bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic and extrinsic inhibitory synaptic inputs to submucous neurones of the guinea‐pig small intestine.
Authors: Bornstein J C , Costa M , Furness J B
Published: December 2014

1. The sources of inhibitory synaptic inputs to neurones in submucous ganglia of the guinea‐pig small intestine were examined by making lesions to cause selective degeneration of nerve terminals of sympathetic or intrinsic origin. Intracellular recordings were used to evaluate the effects of lesions on the inhibitory inputs. Immunohistochemical techniques were used to identify the neurochemical classes of the impaled neurones and to confirm the efficacy of the lesions. 2. The neurones from which recordings were taken were filled with the fluorescent dye Lucifer Yellow. The preparations were then fixed and processed for immunohistochemistry. 3. Thirty‐one neurones reactive for vasoactive intestinal polypeptide (VIP) were examined in control submucous ganglia and all exhibited inhibitory synaptic potentials. In preparations extrinsically denervated by severing the mesenteric nerves, twenty‐seven of twenty‐eight VIP‐reactive neurones had inhibitory synaptic potentials. This indicates that these neurones receive inhibitory synaptic inputs from intrinsic neurones. However, significantly more stimuli were required to evoke a detectable inhibitory synaptic potential in extrinsically denervated preparations than in normal intestine. 4. Extrinsic denervations were combined with removal of the myenteric plexus so that nerve terminals arising from both cell bodies in extrinsic ganglia and in the myenteric plexus degenerated. Under these conditions no inhibitory synaptic potentials could be recorded in any of the nine VIP‐reactive neurones studied. 5. The conductance change underlying the intrinsic inhibitory synaptic potentials appeared to be similar to that underlying the responses in normal intestine. 6. The time courses of the intrinsic inhibitory synaptic potentials differed from those of the control responses. The responses to short trains of stimuli were significantly briefer and the responses to long trains significantly more prolonged in the extrinsically denervated preparations than in normal preparations. 7. The intrinsic inhibitory synaptic potentials were not significantly affected by phentolamine (0.2 microM), guanethidine (1 microM) or naloxone (1 microM), although the first two drugs markedly depressed control inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)
Cellular mechanisms underlying calcium‐proton interactions in cultured chick ventricular cells.
Authors: Kim D , Smith T W
Published: December 2014

1. Cytosolic free Ca2+ concentration ([Ca2+]i) in cardiac muscle cells is influenced by many factors including intracellular pH. Intracellular alkalinization has been shown to reduce, whereas acidification has been shown to augment [Ca2+]i. We examined the cellular mechanisms underlying Ca2+‐H+ interactions using cultured chick embryo ventricular cells. 2. Cells were loaded with fura‐2 or BCECF (2,7‐biscarboxyethyl‐5(6)‐carboxy‐fluorescein) and changes in time‐averaged [Ca2+]i or pHi were monitored continuously using a dual‐wavelength spectrofluorometer. 3. Exposure of cells to 20 mM‐NH4Cl (intracellular alkalinization) produced a rapid decrease in [Ca2+]i; subsequent wash‐out of NH4Cl (intracellular acidification) resulted in an increase in [Ca2+]i to levels above control. Intracellular acidification produced by elevated CO2 content also resulted in an increase in [Ca2+]i. The Na+‐H+ exchange inhibitor ethylisopropylamiloride (10 microM) inhibited completely the rise but not the fall in [Ca2+]i in response to manipulation of pHi with NH4Cl. 4. In the presence of caffeine (20 mM), NH4Cl produced a decrease in [Ca2+]i similar to that observed in the absence of caffeine, but subsequent removal of NH4Cl resulted in an increase in [Ca2+]i that was distinctly smaller than that observed in the absence of caffeine. Ryanodine (10 microM) had no significant influence on NH4Cl‐induced changes in [Ca2+]i. 5. Following treatment with the mitochondrial inhibitors sodium cyanide (5 mM), CCCP (carbonyl cyanide m‐chlorophenyl hydrazone, 10 microM) or rotenone (10 microM), the NH4Cl‐induced decrease in [Ca2+]i was markedly diminished, but wash‐out of NH4Cl resulted in increases in [Ca2+]i similar to those observed in control cells. 6. Inhibition of glycolysis with 20 mM‐2‐deoxyglucose did not significantly alter the changes in [Ca2+]i induced by NH4Cl addition or its wash‐out, but 2‐deoxyglucose plus cyanide abolished the decrease in [Ca2+]i produced by intracellular alkalinization and nearly completely blocked the increase in [Ca2+]i produced by acidification. 7. In all experiments, the increase in [Ca2+]i during wash‐out of NH4Cl was inhibited by ethylisopropylamiloride.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of extracellular calcium on calcium movements of excitation‐contraction coupling in frog skeletal muscle fibres.
Authors: Brum G , Ríos E , Stéfani E
Published: December 2014

1. The effect of low extracellular free calcium ion concentration ([Ca2+]o) on the transient changes in cytoplasmic [Ca2+] associated with membrane depolarization (Ca2+ transients) was studied on single cut skeletal muscle fibres of the frog, voltage clamped in a double‐Vaseline‐gap chamber. The Ca2+ transients were monitored with the dye Antipyrylazo III diffused intracellularly. 2. The Ca2+ transients were substantially reduced in external salines with low [Ca2+] (10(‐5) M or less and Mg2+ substituted for Ca2+). This decrease was more noticeable at late times during 100 ms or longer depolarizing pulses. 3. The rates of the processes that remove Ca2+ from the myoplasmic solution were not altered by the low [Ca2+]o. This implies that the input flux of Ca2+ into the myoplasm was reduced. 4. The Ca2+ input flux, equal to release flux from the sarcoplasmic reticulum (SR) plus Ca2+ influx via the T‐tubule membrane Ca2+ channel, was derived from the Ca2+ transient. In low [Ca2+]o the peak input flux was reduced by 45% (n = 16 fibres) and decayed more rapidly during a depolarizing pulse. 5. The reduction in Ca2+ influx via the T‐tubule membrane Ca2+ channel due to the reduced [Ca2+]o could not account for more than 5% of the reduction in Ca2‐ input flux, which was thus interpreted as an actual reduction of release from the SR. 6. The inward (T‐tubular) Ca2+ current was not associated with this effect of extracellular Ca2+ as the effect was voltage independent at high intracellular voltages at which the Ca2+ inward current was strongly voltage dependent. 7. Low [Ca2+]o made Ca2+ release more readily inactivatable; the effect of low [Ca2‐]o is best described as a left shift by 29 mV of the 'inactivation curve' of Ca2+ release, relating peak release flux to membrane holding potential. 8. The reduction of Ca2+ release by low [Ca2+]o was not accompanied by changes in the voltage dependence of Ca2+ release or in the threshold voltage for just‐detectable release. 9. The results are consistent with a primary effect of Ca2+ on the T‐tubular‐membrane voltage sensor of excitation‐contraction coupling.
Discharges of interpositus and Purkinje cells of the cat cerebellum during locomotion under different conditions.
Authors: Armstrong D M , Edgley S A
Published: December 2014

1. Extracellular microelectrodes were used in free‐to‐move cats to study the locomotor‐related discharges of Purkinje cells in the intermediate part of lobule V of the cerebellar anterior lobe and of neurones in the underlying nucleus interpositus anterior. All cells studied discharged rhythmically during locomotion. 2. The discharges during walking at a speed of 0.5 m/s on a horizontal exercise belt were compared with those during (a) walking at 0.9 m/s (when the duration of the step cycle is shortened considerably and the amplitudes of the locomotor electromyograms (EMGs) recorded from flexor and extensor muscles of the limbs are markedly increased) and (b) during walking at 0.5 m/s with the belt tilted uphill by 30 deg (when step duration is little changed but locomotor EMGs are increased by 70‐100%). 3. In each of thirty Purkinje cells the timing of the discharges relative to the forelimb step cycle showed no major difference between the two speeds of walking. Most cells discharged at slightly higher overall rates at the faster walking speed but the increase was usually modest, the average being only 5.6 impulses/s (i.e. an increase of 8%). Peak rates sometimes underwent larger increases but the average was only 11.9 impulses/s (+11%). Changes in minimum rate were generally small (an average increase of 0.3 impulses/s). 4. Among twenty‐one interpositus neurones there was only one in which discharge timing relative to the step cycle was different between the two speeds. Like the Purkinje cells, most neurones discharged slightly faster at the higher speed but the average increase was only 5.5 impulses/s (+8.5%). Peak firing rates also usually showed a modest increase (averaging 6.2 impulses/s; +6.5%) while minimum rates were little changed. 5. Among nineteen Purkinje cells compared between walking uphill and on the flat only one showed any major difference in discharge phasing; overall firing rates were on average only 1.3 impulses/s (2%) higher for uphill locomotion. 6. Among twenty‐one interpositus neurones discharge phasing differed markedly between walking uphill and on the flat in only two cells. Overall discharge rates were on average slightly higher uphill (by 3.5 impulses/s; 6.7%) and peak rates also usually increased slightly (on average, by 6 impulses/s; 7.7%). Minimum rates were higher, on average, by 1.6 impulses/s (+5%). 7. The findings are discussed in relation to current notions of how the intermediate part of the cerebellum may contribute to movement control and it is concluded that the neurones studies probably make little contribution to determining the vigour of the movements of steady walking.
Potassium transport across rat alveolar epithelium: evidence for an apical Na+‐K+ pump.
Authors: Basset G , Bouchonnet F , Crone C , Saumon G
Published: December 2014

1. Experiments were performed on rat lungs into which various solutions were instilled whilst the lungs were perfused with either whole blood or Ringer solution. Instillation of ion‐free glucose solution led to a net flux of fluid and ions into the alveolar spaces. K+ ions entered faster than Na+ ions and reached a concentration about twice that in the perfusate. Ouabain in the perfusate (basolateral side) prevented the rise in alveolar K+ concentration above that in the perfusate, indicating a transcellular pathway. Ba2+ in the instillate (apical side) hindered the entry of K+ into alveoli, suggesting the presence of apical K+ channels. 2. When Ringer solution was instilled, K+ was continuously removed from the alveoli and the K+ concentration in the instillate remained constant or decreased slightly depending on the rate of fluid absorption. The net K+ efflux from alveoli to blood was 0.23 pmol/(cm2 s). When Ba2+ was added to the instillate the net K+ efflux increased to 0.36 pmol/(cm2 s). Apical ouabain reversed the K+ flux resulting in a net K+ flux of 0.19 pmol/(cm2 s) into the alveoli. This suggests the presence of an Na+‐K+‐ATPase located in the apical membrane of some alveolar cells. 3. The K+ transport from instillate (Ringer solution) to perfusate was traced by means of 86Rb which was added to the instillate. Ouabain in the instillate did not affect fluid absorption but reduced the apparent 86Rb permeability by 50% although the paracellular permeability (estimated with [3H]mannitol) was unaffected. This also indicates the presence of an apical Na+‐K+‐ATPase. When ouabain was added to the perfusate, the apparent 86Rb permeability doubled. These findings indicate that recirculation of 86Rb (and K+) occurs due to the activity of both apical and basolateral Na+‐K+‐ATPases. 4. When ouabain was placed on both sides of the epithelium, preventing transcellular transport, the passive 86Rb permeability was 10.3 x 10(‐8) cm/s (assuming an alveolar surface area of 5000 cm2). This value agrees with the passive permeabilities for mannitol, Na+ and Cl‐ suggesting that the paracellular pathway acts as a water‐filled neutral channel. 5. We conclude that K+ is 'secreted' into the alveoli and is also removed from the alveoli, both processes being energized by Na+‐K+‐ATPases placed on the basolateral and apical sides, respectively. It is likely that two functionally different cell types exist in the alveolar membrane. One type ('B cell') has a Na+‐K+‐ATPase located at the basolateral membrane and K+ channels situated luminally.(ABSTRACT TRUNCATED AT 400 WORDS)
Phosphate inhibition of the human red cell sodium pump: simultaneous binding of adenosine triphosphate and phosphate.
Authors: Sachs J R
Published: December 2014

1. The Na+‐K+ exchange carried out by the Na+ pump of human red cell ghosts and the Na+ + K+‐dependent adenosine triphosphatase (Na+,K+‐ATPase) activity of human red cell membranes are inhibited by MgPO4 rather than by free phosphate; similarly, the substrate for the K+‐K+ exchange carried out by the pump is MgPO4 rather than free phosphate. 2. Inhibition of the Na+, K+‐ATPase activity by MgPO4 is only partially competitive (mixed type) with ATP, and MgPO4 inhibition of the Na+‐K+ exchange measured in Na+‐free solutions and in K+‐free ghosts which contain ATP at relatively high concentration is partially uncompetitive (mixed type) with external K+. 3. When measurements were made in K+‐free ghosts and Na+‐free solutions, or when Na+,K+‐ATPase activity was measured at high ATP concentrations, inhibition by MgPO4 was non‐competitive with cell Na+. This observation is not consistent with the Albers‐Post reaction mechanism of the Na+ pump, and suggests the presence of an alternative reaction pathway in which ATP combines with the enzyme before phosphate is released. 4. MgPO4 monotonically inhibited the uncoupled Na+ efflux which occurs in solutions free of both Na+ and K+. The uncoupled efflux seemed to be more sensitive to MgPO4 inhibition than the Na+‐K+ exchange. 5. Trinitrophenyladenosine‐5'‐tetraphosphate stimulated the K+‐K+ exchange in the presence of MgPO4, and the characteristics of stimulation by TNP adenosine tetraphosphate were little different from the characteristics of stimulation by trinitrophenyladenosine‐5'‐triphosphate or ‐5'‐diphosphate. The nucleotide binding site at which K+‐K+ exchange is stimulated must be able to accommodate a nucleotide with a linear array of four phosphate groups.
Morphology of pyramidal neurones in monkey motor cortex and the synaptic actions of their intracortical axon collaterals.
Authors: Ghosh S , Porter R
Published: December 2014

1. Pyramidal neurones in the precentral motor area of the monkey were studied using intracellular techniques. Pyramidal tract neurones (PTNs) were identified by antidromic activation from the cerebral peduncles or medullary pyramids. Orthodromic responses were recorded in PTNs and in other pyramidal neurones when antidromic volleys were set up by stimulation of the peduncles or pyramids. The neurones were then labelled by intracellular ionophoresis of horseradish peroxidase and their morphology examined. All neurones studied were identified as pyramidal cells according to their morphology. 2. Six pyramidal neurones located in lamina V were well stained; they included two fast PTNs and two slow PTNs. The morphology of all pyramidal neurones in this lamina (fast PTNs, slow PTNs and those pyramidal cells that were not antidromically characterized) was essentially similar. A single apical dendrite branched as it ascended and its terminals arborized subpially. Numerous lateral and oblique dendrites branched from the apical dendrites in lamina V and near its border with lamina III: short basal dendrites arborized in the vicinity of the soma in lamina V. Long basal dendrites had a wider field of arborization in lamina V and sometimes extended into lamina VI. 3. Three to five collaterals arose from the axon of lamina V cells in the cortex and arborized in laminae V and VI. Short collateral branches arborized in the vicinity of the soma in the region of the basal and lateral dendrites. Long collateral branches could be traced over long distances (often more than 1 mm). One pyramidal neurone in this lamina (a fast PTN) lacked short collateral branches from the axon. 4. Four pyramidal neurones in lamina III were stained well. The dendritic morphology of all these neurones was similar. Apical dendrites branched as they ascended and terminated subpially. Lateral and basal dendrites formed a column of dendritic branches around the soma. No long basal dendrites were seen. 5. The number and arborization of intracortical collaterals from the axon of lamina III cells varied widely; from three to twelve collaterals arose from the axon. The biggest arbor of collateral branches involved all the cortical laminae and was about 3 mm wide mediolaterally, while the smallest arbor was restricted mainly to lamina III in the vicinity of the soma. One neurone in this lamina also lacked short collateral branches from the axon. 6. Antidromic volleys from the pyramidal tract evoked excitatory responses in fast PTNs, predominantly inhibitory responses in slow PTNs and either excitatory or inhibitory responses in other pyramidal neurones in lamina V.(ABSTRACT TRUNCATED AT 400 WORDS)
Activity‐dependent and ‐independent synaptic interactions during reinnervation of partially denervated rat muscle.
Authors: Ribchester R R
Published: December 2014

1. Reinnervation of adult rat fourth deep lumbrical muscles was studied, following extensive partial denervation of the hindfoot by crushing the lateral plantar nerve (LPN). Most muscles remained innervated by between one and five motor axons supplied by the sural nerve (SN). Intact SN motor units expanded as a result of collateral sprouting. Virtually complete collateral reinnervation occurred in muscles containing more than two SN motor units. Twitch tension measurements from isolated muscles suggested that most of the sprouts evoked suprathreshold responses from the muscle fibres they innervated. Intracellular recordings suggested that only a small percentage of sprouts evoked subthreshold end‐plate potentials. 2. Lateral plantar nerve motor axons returned to the lumbrical muscles within 15‐18 days and subsequently reinnervated muscle fibres already innervated by SN motor nerve terminals. Nerve conduction in the regenerating axons was then blocked for 7‐15 days by chronic superfusion with tetrodotoxin. In both LPN‐blocked and control (LPN crushed but not blocked) animals, isometric tetanic tension overlap and intracellular recordings showed that some lumbrical muscle fibres became innervated exclusively by regenerating LPN motor axons. 3. With time, the tension evoked by stimulating regenerating motor axons increased and there was a parallel fall in the tension produced by stimulating the intact motor units. The extent of reinnervation by LPN motor axons was inversely related to the number of remaining SN motor units. In comparable muscles, regenerated LPN‐blocked motor units produced only about half the tension of the controls. Selective glycogen depletion of motor units and intracellular recordings of end‐plate potentials indicated that this was due to reduced numbers of muscle fibres innervated by the blocked motor axons. 4. Nerve conduction block prolonged the time course of the isometric twitch in regenerated motor units, and increased the duration of the end‐plate potential in muscle fibres innervated only by the regenerating axons. LPN block did not affect the recovery of the latency of the end‐plate potential. The regenerated motor units were more resistant to fatigue caused by continuous 4 Hz nerve stimulation than intact SN units, but the resistance to fatigue of LPN‐blocked motor units was no different from the controls.(ABSTRACT TRUNCATED AT 400 WORDS)
The dorsal column projection of muscle afferent fibres from the cat hindlimb.
Authors: Fern R , Harrison P J , Riddell J S
Published: December 2014

1. The extent of the projection of hindlimb muscle afferent fibres ascending the dorsal columns has been studied in barbiturate‐anaesthetized cats. This has been investigated using electrical stimulation of the dorsal columns at different spinal levels while recording from (i) peripheral muscle nerves, and (ii) single muscle afferent fibres within the dorsal columns. These two approaches have produced complementary results. 2. The conduction velocity of both group I and group II afferent fibres decreased progressively after entering the dorsal columns. 3. The majority of group I and group II fibres project at least as far as L2 but leave the dorsal columns at or before the lower thoracic segments. 4. By taking advantage of the lower electrical threshold of Ia compared to Ib fibres in the hamstring nerves, it could be shown that both Ia and Ib fibres leave the dorsal columns at similar locations. 5. A small number of afferent fibres were found to project to C1. On the basis of previous work it is likely that such fibres originate from Pacinian or paciniform corpuscles.
The effect of potassium on exocytosis of transmitter at the frog neuromuscular junction.
Authors: Ceccarelli B , Fesce R , Grohovaz F , Haimann C
Published: December 2014

1. Electrophysiology and morphology have been combined to investigate the time course of the exocytosis of quanta of neurotransmitter induced by elevated concentrations of K+ at the frog neuromuscular junction. 2. Replicas of freeze‐fractured resting nerve terminals fixed in the presence of 20 mM‐K+ showed images of fusion of synaptic vesicles with the presynaptic axolemma which were closely associated with the active zones. After 1 min in 20 nM‐K+ fusions appeared also outside the active zones, and by 5 min they became uniformly distributed over the presynaptic membrane. 3. The average total density of fusions was not significantly different at the various times examined since it decreased at the active zones while it increased over the rest of the membrane. 4. Resting terminals fixed in 20 mM‐K+ released 33,000‐45,000 quanta after the addition of fixative; terminals stimulated by 20 mM‐K+ for 1‐5 min released 50,000‐100,000 quanta during fixation. The fixative potentiated K+‐induced transmitter release. 5. Fusions were uniformly distributed in terminals pre‐incubated for 5 min in 20 mM‐K+ without added Ca2+, stimulated by adding Ca2+ for 30 s, and then fixed. Conversely, after 5 min stimulation in hypertonic Ringer solution fusions remained predominantly located near the active zones. A similar distribution was observed after 15 min stimulation by a lower concentration of K+ (15 mM). 6. At all concentrations of K+ tested (10, 15, 20, 25 mM) miniature end‐plate potential (MEPP) rate attained a steady‐state value within 10‐15 min. Values from a single junction were generally lower at higher concentrations of K+, which indicates partial inactivation of the secretion‐recycling process. 7. The data indicate that K+ initially activates exocytosis at the active zones. Subsequently, ectopic exocytosis is activated while sites at the active zones appear to undergo partial inactivation. These phenomena are not related to the intensity or to the amount of previous secretion.
Electrophysiology of neuromuscular transmission in guinea‐pig mesenteric veins.
Authors: Van Helden D F
Published: December 2014

1. Neuromuscular transmission in the smooth muscle of mesenteric veins has been investigated by recording intracellular potential changes resulting from stimulation of the sympathetic nerves and comparing these potential changes with responses obtained by ionophoresis of noradrenaline. 2. Neural stimulation or exogenous noradrenaline acted similarly to cause two excitatory depolarizations, a slow response reported previously (Suzuki, 1981) and a separate fast depolarization. 3. The fast depolarization was distinct from the slow depolarizing response in that it had a different dependence on the level of stimulation, was readily desensitized and was more suppressed in low‐chloride solution. 4. The fast but not the slow depolarization shared certain characteristics with constriction. The fast depolarization and constriction both increased with the intensity of stimulation; inactivation in both was dependent on the recovery interval between trains of stimuli and both were suppressed to a similar degree by antagonists to alpha‐adrenoceptors. The fast depolarization was, however, not a prerequisite for constriction to occur. 5. The fast and slow depolarizations were activated after a long latency which had a high temperature coefficient consistent with the postulate that these responses are rate limited by intracellular biochemical reactions. 6. The fast depolarization was preferentially suppressed by prazosin, an antagonist to the alpha 1‐adrenoceptor subtype. Suppression of the slow depolarization required relatively higher concentrations of antagonist, indicating that these responses were mediated by receptor interactions involving a different alpha‐adrenoceptor subtype. 7. It is concluded that neuromuscular transmission in mesenteric veins occurs through activation of alpha‐adrenoceptors. A number of responses result, including voltage‐independent constriction and two distinct excitatory depolarizations which can lead to voltage‐dependent constriction.
An alpha‐adrenoceptor‐mediated chloride conductance in mesenteric veins of the guinea‐pig.
Authors: Van Helden D F
Published: December 2014

1. The ionic basis of the depolarizing responses resulting from ionophoresis of noradrenaline onto the smooth muscle of mesenteric veins has been investigated using electrically short segments of vessel. 2. Isolated cut segments of vein were effectively isopotential as assessed by the voltage response to a step change in current. The mean input resistance and time constant of the smooth muscle were 24 M omega and 131 ms respectively. 3. Data on the noradrenaline‐induced slow depolarization indicated that it resulted from a decrease in conductance to potassium ions consistent with the finding of Suzuki (1981). 4. The fast noradrenaline‐induced depolarization was found to have a reversal potential of about ‐22 mV. 5. Exposure to low‐chloride solution caused greater than 90% suppression of this fast response with a 50% reduction occurring in less than 2 min. This suppression was not due to a negative shift in reversal potential. 6. The fast response underwent a large positive shift in reversal potential directly after changeover to low‐chloride solution at times when any inactivation of the response was minimal. By contrast the fast response showed no evidence implicating either sodium or calcium as charge‐carrying ions. 7. It is concluded the fast depolarization is carried by chloride ions.
Single‐villus analysis of disaccharidase expression by different regions of the mouse intestine.
Authors: James P S , Smith M W , Tivey D R
Published: December 2014

1. The present results describe how a new technique of whole‐tissue cytochemistry can be combined with automatic scanning of microdissected villi to measure the capacity of individual villi to hydrolyse disaccharides in different parts of the small intestine. 2. Intact villi from the mouse proximal jejunum are found to be eight times more effective than ileal villi in hydrolysing 2‐naphthyl‐alpha‐D‐glucoside, an artificial substrate for enzymes normally hydrolysing sucrose, maltose, isomaltose and trehalose in adult intestine. Homogenates of jejunal scrapings are four times more effective than ileal homogenates in hydrolysing this substrate. This discrepancy arises from relating enzyme activities to homogenate protein in cases where intestinal structure changes. 3. The eightfold difference in villus alpha‐glucosidase activity is associated with a threefold difference in villus surface area. This discrepancy in turn reflects changes in the capacity of individual enterocytes to express alpha‐glucosidase during migration along the crypt‐villus axis. These results emphasize the futility of trying to gauge intestinal function from measurement of intestinal structure. 4. Differences between ileal and jejunal villus alpha‐glucosidase activities have been further partitioned into those depending on villus structure and those depending on enterocyte development. Present results are discussed in relation to the ability of luminal nutrition to maintain a proximal‐distal gradient of digestive enzyme function in the small intestine. The general applicability of this method of analysis to other studies of adaptive response is also emphasized.
Prolonged nerve stimulation causes changes in transmitter release at the frog neuromuscular junction.
Authors: Hinz I , Wernig A
Published: December 2014

1. Synaptic transmission in the two cutaneus pectoris muscles of frog was compared after prolonged unilateral nerve stem stimulation in vivo via surface electrodes. 2. In Mg2+‐blocked preparations at 2 Hz stimulation the mean number of quanta released per impulse (m) was significantly lower in the stimulated muscles. On average, m was reduced to 53% (range 31‐74%) of the values in control muscles. 3. Similarly, in curare‐blocked preparations end‐plate potential (EPP) amplitudes in the stimulated muscles were reduced to 30‐92% (average 63%) of the control values, while no differences in muscle fibre diameter and resting potential were detectable. 4. In most muscles plateau values after tetanic stimulation at 40 Hz for 2 s were also smaller in the stimulated muscles. Compared to the first EPP in the train, however, plateau values were less depressed in stimulated than in unstimulated muscles. Also facilitation, i.e. the amplitude ratio of the largest versus the first EPP was more pronounced in stimulated muscles. 5. No effects of stimulation were noticed in four winter frogs, in which transmitter release is depressed due to seasonal factors. 6. It is concluded that prolonged nerve stimulation can cause under certain conditions profound depression of transmitter release with changes in facilitation and depression.
Conduction of neural impulses in human mechanoreceptive cutaneous afferents.
Authors: Mackel R
Published: December 2014

1. It was the aim of the present study to isolate and identify the components underlying the human sensory compound action potential and to study their axonal conduction velocities and refractory periods. For this purpose the technique of percutaneous microneurography was combined with intradermal electrical stimulation of nerve fibre terminals. Sixty‐four median and ulnar nerve afferents innervating the glabrous skin of the digits were isolated and type identified. 2. The range of axonal conduction velocities was wide (20‐60 m/s), but similar for each afferent category (20‐60 m/s). Most afferents conducted slower than expected from the intrafascicularly recorded compound potential (50‐60 m/s) and their conduction velocities generally decreased from the base to the tip of the digits. 3. The duration of the absolute axonal refractory periods of all types of afferents ranged from 0.7 to 3.5 ms. The duration of the total refractory periods ranged from 3 to 9 ms. Both absolute and total axonal refractory periods were inversely correlated (r = ‐0.70 and r = ‐0.67) with their axonal conduction velocities. 4. The size of individual action potentials was significantly correlated with axonal conduction velocities, although the correlation coefficient was relatively low (r = 0.43), even after correction for variability due to electrode resistance (partial correlation r = 0.44). 5. The results showed that different types of cutaneous afferents cannot be separated on the basis of their axonal conduction properties. The data demonstrate features of neural impulse conduction along the entire axonal tree and which are inaccessible to routine electrodiagnostic procedures. The present approach provides a sensitive means for assessing, in health and disease, nerve conduction in terminal axons.
Influence of right atrial stretch and atrial natriuretic factor on rat intestinal fluid content.
Authors: Kaufman S , Monckton E
Published: December 2014

1. Studies were made on the effects of right atrial stretch and atrial natriuretic factor (ANF) infusion on fluid movement into the intestinal tract. 2. Stimulation of the atrial volume receptors by inflation of an intracardiac balloon in the conscious, unrestrained rat did not change intestinal fluid content under normovolaemic conditions. 3. When the rat was rendered hypovolaemic by peritoneal dialysis (34% deficit in extracellular fluid volume), right atrial stretch significantly increased intestinal fluid content. Under these conditions, inflation of the balloon restored large intestinal fluid content to the pre‐dialysis state, i.e. right atrial stretch completely abolished that component of fluid absorption attributable to the extracellular fluid volume deficit. 4. These data suggest that stimulation of the right atrial receptors inhibits intestinal fluid reabsorption but probably does not initiate fluid secretion. 5. There was no evidence that this might be mediated by ANF since rat ANF (twenty‐eight residue peptide, Ser‐99‐Tyr‐126), infused for 1 h at doses of 0, 0.05, 0.1 and 0.5 microgram/min, did not cause any detectable changes in the fluid content of the large or small intestine of similarly prepared hypovolaemic rats.
Effects of tetraethylammonium on the depolarizing after‐potential and passive properties of lizard myelinated axons.
Authors: Barrett E F , Morita K , Scappaticci K A
Published: December 2014

1. Intra‐axonal recordings were obtained from myelinated axons innervating a lizard skeletal muscle. 2. Bath application of tetraethylammonium (TEA, 1‐10 mM) depolarized the resting potential, prolonged the action potential and increased the amplitude and duration of the ensuing passive depolarizing after‐potential (DAP) in a dose‐dependent and reversible manner. TEA increased the axonal input resistance and the slow time constant of the passive voltage response, not only in depolarized axons, but also in resting and hyperpolarized axons. The resting input resistance was tripled in 10 mM‐TEA. 3. TEA's effects on the resting potential and action potential usually approached a steady state within 5 min, whereas TEA's effects on input resistance and on the amplitude and time course of the DAP increased progressively for 10‐15 min or more, and persisted for 10‐15 min after removal of TEA from the bath. 4. 4‐Aminopyridine (4‐AP, 1 mM), which prolonged the action potential by about the same extent as 10 mM‐TEA, did not depolarize the resting potential or increase the resting input resistance, and produced a much smaller increase in DAP time course than 10 mM‐TEA. Gallamine (1 mM) had effects more similar to those of TEA. 5. These results suggest that the resting input conductance and DAP time course in lizard motor axons are controlled in part by K+ channels that are blocked by TEA and gallamine, but not by 4‐AP. The slow development of the TEA‐induced increase in input resistance and DAP time course suggests that some of these channels are located in paranodal or internodal axolemma. 6. In TEA and gallamine additional depolarizing potentials were superimposed on the falling phase of the action potential and on the passive DAP. These superimposed potentials were abolished by 1 mM‐Mn2+, and were probably caused by Ca2+ influx into motor terminals.
The ionic selectivity of the light‐sensitive current in isolated rods of the tiger salamander.
Authors: Menini A , Rispoli G , Torre V
Published: December 2014

1. Using the method of Hodgkin, McNaughton & Nunn (1985) for rapidly changing the extracellular medium, we analysed the effect of divalent cations on the photocurrent of isolated retinal rods of the tiger salamander. 2. When the extracellular NaCl was replaced by equiosmolar amounts of BaCl2, SrCl2, CaCl2, MgCl2 and MnCl2 the efficacy in carrying the photocurrent at early times was Ba2+ greater than Sr2+ greater than Ca2+ greater than Mg2+ greater than Mn2+. At early times Ba2+ could carry a photocurrent similar to or larger than that carried by Na+. 3. The photocurrent carried by Ba2+ increased by about 50% when [Ca2+]o was reduced from 1 to 0.1 mM. In the presence of 0.1 mM‐Ca2+ in the extracellular medium the photocurrent carried by Ba2+ saturated when [Ba2+]o was close to 50 mM and was half‐activated at 15 mM [Ba2+]o. 4. The photocurrent which can be carried by Sr2+ is not larger than that carried by Ba2+ and does not saturate for [Sr2+]o up to 70 mM. 5. When extracellular Na+ is replaced by the impermeant organic ion choline it is possible to observe a transient photocurrent which is carried by Ca2+. This current has a maximal value of about 11 pA and has a half‐activation constant of about 50 microM. 6. Movements of Mg2+ across the light‐sensitive channel can be seen only when extracellular Ca2+ is reduced below 10 microM. Under these conditions the maximal photocurrent which can be carried by Mg2+ at early times is about 8 pA and has a half‐activation of about 2 mM. Under normal conditions Mn2+ is hardly permeable through the light‐sensitive channel. 7. It is concluded that the selectivity of the light‐sensitive channel in the low ionic concentration range is Ca2+ greater than Sr2+ greater than Ba2+ greater than Mg2+ greater than Na+.
Regional gradient of pacemaker activity in the early embryonic chick heart monitored by multisite optical recording.
Authors: Kamino K , Komuro H , Sakai T
Published: December 2014

1. Regional gradient of pacemaker activity in the early embryonic precontractile chick heart was quantitatively assessed by means of simultaneous multiple‐site optical recordings of changes in membrane potential, using a measuring system with a 10 X 10‐element photodiode array which had a spatial resolution of 30 microns. 2. Absorption changes related to spontaneous electrical activity were recorded simultaneously from many contiguous regions in the area in which the pacemaker site was located in seven‐ to nine‐somite embryonic hearts stained with a voltage‐sensitive merocyanine‐rhodanine dye (NK 2761). 3. The absorption changes related to slow diastolic depolarization were detected, and they were concentrated in and near the pacemaking area. The area in which the absorption changes related to slow diastolic depolarization were detected increased in size as development proceeded. 4. The slope of the absorption change related to diastolic depolarization was measured as an indicator of the pacemaker activity. It was largest in the pacemaking area, and gradually decreased towards the periphery. 5. The maximum slope of the optical change related to slow diastolic depolarization also increased as development proceeded and was related to early development of the heart rate. Thus, these results suggest that formation of a regional gradient of pacemaker activity results in the functional architecture of the pacemaking area in the early phases of cardiogenesis.
Ca2+ sensitivity of volume‐regulatory K+ and Cl‐ channels in cultured human epithelial cells.
Authors: Hazama A , Okada Y
Published: December 2014

1. During exposure to a hypotonic solution, cultured human epithelial cells (Intestine 407) exhibited a regulatory volume decrease (RVD) after initial osmotic swelling. 2. The volume readjustment was slowed by elevating the extracellular K+ concentration and facilitated by reducing the extracellular Cl‐ concentration. Not only putative K+ channel blockers, quinine and Ba2+, but also a stilbene derivative Cl‐ channel blocker (SITS) inhibited the RVD. 3. The volume recovery of hypoosmotically swollen cells was very much suppressed by the deprivation of extracellular Ca2+ ions or by chelation of cytosolic Ca2+ ions with Quin‐2 loaded within the cells. 4. Biphasic membrane potential changes were associated with the RVD process at low extracellular K+ and Cl‐ concentrations. The initial hyperpolarizing response was inhibited by quinine and Ba2+, whereas the late depolarizing response was inhibited by SITS. The deprivation of extracellular Ca2+ inhibited the initial hyperpolarizing phase but not the late depolarizing phase. 5. Two‐microelectrode voltage clamp studies showed that the initial hyperpolarization and late depolarization were associated with quinine‐sensitive outward currents and SITS‐sensitive inward currents, respectively. The reversal potentials estimated from the current‐voltage curves were about ‐80 mV for the initial response and ‐27 mV for the late response. Tenfold changes in the K+ and Cl‐ concentrations shifted these reversal potentials by 50 mV for the initial response and by 42 mV for the late response. 6. Under whole‐cell recordings, similar current changes were observed in the cells exposed to a hypotonic solution, when the intracellular Ca2+ ions were moderately buffered with 1 mM‐EGTA in the dialysing solution filled in a patch pipette. When most Ca2+ ions were chelated with 10 mM‐EGTA in the pipette solution, the initial outward current as well as the corresponding hyperpolarization was suppressed, but the late current associated with the depolarizing phase was preserved. 7. Intracellular Ca2+ injections induced an increase in the quinine‐sensitive K+ conductance but failed to activate the Cl‐ conductance. 8. It is concluded that both K+ and Cl‐ channels are involved in the regulatory volume decrease, and that the former channel is exclusively activated by elevation of the cytosolic Ca2+ concentration in the epithelial cells.
Evidence that mid‐lumbar neurones in reflex pathways from group II afferents are involved in locomotion in the cat.
Authors: Edgley S A , Jankowska E , Shefchyk S
Published: December 2014

1. A group of interneurons in the mid‐lumbar segments of the cat spinal cord which mediate disynaptic excitation or inhibition of motoneurones from group II muscle afferents have recently been described. To test the possibility that the activity of these interneurones is related to the activity in the neuronal networks which subserve locomotion we have investigated whether they are influenced by two procedures which can induce locomotion. These procedures were electrical stimulation within the cuneiform nucleus (the ‘mesencephalic locomotor region’) in anaesthetized preparations and systemic administration of 3,4‐dihydroxyphenylalanine (DOPA) in decerebrate, spinalized, unanaesthetized preparations. The interneurones we have tested were located in the fourth lumbar (L4) segment and were excited by group II muscle afferents; more than half of them were antidromically activated from the hindlimb motor nuclei. 2. Stimuli applied in the cuneiform nucleus evoked excitatory postsynaptic potentials (EPSPs) in a high proportion of these interneurones. The stimuli also evoked distinct extracellular field potentials in the ventral horn of the L4 segment. The properties and latencies of both the intra‐ and extracellularly recorded potentials show that they were evoked disynaptically, via supraspinally located relay neurones and a fast‐conducting descending tract. 3. Stimulation of the cortico‐ and rubrospinal tracts excited or inhibited some of the L4 neurones, often at latencies suggesting mono‐ or disynaptic coupling. The neurones which appeared to be monosynaptically excited from the cortico‐ and rubrospinal tracts tended to be located dorsal to the neurones which were activated from the cuneiform nucleus. 4. Systemic administration of DOPA depressed the responses evoked by stimulation of group II afferents of L4 interneurones which projected to motor nuclei. DOPA also depressed extracellular field potentials evoked by group II afferents in the intermediate zone and in the ventral horn (at the location of the interneurones) but hardly affected those in the dorsal horn. 5. By showing that both stimulation in the cuneiform nucleus and the administration of DOPA influence activity of L4 interneurones which are excited by group II afferents and which project to motor nuclei, the results of this study support the hypothesis that these neurones are in some way involved in locomotion. However, the opposing effects of DOPA administration and of stimulation in the cuneiform nucleus make the interpretation of their role in locomotion rather difficult before it is known to what extent they are active throughout the step cycle.
Psychotomimetic sigma‐ligands, dexoxadrol and phencyclidine block the same presynaptic potassium channel in rat brain.
Authors: Bartschat D K , Blaustein M P
Published: December 2014

1. Efflux of 86Rb from synaptosomes prepared from rat forebrain was used to assess voltage‐gated changes in K+ permeability in mammalian central nerve terminals. 2. Although they are structurally unrelated to phencyclidine (PCP), the sigma‐ligands, N‐allyl‐normetazocine (NANM; SKF 10,047) and cyclazocine, generalize to PCP in behavioral assays, displace [3H]PCP from a high‐affinity binding site in brain, and potently block the same voltage‐gated K+ channel as PCP itself. 3. The block of the voltage‐gated K+ channel in nerve terminals by NANM and cyclazocine was stereoselective and was unaffected by the opioid antagonist naloxone. Moreover, in our experiments the relative activity of the stereoisomers of NANM and cyclazocine compared favourably with their relative activity in behavioural paradigms and binding assays. 4. Dexoxadrol, the D‐isomer of dioxodrol, which produces PCP‐like behavioural effects and displaces bound [3H]PCP, was a potent blocker of the PCP‐sensitive, voltage‐gated K+ channel. The corresponding L‐isomer, levoxadrol, which produces morphine‐like antinociception and sedation, but does not produce PCP‐like behaviour nor displace bound [3H]PCP, was a very weak blocker of the voltage‐gated K+ channel. 5. Levoxadrol, but not dexoxadrol, activated a separate K+ channel, as manifested by an increase in 86Rb efflux. This effect was blocked by naloxone. 6. We conclude that one of the PCP‐sigma‐ligand binding sites in the brain may be associated with the voltage‐gated, non‐inactivating K+ channel we observe in nerve terminals. Our findings are also consistent with the view that some of the behavioural manifestations of PCP intoxication are mediated by block of presynaptic K+ channels.
External and internal actions in the response of salamander retinal rods to altered external calcium concentration.
Authors: Lamb T D , Matthews H R
Published: December 2014

1. The membrane current was recorded from retinal rods isolated from Ambystoma tigrinum using the suction pipette and whole‐cell patch pipette techniques, while the concentration of calcium bathing the outer segment was rapidly reduced. 2. The increase in outer segment current induced by lowered external calcium in darkness could be resolved into two components, one as rapid as the time course of the solution change (as judged by the junction current) and the other somewhat slower. 3. Introduction of the calcium buffer BAPTA (1,2‐bis(o‐aminophenoxy)ethane‐N ,N ,N' ,N'‐tetraacetic acid) into the cell from a patch pipette led to a progressive slowing of the second component of current increase. 4. When several minutes had elapsed following rupture of the patch, to allow a substantial amount of BAPTA into the cell (ca. 10 mM in the patch pipette), the second component was slowed by a factor of about 20‐fold, while the first component continued to have the same rapid time course as the solution change. 5. The rapid component is attributed to a direct effect of external calcium, Ca2+o, and the delayed component to an indirect effect mediated by a reduction in internal calcium, Ca2+i. 6. These results confirm that, in previous experiments in which BAPTA was introduced into photoreceptors, the internal calcium concentration was very significantly buffered. 7. When Ca2+o drops from 1 mM to less than 10(‐8) M, the rapid external component corresponds to an increase in circulating current of 3‐ to 4‐fold, and the internal component corresponds to an increase of at least 4‐ to 5‐fold. However, the total current at late times is limited by electrical factors, so that the size of the internal effect is bound to be considerably greater.