bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of the acetylcholine‐operated channel at twitch and slow fibre neuromuscular junctions of the garter snake.
Authors: Dionne V E , Parsons R L
Published: December 2014

1. Synaptic responses to acetylcholine were recorded from garter snake (sp. Thamnophis) neuromuscular junctions with the voltage clamp. 2. In the following respects the responses were identical in twitch and slow fibres: exponential miniature end‐plate current decay, reversal potential (approximately ‐5 mV), permeant ionic species (Na+, K+, Ca2+, but not Cl‐), two component miniature end‐plate current decay in the presence of procaine, insensitivity to tetrodotoxin, alpha‐bungarotoxin and leiurus toxin. 3. The responses differed in several important ways: miniature end‐plate current decay rate was only half as sensitive to voltage at slow fibre end‐plates as at twitch; while all twitch fibre current fluctuation spectra were single component, about 60% of the slow fibre spectra were not. The latter could be fitted with two Lorentzian components. In all cases the mean end‐plate current was proportional to total induced noise variance. 4. Two mechanisms which might account for the response differences were identified and tested in a fashion independent of specific molecular kinetics. The different responses do not arise from separate ion‐selective channels for the permeant ions at slow fibre end‐plates and seem unlikely to derive from separate populations of synaptic and extrasynaptic channels.
The effects of early visual experience on the cat's visual cortex and their possible explanation by Hebb synapses.
Authors: Rauschecker J P , Singer W
Published: December 2014

1. Kittens were dark‐reared until 4‐6 weeks old, and then for another 4‐7 weeks with various combinations of cylindrical lenses, monocular occlusion, and normal vision. 2. Single unit recordings from 816 neurones of the visual cortex (area 17) were obtained after the end of exposure. Clear‐cut effects on the distributions of the neurones' ocular dominance and orientation preference were found yielding close correlations with the rearing conditions. 3. It was confirmed that most cortical neurones prefer vertical stimulus orientations when experience is restricted to vertical contours in both eyes. It was further confirmed that, if the experienced orientations are different in the two eyes, each eye dominates over those neurones whose orientation preference corresponds to the orientation this eye has experienced. 4. When one eye is covered while the other sees only contours of one orientation, the ocular dominance distribution of cortical neurones shows a bias towards the open eye. Neurones dominated by this eye prefer orientations corresponding to the experienced range. Neurones preferring other orientations are shared between both eyes. 5. When vision is unimpaired in one eye and restricted to vertical contours in the other, binocularity is common among neurones preferring vertical orientations. Neurones with orientation preferences off the vertical are mainly monocular and dominated by the eye with unrestricted vision. 6. When normal monocular vision of one eye precedes restricted monocular vision of the other eye, only a few binocular units are encountered. Reversal of the initial effects of monocular experience is found only in neurones preferring the orientation that has been experienced by the newly opened eye. The other neurones remain dominated by the originally open eye. Thus, complementary distributions of orientation preferences are found for the two eyes. 7. A good correlation was found between the amount of orientational experience as determined by the number of orientations exposed and the number of normally tuned neurones. Conversely, the number of neurones responding to all orientations decreases with increasing amount of experience.
Effects of external cations on calcium efflux from single cells of the guinea‐pig taenia coli and porcine coronary artery.
Authors: Hirata M , Itoh T , Kuriyama H
Published: December 2014

1. Single smooth muscle cells were prepared from the guinea‐pig taenia coli and the porcine coronary artery by treatment with collagenase, in order to measure the 45Ca flux with special reference to the effects of external cations. 2. In excess [K]o solution, cell suspensions prepared from both tissues showed an increased 45Ca uptake within 3‐5 min. In Na‐free solution, the cells prepared from taenia coli, but not from coronary artery showed an increased 45Ca uptake. The Ca uptake of the cells paralleled with the tension increase recorded from tissues of both species. 3. The efflux of 45Ca into Ca‐free EGTA containing solution was markedly increased by [Na]o in cells from the taenia coli, but not in cells from the coronary artery. 4. The [Na]o‐activated 45Ca efflux from cells of the taenia coli was slightly larger in Ca‐free solution than in the Ca‐containing (10)‐4) M) solution. Depolarization of membranes produced by excess [K]o did not effect the [Na]o‐activated 45Ca efflux. 5. Increase in [Na]i by treatment with K‐free solution suppressed the [Na]o‐activated 45Ca efflux in the taenia coli. Re‐addition of [K]o reactivated the [Na]o‐activated 45Ca efflux. This re‐activation was blocked by ouabain. 6. The efflux of 45Ca was slightly activated by [Ca]o in cells from the taenia coli. This [ca]o‐activated 45Ca efflux was larger in Na‐free solution than in Na‐containing solution, thus suggesting interactions between [Na]o and [Ca]o on the Ca efflux. 7. In cells from the taenia coli, 45Ca efflux could still be observed in nominally Na‐and Ca‐free solution. This residual 45Ca efflux made a large contribution to the total 45Ca efflux. 8. When 45Ca uptake was measured in Na‐free (Tris) solution, the [Na]o‐activated, [Ca]o‐activated and residual 45Ca effluxes of cells from the taenia coli were accelerated, non‐selectively. 9. These results obtained with cells prepared from the guinea‐pig taenia coli are comparable to the Ca2+ efflux mechanism seen in the squid axon. However, maintenance of low concentrations of [Ca]i seems to require not only the above three 45Ca efflux mechanisms, but also Ca sequestering mechanisms in the cell.
Increased myometrial blood flow evoked by vasoactive intestinal polypeptide in the non‐pregnant goat
Authors: Carter A. M. , Einer‐Jensen N. , Fahrenkrug J. , Ottesen B.
Published: December 2014

1. The effect of vasoactive intestinal polypeptide (VIP) on myometrial blood flow was evaluated in anaesthetized goats. A solution of VIP, or vehicle alone, was infused into the right internal iliac artery for a period of 10 min. The myometrial blood flow in both uterine horns was measured from the third to the seventh min of the infusion by the gas clearance technique after local injection of 133xenon in 10 μl. saline solution. Blood samples were collected from both utero‐ovarian veins 5 min from the onset of the infusion and the plasma concentration of VIP determined by radio‐immunoassay.

2. During infusion of vehicle before VIP, myometrial blood flow was of the same magnitude in both uterine horns, i.e. 0·06‐0·12 ml./min per g. The blood flow of the right horn increased to 0·20‐0·39 ml./min per g during infusion of VIP (300 p‐mole/min) in the ipsilateral artery, whilst that of the left horn rose to 0·13‐0·26 ml./min per g. The effect was sometimes observed to last for more than 40 min.

3. Increased myometrial blood flow was observed with infusion rates down to 3 p‐mole/min. Once a response to VIP had been provoked, however, the vasculature sometimes became refractory to further stimulation.

4. The plasma concentration of VIP increased in both utero‐ovarian veins during unilateral infusion of the peptide.

5. Methylene blue given through the infusion catheter stained tissue in both uterine horns, further evidencing that their blood supply is not entirely separate.

6. Uterine motility was observed to diminish during the VIP infusions.

7. During infusion of VIP (300 p‐mole/min) heart rate rose from 146 ± 6 to 158 ± 7 beats/min. No significant change occurred in arterial blood pressure.

8. It is concluded that the increase in blood flow is due to a local response and that, since VIP has been demonstrated in uterine nerve endings, it may act as a neuro‐transmitter mediating vasodilatation in the uterus.
Spinal inhibition of phrenic motoneurones by stimulation of afferents from peripheral muscles.
Authors: Eldridge F L , Gill‐Kumar P , Millhorn D E , Waldrop T G
Published: December 2014

1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in two groups of cats. One consisted of paralysed, vagotomized and functionally glomectomized animals with intact central nervous systems. The other included paralysed high (C1) spinal animals whose phrenic nerve activity was either spontaneously tonic or phasic, or evoked by activation of the intercostal‐to‐phrenic reflex. In both groups, end‐tidal PCO2 was maintained at a constant level by means of a servo‐controller. 2. Physical stimulation of calf muscles in animals with intact central respiratory controller and a generally facilitatory effect on frequency, with appropriate changes of both inspiratory and expiratory durations, and on peak magnitude of phrenic (neural tidal) activity. However, for the first few sec after onset of the stimulus, neural tidal activity was inhibited. 3. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve in high spinal animals uniformly caused inhibition of spontaneous phrenic activity and that evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued. Following offset of muscle stimulation, post‐stimulus augmentation of phrenic activity occurred, with subsequent gradual return to control level over a period of 20‐25 sec. 4. We conclude that stimulation of muscle afferents in the leg has a predominantly facilitatory respiratory effect when acting through brain stem controller mechanisms, but also has a purely inhibitory effect on phrenic motoneurones when acting via spinal mechanisms. 5. In addition, the findings are consistent with (1) progressive accommodation of phrenic motoneurones during continued inhibitory input, and (2) with a large and prolonged post‐inhibitory rebound of excitability.
Properties of end‐plate channels in rats immunized against acetylcholine receptors
Authors: Alemà S. , Cull‐Candy S. G. , Miledi R. , Trautmann A.
Published: December 2014

1. Rats injected with purified acetylcholine receptors (AChR) extracted from electric organs of Torpedo marmorata showed clinical symptoms consistent with the development of experimental myasthenia gravis.

2. Sera of rats with this disease contain high levels of anti‐AChR antibodies. However, no simple correlation was found between antibody titre and miniature end‐plate current (m.e.p.c.) amplitude.

3. M.e.p.c.s. at the end‐plates of rats injected with AChR (Anti‐R), emulsified in complete Freund Adjuvant (CFA), were reduced to about one third the size of controls taken from rats injected only with CFA (Anti‐CFA). Mean m.e.p.c. (Anti‐R) = 0.73 ± 0.06 nA; mean m.e.p.c. (Anti‐CFA) = 2.43 ± 0.12 nA (Vm = ‐80 mV, T = 20 °C).

4. The m.e.p.c. decay time constant, τm.e.p.c., is similar at immunized and control rat end‐plates. τm.e.p.c. (Anti‐R) = 1.32 ± 0.06 msec; τm.e.p.c. (Anti‐CFA) = 1.31 ± 0.06 msec (Vm = ‐80 mV, T = 20 °C).

5. The end‐plate current decay time constant, τe.p.c., is similar at immunized and control end‐plates and in both cases depends exponentially on membrane potential. The change in membrane potential required to produce an e‐fold change in τe.p.c. is 102.0 ± 5.72 mV at immunized (Anti‐R) end‐plates and 92.3 ± 6.14 mV at control (Anti‐CFA) end‐plates at T = 10 °C.

6. Acetylcholine noise was examined at immunized and control rat end‐plates at 10 °C. Analysis of noise indicates that the single channel conductance, γ, and mean channel life‐time, τnoise, are essentially unchanged by immunization against AChR. γ (Anti‐R) = 13.15 ± 0.53 pS; γ (Anti‐CFA) = 12.50 ± 0.50 pS; τnoise (Anti‐R) = 2.9 ± 0.18 msec; τnoise (Anti‐CFA) = 2.68 ± 0.14 msec (Vm = ‐80 mV, T = 10 °C).

7. Mean quantal content and Ca2+ dependence of the end‐plate potential are unchanged at immunized end‐plates.

8. It is concluded that at immunized end‐plates the number of activated receptor‐channel complexes is reduced without modification of single channel properties. In this respect the immunized rat end‐plate is a good model for myasthenia gravis affected human end‐plates.
Non‐linear summation of end‐plate potentials in the frog and mouse.
Authors: McLachlan E M , Martin A R
Published: December 2014

1. End‐plate potentials (e.p.p.s) and end‐plate currents (e.p.c.s) were recorded intracellularly from muscle fibres of frog and mouse at various levels of curarization to determine the relation between the potential change and the underlying synaptic conductance change over a wide range of e.p.p. amplitudes. 2. In frog muscle fibres the e.p.p.‐e.p.c. relation was linear for e.p.p. amplitudes up to about 10 mV, beyond which the rate of increase of e.p.p. amplitude became progressively smaller as the e.p.c. amplitude increased. The equation proposed by Martin (1955) to correct for this non‐linearity consistently over‐corrected the e.p.p. amplitudes. 3. When synaptic potentials and currents of long duration were produced by ionophoresis of ACh onto the end‐plate, the voltage‐current relation showed greater non‐linearity than with nerve‐evoked responses, and correction of the synaptic potential amplitudes resulted in a linear relation. 4. The relation between e.p.p. and e.p.c. amplitudes in mouse muscle showed a greater non‐linearity than in frog muscle and over‐correction by the equation was correspondingly smaller. Theoretical voltage‐current relations were calculated for various membrane models and compared with the relations observed experimentally. The results from mouse muscle agreed with those expected for a point synaptic contact on an infinite cable; those from from muscle were consistent with simple resistive‐capacitative model with no cable extending from the synaptic region. 6. The applicability to the experimental results of several correction factors for non‐linear summation is discussed.
Enhancement and diminution of mechanical tension evoked by staircase and by tetanus in rat muscle
Authors: Krarup Christian
Published: December 2014

1. Potentiation of the isometric twitch tension was compared during and after the staircase and after tetanic stimuli in the fast‐twitch extensor digitorum longus muscle of adult Lewis rats at 37‐38°C.

2. With up to 250 stimuli the potentiation rose with an increase in both the frequency and number of stimuli in the staircase (2‐5/sec) and the tetanus (100‐167/sec). After a tetanus of 375 stimuli (125/sec) the potentiation was smaller. The potentiation 2 sec after a tetanus of 250 stimuli (167/sec) was + 132 ± 5% (n = 21,
s.e. of mean) which was greater (P < 0·001) than at the 250th stimulus at 5/sec, +92±3% (n = 21,
s.e. of mean).

3. After the staircase the decay of potentiation was initially slow and later more rapid. This was taken to indicate both the recovery of a process that diminished twitch tension and the decay of a process causing potentiation. After 250 stimuli (5/sec) the rate of decay of the processes causing diminution and potentiation had time constants of 34·5 ± 3·8 sec (n = 18,
s.e. of mean) and 102·2 ± 6·6 sec (n = 20,
s.e. of mean) respectively. Compared with the potentiation, the process causing diminution became relatively more pronounced the greater the frequency of stimuli.

4. The decay of post‐tetanic potentiation showed an initial rapid and a later slower phase of decay. After a tetanus of 250 stimuli (167/sec) the rates of decay had time constants of 5·7 ± 0·8 sec (n = 16,
s.e. of mean) and 113·5 ± 8·7 sec (n = 19,
s.e. of mean) respectively.

5. Compared with the unpotentiated response the time course of the twitch was shortened initially in the staircase and when the post‐tetanic potentiation was low. The contraction time was then increasingly prolonged the greater the potentiation and the greater the number of stimuli in the staircase and in the tetanus. The half‐relaxation time was the more prolonged the greater the number of stimuli.

6. Potentiation can be described in terms of a two‐compartment model of processes which show saturation. Both compartments were activated in a tetanus whereas only the compartment with a slow rate of decay was activated in the staircase. It is speculated that the two compartments are related to the excitation—contraction coupling. The process that caused diminution of twitch tension during the staircase may be due to fatigue. It is suggested that the energy consumption in 250 twitches is about 10 times greater than in a tetanus of 250 stimuli which may explain the presence of fatigue after the staircase whereas it was absent after the tetanus.
Temperature dependence of enhancement and diminution of tension evoked by staircase and by tetanus in rat muscle
Authors: Krarup Christian
Published: December 2014

1. The effect of temperature (20‐37·5 °C) on the potentiation of twitch tension was examined during and after the staircase (250 stimuli, 5/sec) and after the tetanus (188 stimuli, 125/sec) in the extensor digitorum longus muscle of adult Lewis rats.

2. During the staircase at 20°C the twitch tension decreased (negative staircase) by 10‐20%. At 25‐30°C the staircase was initially negative and later positive. At 37·5°C the staircase was positive throughout the train. Both at the end of the staircase and 2 sec after the tetanus the potentiation increased linearly with increasing temperature.

3. After the staircase and the tetanus at 20‐30°C the twitch tension increased initially rapidly and later after the staircase at a slower rate. Maximal potentiation at 20°C was attained 3 min after the staircase (+ 30 ± 3%, n = 10,
s.e. of mean) and 1 min after the tetanus (+ 16 ± 1%, n = 10,
s.e. of mean). At 37·5°C the potentiation decayed rapidly after the staircase and the tetanus.

4. During the staircase the time course of the twitch was shortened twice as much at 20 as at 37·5°C. At the end of the staircase and 2 sec after the tetanus the contraction time was the more prolonged the greater the potentiation. At maximal potentiation the contraction time was prolonged three times as much at 20°C (+ 19 ± 3%, n = 10,
s.e. of mean) as at 37·5°C (P < 0·005). The half‐relaxation time at the end of the staircase was prolonged 10 times more at 20 than at 37·5°C (P < 0·02).

5. When extrapolated to time zero after the staircase and the tetanus the potentiation at 20°C was still marked (20‐50%). The rate of decay of potentiation (time constant, 20°C, 561·2 ± 37·4 sec, n = 20,
s.e. of mean) increased with increasing temperature (Q10 = 2·6). The event of potentiation with a fast rate of decay, present after the tetanus but not after the staircase at 37·5°C, was abolished below 30°C.

6. The increase in twitch tension after the staircase and the tetanus at 20‐30°C was taken to indicate the recovery of events that diminished the twitch, occurring simultaneously with potentiation.

7. (i) One process of diminution, present after the staircase but not after the tetanus, increased on cooling and was assumed to be due to fatigue. The rate of recovery of the process (time constant, 20°C, 79·6 ± 7·4 sec, n = 10,
s.e. of mean) increased with increasing temperature (Q10 = 1·9). The half‐relaxation time of the last twitch in the staircase was the more prolonged the greater the process. (ii) Another process causing diminution was present after the staircase and the tetanus at 20‐30°C. It recovered at 20°C with a time constant of 14·9 ± 2·2 sec (n = 10,
s.e. of mean). This process, possibly responsible for the initially negative staircase, was not thought to be due to fatigue. It may reflect a diminished depolarization of the transverse tubules by repetitive stimuli.
The effect of dantrolene on the enhancement and diminution of tension evoked by staircase and by tetanus in rat muscle
Authors: Krarup Christian
Published: December 2014

1. The effect of Dantrolene on the potentiation of isometric twitch tension was examined during and after the staircase (5/sec, 250 stimuli) and after the tetanus (167/sec, 250 stimuli) in the extensor digitorum longus muscle of adult Lewis rats at 37‐38°C.

2. The study confirmed that Dantrolene decreased the twitch tension much more than the tetanic tension. The drug shortened the contraction time of the twitch. The rate of force development of the twitch was diminished by only half that of the twitch tension. The findings may suggest that the drug both shortened and diminished the activation of the muscle during the twitch.

3. Dantrolene decreased the potentiation produced by a given number of stimuli early in the staircase. At the 250th stimulus the staircase was about 25% larger after than before application of the drug. Dantrolene increased the potentiation 2 sec after the tetanus by about 60%.

4. After application of Dantrolene, the decay of potentiation after the staircase indicated that the process that diminished the twitch during the staircase, present before application of the drug, was absent. The size of the process causing potentiation was the same with and without the drug. Both events of potentiation after the tetanus were increased by Dantrolene. Both after the staircase and after the tetanus, Dantrolene increased the slow phase of decay by 60‐70%. The fast rate of decay after the tetanus was unchanged by the drug.

5. The contraction time was prolonged less in the potentiated twitch after than before application of Dantrolene. This was presumably due to a greater relative increase in activation rather than to a prolongation of the time during which the muscle was activated.

6. A model is proposed where the delay in potentiation during the staircase and the increase in potentiation after the tetanus are due to the proportion of sites in the excitation—contraction coupling occupied by Dantrolene being reduced by repetitive depolarizations of the transverse tubules during trains of repetitive stimuli.
Responses of supraoptic neurones in the intact and deafferented rat hypothalamus to injections of hypertonic sodium chloride.
Authors: Dyball R E , Prilusky J
Published: December 2014

1. Recordings were made from a total of fifty‐three neurones in the supraoptic nuclei of four groups of rats: intact rats, animals in which the hypothalamus had been partly denervated by anteriorly or posteriorly placed semicircular cuts, and rats with a totally deafferented hypothalamus. 2. When first encountered, cells from intact animals fired at a mean rate of 5.08 +/‐ 0.78 spikes/sec, those from posteriorly isolated hypothalami at 3.93 +/‐ 0.63 spikes/sec, those from the anteriorly isolated hypothalami at 2.05 +/‐ 0.83 spikes/sec, and those from totally isolated hypothalami at 0.99 +/‐ 0.46 spikes/sec. 3. When stimulated osmotically by an intraperitoneal injection of ml. 1.5 M‐NaCl, eight out of eight cells in intact rats showed a significant increase in firing rate between 20 and 30 min after the injection. Six out of nine cells in posteriorly isolated hypothalami showed significant but smaller responses. No increase in firing rate could be detected in seven cells from totally isolated hypothalami or from eight cells in hypothalami partly isolated by anterior cuts. 4. The results imply that under the conditions of these experiments by the spontaneous activity of the supraoptic nucleus in intact animals was maintained by an extrahypothalamic excitatory input, that partial hypothalamic isolation reduced its intensity, possibly by unmasking an inhibitory input, and that total isolation reduced it to an even greater extent. Osmotic activation of supraoptic cells was only possible when the anterior connexions of the hypothalamus were intact. Thus the cerebral osmo‐receptors for vasopressin release may be situated outside the supraoptic nuclei.
Comparison of enzyme activities among single muscle fibres within defined motor units.
Authors: Nemeth P M , Pette D , Vrbová G
Published: December 2014

1. Muscle fibres from single motor units of rat extensor digitorum longus were depleted of their glycogen by electrical stimulation and identified by the periodic acid‐Schiff stain after treatment in a medium that selectively enhanced glycogen content in the non‐depleted fibres. 2. Malate dehydrogenase (MDH) and fructose‐1,6‐diphosphatase (FDPase) activities were studied quantitatively in single dissected fibres of individual motor units and in fibres selected randomly from the same muscle. 3. In contrast to the large variability of MDH and FDPase in muscle fibres taken randomly, the muscle fibres from the same motor units had similar enzyme activities. 4. The resistance to fatigue of the motor units correlated well with the capacity of aerobic oxidative metabolism, as judged by the activity of MDH in the muscle fibres.
The inotropic actions of adrenaline on frog ventricular muscle: relaxing versus potentiating effects
Authors: Morad Martin , Sanders Chris , Weiss James
Published: December 2014

1. In frog ventricle, adrenaline increases the size of the action potential, potentiates twitch tension, and enhances relaxation. Because tension development is directly controlled by membrane potential in frog ventricle, experiments were designed to separate the effects of adrenaline on the action potential from its effects on the development of tension.

2. Comparison of the tension—voltage relations in the presence and absence of adrenaline showed that during the initial portion of the voltage clamp step, adrenaline potentiated tension, but beyond 1 sec into the clamp pulse tension was depressed.

3. The time and voltage dependence of the positive inotropic effect of adrenaline during voltage clamp pulses were compatible with the kinetics of the slow inward current, which is known to be augmented by adrenaline in frog and mammalian ventricle.

4. Ni2+, which has been shown to block the slow inward current in frog ventricle, also inhibited the positive inotropic effect of adrenaline.

5. The relaxant effect of adrenaline was demonstrated to be present at least as early as 600 msec after the onset of membrane depolarization. However, generally 1 sec or more of membrane depolarization was required before the relaxant effect of adrenaline predominated over its positive inotropic effect.

6. In catecholamine depleted strips, the augmentation of the action potential and twitch tension in the presence of adrenaline was found to occur at a sixty‐fold lower concentration than the relaxant effect as judged by suppression of KCl‐induced contractures.

7. Pure β‐receptor agonists reproduced completely the electromechanical effects of adrenaline on the frog ventricle. α‐receptor agonists or antagonists had no effect on action potential or development of tension.

8. Cyclic AMP and dibutyryl cyclic AMP were found to augment the frog ventricular action potential and potentiate twitch tension in reserpinized or β‐blocked frog ventricular strips. However, none of the relaxant effects of catecholamines could be reproduced by these agents alone.

9. Theophylline produced changes in the action potential similar to those induced by adrenaline and mimicked both the positive inotropic and relaxant effects of the drug.

10. The results suggest that the positive inotropic effects of adrenaline results mainly from changes induced in the action potential plateau. The changes are both time and voltage dependent, and if inhibited, leave the relaxant effect of adrenaline unopposed.

11. The findings are consistent with a cyclic AMP‐mediated mechanism of the positive inotropic effect of adrenaline. However, the role of cyclic AMP in mediating the relaxant effects of adrenaline is less clear.
Potential and tension changes induced by sodium removal in dog Purkinje fibres: role of an electrogenic sodium‐calcium exchange.
Authors: Croaboeuf E , Gautier P , Giuraudou P
Published: December 2014

1. Isolated dog Purkinje fibres were bathed in K‐free media or in the presence of ouabain 10(‐4) M in order to depress the electrogenic sodium pump activity. Membrane potential and mechanical tension were recorded in the presence of normal external sodium concentration and during lowering or removal of external Na. 2. Lowering or removal of external Na (Na being replaced by choline, Tris, sucrose or Li) induced a hyperpolarization and a contracture which reached a maximum after 1 or 2 min and then decreased progressively. Using Tris, Em increased from ‐40 +/‐ 3 to ‐72 +/‐ 10 mV (n = 39). The Na‐free contracture and hyperpolarization did not occur in the absence of Na pump depression. 3. Tetrodotoxin (1.2 x 10(‐5)M), Mn (4 mM), verapamil (1‐4 x 10(‐5) M) tetraethylammonium (5 mM), 4‐aminopyridine (5 mM) and Cs (20 mM, in the presence of ouabain) did not alter the Na‐free contracture and hyperpolarization. On the other hand Mn (20 mM), acid media (external pH less than 6.0) and low temperatures depressed or suppressed both the hyperpolarization and contracture. Lanthanum (0.4 mM) did not suppress the hyperpolarization and the contracture. On the contrary the Na‐free contracture was generally increased in the presence of La. 4. Caffeine (10 mM) induced strong contractures with no changes in Em, thus demonstrating the possibility for the Purkinje fibers of developing contractures without concomitant hyperpolarizations. 5. It can be concluded that the Na‐free contracture and hyperpolarization are not due to changes in passive conductances but are related to the functioning of an electrogenic Na‐Ca exchange mechanism which carries inwardly 1 Ca and outwardly 3 or more Na.
The influence of vasopressin on hypothalamic corticotrophin releasing activity in rats with inherited diabetes insipidus.
Authors: Buckingham J C
Published: December 2014

1. The corticotrophin releasing activity of hypothalamic extracts from rats congenitally lacking vasopressin (Brattleboro strain) has been studied in the presence and absence of arginine vasopressin and its antiserum. 2. Hypothalamic extracts from Brattleboro rats stimulated the production of corticotrophin by pituitary segments in vitro but both their potency and the slopes of their dose‐response lines were significantly less than those of controls. Arginine vasopressin also stimulated pituitary‐adrenocorticotrophic activity in vitro but only in concentrations considerably greater than those present in hypothalamic extracts from normal rats. 3. In low, physiological concentrations arginine vasopressin did not affect the corticotrophin releasing activity of hypothalamic extracts from controls but potentiated markedly the activity of extracts from Brattleboro rats and rendered the slopes of their dose‐response lines parallel with those of the controls. 4. The antiserum to arginine vasopressin did not affect the corticotrophin releasing activity of Brattleboro extracts but reduced the activity of control extracts and rendered the slopes of their dose‐response lines parallel with those of Brattleboro extracts. 5. The results suggest that vasopressin acts synergistically with the corticotrophin releasing factor and is essential for the full expression of pituitary‐adrenocorticotrophic activity.
The effect of cerebellectomy on the tonic labyrinth and neck reflexes in the decerebrate cat.
Authors: Dutia M B , Lindsay K W , Rosenberg J R
Published: December 2014

1. Tonic labyrinth and neck reflexes were studied separately and in combination in the decerebrate cat before and after acute cerebellectomy. Reflex effects were observed as changes in the length of the medial head of triceps in both forelimbs. 2. In the decerebrate cat with an intact cerebellum the tonic labyrinth reflexes, elicited by side‐up and side‐down head rotations, produced asymmetric length changes in the medial head of triceps in both forelimbs, as described by Lindsay, Roberts & Rosenberg (1976). After cerebellectomy, head movements in either direction produced reflex shortenings in the medial triceps in both forelimbs, in contrast to the normal reciprocal reflex length changes. The presence of the cerebellum is thus required for the occurrence of the normal asymmetric labyrinth reflexes. 3. The direction of the neck reflexes remained unchanged by cerebellectomy. 4. It is suggested that the postural disturbances following cerebellar damage may partly result from the change in the form of the tonic labyrinth reflexes, which in combination with the tonic neck reflexes would no longer act in a stabilizing manner on the trunk.
GABA‐antagonists and spatial summation in Y‐type cat retinal ganglion cells.
Authors: Kirby A W , Schweitzer‐Tong D E
Published: December 2014

1. The effect of GABA‐antagonists on centre size of Y‐type retinal ganglion cells was measured under conditions which ensured that cells were rod driven. 2. Both bicuculline and picrotoxin, administered intravenously, led to reliable and reversible changes in centre size as determined by area‐sensitivity measurements. 3. The administration of GABA‐antagonists produced opposite results in on‐ and off‐centre cells; the centre summing area decreased in on‐centre cells and increased in off‐centre cells.
Inactivation in Myxicola giant axons responsible for slow and accumulative adaptation phenomena.
Authors: Rudy B
Published: December 2014

1. The action potential in Myxicola giant axons is abolished if the nerve is stimulated at frequencies higher than about 5 sec‐1. At 1 sec‐1 the magnitude of the action potential is not maintained upon sequential stimulation but decreases until the response is abolished. 2. The behaviour of the ionic currents underlying the action potential was studied with voltage‐clamp techniques to find the origin of such adaptation. These studies showed a frequency‐dependent decline of the sodium currents. 3. The decline in the Na currents upon repetitive depolarization is shown to be due to a decrease in the Na conductance and not to change in driving force. 4. An analysis of the effects of conditioning depolarizations on the Na current during a depolarizing test pulse demonstrates that in a single short depolarization (less than 10 msec) 15% of the Na conductance enters an inactivated state from which recovery is very slow. Upon repetitive depolarizations the amount of Na conductance available accumulates in this slowly recovering inactivated state. 5. The data are explained by proposing that every time the membrane is depolarized open channels undergo one of two competing reactions. Open channels enter either the traditional inactivated state described by Hodgkin & Huxley (1952b) from which recovery is fast (a few milliseconds) or an inactivated state from which recovery is very slow (seconds). In Myxicola, only 15% of open channels enter the later inactivated state in a single depolarization. Upon repetitive depolarizations, however, the fraction in this state accumulates if the frequency of pulsing is faster than the rate of recovery. 6. Axons in which the amount of open channels entering the slowly recovering inactivated state is significant, such as in Myxicola, have thus a system capable of storing the previous activity of the axon for periods of seconds or minutes.
Specificity of neutral amino acid uptake at the basolateral side of the epithelium in the cat salivary gland in situ.
Authors: Bustamante J C , Mann G E , Yudilevich D L
Published: December 2014

1. Amino acid uptake was measured in resting cat submandibular glands with either a natural blood supply or perfused at constant flow with a Krebs‐albumin solution. Following a bolus arterial injection of a 3H‐labelled amino acid and D‐[14C]mannitol (extracellular reference tracer), the venous effluent was immediately sampled sequentially. The maximal uptake, Umax, from the blood or perfusate was determined from the paired‐tracer dilution curves using the expression: uptake % = (1 ‐‐ (3H/14C) X 100). 2. In glands with a natural blood supply, Umax values up to 46% were measured for short‐chain (serine and alanine) and long‐chain (valine, methionine, leucine, isoleucine, 1‐amino‐cyclopentane cyclopentane carboxylic acid, phenylalanine, tryptophan, tyrosine, histidine and glutamine) neutral amino acids. In contrast, Umax was negligible for amino acids of the imino‐glycine group (proline and glycine) and the nonmetabolized amino acids, 2‐aminoisobutyric acid (AIB) and methylaminoisobutyric acid (MeAIB). 3. In glands with a natural blood supply addition of an unlabelled amino acid to the tracer injectate reduced Umax for the test acid by up to 80%. The pattern of these interactions suggested the presence of two transport systems for neutral amino acids, one preferring short‐chain and the other long‐chain amino acids. 4. In glands perfused at constant flow rates with an amino acid‐free Krebs‐albumin solution high Umax values were measured: L‐serine (66%), L‐alanine (54%), L‐leucine (43%), L‐phenylalanine (42%) and L‐tyrosine (51%). Only a low uptake was observed for L‐proline (8%) and glycine (14%). There was no uptake of methylaminoisobutyric acid which confirms the result obtained in glands with an intact circulation. 5. Saturation of L‐phenylalanine influx was observed in perfused glands as the perfusate concentration of unlabelled L‐phenylalanine was increased from 0.5 to 20 mmol . 1‐1. A Michaelis‐‐Menten analysis based on a single entry system indicated an apparent Km of 6.4 +/‐ 0.8 mmol . 1‐1 and a Vmax of 1719 +/‐ 94 nmol . min‐1g.‐1 6. Since the fenestrated capillaries in the salivary gland are readily permeable to the test amino acid and D‐mannitol, it is most probable that the amino acid carriers are located in the basolateral side of the epithelium. 7. The use of a paired‐tracer dilution technique to measure uptake in a single circulatory passage has enabled a detailed characterization of neutral amino acid transport in the salivary gland and has overcome the limitation of previous studies based on solute transfer from blood to saliva.
Effects of acid‐base changes on excitation‐‐contraction coupling in guinea‐pig and rabbit cardiac ventricular muscle.
Authors: Fry C H , Poole‐Wilson P A
Published: December 2014

1. Respiratory and metabolic acid‐base changes caused similar steady‐state changes in the contractility of cardiac ventricular muscle, but the rate of response was more rapid with the former intervention. 2. Variations in extracellular pCO2 and [HCO3‐] at constant pH caused only a transient change in contractility. 3. An intracellular pH change can describe the above events. 4. The changes in contractility caused by extracellular acid‐base changes could be explained by competition between Ca2+ and H+ ions for a single process. 5. Assuming an electroneutral scheme whereby one extracellular Ca2+ ion or two intracellular H+ ions compete for a binding site, the interior of ventricular cells must be better buffered than the extracellular fluid. 6. H+ ions evoked a release of Ca2+ ions from a mitochondrial suspension with a time course similar to the partial recovery of tension observed during a respiratory acidosis. 7. Respiratory and metabolic acidosis depressed the action potential plateau and prolonged repolarization. 8. The resting potential and the maximum rate of depolarization were unaffected by the above acid‐base changes. 9. An acidosis depressed Ca2+ influx through the slow inward channel by an amount sufficient to account for the observed contractility changes. 10. It is concluded that between pH 7.6 and 6.6 the major physiological effect of an acidosis is to depress the slow inward current as a result of an intracellular pH change.
The effect on salt appetite and the renin—aldosterone system on replacing the depleted ions to sodium‐deficient cattle
Authors: Bell F. R. , Drury P. L. , Sly Jennifer
Published: December 2014

1. Sodium depletion which occurred in cattle following exteriorization of a parotid duct produced depression of both plasma and salivary sodium, acidosis, elevated plasma aldosterone and renin activity. Increased sodium appetite, characteristic of sodium depletion, was assessed by operant behaviour where scoring of panel pressing for NaHCO3 rewards showed change in sodium appetite.

2. Sodium‐depleted calves readily drank the calculated ionic deficit as a hypertonic solution (4 l.) in a few minutes, or as an isotonic solution (16 l.) usually within 30 min.

3. When the ionic deficit was restored by either
i.v. infusion or drinking, sodium appetite was reduced significantly. The suppression of sodium appetite was more rapid when the depleted ions were replaced by drinking (30 min) than by
i.v. infusion (2 hr) but in both circumstances the effect was short lived since sodium appetite redeveloped within 3 hr.

4. The rapid return of sodium appetite following restoration of the ionic deficit occurred even when the plasma sodium level was normal. Other biochemical changes resulting from sodium depletion, such as acidosis and reduced salivary sodium, could not be correlated with variation in sodium appetite.

5. Rapid infusion of Ringer saline (4 l.) did not inhibit the sodium appetite, which suggests that neither vascular volume changes per se nor vascular baroreceptors control sodium appetite in sodium‐deficient calves.

Plasma aldosterone fell rapidly following infusion of the hypertonic solution but only slightly with the isotonic infusion. The change in plasma hormone level was not related to changes in sodium appetite.

6. Drinking the hypertonic solution produced a marked reduction in panel pressing for NaHCO3 with a rapid rise in plasma sodium. Consumption of the larger volume of isotonic solution also inhibited sodium intake but plasma sodium remained low. A secondary increase in plasma renin activity (p.r.a.) occurred following ingestion of the hypertonic solution, but both p.r.a. and aldosterone fell to normal levels over the next 6 hr when the cattle again showed marked sodium appetite. It is possible that these effects may be due to ion and fluid movement between gut and extracellular fluid and reflect osmolality changes or tissue dehydration.

7. It is concluded that the sodium appetite of sodium deficient cattle is only temporarily alleviated by restoration of the depleted ionic loss, and that the behavioural response to seek sodium rewards is independent of plasma sodium, p.r.a., aldosterone and volume changes in the gut and vascular system.

8. Recent reports suggest that sodium appetite may be controlled by receptors in the hypothalamus or by angiotensin II in the brain. In cattle the capacious gut may also be involved, since sodium appetite is inhibited more rapidly when the depleted ions are taken orally than by
i.v. infusion.
On the number and nature of regenerating myelinated axons after lesions of cutaneous nerves in the cat.
Authors: Horch K W , Lisney S J
Published: December 2014

1. Electrophysiological and anatomical techniques were used to investigate normal and regenerating sural and posterior femoral cutaneous nerve fibres in the cat. 2. One and a half years after transection of these nerves it was found that the regenerating neurones supported multiple sprouts in the distal stump of the nerve. The branching occurred at or beyond the level of the neuroma and some of the branched fibres innervated split receptive fields on the skin. 3. Counts of the number of axons in the proximal stumps of transected nerves showed that the whole original population of myelinated fibres persisted for at least 18 months. About 75% of these fibres successfully crossed the unrepaired transection site and regenerated into the distal stump of the nerve to re‐form functional connexions in the skin. 4. After nerve crush all the myelinated axons regenerated. None showed signs of abnormal branching. 5. After crush the conduction velocities of the regenerated axons in the distal stump of the nerve reached nearly normal values by 6 months. After nerve transection the distal conduction velocities were reduced to 50% of normal even 18 months after the injury. 6. The implications of these findings for the recovery of function after nerve injury in man are discussed.
Changes in primary afferent depolarization of sensory neurones during peripheral nerve regeneration in the cat.
Authors: Horch K W , Lisney S J
Published: December 2014

1. Micro‐electrode recordings were made from normal and regenerating sural nerve fibres in cats. Increases in the excitability of the central terminals of these fibres after conditioning stimulation of other sural nerve fibres were taken as evidence for primary afferent depolarization. 2. At all recovery times studied the excitability changes seen were significantly less than those seen in control animals. Two factors contributed to the changes in primary afferent depolarization. First, the proportion of fibres that showed no evidence of primary afferent depolarization increased significantly. This proportion became smaller as recovery progressed. Secondly, where primary afferent depolarization was present, the magnitudes of the effects were slightly but significantly decreased compared with control values. 3. Excitability changes of the central terminals of sural nerve fibres were also measured after conditioning stimulation of the ipsilateral, unlesioned accessory sural nerve. One month after sural nerve transection there was a significant increase in the proportion of fibres showing no evidence of excitability changes following accessory sural nerve conditioning stimulation compared with control animals. Thus, the loss of primary afferent depolarization of regenerating sural nerve fibres was neither simply a consequence of desynchronization of the volley of impulses entering the spinal cord after conditioning stimulation of other regenerating sural fibres, nor due to fewer fibres being activated during conditioning stimulation of the lesioned nerves. 4. A possible explanation of these results is that after peripheral nerve crush or transection the central terminals of the damaged fibres retract or atrophy. Then as regeneration of the nerve proceeds, the central terminals of the fibres re‐form.
The effects of 4‐aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres.
Authors: Bostock H , Sears T A , Sherratt R M
Published: December 2014

1. 4‐Aminopyridine (4AP) and tetraethylammonium ions (TEA), which block voltage‐dependent potassium channels in other nerve membranes, have been used to study nerve conduction in fibres of normal rat spinal roots and those demyelinated with diphtheria toxin. The pharmacological actions have been compared with those of temperature. 2. Both TEA and 4AP increased the amplitude and duration of the monophasically recorded compound action potentials of non‐myelinated fibres in normal rat dorsal roots. Enhancement of the action potential amplitude by 4AP was maximal near 1 mM, and was not readily reversed by washing. At concentrations up to 50 mM the action of TEA was weaker and reversible. 3. In normal dorsal and ventral roots TEA (20 mM) and 4AP (5 mM) had only a mildly depressant action on the compound action potentials of myelinated fibres. Whereas the slight reduction in peak amplitude and increase in width was also found in a single fibres treated with TEA, none was discerned in single fibres exposed to 4AP over a wide temperature range. 4. It is concluded that voltage‐dependent potassium channels occur in significant numbers in mammalian non‐myelinated fibres, but not at nodes of Ranvier. 5. Spinal roots previously treated with diphtheria toxin to cause demyelination were studied by longitudinal current analysis. Fibres affected by diphtheria toxin had a late phase of outward current, either restricted to nodes or, in the case of continuous conduction, distributed along internodes, and this outward current was specifically blocked by 4AP. 6. Both 4AP and TEA increased the temperature at which conduction block occurred in most single demyelinated fibres, so that in some cases fibres blocked at physiological temperatures were enabled to conduct. 4AP was more potent than TEA, but less consistent in its effect. 7. It is concluded that potassium channels are present at widened nodes and in internodal axolemma exposed by demyelination. Their presence enables TEA and 4AP to overcome conduction block in some demyelinated nerve fibres.