bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic physiology of spinal motoneurones of normal and spastic mice: an in vitro study.
Authors: Biscoe T J , Duchen M R
Published: December 2014

Spinal cord reflexes have been examined in a preparation of the mouse spinal cord maintained in vitro. Responses of the motoneurone population of normal and spastic mutant mice to stimulation of a segmental dorsal root were compared. In the normal spinal cord, a monosynaptic response with very little polysynaptic excitation was typical. In the mutant, the monosynaptic response was typically followed by a depolarizing wave on which asynchronous compound action potentials were superimposed. In some spastic cords, an oscillating depolarizing wave was seen, lasting up to 500 ms. The stimulus range from threshold to maximal response was the same for the normal and mutant. The dorsal root reflex (d.r.r.) and dorsal root potential (d.r.p.) were prominent in both normal and mutant, and no consistent difference could be identified. Intracellular recordings were made from motoneurones using electrodes filled with potassium acetate. Mean resting potentials and input resistances were not significantly different in mutant and normal mice. The voltage‐dependent conductances, seen as the after‐depolarization and after‐hyperpolarizations following antidromic action potentials and the responses of motoneurones to depolarizing current injection were similar in both populations. The synaptic responses of motoneurones following stimulation of the segmental dorsal root were clearly abnormal in the mutant. In the normal mice, a monosynaptic excitatory post‐synaptic potential (e.p.s.p.), seen at low stimulus intensities, was followed at higher stimulus intensities by polysynaptic activity lasting up to 100 ms, which rarely reached threshold for action potential discharge. In the mutant mice, the monosynaptic response was typically followed by depolarizing synaptic responses which often evoked action potentials before the monosynaptic response reached threshold. At higher stimulus intensities, the monosynaptic response was followed by at least one and often multiple action potentials generated on prolonged depolarizing synaptic activity. When cells were impaled with potassium‐acetate‐filled electrodes, very little spontaneous synaptic activity was seen in either normal or mutant mice. Spontaneous depolarizing post‐synaptic potentials (p.s.p.s) were prominent in normal motoneurones when potassium chloride was used to fill electrodes and were increased in amplitude by ionophoresis of chloride into the cells. Under these conditions stimulation of a ventral root evoked a depolarizing p.s.p. and the Renshaw i.p.s.p. reversed. The spontaneous p.s.p.s were blocked by ionophoresis or bath application of the glycine antagonist strychnine.(ABSTRACT TRUNCATED AT 400 WORDS)
An investigation of chloride‐bicarbonate exchange in the sheep cardiac Purkinje fibre.
Authors: Vaughan-Jones R D
Published: December 2014

Intracellular Cl activity (aiCl), and intracellular pH (pHi) were measured in isolated sheep cardiac Purkinje fibres using a liquid ion exchanger Cl‐selective micro‐electrode and a glass recessed‐tip, pH‐selective micro‐electrode. Removal of external Cl (glucuronate substituted) produced a fall in aiCl from about 20 to about 4 mmol/l: the residual level is probably caused by intracellular interference on the Cl‐sensitive electrode. Re‐exposure of the fibre to increased levels of external Cl produced, in the steady state, increased levels of aiCl. The dependence of steady‐state aiCl upon external Cl activity, aoCl, was roughly hyperbolic with 50% recovery occurring at an aoCl of about 9.5 mmol/l. At all levels of external Cl tested, Cl was accumulated to a level much higher than that predicted for passive electrochemical equilibrium. Exposure of a Cl‐depleted fibre to various levels of external Cl produced an exponential rise with time in aiCl. The initial rate‐of‐rise in aiCl was estimated to be a saturating function of aoCl, with a half‐maximal effect occurring at an aoCl of about 33 mmol/l. The rate‐of‐rise was about 10‐fold greater than that predicted from constant‐field theory using published values for PCl, the Cl permeability coefficient. Steady‐state aiCl was essentially insensitive to changes in external HCO3 concentration, [HCO3]o, if these changes were made at a constant external pH, pHo, i.e. when a reduction in [HCO3]o was accompanied by a simultaneous reduction in the partial pressure of CO2, PCO2. In contrast, if PCO2 was maintained constant, then a change in [HCO3]o (thus producing a change in pHo) resulted in an inverse change in aiCl. This change in aiCl was also accompanied by a change in pHi: when aiCl increased, pHi decreased and vice versa. The anion‐exchange inhibitor, DIDS (4,4‐diisothiocyanato‐stilbene disulphonic acid) abolished the effect on aiCl of changes in [HCO3]o and pHo (at constant PCO2). Furthermore DIDS reduced the influence of pHo upon pHi. Both the fall of aiCl in Cl‐free solution and the subsequent reuptake of Cl following re‐exposure to Cl‐containing solution were slowed by a reduction in [HCO3]o (constant pHo, reduced PCO2). Both reuptake and wash‐out of Cl were saturating functions of [HCO3]o with half‐maximal effect occurring at an [HCO3]o of 1‐1.3 mmol/l. The reuptake of Cl was little affected by removal of external Na (bis,2‐hydroxy ethyl, dimethyl ammonium substituted). The reuptake of Cl was unaffected by amiloride (1 mmol/l) but slowed by piretanide (1 mmol/l).(ABSTRACT TRUNCATED AT 400 WORDS)
Voltage dependence of two inward currents carried by calcium and barium in the ciliate Stylonychia mytilus.
Authors: Deitmer J W
Published: December 2014

Two voltage‐dependent inward currents in the fresh‐water hypotrichous ciliate Stylonychia mytilus have been investigated, using two intracellular micro‐electrodes, when either Ca ions or Ba ions are the charge carriers. In cells bathed in Ca‐free Ba solution the two inward currents, named current I and current II, could be identified and studied in the absence of outward currents. The two inward currents could also be separated by addition of the plant lectin concanavalin A (0.5 microgram/ml) to the external medium, which resulted in the selective inhibition of current I. When the holding potential was set at values between ‐45 and ‐65 mV (normal resting potential is ‐50 mV), current I was shifted parallel to the holding potential along the voltage axis. This shift was 7.6 mV per 10 mV change in holding potential. The amplitude and voltage relationship of current II was not affected by these changes in the holding potential. The amplitude of current I in Ba solution was maximal when the membrane potential was held at ‐55 mV; it decreased with higher and lower holding potentials. The rate of activation of current I remained virtually unaffected at holding potentials between ‐45 and ‐60 mV, and was somewhat reduced at a holding potential of ‐65 mV. When the extracellular Ca concentration was varied between 0.1 and 5.0 mM, or when the cells were loaded with EGTA to reduce the intracellular level of ionized Ca, the resting membrane potential and the voltage relationships of both current I and II and of the outward current were shifted along the voltage axis according to the expected changes in membrane surface potential. Double‐pulse experiments with varying interval potentials suggested voltage‐dependent inactivation of current I and Ca‐dependent inactivation of current II. Pre‐hyperpolarizing steps of only 1 mV amplitude and 30 ms duration could result in the activation of current I, indicating that the activation voltage of current I closely followed the actual membrane potential. Hence, the same voltage steps elicited similar current I amplitudes with holding potentials between ‐45 and ‐60 mV. The results indicate that current II displays voltage properties described for Ca channels in other ciliates and many multicellular preparations, while current I shows an unusual voltage behaviour, which might be regarded as an 'adaptive type of excitation'.(ABSTRACT TRUNCATED AT 400 WORDS)
Different properties of two voltage‐dependent inward currents of the ciliate Stylonychia mytilus.
Authors: Ivens I
Published: December 2014

1. Membrane currents and membrane potentials of the fresh‐water ciliate Stylonychia mytilus were investigated by voltage‐clamp and constant‐current injection techniques. 2. The Ca‐dependent action potential of Stylonychia in a solution containing 0.1 mM‐CaCl2 was prolonged by the addition of Mg or Na ions. 3. In a nominally Ca‐free solution, containing 2 mM‐MgCl2, the cells generated repetitive, spontaneous action potentials of relatively small amplitude (17 mV). The addition of 0.5 microgram concanavalin A/ml completely inhibited these action potentials in 2 mM‐Mg. 4. In voltage‐clamp experiments in standard solution, the inward current‐voltage relationship has two maxima, confirming the existence of two different voltage‐dependent Ca currents in Stylonychia: inward current I and II. In a nominally Ca‐free, Mg‐containing solution, the remaining inward current was inhibited by concanavalin A, a specific inhibitor of inward current I. No residual second inward current (current II) was detected in a solution containing Mg and concanavalin A. 5. Experiments, with altered ratio of Ca and Mg ions and constant concentration of divalent cations (mole‐fraction experiments), showed that Mg and Ca do not inhibit each other's passage through channel I. Calculations assuming a Ca‐channel model with one cation‐binding site per ion channel I showed good correlation with the experimental data. 6. A similar inward current was seen after replacement of Mg by Na in nominally Ca‐free solution.
Effects of the alpha 2‐adrenergic agonist clonidine and its antagonist idazoxan on the fetal lamb.
Authors: Bamford O S , Dawes G S , Denny R , Ward R A
Published: December 2014

1. The alpha 2‐adrenergic agonist clonidine was given by aortic injection to three groups of unanaesthetized fetal lambs in utero near term. One group was intact, the second had the brain stem transected just above the pons, and the third had bilateral section of the carotid sinus nerves and cervical vagi. 2. Clonidine had similar effects in all three groups. Electrocortical activity entered a high‐voltage, low‐frequency episode: breathing, neck and limb movements ceased; arterial pressure remained unchanged or increased; heart rate fell or remained unchanged, and the variation in both heart rate and blood pressure was much reduced. This state lasted 10‐20 min, and was followed by a period of up to 4 h during which the cycling of electrocortical activity was rapid and irregular. 3. The alpha 2‐adrenergic antagonist idazoxan (0.5‐2.0 mg I.A.) blocked all the actions of clonidine. When given alone it usually induced a short period of low‐voltage electrocortical activity and stimulated breathing movements. These effects were present in both the intact and brain‐stem‐transected groups, though the stimulation of breathing was significantly reduced by brain‐stem transection. There were no consistent effects on heart rate or blood pressure. 4. The effects of clonidine on fetal heart rate and electrocortical activity were similar to those described in adults, but it also had inhibitory effects, not present in adults, on fetal breathing and somatic movements.
Maximum activities of key glycolytic and oxidative enzymes in human muscle from differently trained individuals.
Authors: Blomstrand E , Ekblom B , Newsholme E A
Published: December 2014

1. The maximum activities of hexokinase, 6‐phosphofructokinase and oxoglutarate dehydrogenase, together with capillary density and fibre composition, have been measured in muscle from male and female untrained, medium‐trained and well trained individuals. 2. The activity of hexokinase was almost identical in muscle from the three groups, whereas that of 6‐phosphofructokinase decreased and that of oxoglutarate dehydrogenase increased with increased training. Values of maximum rate of O2 uptake (VO2, max) were also measured and were 21% higher in medium‐trained and 49% higher in well trained compared to untrained individuals, whereas oxoglutarate dehydrogenase activities were 39% and 90% higher respectively. 3. There was a good positive correlation between the activity of oxoglutarate dehydrogenase and the percentage of type I fibres but the correlation between VO2, max and oxoglutarate dehydrogenase activity was less good. Changes in the values of VO2, max represent the effects on the circulatory and respiratory system whereas those in oxoglutarate dehydrogenase represent local effects of endurance training.
Effects of membrane potential on intracellular calcium concentration in sheep Purkinje fibres in sodium‐free solutions.
Authors: Cannell M B , Eisner D A , Lederer W J , Valdeolmillos M
Published: December 2014

1. The intracellular Ca2+ concentration [( Ca2+]i) was measured in voltage‐clamped sheep cardiac Purkinje fibers while recording tension simultaneously. 2. When [Na+]i was elevated (by Na+‐K+ pump inhibition) depolarization produced an increase of tonic tension. 3. Replacement of external Na+ by Li+ or choline produced a contracture which then relaxed spontaneously. Following this relaxation, depolarization either had no effect on tonic tension or produced a small decrease. 4. When external Na+ was replaced by Ca2+, depolarization (over the range ‐120 to ‐20 mV) produced a decrease of tonic tension and [Ca2+]i. Hyperpolarization increased tonic tension and [Ca2+]i. 5. An after‐contraction and accompanying increase of [Ca2+]i were produced by repolarization in both Na+‐free and Na+‐containing solution. This eliminates the possibility that the stimulus for the after‐contraction is the increase of [Ca2+]i during the depolarization and suggests that the stimulus may be the change of membrane potential. 6. The increase of [Ca2+]i on hyperpolarization seen in Na+‐free solutions persisted in the presence of ryanodine. 7. These results show, in contrast to previous work, that in Na+‐free solutions tonic tension is still sensitive to membrane potential. The results support the hypothesis that, in Na+‐containing solutions, the increase of tonic tension on depolarization results from a voltage‐dependent Na+‐Ca2+ exchange. The reduction of tonic tension on depolarization in Na+‐free solutions may be due to the decrease of the electrochemical gradient for Ca2+ to enter the cell.
Irregularity of rest and activity: studies on circadian rhythmicity in man.
Authors: Minors D S , Nicholson A N , Spencer M B , Stone B M , Waterhouse J M
Published: December 2014

1. Rectal temperature, electrolyte excretion and performance were studied in young adults who followed an irregular pattern of work and rest for 9 days in an isolation unit. 2. In the analysis, effects evoked by the pattern of work and rest were separated from the oscillatory component, and rhythms for individual days were examined by the cosinor method. 3. During the schedule, rhythms no longer showed a period of exactly 24 h, and this effect was confirmed by studies using a repeated cycle of irregular work and rest and by studies using constant routines. 4. Temperature and urinary constituents differed in the strength and phase of their rhythms when corrected for evoked effects, as well as in the strength of the evoked effects themselves. 5. There was evidence of deterioration in performance during work periods which exceeded 9 h, but there was no evidence of progressive deterioration in performance over the 9 day schedule.
Capacitance of the rabbit portal vein and inferior vena cava.
Authors: Brown B P , Heistad D D
Published: December 2014

1. We used vessel strips and whole vessels in vitro to determine the length‐tension and pressure‐volume relationships of two veins with similar diameter and wall thickness, the portal vein and inferior vena cava of rabbits. 2. Length‐tension studies indicate that longitudinal and circular strips of the portal vein have significantly smaller elastic moduli than similar strips of the inferior vena cava (P less than 0.05). 3. Pressure‐volume relationships of intact vessels indicate that pressures greater than 5 mmHg do not produce significant increases in volume of the inferior vena cava, whereas volume of the portal vein increases significantly over a range of pressures from 2 to 15 mmHg. 4. Activation of smooth muscle with noradrenaline reduces the volume of the vena cava at distending pressures less than or equal to 5 mmHg. In contrast, noradrenaline reduces the volume of the portal vein at pressures up to 10 mmHg. During inactivation in calcium‐free solution and activation with noradrenaline, the portal vein is more compliant than the inferior vena cava (P less than 0.05). 5. Morphometric studies demonstrate more collagen in the inferior vena cava than in the portal vein. Differences in capacitance of the vessels may be related, in part, to greater collagen content in the inferior vena cava.
A synergistic effect of oxytocin and vasopressin on sodium excretion in the neurohypophysectomized rat.
Authors: Balment R J , Brimble M J , Forsling M L , Kelly L P , Musabayane C T
Published: December 2014

1. Renal function and the effect of oxytocin and vasopressin replacement have been examined in anaesthetized male neurohypophysectomized rats. 2. Rates of urine flow were higher but sodium excretion markedly lower in neurohypophysectomized rats than in intact animals receiving hypotonic saline infusion (33.8 +/‐ 2.3 vs. 27.0 +/‐ 0.7 ml and 472 +/‐ 84 vs. 1946 +/‐ 124 mumol respectively for the third to sixth hour of study). 3. In intact animals, mean arterial blood pressure stabilized at 106 mmHg. Haematocrit (46%) remained stable but glomerular filtration rates declined slightly over the 8 h of study to 2.5 +/‐ 0.2 ml/h. These values in neurohypophysectomized rats did not differ significantly from those in intact rats. 4. Although plasma corticosterone levels (54 +/‐ 13 ng/ml) did not differ significantly from those in intact rats, neurohypophysectomy was associated with greatly reduced aldosterone concentration (0.12 +/‐ 0.03 vs. 0.76 +/‐ 0.04 ng/ml). Trace levels of vasopressin (0.17 +/‐ 0.03 microunit/ml) were found in neurohypophysectomized rat plasma. 5. Oxytocin administration at 15 microunits/min, which produced plasma hormone levels of 1.62 +/‐ 0.19 microunit/ml, had no detectable effect on sodium excretion but increased urine flow. Arginine vasopressin administration (12 microunits/min) inducing plasma levels of 1.24 +/‐ 0.08 microunit/ml, reduced urine flow by 80% and produced a small increase in sodium excretion. 6. Concurrent administration of oxytocin (15 microunits/min) potentiated the natriuretic response to vasopressin (12 microunits/min). Total sodium excretion during the 3 h combined hormone infusion (1256 +/‐ 149 mumol) greatly exceeded that in animals receiving vasopressin alone (549 +/‐ 132 mumol) and approached that observed in intact animals (1946 +/‐ 124 mumol). Combined hormone administration at the lower rate of 5 microunits/min oxytocin and 4 microunits/min vasopressin produced a similar large increment in sodium excretion. 7. It is concluded that replacement of both neurohypophysial hormones, at plasma levels within the physiological range, largely reverses the renal sodium retention of neurohypophysectomized rats, oxytocin considerably potentiating the natriuretic action of vasopressin. This synergism between the two neurohypophysial peptides to promote salt excretion may be an important component of the non‐steroidal management of sodium.
Corticospinal facilitation of hand muscles during voluntary movement in the conscious monkey.
Authors: Lemon R N , Mantel G W , Muir R B
Published: December 2014

1. The method of spike‐triggered averaging has been used to detect a direct influence of pyramidal tract neurones on the activity of hand and forearm muscles in conscious monkeys trained to perform repetitive movements of the hand and fingers. Gross electromyograms (e.m.g.s) from individual muscles were rectified and synchronously averaged with respect to the discharge of single, antidromically identified pyramidal tract cells in the 'hand' area of the pre‐central gyrus. 2. The presence in an average of a post‐spike facilitation which could be revealed reproducibly from successive epochs of recording and was clearly larger than the biggest fluctuations seen in pseudo‐randomly triggered averages of the same e.m.g. data, was taken to indicate a direct cortico‐motoneuronal excitatory influence. 3. 55% of cortical neurones analysed showed post‐spike facilitation in one or more recorded muscle and 7% showed post‐spike suppression. In terms of the total number of muscle‐neurone combinations analysed, the proportions showing post‐spike effects were 18 and 1% respectively. These figures have been influenced by the pre‐selection of neurones for analysis according to restrictive criteria. The neurones selected (a) were recorded at cortical loci where weak intracortical microstimulation could evoke finger movements, (b) could be activated antidromically at short latency by medullary pyramidal tract stimulation, (c) showed natural discharge activity which was clearly modulated in relation to voluntary finger movements, and (d) were located in the anterior bank of the central sulcus. The results provide some evidence to vindicate these criteria. 4. The strongest post‐spike facilitation observed had a peak which was 42% higher than the average pre‐spike level of e.m.g. activity, but most were within the range 5‐20%. Facilitation peaks below about 3% could not have been resolved from the 'noise' in the averages. The mean latency from cell discharge in the cortex to the start of the post‐spike facilitation was 11.2 ms (range 7.4‐17.2) for intrinsic hand muscles and 9.8 ms (range 4.1‐15.0) for forearm muscles. These latencies were compared with the latencies of responses to intracortical microstimulation and to stimulation of the medullary pyramidal tract. 5. Evidence was obtained suggesting that the latency for cortico‐motoneuronal activation of an individual motor unit was commonly subject to considerable variability and that different motor units of a muscle could be facilitated by the one cortical neurone at different latencies. These factors are thought to contribute to an elongation of the time course of post‐spike facilitation.(ABSTRACT TRUNCATED AT 400 WORDS)
Selective facilitation of different hand muscles by single corticospinal neurones in the conscious monkey.
Authors: Buys E J , Lemon R N , Mantel G W , Muir R B
Published: December 2014

1. Post‐spike facilitation of e.m.g. activity by monkey motor cortex neurones has been investigated in different hand and forearm muscles. 2. Seventy‐eight neurones were recorded concurrently with between five and ten different muscles. Forty‐seven neurones were identified as cortico‐motor by the presence of post‐spike facilitation in the spike‐triggered average of at least one of the tested muscles. 3. All forty‐seven cortico‐motor neurones showed clear increases in activity during performance of a precision grip task by the monkey, and all of them were co‐activated with the sampled muscles. 4. To assess the divergence of facilitation from a single cortico‐motor neurone to different muscles, spike‐triggered averages were constructed with all of the concurrently recorded muscles. The number of muscles in the sample, and the number of muscles showing post‐spike facilitation, were corrected by excluding any post‐spike facilitation which could have arisen by cross‐talk between the different pairs of e.m.g. electrodes. 5. Most cortico‐motor neurones produced post‐spike facilitation in a restricted number of tested muscles. The mean number of post‐spike facilitation‐bearing muscles per cortico‐motor cell rose from 1.4 +/‐ 0.5 (S.D.) when five muscles were sampled to 2.0 +/‐ 1.5 when ten were sampled. On average, each cortico‐motor neurone produced post‐spike facilitation in 27% of the tested muscles. Only three of forty‐seven cortico‐motor neurones gave post‐spike facilitation in half or more of the tested muscles. 6. The distribution pattern of post‐spike facilitation among the muscles sampled with a given cortico‐motor neurone was not altered when the spike‐triggered averages were constructed from cortico‐motor cell and e.m.g. activity recorded during two different phases of the precision grip task, or during performance of a quite different, power grip, task. 7. Cortico‐motor cells which produced post‐spike facilitation in two or more different muscles often did so in muscles with synergistic functions. 8. It is suggested that cortico‐motor neurones may contribute to relatively independent finger movements by virtue of their selective facilitation of hand muscles leading to a fractionated pattern of muscle activity.
A gamma‐aminobutyric‐acid‐mediated baroreceptor input to supraoptic vasopressin neurones in the rat.
Authors: Jhamandas J H , Renaud L P
Published: December 2014

1. Extracellular recordings in pentobarbitone anaesthetized male Long‐Evans rats examined the influence of electrical stimulation in the diagonal band of Broca on the excitability of 113 putative vasopressin‐secreting and 22 putative oxytocin‐secreting neurosecretory neurones in the hypothalamic supraoptic nucleus. 2. Single pulse or repetitive (5‐20 Hz) stimulation in the ventral part of the diagonal band evoked a prominent reduction in the excitability of 83% of vasopressin‐secreting neurones with no effect on the remainder. Amongst oxytocin‐secreting neurones, 59% were unresponsive, 27% responded with an increase in activity while only 14% revealed an inhibitory pattern similar to vasopressin‐secreting neurones. 3. Diagonal band stimulation‐evoked inhibitions were reversibly abolished by local pressure applications of bicuculline methiodide (100 microM) to twenty out of twenty vasopressin secreting cells tested, whereas strychnine sulphate (100 microM) was without effect on four out of four cells tested. 4. In five out of five vasopressin‐secreting cells tested, bicuculline applications reversibly abolished the reduction in their activity that follows peripheral baro‐receptor activation. Failure to alter baroreflex‐evoked depressions in firing during similar trials with prazosin hydrochloride (10 microM, six cells tested), timolol maleate (20 microM, six cells tested) or strychnine sulphate (100 microM, three cells tested) indicated the specificity of bicuculline's action. 5. These findings suggest that a GABAergic pathway from the diagonal band of Broca preferentially innervates vasopressin‐secreting neurosecretory supraoptic nucleus (s.o.n.) neurones, and support the view that the baroreflex‐induced depression in firing of s.o.n. vasopressin‐secreting neurones is mediated in large part through this input.
Direct evidence of neurally mediated vasodilatation in hairy skin of the human foot.
Authors: Blumberg H , Wallin B G
Published: December 2014

1. Intraneural stimulation (i.n.s.) was made in the superficial peroneal nerve at the ankle in seventeen healthy subjects. The effect on skin blood flow was monitored by laser‐doppler flowmeters and photo‐electrical pulse plethysmographs inside and outside the innervation zone of the stimulated nerve fascicle. I.n.s. was applied before and after proximal local anaesthesia of the stimulated nerve. 2. Painful i.n.s. (stimulation strength 0.3‐4 V) induced skin vasodilatation with the following characteristics: (a) it occurred on the dorsal side of both feet, (b) the blood flow increase on the opposite foot was blocked by local anaesthesia of the nerve supplying the skin area under study, (c) the blood flow increase on the stimulated foot was abolished by proximal local anaesthesia of the stimulated nerve. The findings show that the vasodilatation was due to activation of a reflex pathway. 3. The reflex vasodilatation was bigger in the stimulated than in the opposite foot. At the same time there were signs of skin vasoconstriction in the fingers. The reflex vasodilatation in the foot was enhanced by body cooling. It was unaffected by atropine or propranolol. 4. After local anaesthesia of the nerve proximal to the stimulation site, i.n.s. with 2‐6 times increased stimulation strength produced skin vasodilatation restricted to the innervation zone of the stimulated nerve fascicle. This response had greater amplitude and longer duration than the reflex vasodilatation. 5. Intravenously administered atropine and propranolol did not affect the local dilatation to i.n.s. but after chronic treatment of the skin with capsaicin (1% in ethanol), i.n.s. after a proximal nerve block induced skin vasoconstriction. In five of seven experiments subcutaneous injection of terbutaline (0.25 mg) in the innervation zone abolished the local dilatation. 6. It is suggested that (a) the reflex vasodilatation is of sympathetic nature and is induced by stimulation of thin (A delta?) afferent fibres, (b) the local vasodilatation is due to centrifugally conducted impulses in (afferent?) non‐myelinated fibres.
Ion activities and potassium uptake mechanisms of glial cells in guinea‐pig olfactory cortex slices.
Authors: Ballanyi K , Grafe P , ten Bruggencate G
Published: December 2014

1. Double‐barrelled ion‐sensitive micro‐electrodes were used to measure changes in the intracellular activities of K+, Na+ and Cl‐ (aiK, aiNa, aiCl) in glial cells of slices from guinea‐pig olfactory cortex during repetitive stimulation of the lateral olfactory tract. 2. Base‐line levels of aiK, aiNa and aiCl were about 66, 25 and 6 mM, respectively, for cells with resting potentials higher than ‐80 mV. During stimulation, intraglial aiK and aiCl increased, whereas aiNa decreased. Within about 2 min after stimulation the ion activities returned to their base‐line levels. 3. The Cl‐ equilibrium potential was found to be close to the membrane potential (Em). There was also a strong correlation between changes of Em and aiCl. These observations indicate a high Cl‐ conductance of the glial cell membrane. 4. In the presence of Ba2+, the usual depolarizing response of the glial cells to a rise of the extracellular K+ activity (aeK) reversed into a membrane hyperpolarization. Furthermore, Ba2+ strongly reduced the stimulus‐related rise of intraglial aiK. An additional application of ouabain blocked both the membrane hyperpolarization as well as the remaining rise of aiK. 5. In conclusion, our data show that glial cells in guinea‐pig olfactory cortex slices possess at least two mechanisms of K+ accumulation. One mechanism is sensitive to the K+ channel blocker Ba2+ and might be a passive KCl influx. The other appears to be the electrogenic Na+/K+ pump, which can be activated by excess extracellular K+.
Studies of the unitary properties of adenosine‐5'‐triphosphate‐regulated potassium channels of frog skeletal muscle.
Authors: Spruce A E , Standen N B , Stanfield P R
Published: December 2014

1. Patch‐clamp techniques were used to study adenosine‐5'‐triphosphate (ATP)‐dependent K+ channels in sarcolemmal vesicles from frog skeletal muscle. In addition to its ATP dependence, opening of these channels was voltage dependent, the open‐state probability (P open) increasing with depolarization. 2. The reversal potential of unitary currents changed with external K+ concentration, [K+]o, as expected if the Na‐K permeability ration (pNa/pK) equals 0.015. Unitary conductance increased with increasing [K+]o from 14.8 +/‐ 0.5 pS (n = 5) in 2.5 mM‐K+ to 42.3 +/‐ 1.0 pS (n = 8) in 60 mM‐K+. This increase was less than that expected from independence. 3. Replacement of 60 mM‐external K+ by 60 mM‐external Rb+ shifted the reversal potential of unitary currents by ‐6.7 mV, suggesting that Rb+ enters channels nearly as easily as does K+ (Rb‐K permeability ration, pRb/pK = 0.76). Unitary currents were much smaller in Rb+, consistent with Rb+ binding within the channel. 4. The ATP‐regulated K+ channel was blocked by both internal and external tetraethylammonium ions (TEA+). 2 mM‐TEA+, applied to the cytoplasmic face of membrane patches, interrupted channel openings. Higher concentrations reduced unitary current amplitude, suggesting an increase in the rapidity of TEA+ block. 5. The reduction in P open by ATP was consistent with 1:1 binding and a dissociation constant of 0.135 mM. ATP appeared not to be hydrolysed to close channels. Adenosine 5'‐diphosphate (ADP) and adenosine 5'‐monophosphate (AMP) were less effective than ATP, but retained channel closing properties. Substitution of adenine with other purines or with pyrimidine bases substantially reduced activity, as did substitution of ribose by 2'‐deoxyribose or by ribose 2',3'‐dialdehyde. 6. Sarcoplasmic Ca2+ did not influence P open. 7. Myotubes, grown from thigh muscles of new‐born rats, appeared to lack ATP‐dependent K+ channels. Adult frog muscle appeared to lack high‐conductance Ca2+‐dependent K+ channels, at least in the surface membrane. Such channels were found in myotube membranes. 8. Open‐ and closed‐time histograms were constructed and were consistent with at least two open and at least three closed states. Channel openings were grouped in bursts. Open times, burst lengths and the number of openings per burst were reduced by ATP. 9. The effects of [K+]o on unitary conductance and of K+ replacement with Rb+ are discussed in terms of a simple Eyring rate theory formulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of potassium conductances by an endogenous neuropeptide in neurones of Aplysia californica.
Authors: Brezina V , Eckert R , Erxleben C
Published: December 2014

1. Macroscopic and single‐channel currents were recorded from voltage‐clamped neurones in the abdominal and pleural ganglia of Aplysia californica in order to investigate conductance changes elicited by application of the endogenous peptide FMRFamide (Phe‐Met‐Arg‐Phe‐NH2) and related neuropeptides to the cell surface. 2. The Ca‐dependent K current, IK(Ca), when elicited at a constant voltage by intracellular injection of Ca2+, was insensitive to FMRFamide or its derivative YGG‐FMRFamide (Tyr‐Gly‐Gly‐Phe‐Met‐Arg‐Phe‐NH2). 3. Under steady voltage clamp, certain cells responded to a brief puff of FMRFamide or YGG‐FMRFamide with a transient outward current lasting about 1 min. Unclamped cells responded with a corresponding hyperpolarization. These responses reversed at about ‐75 mV. Ion substitution indicated that the current is carried by K+. 4. FMRFamide and YGG‐FMRFamide were equally effective in activating the outward current, whereas FMRF, met‐enkephalin and leu‐enkephalin were ineffective. 5. At voltages negative to ‐30 mV and, in the absence of extracellular Ca2+, also at more positive potentials, the FMRFamide‐sensitive current showed no voltage dependence beyond that predicted from constant‐field considerations. 6. The response to FMRFamide was relatively insensitive to extracellular tetraethylammonium (TEA, KD approximately 75 mM) and 4‐aminopyridine (4‐AP, KD approximately 6 mM). It was suppressed in Ba‐containing solutions, but was unaffected by injection of the Ca chelating agent EGTA. The response was blocked by serotonin and other agents known to elevate intracellular adenosine 3',5'‐phosphate (cyclic AMP) levels, and by direct injection of cyclic AMP into the cell. 7. In its pharmacological properties and lack of voltage dependence, the FMRFamide‐activated current resembles the 'S' current, IK(S), a K current suppressed by application of serotonin in Aplysia neurones. 8. The similarity between the FMRFamide‐sensitive current and the 'S' current was confirmed in cell‐attached patch‐clamp studies, in which activity of 'S' channels was found to be reduced by serotonin, and enhanced by FMRFamide. 9. Thus, FMRFamide may function in Aplysia to counteract the serotonergic modulation of 'S' channels, which has been proposed as a mechanism of presynaptic plasticity in this mollusc.
Catecholamines release mediators in the opossum oesophageal circular smooth muscle.
Authors: Daniel E E , Jager L P , Jury J
Published: December 2014

1. Effects of catecholamines applied exogenously to the circular smooth muscle layer of the body of the oesophagus of the opossum (Didelphis marsupialis) were studied, simultaneously measuring changes in the membrane potential, the membrane conductance and the contractility of the muscle, using the double sucrose‐gap technique. 2. Superfusion of the smooth muscle with Krebs solution at 27 degrees C containing dopamine (10(‐6)‐10(‐4) M) dose‐dependently caused a hyperpolarization of the smooth muscle cells and an increased membrane resistance followed after gradual repolarization by oscillations of the membrane potential, often accompanied by muscle action potentials. During the hyperpolarization, the tendency for the membrane potential to sag during prolonged application of hyperpolarizing currents was reduced and the 'off' depolarization following such currents was increased. This muscle did not develop active tension prior to treatment; it therefore did not relax during the hyperpolarizations, but contracted following the depolarized phase of oscillations. 3. The non‐adrenergic, non‐cholinergic nerve‐mediated inhibitory junction potential (i.j.p.) showed a small reduction in amplitude during superfusion with dopamine, explicable as a result of the drug‐induced hyperpolarization. The 'off' response following the i.j.p., decreased transiently when the membrane potential was hyperpolarized to its maximum value. Then it increased to values larger than control as the membrane repolarized. Vasoactive intestinal polypeptide (VIP, 10(‐6) M) produced a similar response but hyperpolarizations were smaller. 4. Of the tested catecholamines, isoprenaline, phenylephrine, butylated hydroxytoluene‐920 (BHT‐920) and clonidine were ineffective whereas the potency order for other catecholamines was dopamine greater than noradrenaline greater than or equal to adrenaline greater than DOPA. The catecholamine‐induced responses were not affected by alpha‐ or beta‐adrenoreceptor antagonists given alone or in combination. Of the dopamine receptor antagonists tested domperidone was without effect, whereas haloperidol reduced and bulbocapnine blocked the response. The findings suggested that a receptor resembling DA1‐type peripheral receptor mediated the effects of dopamine on opossum oesophagus. 5. The catecholamine‐induced responses and those to VIP disappeared completely in Cl‐(‐)free medium (isethionate replacement). 6. Conditioning depolarization of the smooth muscle cells decreased but hyperpolarization increased the amplitude of the hyperpolarization (up to 20 mV). With larger hyperpolarizations the responses decreased and disappeared at around 50 mV hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Effect of cutaneous nerve stimulation on voluntary and stretch reflex electromyographic activity in wrist flexors in humans.
Authors: Becker W J , Hayashi R , Lee R G , White D
Published: December 2014

1. Changes in electromyographic (e.m.g.) activity in the wrist flexors of normal human subjects were studied in response to electrical stimulation of digital nerves and to sudden extension perturbations at the wrist produced by a torque motor. 2. With the subjects maintaining a steady voluntary contraction, stimulation of the digital nerves produced a series of excitatory and inhibitory changes in the tonic e.m.g. activity from the wrist flexors. The most prominent and consistent response was a period of e.m.g. inhibition beginning 39 ms after the stimulus and lasting for approximately 36 ms. 3. The stretch reflex evoked by extension perturbations of the wrist consisted of an early response (M1) with an onset latency of approximately 30 ms, and a late response (M2) with an onset latency of approximately 60 ms. 4. The electrical stimuli and the mechanical perturbations were then delivered together, varying the interval between them so that the period of inhibition resulting from the electrical stimuli occurred at the same time as the M1 or M2 components of the stretch reflex, or during the later voluntary response. 5. The amount of e.m.g. inhibition during the M2 component was significantly greater than that during M1 (P less than 0.02). This result is compatible with the view that M1 and M2 are mediated by separate neural pathways.
Neurotensin and acetylcholine evoke common responses in frog oocytes injected with rat brain messenger ribonucleic acid.
Authors: Hirono C , Ito I , Sugiyama H
Published: December 2014

1. The intracellular reaction mechanism underlying electrophysiological responses evoked by neurotensin (NT) was studied using Xenopus laevis oocytes injected with poly (A)+ messenger ribonucleic acid (mRNA) isolated from rat brains. 2. A few days after the injection of mRNA, oocytes were found to acquire sensitivity to NT and substance P. 3. Under voltage‐clamp conditions (‐60 mV), application of NT to mRNA‐injected oocytes produced transient and oscillatory inward currents which began after a delay of several tens of seconds. These inward currents were accompanied by an increase in membrane conductance. 4. NT receptors on mRNA‐injected oocytes showed essentially the same pharmacological properties as those of native NT receptors. 5. The NT response showed desensitization and was not readily recovered even after extensive washing of cells for more than 30 min. 6. NT response was suppressed when the muscarinic acetylcholine (ACh) response of the same cell, which was also induced by the same mRNA, was desensitized by a large dose of ACh. 7. NT response and ACh response showed many similarities: they were both inhibited by pertussis toxin and intracellular ethyleneglycol‐bis‐(beta‐aminoethylether) N, N'‐tetraacetic acid (EGTA), mimicked by intracellularly injected inositol 1, 4, 5‐trisphosphate (InsP3), and suppressed when cell response to InsP3 was desensitized by a large dose of InsP3. Reversal‐potential analyses indicated that both responses were mediated by an increase in membrane permeability to Cl‐. 8. It is concluded that NT responses and muscarinic ACh responses of Xenopus oocytes induced by rat brain mRNA may most likely share a common reaction mechanism. The reaction sequence includes the activation of receptors, activation of inhibitory guanine nucleotide‐binding regulatory protein, production of InsP3, intracellular Ca2+ mobilization, and increased membrane permeability to Cl‐.
Voltage‐clamp analysis of somatic gamma‐aminobutyric acid responses in adult rat hippocampal CA1 neurones in vitro.
Authors: Ashwood T J , Collingridge G L , Herron C E , Wheal H V
Published: December 2014

1. The response of CA1 pyramidal neurones to somatic application of gamma‐aminobutyric acid (GABA) was studied in adult hippocampal slices using single‐electrode voltage‐clamp techniques. 2. Small ionophoretic applications of GABA produced a pure outward current at the cell resting potential when recording with potassium‐acetate‐filled microelectrodes. This response reversed at a membrane potential of ‐69 +/‐ 5 mV (mean +/‐ 1 S.D.; n = 20). In recordings made with caesium‐chloride‐filled electrodes the GABA response reversed at ‐24 +/‐ 12 mV (n = 9). 3. The effect of different holding potentials on the size of the GABA response was examined in the range of ‐100 to ‐40 mV in twenty neurones using potassium‐acetate‐filled electrodes. In every case outward rectification of the response was observed. For twelve neurones the mean ratio (+/‐ 1 S.D. of the mean) of the conductance increase produced by GABA at ‐55 mV compared to ‐85 mV was 1.9 +/‐ 0.5. 4. Step changes in holding potential resulted in shifts in chloride equilibrium potential (ECl), as determined by time‐dependent changes in the size of GABA‐induced currents. The new value of ECl was generally reached within a few seconds of altering the membrane potential. Shifts in ECl did not appear to affect the extent of rectification but would cause underestimates of conductance measurements unless these were 'instantaneous'. The mean ratio (+/‐ 1 S.D. of the mean) of the 'instantaneous' conductance increase produced by GABA at 13 mV positive to that at 13 mV negative to ECl was 1.8 +/‐ 0.3. 5. The outward rectification was greater than that predicted by the constant‐field equation. Possible factors that might contribute towards the rectification and its physiological significance are discussed.
Comparison of the frequency dependence of venous and arterial responses to sympathetic nerve stimulation in guinea‐pigs.
Authors: Hottenstein O D , Kreulen D L
Published: December 2014

1. Intracellular potentials and measurements of contractions were recorded in adjacent veins and arteries in the colonic mesentery of the guinea‐pig in vitro during stimulation of post‐ganglionic nerve trunks. 2. Repetitive stimulation (0.5‐5 Hz) of lumbar colonic nerve trunks produced frequency‐dependent slow depolarizations in all venous and in 92% of arterial smooth muscle cells. Excitatory junction potentials were observed for each nerve shock in arteries, but not in veins. 3. Low‐frequency stimulations produced slow depolarizations of greater amplitude and longer duration in veins than in arteries. The frequencies at which half‐maximal depolarizations and contractions occurred were always lower for veins than for arteries. 4. The alpha 1‐adrenergic antagonist prazosin (5 X 10(‐7) M) reduced the mean arterial slow depolarizations by 82% and reduced mean venous slow depolarizations by 58% for 5 Hz stimulations. Arterial contractions were completely inhibited by prazosin but venous contractions were incompletely reduced in a frequency‐dependent manner. 5. These findings suggest that functional differences in activation between mesenteric veins and arteries during sympathetic stimulation are a result of differences in neuromuscular transmission.
Identification of sodium‐calcium exchange current in single ventricular cells of guinea‐pig.
Authors: Kimura J , Miyamae S , Noma A
Published: December 2014

1. The Na‐Ca exchange current was investigated in single ventricular cells from guinea‐pig hearts by combining the techniques of whole‐cell voltage clamp and intracellular perfusion. 2. The membrane conductance was minimized by blocking Ca and K channels as well as the Na‐K pump. Under these conditions, when Ca2+ was loaded internally by a pipette solution containing 430 nM‐Ca2+, changing the Li+‐rich external solution to a Na+‐rich one induced a significant inward current. Applying external Na+ in the absence of internal Ca2+ did not appreciably change the current. 3. In contrast, perfusing 1 mM‐external Ca2+ in the presence of internal Na+ which was loaded by a 20 mM‐Na+ pipette solution, induced a marked outward current. Ca2+ superfusion in the absence of internal Na+ caused only a small current change. 4. The current‐voltage relation of external‐Ca2+‐ and external‐Na+‐induced current showed almost exponential voltage dependence as given by the equation i = a exp (rEF/RT), where a is a scaling factor that determines the magnitude of the current and r is a partition parameter used in the rate theory and represents the position of the energy barrier in the electrical field, which indicates the steepness of the voltage dependence of the current. E, F, R and T have their usual meanings. The value of a was 1‐2 microA/microF and r about 0.35 for the Ca2+‐induced outward current. At very positive or negative potentials, the current magnitude became smaller than expected from an exponential relation. 5. The current was blocked by heavy metal cations, such as La3+, Cd2+, Mn2+ and Ni2+ and partially blocked by amiloride and D600. 6. The temperature coefficient (Q10) value of the Ca2+‐induced outward current was 3.6 +/‐ 0.4 (n = 4) at 0 mV and 4.0 +/‐ 0.9 at 50 mV in the range between 21 and 36 degrees C. 7. The outward current magnitude showed a sigmoidal dependence upon the external Ca2+ concentration with a half‐maximum concentration, K1/2 of 1.38 mM and a Hill coefficient of 0.9 +/‐ 0.2 (n = 5). 8. Sr2+ could replace Ca2+ with K1/2 of 7 mM. Mg2+ and Ba2+, however, did not replace Ca2+. 9. The inward current component also showed a sigmoidal external Na+ dependence with K1/2 of 87.5 +/‐ 10.7 mM and a Hill coefficient of 2.9 +/‐ 0.4 (n = 6). 10. The reversal potential of the current was obtained near the values expected for 3 Na+:1 Ca2+ exchange.(ABSTRACT TRUNCATED AT 400 WORDS)