) induced only a small rise in [Ca2+]i (< 10% of that induced by 30 mM extracellular K+). Ca(2+)‐induced Ca2+ release is unlikely, therefore, to contribute greatly to the rise in [Ca2+]i induced by depolarization. 8. Although the replacement of extracellular Na+ with N‐methyl‐D‐glucamine (NMG), but not Li+, inhibited the acid‐induced rise in [Ca2+]i, this was due to membrane hyperpolarization and not to the inhibition of Na(+)‐Ca2+ exchange or Na(+)‐dependent action potentials. 9. The removal of extracellular Na+ (NMG substituted) did not have a significant effect upon the resting [Ca2+]i, and only slowed [Ca2+]i recovery slightly following repolarization from 0 to ‐60 mV. Therefore, if present, Na(+)‐Ca2+ exchange plays only a minor role in [Ca2+]i homeostasis. 10. In summary, in the neonatal rat type I cell, hypercapnic acidosis raises [Ca2+]i through membrane depolarization and voltage‐gated Ca2+ entry.
Proprioceptive, visual and vestibular thresholds for the perception of sway during standing in humans.
Authors: Fitzpatrick R , McCloskey D I
Published: December 2014

1. Thresholds for the perception of postural sway induced by gentle perturbations were determined for five normal standing subjects. In this context we understand ‘perception’ to mean ‘able to give a subjective report’. The thresholds for the perception of movements that were equivalent to sway in velocity and amplitude were determined when the available sensory input was limited to only one, or a pair, of the vestibular, visual, and proprioceptive systems. To examine vestibular inputs alone, vision was excluded and the whole body was moved with the ankles in a fixed position. To examine visual inputs alone, the body was kept stationary and a ‘room’ was moved around the subjects to simulate the relative visual‐field movement that occurs during standing. To limit the available sensory input to proprioception from the legs, subjects were held stationary and balanced a load that was equivalent to their own body using their ankles. In this situation, perturbations were applied to the ‘equivalent body’ and these could only be perceived from the resulting ankle movements. Thresholds for perceiving ankle movements were also determined in the same posture, but with the leg muscles bearing no load. 2. The thresholds for the perception of sway during standing were very small, typically 0.003 rad at a velocity of 0.001 rad s‐1, and even smaller movements were perceived as the mean velocity of the sway increased up to 0.003 rad s‐1. No difference was found between the thresholds for perceiving forward sway and backward sway. Eye closure during standing did not affect the threshold for perceiving sway. 3. When sensory input was limited to proprioception from the legs, the thresholds for the perception of passive ankle movements were equivalent to the thresholds for the perception of sway during standing with all sensory inputs available. When the leg muscles were relaxed, the thresholds for perceiving ankle movements increased approximately twofold. 4. The visual thresholds for perceiving movement were higher than the proprioceptive thresholds at slower velocities of movement, but there was no difference at higher velocities. 5. Both the proprioceptive and visual thresholds were sufficiently small to allow perception of the sway that was recorded when the subjects stood normally in a relaxed manner. In contrast, the vestibular thresholds were an order of magnitude greater than the visual or proprioceptive thresholds and above the largest sway movements that were recorded during normal standing.(ABSTRACT TRUNCATED AT 400 WORDS)
G‐protein control of voltage dependence as well as gating of muscarinic metabotropic channels in guinea‐pig ileum.
Authors: Zholos A V , Bolton T B
Published: December 2014

1. Voltage‐dependent properties of muscarinic receptor cationic current activated by carbachol in single smooth muscle cells have been studied using patch‐clamp recording techniques. Cells were obtained by enzymic digestion from the longitudinal muscle layer of guinea‐pig small intestine. 2. The inward cationic current showed a pronounced U‐shaped current‐voltage relationship (inward current negative). The relationship of cationic conductance to voltage could be described by a Boltzman distribution which was shifted 36 mV in the negative direction on the voltage axis by increasing fractional receptor occupancy (by increasing agonist concentration from 3 to 300 microM), and in the positive direction by desensitization during prolonged application of agonist. Cationic channels opened by low and high concentrations of carbachol at the same potential do not have identical properties. 3. Release of GTP within the cell, by flash photolysis of an inert caged precursor, had the same effect on the current‐voltage relationship as increasing receptor occupancy by the agonist. Release of GDP beta S by flash photolysis had the opposite effect. 4. These various results could be explained if cationic channel opening upon receptor activation required binding of at least one alpha‐GTP subunit, but the position of the activation curve on the voltage axis depended critically on the concentration of activated G‐protein alpha‐subunits in the cell.
Effects of intracellular pH and [Mg2+] on excitation‐contraction coupling in skeletal muscle fibres of the rat.
Authors: Lamb G D , Stephenson D G
Published: December 2014

1. The effects on normal excitation‐contraction (E‐C) coupling of two important intracellular ions, H+ and Mg2+, were examined in skinned fibres from the extensor digitorum longus muscle of rat. 2. A single depolarization (2‐3 s duration) in the presence of 1 mM Mg2+ (pH 7.1, 23 degrees C) released most of the available Ca2+ in the sarcoplasmic reticulum (SR), but a similar depolarization in the presence of 10 mM Mg2+ was unable to release almost any Ca2+. Thus, raised [Mg2+] potently inhibits depolarization‐induced Ca2+ release in mammalian muscle. 3. Depolarization at pH 6.2 (1 mM Mg2+, 23 degrees C) induced a large force response, which was on average 78 +/‐ 2%, n = 6, of the depolarization‐induced response at pH 7.1; this reduction resulted from a corresponding reduction in maximum Ca(2+)‐activated force at pH 6.2. Similar results were obtained at 37 degrees C. Also, a single depolarization at pH 6.2 caused almost complete depletion of the releasable Ca2+ in the SR. Thus, low pH does not prevent depolarization‐induced Ca2+ release in mammalian muscle. 4. Lowering the free [Mg2+] from 1 mM to 15 microM caused massive release of Ca2+, and depletion of the SR, at both pH 7.1 and 6.2, indicating that over this pH range, H+ did not readily substitute for Mg2+ at its inhibitory site on the Ca2+ release channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of Ca(2+)‐mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.
Authors: Pape H C , Budde T , Mager R , Kisvárday Z F
Published: December 2014

1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole‐cell current‐clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole‐cell voltage‐clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage‐dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)‐K(+)‐mediated spikes: the T‐type Ca2+ current (IT) and an A‐type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A‐conductance. 4. In local circuit neurones, the ranges of steady‐state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. ‐82.8 mV), both currents activated at around ‐70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = ‐86.1 vs. ‐69.2 mV), and the activation threshold for IT (at ‐80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = ‐54.9 vs. ‐64.5 mV), whereas the activation range of IA was more negative (Vh = ‐25.2 vs. ‐14.5 mV). 5. Under whole‐cell voltage‐clamp conditions that allowed the combined activation of Ca2+ and K+ currents, depolarizing voltage steps from ‐110 mV evoked inward currents resembling IT in relay cells and small outward currents indicative of IA in local circuit neurones. After blockade of IA with 4‐aminopyridine (4‐AP), the same pulse protocol produced IT in both types of neurones. Under current clamp, 4‐AP unmasked a regenerative membrane depolarization with a low threshold of activation capable of triggering fast spikes in local circuit neurones.(ABSTRACT TRUNCATED AT 400 WORDS)
Spatial cues serving the tactile directional sensibility of the human forearm.
Authors: Norrsell U , Olausson H
Published: December 2014

1. Tactile directional sensibility is considered to rely on the parallel processing of direction‐contingent sensory data that depend on skin stretching caused by friction, and spatial cues that vary with time. A temperature‐controlled airstream stimulus that prevented the activation of stretch receptors was used to investigate directional sensibility for the skin of the forearm. 2. The dependence on contact load and distance of movement was determined for normal subjects with a two‐alternative forced‐choice method. Testing was performed under two conditions, elbow bent or straight. Bracing the skin by straightening the arm did not alter the accuracy of the directional sensibility, in contrast to previous findings with stimuli that caused friction. 3. The accuracy of directional sensibility was correlated linearly to the logarithm of the distance of movement of the air jet. No correlation was found between accuracy and contact load, unlike findings with stimuli that cause friction. 4. Measurements were made with different subjects to determine the threshold distance at constant load. On average, subjects were able to distinguish direction with movements of < or = 8 mm. This acuity is sharper than has been reported with static stimuli. There was no correlation between subjects' threshold distances for judging direction and spatial acuity measured with absolute point localization. 5. The ability to distinguish direction was poor for the airstream stimulus compared with stimuli causing frictional contact with hairy skin. Nevertheless, the present findings are consistent with the suggestion that cutaneous spatial acuity is better for dynamic than for static stimuli.
Constitutive upregulation of calcium channel currents in rat phaeochromocytoma cells: role of c‐fos and c‐jun.
Authors: Cavalié A , Berninger B , Haas C A , García D E , Lindholm D , Lux H D
Published: December 2014

1. Northern blot analysis and cell transfection were used in conjunction with whole‐cell current recordings to examine the involvement of the immediate early genes, c‐fos and c‐jun, in the expression of calcium channel currents. 2. Phaeochromocytoma cells (PC12 clone) were exposed to nerve growth factor (NGF) and to depolarizing concentrations of KCl for 60 min every day. Cells challenged with NGF developed extensive networks of neurites within 3 days. Cells depolarized periodically retained their undifferentiated morphology even after 5 days of treatment. 3. The maximal amplitude of high‐voltage‐activated calcium currents (ICa) increased from the control level of 117.8 +/‐ 48.3 (mean +/‐ S.D.) to 387.2 +/‐ 90.1 pA within 3 days of NGF treatment. omega‐Conotoxin (5‐10 microM) inhibited 24.6 +/‐ 8.5% of ICa in undifferentiated cells and 57.8 +/‐ 6.9% in NGF‐treated cells. 4. The levels of c‐fos and c‐jun mRNAs increased transiently during each daily exposure to NGF. The level of c‐fos mRNA also increased transiently during repeated KCl‐induced depolarizations but c‐jun mRNA remained low or absent. 5. Naive PC12 cells were transiently co‐transfected with expression plasmids that contained the full length of c‐fos and c‐jun cDNA. After 2 days following transfection, the PC12 cells could be grouped according to the size of ICa. In 56% of cells, ICa was similar to control currents (106.1 +/‐ 37.4 pA). In the remaining 44% of cells, ICa showed a 2.2‐fold enhancement with respect to control cells. Transfection of only c‐fos had no effect on ICa but, in 24% of cells transfected with c‐jun, ICa was 176.6 +/‐ 124.6 pA. Since periodic membrane depolarization induced c‐fos but not c‐jun mRNA, c‐jun transfection was combined with a high‐K+ treatment over 3 days. In 18% of treated cells, ICa was 3.7 times larger than control currents. Morphological differentiation was not observed in transfected cells. 6. In PC12 cells co‐transfected with c‐fos and c‐jun or treated with high K+ after transfection of c‐jun, omega‐conotoxin (5‐10 microM) inhibited 68.7 +/‐ 11.9% of ICa when the current amplitude was in the range of 200‐600 pA. since similar concentrations of omega‐conotoxin blocked 19.2 +/‐ 5.4% of ICa in control cells, the current increase induced by c‐fos and c‐jun was supported by up to 11‐fold enhancement of the omega‐conotoxin‐sensitive component of ICa.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of palmitoyl carnitine and related metabolites on the avian Ca(2+)‐ATPase and Ca2+ release channel.
Authors: Dumonteil E , Barré H , Meissner G
Published: December 2014

1. In birds, prolonged cold exposure induces the development of a non‐shivering thermogenesis (NST) of muscular origin that may result from an increase in ATP‐dependent cycling of Ca2+ between the sarcoplasmic reticulum (SR) and the cytosol. 2. Because fatty acids are thought to play a significant role in NST, we investigated the effects of palmitic acid and related metabolites on skeletal SR Ca2+ uptake and release in ducklings. 3. Ca(2+)‐ATPase activity, 45Ca2+ release and [3H]ryanodine‐binding measurements indicated that palmitic acid was without effect on the Ca(2+)‐ATPase and Ca2+ release channel. Palmitoyl carnitine and palmitoyl coenzyme A inhibited the Ca(2+)‐ATPase at concentrations > 20 microM whereas both activated the Ca2+ release channel at concentrations < or = 20 microM in a dose‐dependent manner. 4. Palmitoyl carnitine stimulated [3H]ryanodine binding to skeletal but not cardiac SR vesicles. Induction of 45Ca2+ release was observed with long‐chain (C > or = 14) but not with short‐chain acyl carnitines (C < or = 12). 5. Long‐chain acyl carnitines accumulated significantly in duckling skeletal muscle during cold acclimation. Accordingly, these results suggest that long‐chain acyl metabolites may modulate SR Ca2+ cycling and its associated thermogenesis in vivo.
The roles of K+ conductance in expiratory pattern generation in anaesthetized cats.
Authors: Champagnat J , Richter D W
Published: December 2014

1. The potassium current blockers caesium and tetraethylammonium were injected intracellularly by ionophoretic current into brainstem expiratory neurones of the ventral group. Neurones were identified by their spontaneous activity and by antidromic excitation from the spinal cord at the C2‐C3 level. 2. The duration of action potentials increased and the early and late after‐hyperpolarizations were completely suppressed. These effects on action potentials were reversible, recovered with an exponential time course within 3 min, and could be reproduced when blockers were applied repetitively into the same neurone. They were ascribed to blockade of potassium channels in the somatic membrane region. 3. Potassium channel blockers modified postsynaptic potentials: early‐inspiratory hyperpolarizations were reversibly depressed while postinspiratory and expiratory depolarizations were irreversibly enhanced. The former effect was associated with a decrease of the neuronal input conductance. The latter effect was cumulative upon repetitive ionophoretic applications of potassium blockers. 4. The results demonstrate that potassium currents exert two different roles in expiratory pattern generation. Together with chloride currents, they contribute to the phasic early‐inspiratory inhibition. They seem to be calcium‐dependent and GABAB receptor‐controlled currents which predominate near to the cell body. 5. Potassium currents also operate throughout the postinspiratory and late‐expiratory periods. They seem to include persistent potassium currents which modulate the excitatory respiratory drive provided by the respiratory rhythm generator. We assume that these currents, widely distributed over the somatodendritic membrane area, are a target for neuromodulation by transmitters and intracellular second messengers.
Three cation influx currents activated by purinergic receptor stimulation in rat megakaryocytes.
Authors: Somasundaram B , Mahaut-Smith M P
Published: December 2014

1. Simultaneous patch clamp and fura‐2 fluorescence measurements were used to study ATP‐evoked membrane currents and intracellular [Ca2+] ([Ca2+]i) changes in rat megakaryocytes. 2. At negative potentials, under conditions that blocked K+ currents, 20 microM ATP activated a biphasic inward current and a concurrent biphasic increase in [Ca2+]i. The initial [Ca2+]i increase was due to Ca2+ influx whereas the delayed (1.70 +/‐ 0.13 s, mean +/‐ S.D.) increase was at least partly due to the release of internal Ca2+ stores. 3. The initial current was activated within 100 ms, inactivated within 1‐4 s and was carried by both Na+ and Ca2+. 4. The delayed current was also transient and carried mainly by Na+ when Ca2+ buffering in the pipette was low. This Na+ conductance did not require an increase in [Ca2+]i for activation, but was triggered by inositol 1,4,5‐trisphosphate (IP3), or a metabolite of IP3. 5. Buffering of [Ca2+]i changes with BAPTA revealed a third current activated by Ca2+ release from internal stores. This channel was selective for divalent cations with the permeability sequence Ca2+ >> Ba2+ > Mn2+, Mg2+. 6. Adenosine‐5'‐O‐3‐thiotriphosphate (ATP gamma S), like ATP, evoked all three influx currents, whereas ADP only stimulated Ca2+ release and the two currents associated with it. Increasing the external divalent cation concentration abolished the ATP‐evoked Ca2+ release and delayed currents but not the initial transient current. 7. We conclude that rat megakaryocytes express two types of purinergic receptor. One type, activated by ATP, is closely coupled to a non‐selective cation channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non‐NMDA receptors.
Authors: Turner J P , Leresche N , Guyon A , Soltesz I , Crunelli V
Published: December 2014

1. Intracellular and patch‐clamp recordings were obtained from thalamocortical (TC) cells in the rat and cat dorsal lateral geniculate nucleus (dLGN) in vitro to study the role of N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors in the synaptic potential and burst firing evoked by electrical stimulation of the optic tract. 2. At membrane potentials more positive than ‐65 mV, the sensory synaptic potential consisted of a fast EPSP that was followed by a smaller, slower component. At membrane potentials more negative than ‐65 mV, this slower component became more prominent owing to the presence of a low‐threshold (LT) Ca2+ potential, which in turn evoked a high‐frequency (> 150 Hz) burst of action potentials. The lower, but not the upper limit of the range of membrane potential over which burst firing occurred was dependent on the amplitude of the fast EPSP. 3. The non‐NMDA receptor antagonists 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 5‐10 microM) and 1‐(4‐amino‐phenyl)‐4‐methyl‐7,8‐methylene‐dioxy‐5H‐2,3‐ benzodiazepine (GYKI 52466, 100 microM) greatly depressed the fast EPSP, abolished the burst firing generated by the LT Ca2+ potential, and left a relatively small, slow EPSP, which was sensitive to the NMDA antagonist DL‐2‐amino‐5‐phosphonovaleric acid (DL‐AP5, 50‐100 microM). 4. In the absence of CNQX or GYKI 52466, DL‐AP5 depressed the slow but not the fast EPSP. DL‐AP5 also increased the latency of the first action potential evoked by the LT Ca2+ potential or even abolished the LT Ca2+ potential and associated burst firing. The latter effect was only present when this type of firing occurred within a small membrane potential range. 5. DL‐AP5 had no effect on the properties of the LT Ca2+ current IT, indicating that its effect on the burst firing was not mediated by a direct action on IT. 6. The response of TC cells to high‐frequency (100 Hz) stimulation consisted of an initial burst firing response, followed by a sustained depolarization that could reach firing threshold. This sustained depolarization was markedly depressed by DL‐AP5 but not by CNQX. 7. These results demonstrate that with low‐frequency stimulation of the sensory afferents, the generation of TC cell output in the rat and cat dLGN is mainly controlled by non‐NMDA receptors, while the contribution of NMDA receptors is limited to the burst firing generated by the LT Ca2+ potential, and depends on the membrane potential range over which this type of firing occurs.(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence that antidromically stimulated vagal afferents activate inhibitory neurones innervating guinea‐pig trachealis.
Authors: Canning B J , Undem B J
Published: December 2014

1. We recently described a capsaicin‐sensitive vagal pathway mediating non‐adrenergic, non‐cholinergic (NANC) relaxations of an isolated, innervated rostral guinea‐pig tracheal preparation. These afferent fibres are carried by the superior laryngeal nerves and relaxations elicited by their activation are insensitive to autonomic ganglion blockers such as hexamethonium. In the present study this vagal relaxant pathway was further characterized. 2. Relaxations of the trachealis elicited by electrical stimulation of capsaicin‐sensitive vagal afferents were mimicked by bath application of capsaicin. Relaxations elicited by both methods were abolished when the tissue between the trachea and the adjacent oesophagus was disrupted. Indeed, separating the trachea from the oesophagus uncovered a contractile effect of capsaicin administration on the trachealis. 3. Capsaicin‐induced, oesophagus‐dependent relaxations of the trachealis were blocked by pretreatment with the fast sodium channel blocker tetrodotoxin (TTX). By contrast, capsaicin‐induced contractions of the trachealis (obtained in the absence of the oesophagus) were unaffected by tetrodotoxin. 4. Substance P, neurokinin A (NKA) and neurokinin B (NKB) also elicited NANC relaxations of precontracted trachealis that were abolished by separating the trachea from the oesophagus or by TTX pretreatment. Like capsaicin, the tachykinins elicited only contractions of the trachealis following TTX pretreatment or separation of the trachea from the adjacent oesophagus. 5. Relaxations elicited by stimulation of the capsaicin‐sensitive nerves were unaffected by a concentration of the tachykinin NK2 receptor‐selective antagonist, SR 48968, that is selective for NK2 receptor blockade and were not mimicked by the NK2 receptor‐selective agonist [beta‐Ala8]‐NKA(4‐10). This suggests that NK2 receptors are not responsible for these relaxations. By contrast, the NK3 receptor‐selective agonist, senktide analogue, and the NK1 receptor‐selective agonist, acetyl‐[Arg6, Sar9, Met (O2)11]‐SP(6‐11), elicited oesophagus‐dependent relaxations of the trachealis that were abolished by oesophagus removal. Furthermore, pretreatment with the NK1‐selective antagonists, CP 96345 and CP 99994, or pretreatment with a concentration of SR 48968 that also blocks NK3 receptors, markedly attenuated relaxations elicited by stimulation of the capsaicin‐sensitive vagal pathways. 6. The data are consistent with the hypothesis that relaxations elicited by stimulation of capsaicin‐sensitive vagal afferents involve tachykinin‐mediated activation of peripheral NANC inhibitory neurones that are in some way associated with the oesophagus. The data also indicate that airway smooth muscle tone might be regulated by peripheral reflexes initiated by activation of capsaicin‐sensitive afferent fibres.
A branching dendritic model of a rodent CA3 pyramidal neurone.
Authors: Traub R D , Jefferys J G , Miles R , Whittington M A , Tóth K
Published: December 2014

1. We constructed a branching dendritic compartmental model of a CA3 pyramidal neurone, using experimental data from guinea‐pig and rat cells obtained in vitro. The goal was to understand interactions between synaptic events impinging on dendritic branches and voltage‐ and calcium‐dependent currents. The model contained sixty‐four soma‐dendrite (SD) compartments, an axon initial segment (IS), and four axonal compartments. There were six active conductances in the SD membrane, including a sodium conductance (gNa) and a high‐threshold calcium conductance (gCa), with kinetic properties similar to those reported in a previous study. 2. The distribution of conductance densities across the IS and SD was adjusted by testing the model response to antidromic stimulation and current pulses or sustained currents injected into the soma or apical dendrites. As before, gNa was concentrated on and near the soma with lower density in the dendrites, while gCa had a higher density in apical dendrites than at the soma. 3. The model predicts that CA3 pyramidal neurones in media blocking synaptic transmission should fire a burst of action potentials following antidromic stimulation. This was confirmed experimentally in hippocampal slices. 4. Both in the model and in guinea‐pig neurones, dendritic IPSCs can delay the onset of bursting. If an IPSC begins soon enough after the first fast action potential, the later burst envelope is attenuated. This effect results from suppression of dendritic Ca2+ electrogenesis. 5. The model predicts that an appropriately timed dendritic IPSC (after the first somatic spike but before the dendritic Ca2+ spike) may suppress the transient local [Ca2+] signal, while having a negligible effect on the electrical output of the neurone. This phenomenon has been reported in guinea‐pig Purkinje cells. 6. We conclude that active dendritic currents are critical for regulation of the electrical output of CA3 pyramidal neurones. We suggest also that dendritic [Ca2+] signals might be controlled in individual dendrites independently of action potential outputs, an effect of possible importance for synaptic plasticity.
Conditioning effect in single human motoneurones: a new method using the unitary H reflex.
Authors: Shindo M , Yanagawa S , Morita H , Hashimoto T
Published: December 2014

1. A new method for the study of spinal reflexes using single motor units is described. 2. The excitability of a motoneurone is assessed as the ‘critical firing stimulus’ (CFS), which is the difference between the test stimulus intensity needed to reach the threshold for the lowest threshold Ia fibres and the intensity which evokes firing of a motor unit with the probability of 50% (FP50%). The intensity with FP50% is obtained by modulating stimulator output. When the motor unit is fired by a stimulus, the next intensity is decreased, and vice versa. The Ia threshold is defined as the threshold for homonymous monosynaptic peaks in PSTHs during contraction of the muscle examined. 3. A conditioning effect is represented as a change in CFS, the extent being expressed as a percentage of the unconditioned CFS. 4. Effects obtained by conditioning stimulation with the new and conventional H reflex methods are compared. The sensitivities are almost the same and the extents of the effects have highly correlated linear relations for the two methods. 5. The advantages of the new method are (1) that it shows reflex activities on a single motoneurone, (2) that it is applicable both to muscles at rest and during contraction, and (3) that it quantifies conditioning effects as percentages of the size of test Ia EPSPs.
Flexibility of lower limb reflex responses to painful cutaneous stimulation in standing humans: evidence of load‐dependent modulation.
Authors: Rossi A , Decchi B
Published: December 2014

1. In six human subjects standing without support, the reflex response of the tibialis anterior muscle (TA) was elicited by painful electrical stimulation (500 Hz, 20 ms) of the anterior sole of the foot and analysed by post‐stimulus averages of rectified electromyography. The threshold intensity for the reflex response was very close to the subjective pain sensation (mean value, 1.05 times). Estimation of the afferent conduction velocity gave a mean value of 26.5 m s‐1, suggesting that a contribution from A delta fibres was necessary to evoke the reflex response. The TA reflex response was then used as the pain test reflex. 2. Changes in the TA excitatory pain reflex response (elicited at 1.2 times the pain threshold) were investigated while the subjects maintained different postures in upright stance. Standing on the ipsilateral leg produced a significant decrease in the reflex response with respect to its value in symmetrical stance (standing on both legs), whereas a significant facilitation was observed when the subject was standing on the contralateral leg. A parallel depression of the response in both limbs was present when the subject maintained an upright stance with the lower limbs abducted. Thus, it was apparent that the TA pain responses decreased as the supporting function of the leg increased. 3. A significant inverse correlation between the load to which the limb was subjected and the size of the reflex response was observed in all subjects. We propose that the load to which the limb is subjected, measured from peripheral mechanoreceptors, is used as a measure of the current supporting function of the limb, on the basis of which the reflex is regulated.
Variations of blood flow at optic nerve head induced by sinusoidal flicker stimulation in cats.
Authors: Vo Van Toi  , Riva C E
Published: December 2014

1. The present investigation explored, in thirty‐four anaesthetized cats, the blood flow changes at the optic nerve head elicited by sinusoidally modulated photic stimuli. 2. The stimuli were achromatic, diffuse and had 30 deg diameter field size; the stimulus frequency was varied from 0 to 100 Hz, modulation depth from 0 to 100% and mean retinal illuminance up to 50,000 trolands (td); the blood flow was measured with a near‐infrared (810 nm) laser Doppler flowmeter. 3. At various frequencies, modulation depths and mean retinal illuminance, sinusoidal flicker stimulation always caused an increase in blood flow at the optic nerve head relative to steady stimulation. 4. The frequency response and temporal contrast sensitivity function of the blood flow changes had a bandpass shape; the high‐frequency slope of the frequency response was 3 decades (dec) per decade and that of the temporal contrast sensitivity function was 1.7 dec per dec, close to the slope for cat ‘on’ ganglion cells (2.6 dec per dec). 5. In most cats, the magnitude of the increase in blood flow was a sigmoidal function of modulation depth; in the remainder, the relationship was close to linear. 6. The threshold of blood flow changes varied with respect to mean retinal illuminance similar to Ferry‐Porter's law and the photopic linear slope was 50 Hz dec‐1. 7. In comparison with reported psychophysical and electrophysiological responses elicited by similar stimulations, the results of the present study resemble more those obtained from ganglion cells than those from electroretinograms, visual‐evoked potentials and psychophysics. It is suggested that the blood flow changes at the optic nerve head are induced by the activity of ganglion cells.
Eccentric exercise decreases glucose transporter GLUT4 protein in human skeletal muscle.
Authors: Asp S , Daugaard J R , Richter E A
Published: December 2014

1. Eccentric exercise causes impaired postexercise glycogen resynthesis. To study whether changes in muscle concentration of the glucose transporter (GLUT4) protein might be involved, seven healthy young men performed one‐legged eccentric exercise by resisting knee flexion enforced by a motor‐driven device. 2. The GLUT4 protein concentration in the exercised and in the control thigh was unchanged immediately after exercise. On days 1 and 2 after exercise, the GLUT4 protein concentration in the exercised muscle was 68 +/‐ 10 and 64 +/‐ 10% (means +/‐ S.E.M.; P < 0.05), respectively, of the concentration in the control muscle, and had returned to control values on days 4 and 7. 3. The muscle glycogen concentration decreased from 404 +/‐ 44 to 336 +/‐ 44 mmol (kg dry wt)‐1 (P < 0.05) during exercise. The glycogen concentration remained significantly lower than in the control thigh on days 1 and 2 after exercise but on days 4 and 7 no differences were found. 4. Although no cause‐effect relationship was established, these findings may suggest that decreased muscle concentrations of GLUT4 protein, and, hence, a decreased rate of glucose transport into muscle cells, may be involved in the sustained low glycogen concentration seen after eccentric exercise.
Activation of ATP‐dependent K+ channels by hypoxia in smooth muscle cells isolated from the pig coronary artery.
Authors: Dart C , Standen N B
Published: December 2014

1. The perforated patch technique with amphotericin B was used to record whole‐cell currents activated by hypoxia in smooth muscle cells, isolated enzymatically from pig coronary arteries. 2. Superfusion with hypoxic solution (O2 partial pressure, 25‐40 mmHg) activated an inward current at ‐60 mV in 143 mM extracellular K+. The reversal potential of the current induced by hypoxia shifted with extracellular [K+] as expected for a K+ current, while its current‐voltage relation was consistent with the channels showing little voltage dependence. 3. The hypoxia‐induced current was inhibited by glibenclamide (10 microM), but was unaffected by charybdotoxin (50 nM). 4. In whole‐cell recordings at ‐60 mV in 143 mM K+ solution, openings of single channels passing a current close to ‐2 pA could sometimes be detected in normoxic solution. Openings became more frequent during the onset of the response to hypoxia, when several levels could be detected. Channels with a similar conductance were activated by hypoxia in cell‐attached patches. 5. Our results suggest that hypoxia activates ATP‐dependent K+ channels. We discuss possible mechanisms by which this activation may occur.
Role of nitric oxide in non‐adrenergic, non‐cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway.
Authors: Jing L , Inoue R , Tashiro K , Takahashi S , Ito Y
Published: December 2014

1. The effects of nitrosocysteine (cys‐NO), L‐N omega‐nitroarginine (L‐NNA) and L‐N omega‐nitro‐L‐arginine methylester (L‐NAME), oxyhaemoglobin and Methylene Blue were observed on the resting membrane potential, muscle tone and excitatory junction potentials (EJPs) of cat tracheal smooth muscle tissue. 2. Cys‐NO (10(‐9) to 10(‐6) M) showed no effect on the resting membrane potential of smooth muscle cells of the cat trachea but it dose‐dependently relaxed the tracheal tissue in the presence of 5‐HT, atropine and guanethidine. 3. Electrical field stimulation (EFS) applied during contraction evoked by 5‐HT in the presence of atropine and guanethidine evoked non‐adrenergic, non‐cholinergic (NANC) muscle relaxation. L‐NNA (10(‐4) M) and L‐NAME (10(‐4) M) completely suppressed the relaxation when single or short repetitive stimuli were applied, but suppression was incomplete with repetitive stimuli of 4 ms pulse duration applied at 20 Hz. A substantial part of the L‐NNA‐ or L‐NAME‐insensitive relaxation was abolished by tetrodotoxin. 4. Cys‐NO dose‐dependently suppressed the EJPs without changing the resting membrane potential, and L‐NNA, L‐NAME, Methylene Blue and oxyhaemoglobin enhanced the amplitude of the EJP to 1.2‐1.5 times the control value. 5. EJPs showed some summation when repetitive field stimulation was applied at 20 Hz. L‐NNA or L‐NAME enhanced the summation, and the mean slopes were increased from 0.61 +/‐ 0.22 to 2.0 +/‐ 0.3, or 1.9 +/‐ 0.2 mV per stimulus. Vasoactive intestinal polypeptide (VIP) antiserum and VIP antagonists further enhanced the summation in the presence of L‐NNA. 6. These results indicate that NANC relaxation can be classified into two different components according to the threshold for activation, and nitric oxide is involved in one. The present results also suggest that endogenous or exogenous nitric oxide has a prejunctional action in inhibiting excitatory neuroeffector transmission in addition to a direct action on the smooth muscle cells, presumably by suppressing transmitter release from the vagus nerve.
Glycogen resynthesis in human muscle fibre types following exercise‐induced glycogen depletion.
Authors: Casey A , Short A H , Hultman E , Greenhaff P L
Published: December 2014

1. Studies investigating muscle glycogen resynthesis in man have usually examined mixed‐fibred biopsies or have used histochemical methods to estimate single fibre resynthesis. Since the accuracy of the latter is open to debate, this study investigated glycogen resynthesis in type I and II fibres using biochemical methods of analysis. 2. Seven subjects performed one‐legged cycling exercise to exhaustion. During the initial 2 h of recovery, subjects consumed 3 g of glucose (kg body mass (BM))‐1, and a high carbohydrate diet thereafter. Muscle biopsy samples were obtained from both legs at exhaustion, and from the exercised leg after 3, 10 and 24 h of recovery. 3. In the initial 3 h of recovery, there was a 25 +/‐ 8% higher rate of resynthesis in type I compared with type II fibres (41 +/‐ 3 and 31 +/‐ 4 mmol glucosyl units (kg dry mass (DM))‐1 h‐1, respectively; P < 0.05). Between 3 and 10 h of recovery, resynthesis in type I fibres declined by 60 +/‐ 13% to 15 +/‐ 4 mmol glucosyl units (kg DM)‐1 h‐1 (P < 0.01), whilst the rate in type II fibres was maintained. Good agreement was found when relating the mixed‐fibred muscle glycogen concentration to the mean concentration found in type I and type II fibres (r = 0.96). 4. A discrepancy was found to exist with histochemically derived data reported in the literature. The higher initial glycogen resynthesis rate in type I fibres may be attributable to fibre‐type differences in glucose uptake and disposal.(ABSTRACT TRUNCATED AT 250 WORDS)
Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus.
Authors: Andreasen M , Lambert J D
Published: December 2014

1. Intracellular recordings were obtained from 184 distal apical dendrites and twenty‐six somata of CA1 pyramidal neurones in the rat hippocampal slice preparation. In the presence of 3.25 mM K+ 200 ms suprathreshold current pulses evoked three different types of firing patterns in the apical dendrites, all of which were distinct from regular somatic firing. Fast tetrodotoxin (TTX)‐sensitive spiking was evoked in 38.8% of the dendrites. Compound spiking, consisting of an initial fast spike followed by one or more secondary slow spikes of variable amplitude and duration, was seen in 44.1% of dendrites. ‘Classical’ burst firing, resembling intrinsic somatic bursts, was evoked in 17.1% of the dendrites. 2. In fast spiking dendrites, the spikes evoked by long depolarizing pulses were rarely overshooting, showed prominent accommodation and declined progressively to about one‐third of the initial amplitude. The amplitude of single dendritic fast spikes (50.6 +/‐ 1.5 mV; mean +/‐ S.E.M.) was smaller than that of somatic spikes (82.2 +/‐ 1.9 mV) and their rate of rise (81.3 +/‐ 4.3 V s‐1) was markedly slower than that of somatic spikes (291.5 +/‐ 17.8 V s‐1). However, the thresholds were not significantly different (dendrites, ‐49.8 +/‐ 0.8 mV; somata, ‐50.8 +/‐ 1.3 mV). These results indicate that fast spikes in the distal parts of apical dendrites are generated by a local regenerative Na+ current. 3. 4‐Aminopyridine (4‐AP, 0.1‐0.5 mM) caused a dose‐dependent slowing of the repolarization of the fast spikes, while tetraethylammonium (TEA, 2 mM) and Co2+ (2 mM) induced a slowing of the late phase of the repolarization. These results indicate that the transient outward K+ current, IA, and the Ca(2+)‐activated K+ current, IC, are involved in the repolarization of dendritic Na(+)‐dependent spikes. 4. Compound spiking was completely blocked by TTX (0.5‐1 microM). The secondary slow spikes within the complex were blocked by Co2+ (2 mM), nifedipine (10 microM) and high concentrations (> 50 microM) of verapamil, while Ni2+ (100‐300 microM) had no effect. Thus, compound spiking consists of an initial Na(+)‐dependent spike followed by one or more slow Ca(2+)‐dependent spikes mediated by L‐type Ca2+ channels located in the apical dendrites. 5. In fast spiking dendrites, 4‐AP (0.5‐2.5 mM) changed the firing pattern from regular fast spiking to compound spiking. In the presence of 4‐AP (0.1‐0.5 mM), the single fast spike evoked by a short (20 ms), threshold current pulse, was followed by secondary slow spikes of variable amplitude and duration.(ABSTRACT TRUNCATED AT 400 WORDS)
Short term synchronization of human motor units and their responses to transcranial magnetic stimulation.
Authors: Mills K R , Schubert M
Published: December 2014

1. The voluntary discharge characteristics, short term synchronization, coherence and responses to transcranial magnetic stimulation of a sample of twenty‐two pairs of simultaneously recorded low threshold motor units in the right human first dorsal interosseus muscle have been determined. 2. Peristimulus time histograms and cumulative sums (cusums) of motor unit discharge showed either excitatory or inhibitory responses to cortical stimuli. Over the whole motor unit sample, the primary excitatory response had a mean onset of 24.6 ms and the inhibitory response a mean onset of 31.0 ms. Responses of pairs of motor units to magnetic stimulation could be dissimilar; at some stimulus intensities one of the motor unit pair could be excited by the stimulus whilst the other was inhibited. 3. Most pairs of motor units showed short term synchrony in their voluntary discharge, but the same motor units driven by magnetic cortical stimuli showed little tendency to discharge together more frequently than would be predicted from their independent behaviour. This held true for discharges in both the early primary excitatory peak and in the later secondary peak in peristimulus time histograms. 4. Series of magnetic stimuli, causing either excitation or inhibition of individual tonically active motor units, had no effect on the size of the central peak of the cross‐correlogram of the motor unit pair. However, frequency analysis of pairs of motor unit spike trains showed an increase in coherence in the 16‐32 Hz band during magnetic stimulation. 5. It is concluded that, whilst many corticospinal fibres branch extensively within motoneurone pools, there are also fast conducting corticomotoneuronal fibres allowing the independent monosynaptic activation of individual motoneurones. 6. It is also suggested that during sustained voluntary tonic activity, magnetic stimuli applied to the brain can increase the synchrony in common input fibres to pairs of motoneurones.