bluuebunny/crossref_metadata_2025 huggingface dataset:
Light induced changes of internal pH in a barnacle photoreceptor and the effect of internal pH on the receptor potential.
Authors: Brown H M , Meech R W
Published: December 2014

1. Intracellular pH (pH1) was measured in Balanus photoreceptors using pH‐sensitive glass micro‐electrodes. The average pH1 of twelve photoreceptors which had been dark adapted for at least 30 min was 7.3 +/‐ 0.07 (S.D.). 2. Illumination reduced the recorded pH1 by as much as 0.2 pH unit. The change in pH1 was graded with light intensity. 3. When the cells were exposed to CO2 in the dark, pH1 declined monophasically. Saline equilibrated with 2% CO2; 98% O2 produced a steady reduction in pH1 of about 0.25 unit in 2‐‐3 min. The buffering capacity of the receptor cell cytoplasm calculated from such experiments is approximately 15 slykes. 4. In the presence of HCO3‐1, CO2 saline produced smaller, biphasic changes in pH1. 5. The membrane depolarization produced by a bright flash (depolarizing receptor potential) was reversibly reduced in the presence of external CO2 or by injection of H+. Iontophoretic injection of HCO2‐ increased the amplitude of the receptor potential. 6. In individual cells there was a close correlation between the amplitude of the receptor potential and pH1. 7. Saline equilibrated with CO2 reduced the light induced current (recorded under voltage‐clamp) by 40‐‐50% without affecting its reversal potential. 8. Exposure of the receptor to 95% CO2 saline for several minutes (pH0 5.5) not only abolished the receptor potential but also reversibly decreased the K conductance of the membrane in the dark. These effects were not reproduced by pH0 5.5 buffered saline or by a 5 min exposure to saline equilibrated with N2. 9. It is suggested that changes in pH1 induced by light modulate the sensitivity of the receptor under physiological conditions.
Input‐output relations in the pathway of recurrent inhibition to motoneurones in the cat.
Authors: Hultborn H , Pierrot‐Deseilligny E
Published: December 2014

1. The output from Renshaw cells caused by a phasic motor volley was investigated when these neurones were submitted to a background firing secondary to a tonic motor discharge elicited by a repetitive stimulation of muscle group I afferents. It was invariably found in individual Renshaw cells that tonic excitation produced an increase in the additional ouput caused by the phasic motor volley. The curves displaying this increase exhibited a significant ‘jump’ when the output resulting from the combined tonic and phasic motor discharges ranged between 2 and 5 spikes during the first 10 msec following the phasic volley. 2. The whole pool of Renshaw cells was also considered by assessing the amount of recurrent inhibition in motoneurones following a phasic motor volley. Similarly it was found that additional recurrent inhibition elicited by a phasic motor volley was enhanced when the Renshaw cells received a tonic excitatory input. 3. The Renshaw cell discharges elicited by stimulation of two different nerves were compared when a conditioning stimulus was previously applied to only one of them. The results strongly suggest that a preceding volley caused a decrease in synaptic efficacy at the terminals of the recurrent collaterals. 4. The firing produced by current injected through the recording micro‐electrode was investigated in one intracellularly recorded Renshaw cell. It was found that the current‐frequency curve was linear for ‘steady‐state’ firing but displayed a clearcut sigmoid shape for the earliest intervals before the final adaptation. 5. It is demonstrated that this sigmoid input‐output relation in individual Renshaw cells is sufficient to explain how the controls acting on these neurones may change the gain in the recurrent pathway when Renshaw cells are fired by a phasic motor discharge. When Renshaw cells are fired by a longlasting tonic motor discharge the linear input‐output relation in individual cells should not cause any modifications of the gain in the recurrent pathway. A change in this gain secondary to the effects of segmental and supraspinal control systems is, however, possible if the motor discharge creates a subliminal fringe within the pool of Renshaw cells.
Evidence for a dual pelvic nerve influence on large bowel motility in the cat
Authors: Fasth S. , Hultén L. , Nordgren S.
Published: December 2014

1. The effects of efferent electric pelvic nerve stimulation on colorectal motility and blood flow with emphasis on the motor responses in consecutive colonic and rectal segments were studied in anaesthetized cats. It was considered of particular interest to explore whether selective pharmacological blockade and graded nerve stimulations might reveal the presence of functionally differentiated efferent fibres controlling colonic motility.

2. Pelvic nerve stimulation induced immediate and sustained colorectal contractions and a simultaneous increase of the over‐all colonic blood flow. The excitatory responses declined immediately on cessation of a shortlasting stimulation (< 2 min); after a longlasting one, however, the rectal contraction was maintained for several min.

3. The colonic contraction on pelvic nerve stimulation remained unchanged after atropine but was delayed in onset. Moreover, in the transverse and distal colon it was preceded by a relaxation which was most pronounced in the distal part. The vasodilator response was unchanged.

4. After atropine the rectal segment showed a purely relaxatory response. Despite continuous pelvic nerve stimulation the relaxation vanished, however, and rectal volume returned to resting level with 3‐5 min. On cessation of such a prolonged stimulation there was a marked rectal ‘after‐contraction’.

5. The excitation thresholds for the efferent nerve fibres eliciting these different responses could not be separated. The motility and the vasodilator responses were not influenced by adrenergic or by serotoninergic blockade.

6. The results indicate that direct preganglionic stimulation of the cat pelvic nerves activates intramural cholinergic excitatory neurones as well as non‐cholinergic excitatory neurones and furthermore, non‐adrenergic non‐cholinergic inhibitory neurones, which together result in most complex colonic and rectal motor responses. From a functional point of view these centrally controlled responses may well be independently controlled by separate preganglionic neurones though they do not differ concerning excitation thresholds.

7. The effects are consistent with a dual function of the distal colon and rectum. Such a dual parasympathetic influence on the large bowel simulates the vagal control of the stomach, where specific vagal relaxatory fibres convey a reflex widening of the corpus‐fundus reservoir during food intake.
Innervation of sympathetic neurones in the guinea‐pig thoracic chain.
Authors: Lichtman J W , Purves D , Yip J W
Published: December 2014

We have investigated the organization of the guinea‐pig thoracic chain by studying the innervation of the stellate and fifth thoracic sympathetic ganglia with intracellular recording. 1. These ganglia receive preganglionic innervation from different but overlapping sets of spinal cord segments: the stellate ganglion is innervated by preganglionic axons from spinal segments more rostral than those supplying the fifth thoracic ganglion, but somewhat more caudal than those innervating the superior cervical ganglion. 2. Individual thoracic ganglion cells are innervated by only some of the spinal segments that supply each ganglion as a whole. In general, the subset of spinal segments innervating a ganglion cell is contiguous; one of these segments provides the strongest innervation, with progressively weaker innervation arising from spinal levels adjacent to the dominant one. This selective pattern of innervation is similar to that in the superior cervical ganglion (Njå & Purves, 1977 a). 3. Preganglionic axons frequently innervate neurones in more than one ganglion. 4. Although neurones innervated by the same spinal cord segments are found in both the stellate and the fifth thoracic ganglion, as well as in the superior cervical, the number of ganglion cells receiving innervation from particular spinal segments is different in each ganglion. Moreover, neurones dominated by the same segment but located in different ganglia receive somewhat different average innervation from adjacent segments as a function of the ganglion in which they reside. 5. These results indicate that neurones in the thoracic chain ganglia, as those in the superior cervical ganglion, are selectively innervated by particular spinal cord segments. We suggest that the different average innervation of sympathetic ganglia reflects at least two related factors: the selective qualities of their constituent neurones, and the availability of different preganglionic axons to each ganglion.
Specific features of smooth muscle cells recorded from the placental region of the myometrium of pregnant rats
Authors: Kanda S. , Kuriyama H.
Published: December 2014

The muscle membrane and contractile properties of placental and non‐placental regions of pregnant and postpartum myometria of the rat were investigated.

1. The membrane potential of the myometrium varied during the progress of gestation, but the membrane potential in the placental region was consistently higher than that in the non‐placental region up to the last stage of gestation. The maximum difference in the membrane potential recorded from both regions was observed at 17‐21 days gestation.

2. The conduction velocity of the excitation measured from muscle cells of the non‐placental region was consistently larger than that of the placental region at any stage of the gestation (7‐22 days). At 7 days gestation, the conduction velocity in the placental region could not be measured due to widely scattered values of the latencies for the spike generation. During the progress of gestation, the conduction velocity increased, and the value was consistently larger (about 10 times) in the nonplacental region than that in the placental region at any stage of gestation up to the last stage.

3. The length constant of the tissue measured from the non‐placental region was larger (2·3 mm) than that in the placental region (1·1 mm) at 14 days gestation. The propagation of the excitation seems to be blocked from the cells of the non‐placental region to the placental region, but not vice versa.

4. The shape of the spike in the non‐placental region changed markedly during the progress of gestation. The spike could be recorded from the cells of the placental region but not consistently. However, the electrical activity of muscle cells recorded at the full term was much the same in both regions.

5. Various concentrations of [K]o or [Na]o modified the membrane potential. The differences in the membrane response to the above ionic environments appeared more significantly at the different stages of gestation, rather than topical differences.

6. Sensitivity of the muscle cell membrane to oxytocin in the placental region was higher than that in the non‐placental region at any stage of gestation, while that to prostaglandin F2α was much the same in the cells recorded from both regions.

7. At 8 days gestation, the circular muscle layer is lost from the area of implantation and only the longitudinal muscle layer remains. The width of the placenta and the thickness of the muscle layer increased during the progress of gestation.

8. From the above results, the role of smooth muscle cells in the placental region is discussed in relation to hormonal controls in the myometrium, i.e. the activity of the muscle cell membrane in the placental region was markedly suppressed up to the last stage of gestation, however, there was no apparent direct relation between the inhibitory responses and the actions of progesterone.
Mechanical and thermal responses of polymodal receptors recorded from the superior spermatic nerve of dogs.
Authors: Kumazawa T , Mizumura K
Published: December 2014

1. One hundred and fifty‐three units were recorded from the superior spermatic nerve of dogs and were tested with mechanical, chemical or heat stimulation. Among 104 units tested with all three methods of stimulation ninety‐three units responded to all of them; thus 90% of the superior spermatic nerve units are considered to be polymodal receptors. Only mechanical and thermal responses are reported in this paper. 2. Conduction velocities measured at the nerve trunk in the abdominal cavity were mostly within the A‐delta fibre range (average conduction velocity: 11.1 m.s‐1, n = 63), but in the receptive region much delay was observed. In contrast to the cutaneous polymodal receptors, polymodal receptors in the superior spermatic nerve usually had multiple receptive sites, up to nine in number. 3. Mechanical responses of these polymodal receptors consisted of dynamic and steady‐state responses and sometimes were followed by after‐discharges. Maximum responses were obtained with a noxious intensity of stimulation, but thresholds scattered over a wide range including non‐noxious intensities. 4. In response to heating, these polymodal units gave an irregular discharge that increased roughly in parallel to temperature rise with an average threshold and S.E. of mean, 42.6+/‐0.4 degrees C (n = 73). They showed sensitization or deactivation or both on repetition of heating. Cooling the receptive site caused only transient and weak responses, if any.
The relationship between muscarinic receptor binding and ion movements in rat parotid cells.
Authors: Putney J W , Van De Walle C M
Published: December 2014

1. The relationship of muscarinic receptor binding to ion fluxes induced by muscarinic agonists was investigated in rat parotid cells. 2. Receptor binding was measured with [3H]quinuclidinyl benzilate in living, dispersed parotid acinar cells. These same cells were used to determine concentration‐effect relationships (ion fluxes) for agonists. 3. Receptor binding of antagonists accurately reflected the pharmacologically determined affinities. In the case of agonists, apparent pharmacological affinities were greater than binding affinities by a factor of 12.5 for methacholine and 18.7 for carbachol. 4. The reason for the discrepancy between agonist binding and effect is not known with certainty, but the existence of "spare" receptors is considered a possibility. 5. The total number of muscarinic receptors is estimated to be 23,000/cell. If some are spare, as few as 1800/cell may suffice to fully activate the available Ca channels.
Interaction between nerve‐related acetylcholine and bath applied agonists at the frog end‐plate.
Authors: Feltz A , Trautmann A
Published: December 2014

1. The interaction between acetylcholine (ACh) and carbachol (CCh) has been studied at the frog end‐plate. The conditioning agonist, CCh, can cause desensitization (reduction of the ACh test response) and potentiation (increase of the test response). 2. Nerve‐evoked end‐plate currents (e.p.c.s), minature e.p.c.s and "slow" responses to ACh ionophoresis can all be potentiated by bath or ionophoretically applied CCh. 3. Since potentiation was found to be particularly visible at low temperatures, most experiments were performed at 5‐8 degrees C. Potentiation results in an increase of both e.p.c. amplitude and e.p.c. decay time. Potentiated e.p.c.s teminate with a slow tail, the amplitude of which shows a high voltage sensitivity. Potentiation increases with CCh concentration (range studied 0‐100 microM). It appears to persist throughout the application of CCh, even when desensitization is apparently the dominant phenomenon. 4. It is suggested that cross‐potentiation of ACh by CCh results from the formation of intermediate non‐conducting CCh‐receptor complexes which have a high probability of being subsequently activated by ACh, yielding a conducting ACh‐CCh‐receptor complex. 5. Desensitization induced by fast bath application of CCh (or ACh) develops in two phases and can be fitted by the sum of two exponentials. Their time constants are in the second and the minute range, respectively. 6. The possibility that the slow phase is linked to the presence of agonist inside the cell is rejected.
Relations between the inactivation of sodium channels and the immobilization of gating charge in frog myelinated nerve
Authors: Nonner W.
Published: December 2014

1. Single, voltage‐clamped nerve fibres of Rana esculenta were stimulated with ‘P/2’ pulse patterns for measuring Na and gating currents at 13 °C.

2. Gating currents during test pulses to ‐ 122 or + 10 mV were measured after 45 msec conditioning steps to voltages between ‐ 122 and ‐ 18 mV. As the conditioning voltage was made more positive than ‐ 80 mV, the movable gating charge diminished along a sigmoid curve, approaching a value of nearly one third of the maximum charge. On the other hand, Na inactivation began at a more negative potential and proceeded to undetectable levels.

3. After a depolarizing prepulse, both time constant and size of the charge movment depended less steeply on the test voltage than normally. The prepulse reduced gating currents associated with steps from ‐ 122 to test voltages ≥ ‐ 40 mV, but enhanced gating currents obtained with test voltages < ‐ 40 mV.

4. Increasing the duration of a depolarizing pulse (‐ 54 to + 42 mV) reduced the fast ‘off’ gating current at the end of the pulse and enhanced a slow component. Their total charge corresponded approximately to that carried during the pulse. During depolarization, Na current inactivated in a fast and a slow phase. The fast phase was also reflected in the loss of fast charge movement (immobilization) as seen after the pulse was interrupted at various durations.

5. The available Na current and the fast movement of gating charge diminished in parallel during prepulses more positive than ‐ 54 mV, and recovered in parallel upon repolarization to levels between ‐ 102 and ‐ 46 mV. During prepulses between ‐ 62 and ‐ 78 mV, however, Na inactivation occurred up to 4 times faster than charge immobilization. Also, at ‐ 78 mV, Na current was inactivated 3 times faster than it recovered.

6. These findings indicate that Na inactivation and charge immobilization are linked, but proceed with high‐order kinetics. The simplest scheme that accounts for their relation is [Formula: see text] Depending on voltage, either state h2 (E > ‐ 45 mV) or h3 (E < ‐ 45 mV) becomes kinetically undetectable.

7. A model of the Na channel is developed in which inactivation gains most of its voltage dependence by a coupling to the fast charge movement (activation). The model is shown to be quantitatively consistent with the results. In particular, the change of kinetics observed near ‐ 45 mV can be explained as an effect of the redistribution of charges on the inactivation process.
Co‐ordination of head and eyes in the gaze changing behaviour of cats
Authors: Blakemore Colin , Donaghy Michael
Published: December 2014

1. Saccadic changes of gaze have been studied in conscious cats implanted with electro‐oculographic electrodes to register eye position and held in a device for measuring head position.

2. When the head is free to move, almost all saccades larger than 4 deg in amplitude are accompanied by head rotation. This head movement starts at a variable delay after the beginning of the eye movement. Most frequently, the latency is 30 msec.

3. After finishing its saccade, the eye rotates retrogressively in the orbit so as to maintain a constant direction of gaze during the remaining portion of the head movement. This compensatory eye movement has an average gain of 0·96 in the absence of visual feed‐back.

4. The duration and peak velocity characteristics of head‐fixed saccades were measured. A typical horizontal saccade of 20 deg in amplitude attains a peak velocity of 250 deg/sec and lasts 110 msec. The duration—amplitude relationship increases by 2·1 msec/deg.

5. Saccades aimed obliquely within the orbit possess the same duration/peak—velocity/amplitude relationships as purely horizontal saccades. Consequently, the horizontal component of an oblique saccade lasts longer, and has a lower peak velocity, than a purely horizontal saccade of the same amplitude as this component. This finding is discussed in relation to brain‐stem control of oblique saccades.

6. A saccade is initially programmed to achieve the desired gaze change without aid from the head. Consequently, the saccade is slowed down so as to prevent gaze overshoot when the head moves too. Since this saccadic attenuation occurs even during passive head movement, it must be due to feed‐back from peripheral sensors of head rotation, and probably represents the initial stage of the compensatory eye movement.

7. Since the axes of horizontal head and eye rotation are horizontally separated, it may be predicted that the gain of compensatory eye movements must rise as the viewing distance decreases if they are to maintain fixation during head movements. This prediction was confirmed.
Intracellular recordings from the paraventricular nucleus in slices of rat hypothalamus.
Authors: Dudek F E , Hatton G I , Macvicar B A
Published: December 2014

1. The electrical activity of thirty‐five neurones in the lateral area of the paraventricular nucleus (p.v.n.) was recorded intracellularly in vitro from slices of rat hypothalamus. 2. Spontaneously occurring action potentials were observed in twenty‐four of the neurones. The temporal pattern of action potentials was generally slow and irregular; occasionally some cells fired bursts of action potentials. 3. Depolarizations with a fast rising phase and slow decay occurred spontaneously in most cells. These depolarizations exhibited a wide range of amplitudes in each cell (up to 33 mV), showed temporal summation, and could serve as pre‐potentials for spontaneously occurring action potentials. Presumably, these depolarizations were excitatory post‐synaptic potentials (e.p.s.p.s.). 4. Depolarizing current injection could evoke action potentials. Extracellular stimuli dorsolateral to the fornix column occasionally elicited action potentials which had a short and invariant latency and which could respond to stimulation rates of 100 Hz. In some cases, extracellular stimuli in the same area evoked depolarizations which had long and variable latency and were similar to those occurring spontaneously. These two types of responses probably represent antidromic and orthodromic activation respectively. 5. Intracellular injections of horseradish peroxidase suggest that these recordings were obtained primarily, but not exclusively, from magnocellular neuroendocrine cells. This is consistent with previous anatomical studies on the location of magnocellular elements in p.v.n.
Effects of neonatal enucleation on the functional organization of the superior colliculus in the golden hamster.
Authors: Rhoades R W
Published: December 2014

1. The responses of visual, auditory and somatosensory superior collicular neurones were investigated using extracellular single unit recording techniques in hamsters which were subjected to the removal of one eye on the day of birth. 2. Neonatal enucleation resulted in a marked increase in the region of the colliculus from which visual neurones activated by stimulation of the ipsilateral eye could be recorded. In most cases the visuotopic representation in the colliculus ipsilateral to the remaining eye mirrored that observed in the contralateral tectum along both the rostrocaudal and mediolateral axes: in both colliculi temporal retina projected rostrally and inferior retina medially. In some animals, however, there appeared to be a dual mapping of the remaining eye onto the ipsilateral tectum. In these hamsters the central portion of the visual field was represented twice along the rostrocaudal axis of colliculus. 3. No changes in the topography of the somatosensory and auditory representations in the tectum were observed following neonatal enucleation. 4. The laminar distribution of visual neurones in the ipsilateral colliculus was markedly altered in the neonatally enucleated hamsters. Very few exclusively visual units were encountered in the layers ventral to the stratum opticum and almost all of the visual cells recorded in the ipsilateral colliculus were isolated within 150 microM of the tectal surface. 5. In the posterior half of the ipsilateral tectum a large number of extravisually responsive cells were encountered in the stratum griseum superficiale and stratum opticum. This was not the case in the colliculus contralateral to the remaining eye, nor has it ever been observed in normal hamsters. 6. Recordings from animals subjected to both neonatal enucleation and acute bilateral removal of somatosensory and auditory cortex indicated that the projections from these areas to the colliculus were not essential to the observed changes in laminar organization. 7. Recordings from normally reared hamsters which were subjected to removal of one eye at the time of the recording experiment suggested further that the isolation of extravisual cells in the superficial tectal aminae of the neonatal enucleates was probably not the result of the ‘unmasking’ of extravisual influences in the superficial layers which are present, but ineffective, in the normal case.
A dopamine‐5‐hydroxytryptamine link in the hypothalamic pathways which mediate heat loss in the rat.
Authors: Cox B , Kerwin R W , Lee T F , Pycock C J
Published: December 2014

1. Intrahypothalamic injection of either dopamine or 5‐hydroxytryptamine (5‐HT) in a dose volume of 1 microliters caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/‐ 1 degree C. 2. Haloperidol (6.5 n‐mole), a dopamine antagonist, prevented the hypothermic effect of dopamine (65 n‐mole), but was ineffective against the response to either intrahypothalamic 5‐HT (114 n‐mole) or oxotremorine (6.0 n‐mole). 3. Methysergide (14 n‐mole) and cryproheptadine (17 n‐mole) blocked the effect of both 5‐HT and dopamine. However, these same doses failed to antagonise the effect of oxotremorine. 4. Rats placed on 0.65 m below a 250 W infra‐red lamp responded to the imposed heat load vasodilation of tail skin blood vessels, as indicated by an increased tail skin temperature. 5. Rats tested 2 weeks after bilateral intrahypothalamic injection of 5,6‐dihydroxytryptamine (42 n‐mole in 2 microliters) showed a significant reduction in their tail skin temperature response and were less able to withstand the imposed heat load. 6. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the previously defined dopamine‐sensitive site. 7. Pretreatment with 5,6‐dihydroxytryptamine significantly reduced the 5‐HT concentration in the dopamine sensitive site, but had no effect on the concentration of dopamine. This pretreatment blocked dopamine but not 5‐HT‐induced hypothermia. 8. The 5‐hydroxyindoleacetic acid (5HIAA) concentration in the hypothalamus of the normal rat exposed to a heat load was found to be significantly elevated, whereas there was no change in the 5HIAA concentration in the cortex. 9. Slices of rat preoptic hypothalamus and hippocampus were incubated with [3H]5‐HT (0.2‐2 microM). These slices accumulated 5‐HT with properties characteristic of a neuronal uptake process. 10. Perfusion with either dopamine (greater than 50 microM) or apomorphine (greater than 200 microM) enhanced the release of [3H]5‐HT from the prelabelled hypothalamic slices, but failed to stimulate release from hippocampal slices. 11. The release of [3H]5‐HT from preoptic slices by dopamine and apomorphine was antagonised by the dopamine antagonists haloperidol (2 microM) and (+) isomer of butaclamol (1 microM), the (‐) isomer of butaclamol was inactive. 12. These results support the hypothesis of a dopamine‐5HT link in the hypothalamic thermoregulatory pathways of the rat.
Effect of calcium withdrawal on mechanical threshold in skeletal muscle fibres of the frog.
Authors: Chiarandini D J , Sanchez J A , Stefani E
Published: December 2014

1. Voltage‐clamp experiments were performed on frog skeletal muscle fibres using two intracellular micro‐electrodes. The threshold for the Na current and the strength‐duration curve for mechanical threshold were determined. 2. The change in threshold for the Na current was studied as a function of the external Ca and Mg concentrations which ranged from 0.1 to 50 mM. 3. The resting potential, effective resistance and threshold for the Na current were unchanged when 1.8 mM‐Ca was replaced by 3 mM‐Mg, indicating that the surface potential and the electrical properties of the fibres were not modified. The additon of 5 mM‐EGTA did not affect these parameters. 4. In Ca‐free saline (3 mM‐Mg and 5 mM‐EGTA) the mechanical threshold was significantly increased for short pulses (less than or equal to 20 msec.). In isolated single muscle fibres this effect was observed shortly after applying the Ca‐free saline, and was rapidly reversed upon the return to control saline. 5. In isotonic EGTA (85 mM‐EGTA) the muscle fibres were depolarized and were unable to contract even if they were hyperpolarized to ‐‐90 mV for 12 min prior to stimulation. If 3 mM‐Mg was added, most fibres contracted locally. 6. In single muscle fibres caffeine contractures were unmodified after a 30 min exposure to Ca‐free saline. 7. It can be concluded that external Ca withdrawal impairs Ca release from the sarcoplasmic reticulum and that external Ca is not essential for triggering contraction.
The effect of tetraethylammonium chloride on calcium fluxes in smooth muscle from rabbit main pulmonary artery.
Authors: Haeusler G , Kuhn H , Thorens S
Published: December 2014

1. In the first part of this investigation we studied the experimental conditions under which the ‘lanthanum method’ gives valid estimations of the changes in intracellular calcium induced by either tetraethylammonium chloride (TEA) or high K in the rabbit main pulmonary artery. Subsequently, the effect of TEA on Ca movements in this blood vessel was measured. 2. The uptake of 140La by the vascular tissue is time‐ and concentration‐dependent; it is separated into an early and a late phase. La binds to at least two classes of extracellular sites with affinities of 0.06 and 4.76 M. 3. A 1 hr exposure of the vascular strips to a 1 mM‐La solution appears to be a convenient treatment for removal of Ca from the extracellular space. Under these conditions (a) 45Ca efflux from an intracellular compartment loaded with Ca during exposure to TEA or K is virtually blocked, (b) there is no major penetration of La into the smooth muscle cells as revealed by electron microscopy, and (c) there is no change in the size of the extracellular space. 4. TEA increases in a concentration‐dependent manner the La‐resistant 45Ca content (maximum increase 0.18 m‐mole 45Ca/kg wet weight in response to 70 mM‐TEA). There is a linear relationship between log concentration TEA and 45Ca influx. 5. The calcium antagonist verapamil (10(‐6) and 10(‐5) M) inhibits the TEA‐induced 45Ca influx. 6. The increase in 45Ca influx produced by K (20 or 30 mM) is markedly enhanced by TEA. 7. The noradrenaline‐induced increase in 45Ca accumulation is not influenced by TEA. 8. 45Ca efflux from the La‐resistant Ca space is increased by TEA both in the presence and in the absence of non‐radioactive Ca in the medium. 9. It is concluded that TEA contracts the vascular smooth muscle cells of the rabbit main pulmonary artery by an increase in the Ca permeability of the cell membrane.
Inotropic responses of the frog ventricle to adenosine triphosphate and related changes in endogenous cyclic nucleotides.
Authors: Flitney F W , Singh J
Published: December 2014

1. A study has been made of a well documented but poorly understood response of the isolated frog ventricle to treatment with exogenous adenosine 5' triphosphate (ATP). Measurements of membrane potential, isometric twitch tension and levels of endogenous 3',5'‐cyclic nucleotides have been made at various times during the ATP‐induced response. 2. ATP elicits a characteristic triphasic response, which comprises an initial, abrupt increase in contractility, rising to a maximum within a few beats (first phase); followed by a period when the twitch amplitude falls, sometimes to below the control level (second phase); and superceded by a more slowly developing and longer‐lasting increase in contractile force (third phase). The response is unaffected by atropine, propranolol or phentolamine. However, the prostaglandin synthetase inhibitor indomethacin depresses the first phase and entirely suppresses the third phase. 3. The inotropic effects of ATP are accompanied by changes in the shape of the action potential. These effects are dose‐related. The duration of the action potential (D‐30mV) and its positive overshoot (O) are increased during all phases of the response, for [ATP]o's up to 10(‐5) M. However, at higher [ATP]o's, D‐30mV and O ar both reduced during the second phase (but not the first or third phase), when isometric twitch tension is also depressed. The relationship between action potential duration and twitch tension (P) for different [ATP]o's is linear for all three phases of the response, but the slopes of the curves (delta P/delta D) are markedly different, indicating that the sensitivity of the contractile system to membrane depolarization is not constant, but varies continuously throughout the response. 4. ATP has a potent stimulatory effect on the metabolism of endogenous 3',5'‐cyclic nucleotides. The time courses of the changes in adenosine 3','5‐cyclic monophosphate (3',5'‐cyclic AMP) and guanosine 3',5'‐cyclic monophosphate (3',5'‐cyclic GMP) are complex, but the accompanying change in isometric twitch tension is paralleled closely by corresponding changes in the ratio 3',5'cyclic AMP:3',5'‐cyclic GMP. 5. It is concluded that ATP exerts a dual effect on the ventricle and that the contractile response is regulated by changes in the metabolism of 3',5'‐cyclic nucleotides. The effects of indomethacin indicate a possible involvement of prostaglandins in mediating the ATP response. It is suggested that the initial effect of ATP on the ventricle is to increase the permeability of the fibres to Ca2+. 6. The relationship between 3',5' cyclic nucleotide levels and ventricular contractility is discussed. It is postulated that the antagonistic effects of 3',5'‐cyclic AMP and 3',5'‐cyclic GMP are expressed at the level of certain phosphoproteins which regulate both the availability of Ca2+ and the sensitivity of the contractile proteins to Ca2+.
Studies on the mechanisms of renin release from rat kidney slices: calcium, sodium and metabolic inhibition
Authors: Lyons H. Jay
Published: December 2014

1. The coincident release of renin and lactic dehydrogenase (LDH) from rat renal cortical tissue slices was studied during calcium depletion, metabolic inhibition, and with the addition of ouabain (1 m
M) to the incubation medium.

2. The results indicate that although LDH accumulated in the medium during incubation, the pattern was dissimilar to that of renin. Ouabain significantly inhibited renin release in calcium containing medium, but had no effect on LDH release. Renin release was potentiated in calcium ‘free’ media, while calcium depletion reduced the release of LDH.

3. The addition of potassium cyanide (2 m
M) significantly inhibited the release of renin from these tissue slices. Cyanide was ineffective, however, when administered in calcium ‘free’ medium.

4. At reduced incubation temperatures (5 °C) the release of both renin and LDH were significantly reduced.

5. Medium sodium depletion caused a significant inhibition of renin release. The simultaneous removal of calcium from the medium did not restore renin release to control levels.

6. These results are not consistent with the hypothesis that spontaneous renin release during calcium depletion and metabolic inhibition is a result of cell enlargement and increased membrane permeability. On the other hand, the in vitro release of renin during these experiments appeared to be inversely related to the intracellular concentration of calcium.
Oxygen consumption and phosphate efflux in mammalian non‐myelinated nerve fibres.
Authors: Ritchie J M , Straub R W
Published: December 2014

1. A comparison has been made between the efflux of labelled phosphate from the non‐myelinated fibres of the desheathed rabbit vagus nerve at 37 degrees C and the corresponding O2 consumption at rest and during activity, and during a variety of experimental interventions. 2. The resting rate constant of phosphate efflux was 2.61 X 10(‐3) min‐1: electrical stimulation (10 sec‐1, 3 min) produced an extra fractional loss of 6.75 X 10(‐6) impulse‐1. 3. The corresponding resting O2 consumption was 0.484 m‐mole x kg‐1 impulse‐1. 4. Ouabain (100 microM) produced a sustained depression (of about 40%) of the resting O2 consumption, accompanied by a transient fall (of about 14%) in the rate constant of phosphate efflux. 5. Na salicylate (10 mM) or Na arsenate (1 mM) produced a much larger increase in phosphate efflux than in resting O2 consumption. 6. Changing the external phosphate concentration (between 0.02 and 2 mM), addition of acetylcholine (1.7 mM), and addition of lanthanum (20 microM)‐‐all of which are known to affect markedly the phosphate efflux in rabbit non‐myelinated fibres‐‐had little or no effect on the resting O2 consumption or, where tested, on the extra O2 consumption with electrical stimulation. 7. Changing the external Ca concentration (between 0.09 and 9 mM) had only minor effects on the O2 consumption (resting and stimulated) and on the rate constant of resting phosphate efflux. 8. It is concluded that although changes in metabolism of the nerve produce changes in the phosphate efflux expected on the basis of the concomitant changes in the internal concentration of inorganic phosphate, the converse is not true; and increases and decreases in the rate constant of phosphate efflux do not necessarily signal the corresponding metabolic changes.
Coupling of aerobic metabolism to active ion transport in the kidney.
Authors: Balaban R S , Mandel L J
Published: December 2014

1. The redox state of mitochondrial NAD was monitored fluorometrically as a function of active ion transport work in the isolated doubly perfused bullfrog kidney. 2. Initial experiments to measure the O2 consumption (QO2) of small pieces from the bullfrog kidney gave a basal QO2 ‐ 3.0 (+/‐ 0.43) nmoles O2/mg dry wt. min. Addition of 50 microM‐ouabain inhibited QO2 by 72.7%. Subsequent addition of the mitochondrial uncoupler 1799 stimulated QO2 by 226%, while cyanide totally inhibited respiration. 3. Ion transport functional parameters and NADH fluorescence were simultaneously monitored during systematic reductions in perfusate PO2 to test the sufficiency of O2 delivery to the isolated perfused frog kidney. No significant changes in transport functions or fluorescence were observed until the PO2 dropped to 184 mm Hg or below. O2 tensions of 184 mm Hg or below caused decreases in G.F.R. and transport functions which were accompanied by an increase in NADH fluorescence. The lack of changes in kidney function in the PO2 range 550‐340 mmHg suggested that the tissue is adequately oxygenated at the normal perfusate PO2 of 550 mmHg. 4. The relationship between active transport rate and NAD redox levels was studied by increasing transport work (via increased G.F.R. or ADH) or by decreasing transport work (via decreased G.F.R. or ouabain) while simultaneously monitoring the NAD redox state of the intact tissue fluorometrically. In all cases, an increase in work caused a net oxidation of NAD while a decrease in work caused a reduction of NAD. 5. It is concluded that the NADH fluorescence responses are indicative of mitochondrial active to passive transitions in response to changes in active transport work. The aerobic production of ATP and the normally functioning Na‐K‐ATPase appear to be essential to maintain active transport and to elicit the appropriate state transitions. Thus, ATP (and, possibly, ADP and Pi) may be part of the coupling mechanism linking active ion transport and aerobic metabolic rate in the kidney.
The discharges during movement of cells in the ventrolateral thalamus of the conscious monkey.
Authors: Horne M K , Porter R
Published: December 2014

1. Monkeys were trained to perform a stereotyped movement task in return for food rewards. On completion of training a headpiece which allowed microelectrode access to the thalamus for single cell recordings during performances of the task was attached at a surgical operation. The location of each cell studied was determined by histological examination of the fixed brain and precise identification of electrode tracks. 2. Ninety‐three of ninety‐seven cells discharging in association with arm movements but not responding to natural activation of peripheral receptors in the forelimb were located predominantly in the rostral part of nucleus VPLo and the caudo‐ventral part of VLo. These cells appeared to be associated with active movement in one direction of a specific joint. 3. 52% of these ‘motor’ cells discharged in association with movements of either forelimb. The other 48% discharged in association with movement of the contralateral arm and hand only. 4. Sixty cells responded to stimulation of deep receptors or to passive limb manipulation in the relaxed and cooperative animal. These cells were predominantly located in the ventro‐caudal part of VPLo and all the responses were obtained from contralateral receptors. Their discharges during performances of the motor task were indistinguishable from those of ‘motor’ cells. 5. Ninety‐two cells were driven by limb manipulation and by natural activation of superficial cutaneous receptors and these were found predominantly in VPLo and VPLc. All responses were from contralateral receptors. These cells discharged during performance of the motor task; for some of them, their afferent input zones were not being stimulated by contact with the manipulandum when their ‘motor’ discharges commenced. 6. Although responses in each of the above groups of cells were sought by imposing a sudden perturbation of the limb during the performance of the active movement task, no responses were seen.
Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices.
Authors: Llinás R , Sugimori M
Published: December 2014

1. Intradendritic recordings from Purkinje cells in vitro indicate that white matter stimulation produces large synaptic responses by the activation of the climbing fibre afferent, but antidromic potentials do not actively invade the dendritic tree. 2. Climbing fibre responses may be reversed in a manner similar to that observed at the somatic level. However, the reversal does not show the biphasicity often seen at somatic level. 3. Input resistance of these dendrites was found to range from 15 to 30 M omega. The non‐linear properties seen at the somatic level for depolarizing currents are also encountered here. However, there seems to be less anomalous rectification. 4. Detailed analysis of repetitive firing of Purkinje cells elicited by outward DC current shows that, as in the case of the antidromic invasion, the fast somatic potentials (s.s.) do not invade the dendrite actively. However, the dendritic spike bursts (d.s.b.s) interposed between the s.s. potentials are most prominent at dendritic level. 5. Two types of voltage‐dependent Ca responses were observed. At low stimulus level a plateau‐like depolarization is accompanied by a prominent conductance change; further depolarization produces large dendritic action potentials. These two classes of response are TTX‐resistant but are blocked by Cd, Co, Mn or D600, or by the removal of extracellular Ca. 6. Following blockage of the Ca conductance, plateau potentials produced by a non‐inactivating Na conductance are observed mainly near the soma indicating that this voltage‐dependent conductance is probably associated with the somatic membrane. 7. Spontaneous firing in Purkinje cell dendrites is very similar to that observed at the soma. However, the amplitude of these bursts is larger at dendritic level. It is further concluded that these TTX‐insensitive spikes are generated at multiple sites along the dendritic tree. 8. Six ionic conductances seem to be involved in Purkinje cell electroresponsiveness: (a) an inactivating and (b) a non‐inactivating Na conductance at or near the soma, (c) a spike‐ and (d) a plateau‐generating Ca conductance, and (e) voltage‐dependent and (f) Ca‐dependent K currents. 9. The possible role of these conductances in Purkinje cell integration is discussed.
Synaptic modulation of calcium‐dependent potassium conductance in myenteric neurones in the guinea‐pig.
Authors: Grafe P , Mayer C J , Wood J D
Published: December 2014

1. Ganglion cells of the myentric plexus of the guinea‐pig small intestine were studied with intracellular recording methods. 2. Electrical stimulation of the interganglionic connectives elicited slow synaptic excitation (slow e.p.s.p.) that was associated with an increase in the input resistance of the cell. The slow e.p.s.p.s continued for several seconds after termination of stimulation, and they occurred only in neurones in which prolonged hyperpolarizing after‐potentials followed an action potential. 3. Superfusion of the neurones with solutions containing either 1‐5 mM‐Mn2+ or 16 mM‐Mg2+ and 1 mM‐Ca2+ mimicked the slow e.p.s.p. The common characteristics of Mn2+, Mg2+ and the slow e.p.s.p. were: (a) depolarization of the membrane potential, (b) increased input resistance of the cell, (c) augmented excitability, (d) blockade of post‐pike hyperpolarizing potentials and (e) reversal potential between ‐70 and ‐75 mV. 4. Analyses based on the ‘constant field equation’ indicated that the permeability ratios of K+ to other permeant ionic species were reduced when Ca2+ influx was blocked by Mn2+ or Mg2+. 5. The organic Ca antagonist D‐600 did not affect the neurones. 6. The results suggest that slow synaptic modulation of excitability within the myenteric plexus involves a reduction of both resting GK and post‐spike GK which is secondary to suppression of Ca2+ influx by the neurotransmitter for the slow e.p.s.p.
Fusimotor activity in masseter nerve of the cat during reflex jaw movements.
Authors: Appenteng K , Morimoto T , Taylor A
Published: December 2014

1. Unit recordings have been made from the central ends of filaments of the masseter nerve in lightly anaesthetized cats. Evidence is presented to show that fusimotor activity may be distinguished from alpha motor activity. 2. During reflex cyclic movements induced by intra‐oral stimulation, two distinct patterns of fusimotor firing emerged. One type of unit increased firing at the beginning and sustained this with little modulation throughout the movements. The other type was strongly modulated approximately in parallel with the alpha motor activity. 3. By comparison with records of jaw elevator spindle afferents under similar conditions, it was deduced that the sustained type of action was due to dynamic fusimotor neurones while the modulated type was due to static fusimotor neurones. 4. The patterns of fusimotor activity seen in these rhythmic movements under light anaesthesia agree well with the patterns deduced from spindle recordings in the conscious cat during mastication. 5. The results emphasize the importance of looking beyond a simple hypothesis of ‘alpha‐gamma co‐activation’ to explain fusimotor function. It is proposed that tonic dynamic fusimotor activity is set at the beginning of a movement to determine the incremental sensitivity of primary endings to stretch. The static fusimotor fibres are activated principally during shortening to help keep both primary and secondary endings active.