bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of a disulphonic stilbene on chloride and bicarbonate transport in the turtle bladder.
Authors: Brodsky W A , Durham J , Ehrenspeck G
Published: December 2014

1. In turtle bladders bathed by Na‐free media containing Cl and HCO3, the mucosa is electropositive to the serosa. Serosally applied 4‐acetamido‐4'‐isothiocyano‐2,2'‐disulphonic stilbene (SITS) reduces the p.d. and Isc by 100%, and reduces the rate of net Cl reabsorption in some bladders but not in others. 2. In the absence of exogenous HCO2 (Cl present), SITS reduces the p.d. and Isc by 100%, and reduces the rate of mucosal acidification by 80%; net Cl reabsorption is not detectable under these HCO3‐free bathing conditions. 3. In the absence of exogenous Cl (HCO3, present), the mucosa is also electropositive to the serosa and serosally applied SITS reverses the orientation of the p.d. and Isc so that the mucosa becomes electronegative to the serosa. 4. This constitutes sufficient evidence for the active, electrogenic secretion of an anion, probably HCO3. These data are explained by an analogue of discrete, electrogenic pumps and paths for the reabsorption of Na, Cl, and HCO3, and the secretion of HCO3.
Sodium ions, acting at high‐affinity extracellular sites, inhibit sodium‐ATPase activity of the sodium pump by slowing dephosphorylation.
Authors: Beaugé L A , Glynn I M
Published: December 2014

1. It is known that extracellular Na+ ions, in low concentrations, inhibit Na+‐ATPase activity in resealed red cell ghosts and that this inhibition is reversed by high concentrations of extracellular Na+. We have attempted to elucidate these actions of extracellular Na+ by investigating the dependence on Na+ concentration of (a) ATP‐ADP exchange and Na+‐ATPase activity both in native and in N‐ethylmaleimide (NEM)‐treated (Na+ + K+)‐ATPase from pig kidney, and (b) the rate of hydrolysis of the phosphorylated kidney enzyme in the absence of K+ ions. 2. With the native enzyme, ATP‐ADP exchange and Na+‐ATPase activity showed similar responses to changes in Na+ concentration: a steep but S‐shaped rise between 0 and 2.5 mM, a slight fall (exchange) or a plateau (ATPase) between 2.5 and 10 mM, and a roughly linear rise between 10 and 150 mM. With NEM‐treated enzyme, the ATP‐ADP exchange, which was greatly accelerated, showed no sign either of inhibition at intermediate Na+ concentrations or of the reversal of that inhibition at higher concentrations. The exchange rate increased with Na+ concentration in a smooth curve and was half‐maximal at about 7 mM. 3. The effects, on ATP‐ADP exchange, of changing the concentrations of ATP, ADP and Mg have also been investigated. With both native and NEM‐treated enzyme, the interactions of ATP, ADP and Mg are complicated; they show that, for the reaction leading to ATP formation, either free ADP rather than MgADP is the substrate, or Mg2+ ions are inhibitory (or both). 4. Since NEM, in the conditions in which we have used it, is believed to act by inhibiting the conversion of an ADP‐sensitive form of the phosphoenzyme (E1P) to an ADP‐insensitive form (E2P), the absence of Na+ inhibition of ATP‐ADP exchange in NEM‐treated enzyme, together with the parallel effects of Na+ ions on the ATP‐ADP exchange activity and on the Na+‐ATPase activity of native enzyme, suggests that the inhibitory effect of external Na+ occurs after the conversion of E1P into E2P. 5. To test whether this inhibitory effect of Na+ reflected inhibition of the hydrolysis of E2P, we measured the rate of loss of incorporated 32P when enzyme, newly phosphorylated by [gamma32P]ATP, was squirted into a large volume of ice‐cold solution containing 1,2‐cyclohexylenedinitrilotetraacetic aicd (CDTA), unlabelled ATP and 0, 5 or 150 mM‐Na+. The rate of loss of radioactivity from the membranes was least at 5 mM‐Na+, about twice as great at 150 mM‐Na+, and about 5 times as great at 20 microM (final) Na+. 6. An unexpected feature of the results was that the pattern of stimulation of ATP‐ADP exchange in intact cells. If Na+ ions are absent externally, a different could be fitted better on the assumption that activation by internal Na+ occurs at two sites with equal affinities, than on the assumptions that activation occurs at a single site or at three sites with equal affinities.
Sugar transfer from the lumen of the rat small intestine to the vascular bed.
Authors: Bronk J R , Ingham P A
Published: December 2014

1. A modification of the vascular perfusion technique was used to investigate sugar transfer from the lumen of the rat small intestine to the vascular perfusion technique was used to investigate sugar transfer from the lumen of the rat small intestine to the vascular bed. 2. With this method the transfer of both D‐[3H]galactose and L‐[14C]glucose were followed in the same experiments. The results indicate that when equimolar concentrations of the two sugars are perfused through the lumen there is a preferential transfer of galactose from the mucosal epithelium to the vascular bed as well as from lumen to the epithelial layer. 3. At high rates of galactose transfer from the lumen to the vascular bed, accumulation of the sugar within the mucosal epithelium is minimal unless the vascular flow is stopped. 4. Phlorizin inhibits galactose transfer from the lumen to the vascular bed, but the inhibition of sugar transfer appears to be restricted to the luminal face of the epithelial cells since the selectivity of the basolateral exit process is unaffected. 5. Replacement of Na+ by K+ in the luminal perfusate reduces the rate of galactose transfer by a factor of 40, but does not completely abolish the preferential transfer of galactose. The presence of luminal Na+ also stimulates the exit of galactose from the mucosal epithelium to the vascular bed. 6. The presence of D‐glucose in the vascular perfusate produces a two‐ to threefold increase in the rate of sugar transfer from the lumen to the vascular bed. This effect is not observed with vascular galactose or luminal glucose.
Contraction time and voluntary discharge properties of individual short toe extensor motor units in man.
Authors: Grimby L , Hannerz J , Hedman B
Published: December 2014

1. The contraction time and the voluntary discharge properties of forty‐five short toe extensor motor units were studied in man. 2. The contraction time of the individual motor unit was studied by using selective electrical nerve stimulation or by averaging the increase in force related to its electromyographic potential in tonic voluntary contraction. 3. Both methods showed a range of contraction times from 40 to 90 ms. 4. The discharge properties of the individual motor unit were studied with e.m.g. techniques, permitting the identification of its potentials during maximum voluntary effort. 5. A motor unit which could be driven continously and had a minimum rate of about 10/s and a maximum rate of about 30/s had a contraction time between 60 and 90 ms. 6. A motor unit which could not be driven continously and had a minimum rate of about 20/s and a maximum rate above 40/s had a contraction time between 40 and 55 ms. 7. A motor unit with intermediate voluntary discharge properties had an intermediate contraction time. 8. It is concluded that each motor unit fires at its fusion frequency in voluntary contraction and that the voluntary discharge frequency range of a motor unit can be used as an indication of its contraction time.
Initiation and spread of action potentials in granule cells maintained in vitro in slices of guinea‐pig hippocampus.
Authors: Jefferys J G
Published: December 2014

1. Laminar field potentials due to the synchronous activation of granule cells were studied in slices of guinea‐pig hippocampus maintained in vitro. 2. Extracellular recordings confirmed that stimulation of afferent laminae in the molecular layer caused excitatory synaptic current to enter the granule cell dendrites. If large enough this current initiated action potentials at, or near to, the somata 100‐‐200 micrometers away. 3. After a population spike had been initiated via excitatory synapses or via antidromic invasion, the lcoation of inward membrane current (sink) appeared to move from the cell body layer into the dendrites at a velocity of 0.08‐0.12 m/sec, for a distance of up to 250 micrometers. 4. The sink movement into the dendrites was blocked by tetrodotoxin and not by agents that blocked synaptic activation. Together with other observations these results led to the conclusion that granule cell dendrites were invaded by action potentials from the cell body region. There was no evidence of dendritic action potentials from the cell body region. There was no evidence of dendritic action potentials preceding the cell body spike initiated by synaptic inputs. Possible functions of this dendritic invasion are discussed.
Non‐parallel enzyme secretion from rat pancreas in vitro studies.
Authors: Dagorn J C , Estival A
Published: December 2014

1. The relative variations of rat pancreatic amylase versus lipase and chymotrypsinogen secretions have been studied in vitro with the help of two different techniques: in situ organ perfusion and incubation of pancreatic lobules. 2. In experiments on the perfused pancreas, with 8 C u.kg‐1 hr‐1 secretin added to the perfusion fluid, cholecystokinin‐pancreozymin (8 ID u.kg‐1) or pilocarpine (15 mg kg‐1) both resulted in a significant change in the enzyme proportions in the juice. 3. In experiments on pancreatic lobules, the addition to the incubation medium of secretin (10(‐7) M), alone or associated with cholecystokinin‐pancreozymin (8 x 10(‐7) M) or pilocarpine (10(‐4) M) did not induce any change in the enzyme proportions in secretion. 4. It was concluded that the non‐parallelism between enzyme secretions can occur in the rat upon pancreozyminic or cholinergic stimulation in vitro as well as in vivo (Dagorn, 1978) provided basal protein output is low enough. This is not the case when the tissular integrity of the pancreas is lost, such as in experiments on lobules. 5. This work confirms that pancreatic secretion derives from two intrapancreatic pools of different enzymatic composition, and gives a possible explanation for some discrepancies from the literature on the existence of non‐parallel secretion.
Dorsal root potentials and changes in extracellular potassium in the spinal cord of the frog.
Authors: Nicoll R A
Published: December 2014

1. In the present study changes in extracellular potassium, ([K]e), were recorded in the isolated spinal cord of the frog with glial cell recordings and K‐selective micro‐electrodes to test the hypothesis that elevations in [K]e during neuronal activity produce the dorsal root potential (d.r.p.). 2. Sucrose gap recording from the dorsal root (d.r.) was used to record responses to root stimulation and to exogenously applied K+. 3. Stimulation of the ventral root, which elicits a d.r.p. in the frog spinal cord, was not associated with any change in [K]e, suggesting that d.r.p.s produced by ventral root stimulation are not due to changes in [K]e. 4. The largest change in [K]e observed following single stimuli to the dorsal root was 0.4 mM. Such a change in [K]e, if evenly distributed, would depolarize the dorsal root by about 1 mV and yet the simultaneously recorded d.r.p. evoked by stimulating an adjacent dorsal root (d.r.‐d.r.p.) was over 10 mV. 5. The time‐to‐peak of the glidal cell responses was 10 times that of the d.r.‐d.r.p. Low frequency (1‐10 Hz) d.r. stimulation caused a decremental summation of glial cell responses, while there was no summation in the d.r.‐d.r.p. These results suggest that the d.r.p. produced by single d.r. stimulation is generated in large part by a mechanism other than a change in [K]e. 6. During high frequency d.r. stimulation, which evoked 6‐8 mM increases in [K]e, the adjacent d.r. was depolarized to a greater extent than that produced by single stimuli. The magnitude of this depolarization was similar to that produced by applying a [K]e equivalent to that observed in the spinal cord during high frequency stimulation. Thus, a substantial component of the sustained d.r. depolarization during high frequency d.r. stimulation may result from changes in [K]e. 7. In the presence of magnesium, high frequency d.r. stimulation evoked a picrotoxin resistant depolarization of an adjacent d.r. whose magnitude correlated well with the changes in [K]e recorded in the spinal cord. 8. In the presence of picrotoxin a slow, long duration depolarization of the d.r. occurred following single stimuli to the adjacent d.r. and the appearance and time course of this response correlated well with the time course of changes in [K]e. 9. Addition of K+ to the Ringer solution in concentrations up to 12 mM had a facilitatory action on reflex activity in the frog spinal cord. 10 The present results suggest that although changes in [K]e play a relatively minor role in generating d.r.p.s. elicited by single d.r. stimulation, the sustained dorsal root depolarization evoked either by high frequency stimulation or by single stimuli in the presence of picrotoxin may be due to a considerable extent to [K]e.
Descending influences on the responses of spinocervical tract neurones to chemical stimulation of fine muscle afferents
Authors: Hong S. K. , Kniffki K.-D. , Mense S. , Schmidt R. F. , Wendisch Marion
Published: December 2014

1. In cats, extracellular micro‐electrode recordings were made from axons of the spinocervical tract (s.c.t.) in both the decerebrate state and during cold block of the spinal cord (reversible spinal state) to examine the effects of intra‐arterial injection of algesic agents (bradykinin, potassium, 5‐hydroxytryptamine) into the gastrocnemius‐soleus (g.s.) muscle on the discharge behaviour of s.c.t. neurones.

2. In the decerebrate state without cooling the spinal cord 13% of the cells (eleven out of eighty‐three) responded to intra‐arterial injection of bradykinin, 33% (twenty‐two out of sixty‐nine) to 5‐hydroxytryptamine, and 38% (thirty‐five out of ninety‐one) to potassium injection.

3. The general time course and the latency of the responses of s.c.t. cells induced by injection of pain‐producing substances into the g.s. muscle reflect in many respects the activations of g.s. group III and group IV primary afferent units studied previously.

4. For twenty‐seven s.c.t. neurones the period of recording was long enough to record the responses of the same cell to injections of algesic agents in both the decerebrate and the reversible spinal state. In the reversible spinal state 83% (nineteen out of twenty‐three) of the s.c.t. neurones tested with all the three substances responded to at least one of the algesic agents. In the decerebrate state the percentage was lower (39%).

5. Reversible spinalization led not only to a significant increase in the number of s.c.t. neurones responding to the algesic agents used but also to an increase in the magnitude of the chemically induced responses.

6. The mean latency of the responses of neurones that were activated in both preparations were shorter in the reversible spinal state than in the decerebrate state.

7. Control experiments showed that the responses to bradykinin and potassium were entirely due to the nervous outflow from the g.s. muscle. In contrast, intra‐arterially applied 5‐hydroxytryptamine influenced the s.c.t. cells via unknown additional sites of action.

8. The results indicate that muscular group III and/or group IV units excitable by algesic substances do project on to neurones of the spinocervical tract. Furthermore it is concluded that the responses of s.c.t. neurones to activation of fine muscle afferents by algesic agents are subject to a descending control similar to the well known descending modulation of their responsiveness to cutaneous input. Therefore, in addition to serving as a cutaneous pathway the spinocervical tract may take part in muscular nociception.
Relation between catecholamine‐induced cyclic AMP changes and hyperpolarization in isolated rat sympathetic ganglia
Authors: Kirby P. J. , Brown D. A. , Caulfield M. P.
Published: December 2014

1. The effect of catecholamines on cyclic adenosine 3′5′‐monophosphate (cyclic AMP) production in isolated rat superior cervical ganglia has been measured under experimental conditions in which they also produce ganglion hyperpolarization.

2. (±)Isoprenaline (1 μ
M) increased cyclic AMP levels by 8‐100 times after 15 min incubation at 25 °C. Half‐maximal stimulation occurred at about 0.03 μ
M. This was due to stimulation of β‐receptors, since it was prevented by 1 μ
M‐propranolol but not by 1 μ
M‐phentolamine.

3. The α‐agonists phenylephrine (100 μ
M), dopamine (100 μ
M) and clonidine (1 μ
M) did not produce a detectable increase in ganglionic cyclic AMP. Dopamine (100 μ
M) was also ineffective at 37 °C in the presence of 10 m
M‐theophylline.

4. Exogenous cyclic AMP (0.01‐1 m
M) hyperpolarized the ganglion. This effect was replicated by other adenosine compounds, most effectively by adenosine and by adenosine 5′‐monophosphate, and was antagonized by theophylline. Dibutyryl cyclic AMP was weaker than cyclic AMP.

5. Neither theophylline nor the non‐xanthine phosphodiesterase inhibitor, Ro 20‐1724, enhanced the hyperpolarizing actions of noradrenaline or dopamine.

6. Since catecholamine‐induced hyperpolarization of the isolated rat ganglion is induced via α‐receptors, whereas cyclic AMP‐production is induced via β‐receptors, it is concluded that cyclic AMP is unlikely to mediate the hyperpolarization. The effect of exogenous cyclic AMP may be due to an action on external adenosine‐receptors.
Calcium‐dependent potentials in the mammalian sympathetic neurone.
Authors: McAfee D A , Yarowsky P J
Published: December 2014

1. Intracellular recordings from post‐ganglionic neurones of the rat superior cervical ganglion revealed two non‐synaptic potentials dependent upon Ca2+, a hyperpolarizing afterpotential (h.a.p.) and a tetrodotoxin (TTX)‐insensitive spike. 2. The h.a.p. followed regeneration discharge of the membrane potential in normal and TTX‐containing Locke solution. 3. The h.a.p. appeared to arise from an increased K+ conductance because it was associated with a decrease in input resistance, reversed at ‐90 mV, and was proportional in magnitude to the extracellular K+ concentration. 4. Tetraethylammonium (TEA) and 4‐aminopyridine (4‐AP) apparently antagonized a voltage‐sensitive K+ conductance because they broadened the action potential. However, these substances reduced only slightly the peak amplitude and earliest phases of the h.a.p. 5. The TTX‐insensitive spike was most apparent when TEA was present and was invariably followed by an h.a.p. with a magnitude proportional to that of the spike. 6. The magnitude of the h.a.p. and the TTX‐insensitive spike was directly proportional to the external Ca2+ concentration and was antagonized by Co2+ and Mn2+ in a dose‐dependent fashion. 7. In normal Locke solution, Ba2+ antagonized the h.a.p. and allowed the neurone to sustain discharge during prolonged depolarization. In Locke solution containing TTX and TEA, Ba2+ reduced the magnitude of the h.a.p. but greatly increased the duration of the TTX‐insensitive spike. 8. The h.a.p. was not significantly affected by altering external Cl‐ concentration and the TTX‐insensitive spike was not reduced by altering external Na+ concentration. 9. It is concluded that the post‐ganglionic neurone supports a regenerative Ca2+ conductance mechanism which in turn triggers an increased K+ conductance. The h.a.p. appears to result from outward K+ current in both a Ca2+ and voltage‐dependent fashion.
Discharge patterns of Purkinje cells in cats anaesthetized with alpha‐chloralose.
Authors: Armstrong D M , Cogdell B , Harvey R J
Published: December 2014

1. Micro‐electrodes have been used to record from 119 Purkinje (P) cells in the paramedian lobule of the cerebellum in cats anaesthetized with alpha‐chloralose. 2. The spontaneous discharge rate and degree of irregularity of the discharge varied very much from one cell to another; the over‐all mean rate (about 25/sec) was a little lower than has been reported either for barbiturate anaesthetized or for decerebrate unanaesthetized preparations. 3. Following electrical stimulation of a peripheral nerve, most P cells responded with both simple spikes and a climbing fibre response. This initial response was usually succeeded by a prolonged period of silence (over‐all mean duration 350 msec) before resumption of the tonic simple spike discharge. Similar response‐silence sequences could also be evoked by mechanical stimulation such as a tap applied to the pads of the forepaw. 4. Electrical stimulation of the inferior olive evoked climbing fibre responses followed by a prolonged pause in the simple spike discharge of the cell. 5. In six individual preparations, recordings were made both from P cells of the paramedian lobule and from neurones of nucleus interpositus (to which the former project). Comparison of the responses of the two types of neurone to peripheral nerve and inferior olivary stimulation showed that the end of the pauses in P cell firing correlated well with the end of a prolonged period of facilitation of the interpositus neurones. 6. These results support the hypothesis advanced in an earlier report (Armstrong, Cogdell & Harvey, 1975) that the prolonged facilitatory responses of interpositus neurones are essentially disinhibitory responses resulting from reduction in the activity of overlying cells, and that responses of P cells and of interpositus neurones consist, in general, of modulations of activity which are mutually out of phase.
Sodium and calcium gating currents in an Aplysia neurone.
Authors: Adams D J , Gage P W
Published: December 2014

1. Currents generated by depolarizing the hyperpolarizing voltage pulses were recorded at temperatures of 4‐‐12 degrees C in the voltage‐clamped soma of R15 in aplysia abdominal ganglia exposed to solutions which suppressed ionic currents. 2. Subtraction of linear capacitive and leakage currents from current generated by voltage pulses to levels more positive than ‐20mV revealed non‐linear transient outward displacement currents at the onset of the clamp step (on‐current) and transient inward displacement currents after the membrane potential returned to the holding potential (off‐current). Only on‐currents were studied. 3. Pulses to membrane potentials of ‐20 to 0 mV generated a displacement current with rapid onset and exponential decay. At membrane potentials more positive than o mV a second displacement current with a much slower onset and slower exponential decay was seen. Because the different threshold potentials for the two displacement currents were close to the different threshold potentials for Na and Ca ion currents, the two displacement currents were called Na and Ca ‘gating’ currents. 4. The amount of charge transfer during Ca gating currents increased sigmoidally with increasing depolarization, reaching a maximum at +30 to +40 mV. Half‐maximum charge transfer occurred at +15 mV. 5. Total charge movement during Ca gating currents was maximal with holding potentials of ‐30 to ‐40 mV. More positive or more negative holding potentials produced a decrease in charge movement. 6. The time course of the gating currents, but not the total charge displaced, was very sensitive to temperature. The time constant of decay of Ca gating currents had a Q10 of about 3, whereas the total amount of charge displaced had a Q10 of 1.2. 7. The charge transfer during both Na and Ca gating currents and the amplitude of Na and Ca (but not K) ionic currents were reduced in solutions containing 1 mm‐n‐octanol.
On the kinetics and maximal capacity of the system for rapid axonal transport in mammalian neurones.
Authors: Brimijoin S
Published: December 2014

1. Rabbit peroneal nerves were incubated in vitro in two‐compartment chambers. Step‐gradients of temperature were established so that the proximal part of each nerve was slightly warmer than the distal part. After incubation, the distribution of dopamine‐beta‐hydroxylase (DBH) activity along the nerves was examined as an indication of the behaviour of rapid transport in adrenergic axons. 2. With temperature gradients of 5 and 8 degrees C, transport velocity in the proximal regions was expected from previous work to be, respectively, 1.5 and 2 times faster than in the distal regions. Exposing nerves to these gradients induced a significant increment in the concentration of DBH activity, beginning at the boundary between regions. This increment was up to 50% of the normal activity and it propagated distally at the velocity expected for transport at the local temperature. 3. A temperature gradient of 13 degrees C was expected to produce a threefold difference in transport velocity between proximal and distal regions. This gradient produced a slightly larger increment of DBH activity propagating distally, again at the expected velocity. However there was also a disproportionate accumulation of enzyme activity at the boundary between regions. Further increases in the temperature gradient did not enhance the size of the propagating increment but only the rate at which enzyme accumulated at the temperature boundary. 4. It was concluded that adrenergic nerves can transport between two and three times as much material per unit time as they normally do. The ability to increase the flux of material appeared to depend on increases in the concentration of material in motion. There was no indication that such increases led to significant changes in the velocity of transport.
The actions of tubocurarine at the frog neuromuscular junction.
Authors: Colquhoun D , Dreyer F , Sheridan R E
Published: December 2014

1. The action of tubocurarine on voltage‐clamped frog muscle end‐plates has been re‐examined by means (a) equilibrium dose‐ratio measurements, (b) current fluctuation measurements and (c) voltage‐jump relaxation measurements. 2. The equilibrium measurements can be interpreted as implying that tubocurarine has (a) a competitive blocking action, with a dissociation constant of 0.34 microM, which is not dependent on membrane potential, and (b) an additional voltage‐dependent blocking action. 3. In the presence of tubocurarine two kinetic components can be seen. The faster one is similar to, but rather faster than, the normal ion channel closing rate. The other is much slower (1‐‐3 sec), and, in relaxation experiments it is in the opposite direction to the fast relaxation. 4. A number of alternative explanations for the results are discussed. The mechanism that fits them best appears to be a combination of competitive block (or block of shut channels), with a strongly voltage‐dependent block of open ion channels by tubocurarine. Estimates of the rate constants for channel blocking (and their voltage dependence) are derived. From these estimates the dissociation constant for the binding of tubocurarine to open channels appears to be roughly 0.12 microM at ‐‐70 mV and 0.02 microM at ‐‐12 mV. 5. Several potential sources of error in the experiments, and in their interpretation, are discussed. The most serious of these are problems associated with diffusion in the small volume of the synaptic cleft, viz. (a) changes in cleft concentration consequent on changes in binding, and (b) ionophoretic flux of antagonist and agonist into the synaptic cleft.
Glycine, GABA and synaptic inhibition of reticulospinal neurones of lamprey.
Authors: Matthews G , Wickelgren W O
Published: December 2014

1. Intracellular recordings were made from the cell bodies and axons of giant reticulospinal neurones (Müller cells) of the lamprey and the effects of a variety of putative neurotransmitters tested. Bath‐applied acetylcholine, carbamylcholine, norepinephrine, dopamine, histamine and serotonin were without effect. Glycine and gamma‐aminobutyric acid (GABA) hyperpolarized and reduced the input resistance of cell bodies but had no effect on the membrane conductance of axons. 2. The threshold dose of bath‐applied GABA or glycine for a conductance change in somata was about 0.5 mM and the maximum effect was reached at about 10 mM. The maximum conductance change produced by glycine was always greater than that produced by GABA. 3. Replacement of the sodium in the bathing saline with lithium or choline prolonged the conductance change produced by ionophoretically applied glycine or GABA, suggesting the presence of sodium‐dependent uptake systems for glycine and GABA. 4. The reversal potentials for responses to ionophoretically applied glycine and GABA average about ‐‐83 mV, the same as that for the inhibitory post‐synaptic potential (i.p.s.p.) produced in Müller cells by stimulation of the ipsilateral vestibular nerve. 5. The i.p.s.p. and drug responses appeared to involve an increase in chloride conductance, since their reversal potentials were shifted appropriately by changes in either internal or external chloride. 6. Changes in extracellular potassium concentration also changed i.p.s.p. and drug reversal potentials. However, these effects could be attributed to secondary changes in internal chloride. 7. The receptors for GABA and glycine appeared to be different because of the absence of cross‐desensitization and because, at doses below 20 microM, picrotoxin and bicuculline selectively blocked GABA responses while strychnine selectively blocked glycine responses. 8. At concentrations of 20 microM, strychnine eliminated the i.p.s.p. while picrotoxin and bicuculline had no effect. Further, the i.p.s.p. and glycine response of Müller cells located in the isthmic region of the midbrain had the same threshold sensitivity to strychnine. However, the glycine response of other Müller cells was more sensitive to strychnine than was the i.p.s.p. 9. We conclude that glycine is a better candidate for the inhibitory transmitter onto Müller cells than is GABA.
Glutamate and synaptic excitation of reticulospinal neurones of lamprey.
Authors: Matthews G , Wickelgren W O
Published: December 2014

1. Intracellular recordings were made from the cell bodies and axons of giant reticulospinal neurones (Müller cells) of the lamprey, and responses to bath‐ and ionophoretically applied glutamate and aspartate were studied. 2. Bath‐applied glutamate and aspartate depolarized both cell bodies and axons, but there appeared to be an associated conductance increase only in the cell bodies. The depolarization of Müller axons by the bath‐applied drugs probably resulted from the passive flow of current into them from spinal cells to which the axons are coupled electrically. 3. The reversal potentials for responses to ionophoretically applied glutamate and for excitatory post‐synaptic potentials (e.p.s.p.s) evoked by stimulation of the contralateral vestibular nerve were directly determined in Müller cell bodies which had been damaged by penetration with low‐resistance electrodes. The glutamate and e.p.s.p. reversal potentials were identical, the average difference in eight cells being 0.31 mV. The absolute value of the e.p.s.p.‐‐glutamate reversal potential varied from ‐‐16 to ‐‐35 mV in different cells, with the more negative values occurring in less damaged cells with higher resting potentials. 4. Injection of Cl into Müller cell bodies had no effect on the e.p.s.p.‐‐glutamate reversal potential. Reduction of the extracellular Na concentration to 1 over 10 normal produced a negative shift in the glutamate reversal potential. 5. It is proposed that the natural excitatory transmitter and glutamate produce identical conductance changes in Müller cells, involving an increase in Na and K conductance.
Selective response of rat peripheral sympathetic nervous system to various stimuli
Authors: Ulus I. H. , Wurtman R. J.
Published: December 2014

1. We utilized the induction of tyrosine hydroxylase, a catecholamine‐synthesizing enzyme, in sympathetic ganglia and adrenal medullae to explore the central and peripheral mechanisms through which choline, various environmental stresses, and drugs that alter blood pressure or central neurotransmission affect various portions of the sympathetic nervous system. Animals received each treatment chronically, and enzyme activity was measured in the superior cervical, stellate, and coeliac ganglia and in the adrenal medullae.

2. Choline administration increased tyrosine hydroxylase activity in all four tissues, probably by increasing the release of acetylcholine from preganglionic sympathetic neurones that synapse on catecholamine‐producing ganglion and chromaffin cells; carbachol and nicotine had similar effects.

3. Insulin enhanced tyrosine hydroxylase activity primarily in the coeliac ganglion and the adrenal medullae, but not in the superior cervical ganglia.

4. Reserpine and phenoxybenzamine increased the activity of the enzyme in all four tissues.

5. Prolonged exposure to a cold environment increased enzyme activity in all four tissues, but especially in the stellate and coeliac ganglia; forced swimming affected tyrosine hydroxylase only in these two ganglia.

6. Several drugs known to modify central neurotransmission were found to increase tyrosine hydroxylase activity in some portions of the sympathetic nervous system but not in others. 5,7‐Dihydroxytryptamine, which destroys terminals of serotoninergic neurones, enhanced enzyme activity in all four tissues, but primarily in the coeliac ganglion and adrenal medullae. ET‐495 (a dopaminergic agonist),
D‐amphetamine, and morphine induced tyrosine hydroxylase activity in the adrenal medullae and the coeliac ganglion, but not in the superior cervical ganglia. Oxotremorine, a centrally acting muscarinic agonist, increased tyrosine hydroxylase activity only in the adrenal medullae; its effect was not blocked by methylatropine, a peripheral muscarinic blocker.

7. These data indicate that specific neurones in the central nervous system, which utilize specific neurotransmitters and which are differentially affected by drugs and environmental inputs, selectively influence the outflows through the various zones of the sympathetic nervous system.
The reversible replacement of internal potassium by caesium in isolated turtle heart.
Authors: Guerin M , Wallon G
Published: December 2014

1. By perfusing the isolated turtle heart with Cs solution, most of the intracellular K can be replaced by Cs. After 3‐‐4 hr, Cs approaches a steady‐state distribution with a concentration slightly below initial K concentration. 2. During the initial stages of perfusion, the heart accumulated Cs and lost K, the exchange ratio of K for Cs was estimated to be about 0.6. Subsequently perfusion yielded an equi‐ionic substitution of K by Cs. 3. In presence of DNP (2 x 10(‐4) M), K efflux and Cs accumulation increased but the low initial K‐‐Cs exchange was abolished. Then, the replacement of K by Cs took place at a ratio of K:Cs of about 0.8. Ouabain (10(‐5) M) suppressed uptake of Cs whereas K loss was the same as with DNP. 4. These results confirm that permeability of the cardiac sarcolemma to Cs is low, and suggest that the movement of Cs must be mainly attributed to its active transport into cells by the ionic exchange which normally transports K+ and is coupled to the extrusion of Na. The initial low net K efflux could be explained by an accumulation process which facilitates retention of K by the heart. A mechanism of this kind would be described as active reabsorption of some K present in extracellular space and would consequently reduce the uptake of Cs. 5. After loading the heart with Cs, perfusion with K solution showed the exchange of Cs for K at a ratio of Cs:K of about 0.5. K reaccumulation is reduced by ouabain (10(‐5) M) and comes back to a normal steady‐state distribution after 5 hr. At this time, K concentration was slightly below normal K value, but only half Cs content was eliminated. After 15 hr of perfusion, intracellular K remained constant whereas 15% of the original Cs remained.
Inhibitory effects of cholinergic agents on the release of transmitter at the frog neuromuscular junction.
Authors: Duncan C J , Publicover S J
Published: December 2014

1. The cholinesterase inhibitors neostigmine, edrophonium and eserine (7 x 10(‐7) M) reduced m.e.p.p. frequency by some 50% at the frog neuromuscular junction. Neostigmine also produced a small reduction in quantal content. 2. Tetraisopropylpyrophosphoramide, with a high specificity for non‐specific cholinesterase, has a similar effect on m.e.p.p. frequency but ambenonium, with a high specificity for acetylcholinesterase, was markedly less effective in this respect. 3. Carbachol (10(‐5) M) and the muscarinic agonists muscarine and metacholine (7 x 10(‐7) M) also reduced the rate of spontaneous release. 4. The action of neostigmine was antagonized by atropine, but not by D‐tubocurarine. Muscarine did not have any further effect when m.e.p.p. frequency was reduced with neostigmine. 5. Experiments with reduced extracellular Ca2+ concentration suggest that the cholinergic agents reduce Ca2+ permeability directly at the presynaptic terminals and that they do not act via a change in PNa or PK. It is suggested that the consequent reduction in Ca2+ entry causes a fall in both evoked release and in intracellular Ca2+ concentration, thereby reducing m.e.p.p. frequency. 6. It is concluded that non‐specific cholinesterases present on the presynaptic terminals can act as inhibitory muscarinic cholinergic receptors. This form of presynaptic inhibition at the amphibian neuromuscular junction contrasts with that described in the mammalian preparation in which the sites are blocked by D‐tubocurarine and are excitatory.
Potent stimulation of the avian exocrine pancreas by porcine and chicken vasoactive intestinal peptide.
Authors: Dimaline R , Dockray G J
Published: December 2014

1. The actions of chicken and porcine secretins and vasoactive intestinal peptides (VIPs) were compared on the rate of flow and rate of protein secretion from the exocrine pancreas in urethane anaesthetized turkeys and rats. 2. Chicken VIP was about twice as potent as porcine VIP and 100‐150 times as potent as chicken and porcine secretins in stimulating the flow of pancreatic juice in the turkey. 3. Porcine secretin was a strong stimulant of the flow of pancreatic juice in the rat, but chicken secretin and the two VIPs were only active in doses 20‐50 times higher than those of porcine secretin. 4. Neither the two VIPs nor the two secretins significantly stimulated the rate of pancreatic protein secretion in the turkey or rat. 5. In the turkey I.V. infusion of graded doses of chicken VIP produced graded increases in the flow of pancreatic juice; in the presence of an infusion of a low dose of CCK8 the flow of juice secreted in response to the highest dose of chicken VIP was significantly lower compared with the infusion of VIP alone, and responses to the other doses of VIP were lower but not significantly so. The infusion of chicken secretin reduced the flow of juice in response to infusions of chicken VIP, but the differences were not significant. There was no significant difference in either the rate of flow, or rate of protein secretion from the turkey pancreas in response to an infusion of chicken secretin and CCK8, compared with CCK8 alone. 6. The results cast doubt on the importance of secretin for regulation of the avian pancreas, and suggest instead that VIP might have a physiological role in regulating the flow of pancreatic juice in birds.
Potassium depletion and sodium block of potassium currents under hyperpolarization in frog sartorius muscle.
Authors: Standen N B , Stanfield P R
Published: December 2014

1. A three‐electrode voltage clamp method was used to investigate the mechanism of the fall in resting potassium permeability which occurs under extreme hyperpolarization in frog sartorius muscle fibres. 2. Experiments were performed which show that this permeability change is due to a potential dependent block by Na+ ions present in the external solution. 3. Inward K‐currents recorded on hyperpolarization turned off exponentially with time. In the presence of Na the steady‐state current‐voltage relation had a region of negative slope beyond ‐140 mV. This negative‐slope region was removed when Na was replaced by TMA, Tris or Li. Increasing [Na] to 140 mM shifted the negative‐slope region to less negative membrane potentials; reducing [Na] to 14 mM shifted the region to more negative potentials. 4. The time constant for the turn‐off of the currents (tau) was the same in Na and TMA‐containing solutions at membrane potentials positive to ‐140 mV. At more negative membrane potentials the tau s in Na became progressively shorter than those in TMA. Increasing [Na] to 140 mM (from 70 mM) gave smaller tau s at all potentials. 5. If fibres were hyperpolarized to ‐240 mV and then repolarized to ‐160 mV in 70 mM‐Na the current recorded during the second pulse turned on with time, often reaching a value greater than that at the end of the first pulse. This behaviour was removed when Na was replaced by TMA or Tris. 6. An estimate of the steady‐state relationship between the degree of block and membrane potential was obtained, and could be fitted by an expression for a potential‐dependent ionic block with a very low affinity binding site for Na+ in the membrane. 7. The recovery after hyperpolarization of K‐currents at the holding potential was examined in two‐pulse experiments. In 70 mM‐TMA recovery occurred at the same rate whether the initial hyperpolarization was to ‐120 or to ‐210 mV. In 70 mM‐Na recovery after an initial pulse to ‐120 mV occurred at the same rate as in TMA, but recovery after a pulse to ‐210 mV occurred about 9 times faster. These results are consistent with depletion of K from the lumen of the T‐system dominating the turn‐off of K currents in TMA and in Na for the hyperpolarization to ‐120 mV, but a different mechanism being involved for the ‐120 mV pulse in Na. 8. A three‐compartment model is presented which attempts to describe the depletion of K from the T‐system. The model accurately predicts the time‐course for the decline of inward K‐currents, both in 10 and 80 mM‐K solutions.
The properties of bovine lens membranes measured by a conventional double‐chamber method
Authors: Delamere N. A. , Duncan G.
Published: December 2014

1. When the bovine lens was mounted in a divided chamber, an asymmetry potential of 4·3 mV (anterior face positive) was measured across the lens and values of 0·48 and 0·60 were obtained for PNa/PK of the anterior and posterior faces respectively.

2. The half‐times for the depolarization of the anterior and posterior face potentials on increasing the external K concentration were 20 and 14 min respectively compared to less than 2 min for the corresponding change determined previously from the totally immersed lens.

3. The electrical resistance of the anterior surface was significantly smaller than that of the posterior and both resistances were much smaller than the value previously obtained from the bovine lens immersed in solution.

4. The K permeability of the anterior surface, measured by 42K efflux experiments, was greater than the value for the posterior surface and both were again very much higher than the value obtained for the totally immersed lens.

5. The discrepancies between the present double‐chamber preparation and the data obtained previously can be explained if it is assumed that the capsule provides a short‐circuit pathway between the chamber port and the lens membranes. As the capsule is thicker at the anterior face, the short circuit there would be greater and this may explain many previously observed ‘asymmetry’ properties for the lens.
Ionic basis for electrical properties of tonic fibres in rat extraocular muscles
Authors: Bondi Ardith Y. , Chiarandini D. J.
Published: December 2014

1. The ionic conductances underlying some of the electrophysiological properties of multiply innervated or tonic fibres of rat extraocular muscles were examined in vitro with double‐barrelled micro‐electrodes.

2. Exposure of the muscle to a Cl‐free saline did not change the effective resistance (Reff) of tonic fibres which was 5·14 ± 0·45 MΩ (n = 7) in control saline and 4·78 ± 0·45 MΩ (n = 12) in Cl‐free saline (P > 0·1). In contrast, in singly innervated or twitch fibres Cl removal increased Reff from 1·77 ± 0·21 MΩ (n = 19) to 2·69 ± 0·12 MΩ (n = 22) (P < 0·001).

3. Tonic fibres with membrane potentials restored to ‐ 80 mV by injecting current responded to intracellular depolarizing pulses with a brief, slow response (slow peak potential) which added to the rising phase of the electrotonic potential. The slow peak potential began at a membrane potential of ‐ 40 to ‐ 35 mV and was graded. Increasing depolarizations evoked faster and larger responses which did not over‐shoot the zero level of membrane potential.

4. The slow peak potential was not blocked by 10 μ
M‐D‐600 hydrochloride but was markedly reduced by the absence of Na and by 10 μ
M‐tetrodotoxin. The response was broadened about five times by 25 m
M‐tetraethylammonium.

5. Raising bath temperature from 21‐25 °C to 37 °C reversibly depressed and shortened the slow peak potential but did not transform it into an action potential.

6. It is concluded that the characteristic high Reff of tonic fibres results from a lack of a membrane conductance to Cl and that the slow peak potential involves the transient activation of Na and K channels which are pharmacologically similar to the respective channels of twitch fibres.
Rabbit diaphragm: two types of fibres determined by calcium strontium activation and protein content.
Authors: Hoar P E , Kerrick W G
Published: December 2014

1. Submaximum Ca2+‐ and Sr2+‐activated tensions were measured in functionally skinned fibres from the rabbit diaphragm. 2. The fibres could be classified into two types on the basis of activation by divalent cations. Type S fibres required a slightly higher [Ca2+] than [Sr2+] for half‐maximal activation of tension. Type F fibres required 2 times higher [Ca2+] than type S and 8.5 times higher [Sr2+]. 3. Sodium dodecyl sulphate disc gels of type F fibres showed protein band patterns similar to those of fast‐twitch muscle; those of type S fibres were identical to those of slow‐twitch fibres. 4. Sodium dodecyl sulphate disk gels of mixed, non‐classified diaphragm fibres and an actual count of randomly selected fibres classified by Ca2+/Sr2+ tension characteristics showed the diaphragm to be composed of 60% fast‐twitch fibres and 40% slow‐twitch fibres. 5. The protein stoichiometries of the two fibre types are consonant with the accepted stoichiometries for skeletal muscle. 6. The percentages of type F and type S fibres in the diaphragm suggest that high adenosine‐triphosphatase activity shown by histochemical techniques (Davies & Gunn, 1972) is associated with the type F fibres, and low activity with the type S fibres.