bluuebunny/crossref_metadata_2025 huggingface dataset:
Some limitations of the double sucrose gap, and its use in a study of the slow outward current in mammalian ventricular muscle. With an Appendix
Authors: McGuigan John A. S. , Tsien R. W.
Published: December 2014

1. A double sucrose gap method to clamp small bundles (diameter 0·8–1·2 mm) of sheep or calf ventricular fibres is described.

2. Comparison between micro‐electrode recordings from the central gap and the externally recorded potentials showed good agreement between the time course and amplitude of the action potentials. The rapid sodium inward current was not controlled on depolarizing clamp steps. On repolarization, control was obtained within 20 msec. The method is regarded as only suitable for a study of slow currents.

3. During clamps of several seconds duration slow changes in outward current can be demonstrated. The potential, where the instantaneous current—voltage relationship crosses the voltage axis, shifted in a positive direction as the clamp duration was increased (clamp amplitude constant), and did not alter much if the clamp amplitude was increased while the duration remained constant. For these reasons it is concluded that K ions accumulate round the cells.

4. A comparison between the instantaneous current—voltage relationship in various K solutions and after a depolarizing clamp, showed that an increase in external K could not exactly mimic the changes during a clamp. Because of this, a conductance change, unrelated to accumulation, is also postulated.

5. To measure the influence of the slowly increasing outward current during an action potential, slowly increasing inward current (to reduce net outward current) was applied during an action potential and the prolongation of the action potential measured. In the same experiment the increase in outward current during a clamp in a solution with tetrodotoxin and Mn was measured. From these experiments it is concluded that the slow increase in outward current does not contribute much to repolarization in sheep or calf.

6. Equations are derived for the voltage distribution and leakage current in the double sucrose gap. From the equations it is possible to calculate an optimal gap width. Too small a gap causes the membrane current to be swamped by the leakage current. Too wide a gap gives unequal potential distribution.
A kinetic approach to the study of absorption of solutes by isolated perfused small intestine
Authors: Fisher R. B. , Gardner M. L. G.
Published: December 2014

1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine.

2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen‐carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid.

3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions.

4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume.

5. In the steady state the concentration of glucose in the tissue fluid is 71 m
M when the luminal concentration is 28 m
M, and is 45 m
M when the luminal concentration is 8·3 m
M.

6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50–60 min.

7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15–20 min.

8. The Km for glucose absorption (14–19 m
M) is much lower than is found with unsegmented flow perfusion.

9. These findings emphasize problems in interpreting results from other types of intestinal preparation.

10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions.
Calcium movements in single crustacean muscle fibres
Authors: Ashley C. C. , Ellory J. C. , Hainaut K.
Published: December 2014

1. Internal microinjection of the Ca‐sensitive photoprotein aequorin or the isotope 45Ca have been used to assess Ca movements in single muscle fibres from the barnacle Balanus nubilus and the crab Maia squinado.

2. Progressive isosomotic replacement of external Na by Li, choline, sucrose or Tris was associated with a rapid increase in the level of light emission from internally injected aequorin. This response was dependent upon the presence of external Ca. The light output was maximal for Na concentrations < 50 m
M in the replaced salines, while Na concentrations > 350 m
M produced no apparent increase in the resting light emission.

3. If the Ca concentration in the external saline was altered, no effect was observed in Na replaced salines when the Ca concentration was < 1 m
M, but maximal effects were observed at concentrations of Ca of ca. 100 m
M.

4. The increased light emission from aequorin in Na‐replaced salines was substantially inhibited by 1 m
M‐La3+ applied externally, but not by
N‐ethyl maleimide (NEM), propanolol or D‐600.

5. Following microinjection of 45Ca and 2 hr equilibration, the residual efflux of Ca was shown to be sensitive to the removal of external Ca and Na, the extent of each component being variable.

6. The Na‐sensitive Ca efflux was partially inhibited by external La3+ (1 m
M), but not by high concentrations of Mg2+, Ca2+, Mn2+ or Co2+. It was stimulated by NEM and ethacrynic acid, which was considered to be due to an indirect effect upon the sarcoplasmic reticulum.

7. It is concluded that Ca movements in these single crustacean muscle fibres involve Na gradients and a Ca: Ca exchange and from the relative insensitivity of Ca movements to various inhibitors, in contrast to the Mg system, it seems that there may be two independent modes for divalent cation transport in this preparation.
Persistent modification of synaptic interactions between sensory and motor nerve cells following discrete lesions in the central nervous system of the leech
Authors: Jansen J. K. S. , Muller K. J. , Nicholls J. G.
Published: December 2014

We have examined changes that develop in the synaptic interactions of sensory and motor nerve cells following surgical lesions to the central nervous system of the leech. In one type of operation an individual ganglion was isolated from the rest of the nervous system by severing all the incoming and outgoing fibres. During the next few weeks, marked changes appeared in synaptic interactions.

1. In chronically isolated ganglia inhibitory potentials were recorded in the motoneurone which raises the skin into ridges (the AE cell) following impulses in sensory neurones that respond to pressure (P) or noxious (N) stimuli. In contrast the same AE cell in ganglia taken from normal animals shows excitatory synaptic potentials when the P or N sensory cells are stimulated.

2. Another altered synaptic interaction in ganglia isolated by lesions was that between sensory cells responding to touch and a motoneurone that supplies longitudinal muscles (L cell). Instead of the pure, electrical coupling potential seen normally, a large, additional chemically mediated excitatory potential was also apparent.

3. Some of the changes in synaptic interactions were not restricted to synapses within the isolated ganglion, but appeared gradually over the following year in successive ganglia along the length of the ventral nerve cord.

4. Indirect evidence suggests that the altered synaptic potentials that became conspicuous after operations are also present but smaller and obscured in normal animals.

5. It is concluded that some synapses in the leech nervous system are more readily changed than others by cutting the connectives. Furthermore, these changes influence in a predictable manner the way in which the animal behaves in response to mechanical stimuli.
Changes of intracellular sodium and potassium ion concentrations in isolated rat superior cervical ganglia induced by depolarizing agents
Authors: Brown D. A. , Scholfield C. N.
Published: December 2014

1. Na and K contents of isolated rat superior cervical ganglia were measured by flame photometry, and intracellular Na and K concentrations ([Na]i and [K]i) calculated using Li and 35SO4 to determine extracellular space (e.c.s.).

2. Resting concentrations after 1‐2 hr incubation at 25° C in normal Krebs solution were: [Na]i, 19·8 ± 0·9 m‐mole (kg cell water)−1; [K]i, 192·7 ± 2·8 m‐mole (kg cell water)−1 (mean ±
S.E. of mean of thirty‐five ganglia). Correction for losses during e.c.s. measurement gave 22 m
M [Na]i and 207 m
M [K]i as probable fresh concentrations.

3. Carbachol (180 μ
M for 4 min) increased [Na]i by 47·8 ± 2·9 m‐mole (kg cell water)−1 and decreased [K]i by 54·6 ± 4·3 m‐mole (kg cell water)−1. Maximal exchange with carbachol or nicotine (at ∼ 1 m
M for 4 min) amounted to 80–100 m‐mole (kg cell water)−1. On washing with Krebs solution containing 2·5 m
M hexamethonium recovery of ionic concentrations occurred with a rate constant of 0·3–0·4 min−1.

4. Restitution of ganglionic Na and K after carbachol was inhibited by washing with K‐free solution, and slowed by ouabain (0·14 m
M), cyanide (2 m
M) or cooling (Q10 2·7 between 17 and 27° C).

5. Equilibrium potentials for Na and K (ENa, EK) at rest were calculated to be +49 and −88 mV. At a membrane potential (Em) of −70 m
V, the permeability ratio PNa:PK was calculated at 0·04:1 (assuming PCl:PK < 0·1).
Intracellular chloride activity and the effects of acetylcholine in snail neurones
Authors: Neild T. O. , Thomas R. C.
Published: December 2014

1. Cl−‐sensitive micro‐electrodes were used to measure intracellular Cl− in snail neurones. The electrodes consisted of a sharpened and chlorided silver wire mounted inside a glass micropipette.

2. The electrodes appeared to record changes in internal Cl− accurately but in H cells the chloride equilibrium potential (ECl) as measured by the Cl−‐sensitive electrode was always less negative than EACh.

3. In some H cells ACh caused a measurable increase in internal Cl− when the cell was at its resting potential. In voltage‐clamped cells there was a close correlation between the change in internal Cl− and the extra clamp current caused by a brief application of ACh. This confirmed that ACh increases the cell's membrane permeability only to Cl− ions, and that EACh was equal to ECl.

4. There was good agreement between the measured change in internal Cl− and that calculated from the cell size and clamp charge only when it was assumed that a constant voltage offset was added to the potential of the Cl−‐sensitive electrode while it was inside the nerve cell.

5. Cl−‐sensitive electrodes with AgCl as the sensitive material appear to be unsuitable for intracellular measurement of Cl−, although they might be suitable for following changes in ECl.

6. In certain D cells ACh also caused an increase in internal Cl− although it decreased the membrane potential. In the presence of hexamethonium, ACh caused a hyperpolarization and a smaller increase in internal chloride.

7. It is concluded that the intracellular Cl− in both H and D cells is about 8·3 m
M, giving an ECl of about −58 mV.
Regenerations of the noradrenergic innervation of the cardiovascular system of the chick following treatment with 6‐hydroxydopamine
Authors: Bennett T. , Malmfors T.
Published: December 2014

1. Fluorescence histochemical and pharmacological studies were made of the noradrenergic innervation of inferior venae cavae and left atria from 2‐ and 6‐week‐old chicks before, and following, treatment with 6‐hydroxydopamine.

2. Noradrenergic nerves in the younger animals appeared to be relatively resistant to the toxic effects of 6‐hydroxydopamine.

3. In the older animals, the time course of recovery from the effects of 6‐hydroxydopamine appeared to reflect the rate of regeneration of destroyed noradrenergic nerves.

4. Marked presynaptic supersensitivity to adrenaline and noradrenaline was observed in left atria and inferior venae cavae following treatment with 6‐hydroxydopamine.
The distribution, activity, and function of the cilia in the frog brain
Authors: Nelson Deborah J. , Wright Ernest M.
Published: December 2014

1. The distribution, activity, and function of the cilia in the brain was studied using in vitro preparations of the frog choroid plexuses and ependyma.

2. Scanning electron microscopy revealed that twenty to forty cilia, about 20 μm long, project from the cells of the choroidal epithelium and ependyma into the ventricular system of the brain.

3. These cilia beat at a constant frequency which ranged from 5 to 20 c/s. Ciliary activity was enhanced by ATP, cyclic AMP, theophylline, and acetylcholine, and was depressed by DNP, IAA, Ni2+, La3+, and Co2+.

4. Ciliary motion produced a flow of c.s.f. over the surface of the cells lining the ventricles, and in the choroid plexus this flow reduced the effective thickness of the unstirred layer adjacent to the epithelium by about 100 μm.

5. These results are discussed in relation to the factors that control the frequency of ciliary beating, and the role of the cilia in the circulation of the c.s.f.
The postural response of normal dogs to sinusoidal displacement
Authors: Brookhart John M. , Talbott Richard E.
Published: December 2014

1. Normal dogs were trained to adopt a laterally symmetric stance on a horizontal platform. Sinusoidal oscillation of the platform in the cephalocaudal direction caused the dogs to adopt a strategy of response which would keep them from falling down during the period of imposed motion or perturbation.

2. A Fourier analysis of the response variables provided a quantitative measure of the distortion in the induced movement at the various hind leg joints and in the motion of the body. Certain aspects of the distortion could be accounted for by recognized random events such as drift and panting. The remainder of the distortion was task related and therefore provided evidence that the dog's postural control system behaved essentially as a non‐linear system.

3. The motion of the body was less distorted than the motion at the joints. The frequency response of the body motion resembled that of a second order linear system, but the amplitude of the body motion did not vary in constant proportion with changes in the amplitude of the input. Further, the phase relation between body motion and platform motion was not constant when the amplitude of the input was changed. Therefore, it was concluded that the control of the body position was probably non‐linearly related to the input disturbance but that the low pass filter characteristics tended to minimize the appearance of distortion in that system output.

4. Control of the position of the hind limb is related to the control of the torque generated at the hind limb joints. To the extent that joint angle and change in joint angle are related to the torque at a joint, the distortion of the motion at the joints clearly demonstrates that control of the hind limb during this postural task was non‐linearly related to the sinusoidal input.

5. The uniformity of the response parameters, as assessed from the Fourier coefficients, indicated that all of the tested dogs adopted the same or nearly the same strategy for solving the problem of adjusting their postural control in response to the perturbation. Therefore, a reasonable hypothesis for future testing is that the central programme which generates this particular postural response will be structured similarly from one dog to the next.
Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5‐hydroxytryptamine
Authors: Gerschenfeld H. M. , Tritsch Danièle Paupardin
Published: December 2014

1. Molluscan neurones have been found to show six different types of response (three excitatory and three inhibitory) to the iontophoretic application of 5‐hydroxytryptamine (5‐HT). The pharmacological properties of the receptors and the ionic mechanisms associated with these responses have been analysed.

2. Four of the responses to 5‐HT (named A, A′, B and C) are consequent upon an increase in membrane conductance whereas the other two (named α and β) are caused by a decrease in membrane conductance.

3. The A‐response to 5‐HT consists of a ‘fast’ depolarization due to an increase mainly in Na+‐conductance; the A′‐response is a ‘slow’ depolarization also associated with a Na+‐conductance increase. Receptors mediating the A‐ and A′‐depolarizations have different pharmacological properties and may exist side by side on the same neurone.

4. Both the B‐ and C‐responses are inhibitory. The B‐response is a ‘slow’ hyperpolarization due to an increase in K+‐conductance, the C‐response is a fast hyperpolarization associated with an increase in Cl−‐conductance.

5. The α‐response to 5‐HT is a depolarization which becomes reduced in amplitude with cell hyperpolarization and reverses at −75 mV; it is caused by a decrease in K+‐conductance. The β‐response is an hyperpolarization which increases in amplitude with cell hyperpolarization and reverses at −20/−30 mV. It results from a decrease in conductance to both Na+ and K+ ions.

6. The receptors involved in the 5‐HT responses associated with a conductance increase may be recognized by the action of specific antagonists: 7‐methyltryptamine blocks only the A‐receptors, 5‐methoxygramine only the B‐receptors and neostigmine only the C‐receptors. Curare blocks the A‐ and C‐receptors and bufotenine, the A‐, A′‐ and B‐receptors. No specific antagonists have yet been found for the 5‐HT responses caused by a conductance decrease.

7. The significance of the multiplicity of receptors is discussed. Their functional significance at synapses is analysed in the following paper.
Phosphenes produced by electrical stimulation of human occipital cortex, and their application to the development of a prosthesis for the blind
Authors: Dobelle W. H. , Mladejovsky M. G.
Published: December 2014

1. To explore the feasibility of a visual prosthesis for the blind, human visual cortex has been stimulated during a series of surgical procedures on conscious volunteers undergoing other occipital lobe surgery.

2. Area no. 17 seems the most effective locus for such stimulation, at least in sighted or recently hemianopic patients.

3. Changes in electrode size and configuration, or in stimulus parameters, have little effect on subjective sensation.

4. Thresholds do vary depending on parameters, but not electrode size, and these effects have been studied.

5. Painful effects are associated with stimulation of the dura, but not of the calcarine artery and associated vessels.

6. Stimulation of a single electrode usually produces one phosphene, whose size ranges from tiny punctate sensations like ‘a star in the sky’ up to a large coin at arm's length. Very large elongated phosphenes, like those seen by Brindley's second patient, have not been reported despite the number of patients, electrodes, and combinations of stimulus parameters tested. These large phosphenes may be an effect of prolonged blindness.

7. Stimulation substantially above threshold may produce a second conjugate phosphene, inverted about the horizontal meridian.

8. Stimulation of a single electrode may also produce multiple phosphenes with no differential threshold.

9. Chromatic effects and/or phosphene flicker may, or may not occur. This can vary from point to point on the same patient.

10. Phosphenes fade after 10–15 sec of continuous stimulation.

11. All phosphenes move proportionately with voluntary eye movements, within the accuracy of our mapping techniques.

12. Brightness modulation can easily be achieved by changing pulse amplitude.

13. The position of phosphenes in the visual field corresponds only roughly with expectations based on classical maps showing the projection of the visual field onto the cortex.

14. Patients can usually discriminate phosphenes produced by 1 mm2 electrodes on 3 mm centres, although this seems to be close to the limit of resolution.

15. Patterns of up to four phosphenes produced by four electrodes have been recognized. However, a variety of complex interactions have been reported.

16. Multiple phosphenes are co‐planar, although patients are unable to estimate their distance.

17. Phosphenes appear immediately when stimulation is begun, and disappear immediately upon cessation of stimulation.

18. Future work must concentrate on blind volunteers to explore possible differences in subjective sensation produced after prolonged blindness, and to explore more complex pattern presentation which requires substantial periods of time with any given patient.
Response patterns of amphibian olfactory bulb neurones to odour stimulation
Authors: Kauer John S.
Published: December 2014

1. Responses of 199 single olfactory bulb neurones in the frog were observed with odour stimulation.

2. To effect control over the concentration, flow rate and time course of the stimulus application, a simple olfactometer was developed and calibrated using a gas chromatograph. The stimulus pulses were monitored by recording the electro‐olfactogram from the olfactory mucosa.

3. Several categories of unit activity became evident after delivering many odour applications (637). Some odour applications did not cause any change in the spontaneous activity of the unit. This was classified as type N (no response) activity. Some applications caused a suppression of ongoing activity (type S activity). Some applications caused an excitation during the rising concentration phase of the stimulus pulse (type E activity). Three temporal patterns of excitatory responses were seen and these were categorized as subgroups of activity type E.

4. Since each response type was seen with about the same frequency regardless of the odour used, this suggested that the temporal patterns of response per se were not coding for odour type.

5. When odour concentration was manipulated for a unit showing suppressive (type S) activity at one concentration, then the unit tended to show qualitatively similar suppression at other concentrations as long as they were above threshold.

6. When peak concentrations were manipulated for units showing excitatory (type E) activity, the temporal patterns of response could change dramatically. In many cases the units fired after one level of concentration had been reached and were subsequently suppressed with increase in concentration. Such ‘concentration tuning’ suggested that excitatory temporal patterns, in contrast to suppressive ones, were coding odour concentration information.

7. The significance of the changes in temporal response patterns seen here, for experiments examining the relationships between odours using single unit response data, is discussed.
Optical quality of the living cat eye
Authors: Bonds A. B.
Published: December 2014

1. The optical quality of the living cat eye was measured under conditions similar to those of cat retinal ganglion cell experiments by recording the aerial image of a nearly monochromatic thin line of light.

2. Experiments were performed to assess the nature of the fundal reflexion of the cat eye, which was found to behave essentially as a diffuser.

3. The optical Modulation Transfer Function (MTF) was calculated from the measured aerial linespread using Fourier mathematics; the MTF of a ‘typical’ cat eye was averaged from data collected from ten eyes.

4. The state of focus of the optical system, the pupil size and the angle of the light incident on the eye were all varied to determine their effect on image quality.

5. By using an image rotator, the aerial linespread was measured for several orientations of the line; these measurements yielded an approximation of the two‐dimensional pointspread completely characterizing the optical system.

6. Evidence is reviewed to show that the optical resolution of the cat, albeit some 3‐5 times worse than that of human, appears to be better than the neural resolution of its retina and its visual system as a whole.
Pancreatic acinar cells: effects of lanthanum ions on amylase release and calcium ion fluxes
Authors: Chandler D. E. , Williams J. A.
Published: December 2014

1. The effect of La3+ on amylase release and Ca2+ fluxes in mouse pancreatic fragments in vitro was studied.

2. Amylase release was increased by 0·1 m
M‐La3+ and progressively inhibited by 1·0–10 m
M‐La3+. Non‐stimulated and bethanecol stimulated secretion were altered in an identical manner. Inhibition of amylase release was rapid and reversible.

3. Uptake of 45Ca2+ was multiphasic with equilibrium with stable Ca2+ still not complete after 2 hr. La3+ (10 m
M) limited uptake of 45Ca2+ to the extracellular space and slightly decreased total Ca2+ content. Lower concentrations of La3+ affected 45Ca2+ uptake and total Ca2+ content in a biphasic manner which paralleled effects on amylase release.

4. La3+ restricted washout of 45Ca2+ to isotope in the extracellular space and abolished the bethanecol‐stimulated increase in 45Ca2+ efflux.

5. Uptake of 45Ca2+ into intracellular space, as measured by the ‘lanthanum’ method, was not affected by bethanecol.

6. Tissue ultrastructure and Na+ and K+ content were not affected by La3+.

7. It is concluded that an influx of extracellular Ca2+ is not important for triggering of secretion and that La3+ may inhibit amylase release by acting on the release process rather than on Ca2+ influx.
Regenerative hyperpolarization in rods.
Authors: Werblin F S
Published: December 2014

1. The electrical properties of the rods in Necturus maculosus were studied at the cell body and the outer segments in dark and light under current and voltage clamp with a pair of intracellular electrodes separated by about 1 mum. 2. The membrane resistance in the dark was voltage‐ and time‐dependent both for the cell body and the outer segment. Slight depolarizations in the cell body reduced the slope resistance from 60 to 10 M omega with a time constant of about 1 sec. Polarization in either direction, at the outer segment, when greater than about 20 mV, reduced the slope resistance from 60 to 30 M omega. The dark potential in the cell body was typically −30 to −35 m V; at the outer segment it was typically only −10 to −15 mV. 3. The light‐elicited voltage response in both the cell body and the outer segment was largest with the membrane near the dark potential level. In both regions, the response was reduced when the membrane was polarized in either direction. 4. Under voltage‐clamp conditions, a reversal potential for the light response near + 10 mV was measured at the outer segment. At the cell body no reversal potential for the light response was measured; there the clamping current required during the light response was almost of the same magnitude at all potential levels. 5. When the membrane at the cell body was hyperpolarized in the dark under voltage clamp, a transient outward current, typically about one‐half the magnitude of the initial inward clamping current was required to maintain the membrane at the clamped potential level. This outward current transient was associated with a decrease in membrane resistance with similar time course. The transient outward current reversed and became inward when the membrane was clamped to potentials more negative than −80 mV. Thus, the transient outward current appears to involve a transient activation initiated by hyperpolarization. I is regenerative in that it is initiated by hyperpolarization and tends to further hyperpolarize the membrane. 6. The reversal potential for the light response was measured at the outer segment but not at the cell body. The regenerative hyperpolarization was measured at the cell body but not at the outer segment. Thus, the outer segment and cell body appear to have different electrical properties: a light‐elicited resistance increase at the outer segment causes a potential‐dependent transient decrease at the inner rod. 7. An electrical model of the rod, based upon estimates of the membrane resistances and membrane e.m.f.s. in the dark, was derived from the data. This model predicts the appropriate response potentials at outer segment and cell body when perturbed by the measured light‐elicited resistance increase at the outer segment. An estimate of membrane current in dark, of 0–2 mA, is also derived from the model.
Sodium and calcium components of the action potential in a developing skeletal muscle cell line.
Authors: Kidokoro Y
Published: December 2014

1. Developmental changes in action potential properties were studied in a clonal rat skeletal muscle cell line. 2. Small action potentials were evoked in mononucleate myoblasts. No spike was seen in Na‐free saline. A similar spike was evoked in a medium where all NaCl was replaced by LiCl. No spike was evoked when NaCl was replaced by CsCl. 3. Action potentials overshot zero membrane potential in multinucleate myotubes. The action potential was composed of two components, an initial fast spike and a hump on the falling phase or in some cases a distinct second peak. 4. Teh overshoot of the initial fast spike decreased when the external Na concentration was decreased. 5. In saline with 10 mM‐Ca the second component often formed a distinct peak following the initial fast spike. A slow regenerative potential was evoked in Na‐free media with a depolarizing current pulse. 6. In saline containing BaCl‐2 instead of CaCl‐2 there was always a second peak, the overshoot of which changed with external Ba concentration. A slow regenerative potential was evoked in Na‐free, Ba‐saline. The membrane conductance at the peak of the Ba‐action potential was larger than in the resting state. 7. In adult rat skeletal muscle, the shape of the action potential was not changed when Ca was replaced by Ba. No action potential was evoked in Na‐free Ba‐saline or Ba‐saline with tetrodotoxin (3 times 10–7 M). 8. The significance of the Ca component in the developing muscle is discussed.
Behavioural and autonomic induction of prostaglandin E‐1 fever in squirrel monkeys.
Authors: Crawshaw L I , Stitt J T
Published: December 2014

1. Prostaglandins E1 (PGE1) was injected into the preoptic/anterior hypothalamic (PO/AH) area of the squirrel monkey. 2. Increases in rectal temperature (Tre) produced by PGE1 injections of 20 ng to 500 ng were dose‐dependent. 3. When ambient temperature (Ta) was below the thermoneutral zone, increases in Tre were produced entirely by increases in metabolic rate. With Ta at the upper end of the thermoneutral zone, increases in Tre were produced by vasoconstriction in addition to lesser increases in metabolic rate. 4. During sessions of behavioural temperature regulation, PGE1 injections were followed by the selection of a higher Ta, increased skin temperature and subsequent increases in Tre. 5. PGE1 injections produce dose‐dependent increases in Tre which are similar regardless of ambient temperature or whether behavioural or autonomic means are utilized to raise the heat content of the body.
Estimates of statistical release parameters from crayfish and frog neuromuscular junctions.
Authors: Wernig A
Published: December 2014

1. Transmitter release at crayfish and frog neuromuscular junctions was studied by recording synaptic potentials with extracellular or intracellular glass micro‐electrodes. 2. The binomial release parameters n and p were calculated using the experimental observations for the mean number of quanta (m) released in a series of trials, the variance (var) of the quantum content distribution and the number of transmission failures (n–o). 3. In one series of experiments on frog neuromuscular junction, action potentials were blocked by tetrodotoxin. Transmitter release was limited to a circumscribed part of the nerve terminal by focal stimulation with a glass micro‐electrode. Values for m were between 0–6 and 5‐7 and calculated values for n ranged from 3 to 23. p was between 0–05 and 0–48. In a second series of experiments on frog neuromuscular junction transmitter release was evoked by conventional stimulation of the nerve trunk in Mg‐Ringer. m was mostly between 20 and 60 and in the same experiments n was calculated to be between 70 and 125. Values for p ranged from 0–25 to 0–48. 4. It can be concluded from the present results that transmitter release at frog neuromuscular junction is described by binomial statistics as is the case for neuromuscular junction of crayfish. 5. In comparing the values for n for the two series of experiments on frog neuromuscular junction it appears that n is dependent on the length of the activated synaptic contact. The numbers for n calculated from frog neuromuscular junction are of the same order of magnitude as the number of ‘active zones’ seen in the corresponding length of the synaptic nerve terminal.
Factors affecting the time course of decay of end‐plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction.
Authors: Magleby K L , Terrar D A
Published: December 2014

1. End‐plate currents have been studied in gylcerol‐treated frog sartorius nerve‐muscle preparations with the voltage‐clamp technique. 2. Adding the anticholinesterase prostigmine (3 muM) to the solution bathing the muscle caused a 2‐7 (mean 3‐3) times increase in the time constant of decay of end‐plate currents. The anticholinesterase edrophonium (15 muM) also prolonged the time course of end‐plate currents. 3. Pre‐treatment of the preparation with collagenase, which leads to the removal of acetylcholinesterase in the synaptic cleft, prolongs the time course of end‐plate currents. 4. Curare (1–2 muM), cobratoxin (0–13 muM), or alpha‐bungarotoxin (0‐13‐0‐26 muM) decreased the time constant of decay of end‐plate currents in the presence of prostigmine. 5. These observations are consistant with the suggestion that repeated binding of acetylcholine (ACh) molecules to receptors as the ACh escapes from the synaptic cleft can contribute to the prolongation of end‐plate currents which occurrs when acetylcholinesterase activity is eliminated. 6. Increasing the amount of transmitter released from the presynaptic nerve terminal leads to a prolongation of end‐plate currents in the presence of prostigmine. 7. In the presence of prostigmine, the second of two end‐plate currents (interval 2‐10 msec) decays more slowly than the first. 8. ACh (1–40 muM) or carbachol (40 muM) applied in the solution bathing the muscle prolongs end‐plate currents in the presence of prostigmine. 9. It is suggested on the basis of the observations described in paragraphs 6 to 8 that the time constant of decay of end‐plate currents in the presence of prostigmine increases with increasing concentrations of ACh in the synaptic cleft. In the absence of prostigmine, increasing the concentration of ACh in the synaptic cleft did not change the time constant for decay of end‐plate currents. 10. We interpret these results to suggest that ACh can have a cooperative action on receptors such that the association of ACh with one receptor (defined as binding a single ACh molecule) favours the binding or retention of ACh at other receptors. This implies that receptors can interact.
Circadian rhythms in the flow rate and composition of unstimulated and stimulated human submandibular saliva.
Authors: Dawes C
Published: December 2014

1. Nine subjects recorded oral temperature and collected unstimulated submandibular saliva and submandibular saliva stimulated by sour lemon drops at a constant flow rate of 1 ml./min, at about 07.00, 11.00, 14.00, 17.00 and 22.00 h daily for time spans of about 11 days. 2. Least‐squares cosine waves were fitted to the data to test for the presence and characteristics of circadian rhythms and the results were subjected to cosinor analysis and the Rayleigh test to assess the statistical significance of any rhythms for the group of subjects as a whole (i.e. whether or not the computed acrophases were randomly distributed throughout the 24 h of the day). 3. Unstimulated submandibular saliva showed circadian rhythms, significant for the group as a whole, in flow rate and in the concentrations of sodium, potassium, magnesium, chloride and inorganic phosphate but not in protein or calcium. 4. Stimulated submandibular saliva showed circadian rhythms, significant for the group as a whole, in sodium, potassium, calcium, magnesium, chloride and inorganic phosphate but not in protein. Oral temperature also showed a significant circadian rhythm. 5. Because of the high amplitude of many of these rhythms, they must be taken into account when establishing the normal range of salivary values, or when salivary composition is to be used as an indicator of systemic disease or to be implicated in the aetiology of oral disease.
Anomalous rectification in horizontal cells.
Authors: Werblin F S
Published: December 2014

1. The electrical properties of horizontal cells in the mudpuppy in light and dark were measured with a pair of micropipettes separated by about 1 mum with low coupling resistance so that no bridge circuitry was required. 2. All horizontal cells studied showed significant anomalous rectification: the current‐voltage characteristic for about 60 per cent of the cells studied had a slope resistance of about 20–30 M omega at the dark potential level; the slope resistance increased by about 15% for each 10 mV depolarization and decreased by about 15% for each 10 mV hyperpolarization. The remaining 40% of the horizontal cells showed a higher input resistance at corresponding potential levels but had similar rectifying properties. 3. The increase in resistance with depolrization developed with a time course of about 1/2 sec when steady steps of outward current were passed across the membrane, but the time course for resistance decrease with hyperpolarization was much shorter for steady inward current steps. In about half the horizontal cells there was a transient decrease in resistance lasting about 100 msec immediately following the outward current steps superimposed upon the slower sustained resistance increase. 4. The normal 20–30 mV hyperpolarizing light response was associated with little or no change in input resistance. However, if the membrane potential was held at the dark potential level with extrinsic current, thereby eliminating the potential‐dependent resistance change, a light‐elicited resistance increase of about 10 M omega was measured. 5. The time‐dependent change in membrane resistance elicited by polarizing steps of current obscured the reversal potential for the response. However, when the reversal potential was measured at short times following polarization of the membrane, before the time‐dependent resistance change developed, it was estimated at between +15 and +50 m V. 6. The results suggest that the horizontal cell response is mediated by a light‐elicited resistance increase at the synaptic membrane which is obscured by a potential‐ and time‐dependent resistance decrease at another part of the membrane.
Effect of growth in lithium on ouabain binding, Na‐K‐ATPase and Na and K transport in hela cells.
Authors: Boardman L J , Hume S P , Lamb J F , Polson J
Published: December 2014

1. HeLa cells were grown for 24 hr in growth medium in which part of the Na was replaced with Li. Ion contents, cell volumes and numbers, Na‐K‐ATPase and specific ouabain binding were measured. In some experiments the Na efflux and net Na transport was also measured. 2. Growth in Li caused a rise in the specific ouabain binding and membrane Na‐K‐ATPase of these cells. The Li concentrations in the cells necessary to produce this effect ranged up to 50 mM. 3. It is suggested that Li, like Na, acts on the genetic material of the cells to cause the production of more Na pumps within the membrane.
The distribution of acetylcholine sensitivity at the post‐synaptic membrane of vertebrate skeletal twitch muscles: iontophoretic mapping in the micron range.
Authors: Kuffler S W , Yoshikami D
Published: December 2014

1. The distribution of acetylcholine (ACh) sensitivity was mapped in skeletal twitch muscles of the snake, frog and mudpuppy with iontophoretic methods that provide a resolution in the mum range. 2. The preparations were thin sheets of muscle fibres that were viewed with Nomarski optics, giving sharp definition of cellular detail. The muscles in the snake were especially suitable. Their motor nerves terminate in a compact cluster of synaptic boutons that rest in distinct craters on the muscle surface. After treatment with collagenase the motor nerve and its terminal boutons can be removed, exposing the subsynaptic membrane in the craters. 3. The slopes of dose‐response curves obtained by iontophoretic application of ACh were expressed in mV/nC and used as an index of ACh sensitivity. The areas of highest sensitivity, tested either with the terminals in place or removed, were those immediately under the presynaptic terminals. The greatest subsynaptic sensitivities were about 5000 mV/nC, and the time course of the potentials caused by ACh released iontophoretically closely matched that of synaptic potentials set up by ACh released by the nerve. 4. The sensitivity of the extrasynaptic surface less than 2 mum away was at least 50 times lower than that of the subsynaptic membrane. The low extrasynaptic sensitivity declined still further at greater distances. 5. Acetylcholinesterase was shown physiologically to be confined to subsynaptic areas. No activity of the enzyme was detected in extrasynaptic areas beyond about 2 mum from the edge of the synapse. 6. The confinement of high densities of receptors and of acetylcholinesterase to the subsynaptic membrane in muscles is also a feature in parasympathetic neurones. It is suggested that similar specialization may be a widespread property of neurones with chemical synapses.
Observation on the localization of mechanoreceptors in the kidney and afferent nerve fibres in the renal nerves in the rabbit.
Authors: Niijima A
Published: December 2014

1. The distribution and localization of mechanoreceptors in the kidney were studied by recording afferent impulses from the renal nerve bundle or from single nerve fibres in the isoloted kidney preparation in the rabbit. 2. It was observed that mechanoreceptors are distributed in the cranial, central and caudal portions as well as the pelvic portion of the kidney. Diameter range of single nerve fibres from which afferent impulses were recorded was from 2 to 8 mum. 3. Histological studies show that the renal nerve possesses abundant non‐myelinated nerve fibres with a relatively small number of myelinated nerve fibres. The myelinated axons had diameters ranging from 0–5 to 13–4 mum and the peak of the unimodal distribution curve was 1–5‐‐2–4 mum.
Secretion of calcium in pancreatic juice.
Authors: Ceccarelli B , Clemente F , Meldolesi J
Published: December 2014

1. The orgin of the calcium secreted by the pancreas has been investigated in vivo in the guinea‐pig by a study carried out in parallel (a) in the juice secreted in response to the injection of either secretin or caerulein and (b) in the pancreatic tissue and in cell fractions isolated thereform. 2. In agreement with previous findings we observed that the concentration of calcium is low in the secretin‐stimulated and high in the caerulein‐stimulated juice. In the latter calcium and protein are proportional (cal0 n‐mole:mg). 3. After I.V. injection of 45Ca the radioactivity decreases rapidly and quasi‐exponentially in the blood plasma. A roughly parallel time course is found in the secretin‐stimulated juice: the evolution of the juice: plasma radioactivity ratio resembles that observed with the extraceullar space marker [3H]D‐sorbitol. In contrast, the time course of 45Ca in plasma and caerulein‐stimulated juice are not proportional: the high levels characteristic of this juice are reached several minutes after the injection and maintained thereafter. This increase is followed ca. 50 min later by the appearance of the newly synthesized [3H]L‐leucine‐labelled proteins. 4. The pancreatic tissue is rich in calcium which is localized primarily in zymogen granules (Ca.36 n‐mole:mg protein) and mitochondria; the soluble cytoplasm is low in calcium. 5. The injected 45Ca accumulates in zymogen granules faster than [3H]L‐leucine‐labelled proteins. The 45Ca:protein ratio of these organelles is considerably lower than that of the caerulein‐stimulated juice. 6. It is concluded (a) that calcium is secreted in to the pancreatic juice in two fractions, one (possibly released by simple diffusion) associated with the electrolyte component, the other with protein of the juice, (b) that zymogen granules are the major, but not the only source of the latter fraction, and (c) that the zymogen granule‐associated calcium joins the exportable proteins some time after their synthesis, possibly in the Golgi complex and/or in the condensing vacuoles.
Ionic currents in the uterine smooth muscle.
Authors: Kao C Y , McCullough J R
Published: December 2014

1. Short segments of isolated longitudinal myometrium from the pregnant rate uterus have been studied in a double sucrose‐gap voltage‐clamp arrangement. The clamped segment averaged 65 mum times 240 mum times 100 mum, has an average total capacitance of 0–14 muF, and may contain 50–200 individual myometrial cells. 2. A significant resistance exists in series with the membrane, and limits theprecision of the quantitative information. However, it is argued that some qualitative and some comparative information is useful. 3. In Krebs‐bicarbonate solution, depolarizing steps produced initial transient inward currents followed by delayed outward currents. 4. When [Na+]o was reduced by 50%, the equilibrium potential Ea shifted by an average of −17–6 mV, the maximum inward current was reduced to 0–5, the time to peak of the early current was delayed by 1–1 msec, and the maximum chord conductances for the early(Ga) and late (GK) currents remained unchanged as compared with those in normal [Na+]o. 5. When [Ca2+] was reduced to 25% of normal, Ea shifted by an average of −20–3 mV, the maximum inward current was reduced to 0–5, the time to peak was delayed 3–1 msec, and Ga was significantly reduced, while GK was unaffected. 6. The early current, and its tail when repolarization was imposed, reversed direction from inward to outward when [Na+]o was reduced from 143 mM to zero, with [Ca2+]o remaining constant at 1–9 mM. 7. From the observations in 4, 5 and 6, it was concluded that Na+ is the main charge carrier for the early current, and that Ca2+ is important in regulating Ga. 8. The late current is outwards when [K+]o equals 5‐9 mM, but inwards in some voltage range when [K+]o was elevated to 120 or 148 mM. K+ is the main charge carrier for the late current. 9. The equilibrium potential for the late current, EK, is about 15 mV more negative than the natural resting potential. 10. Prolonged holding of the preparations at voltages that differ significantly from the natural resting potential tends to shift EK in a way consistent with passive changes in [K+]i by the holding current. 11. The steady‐state inactivation of the early current, h, is unusual. Inward current is macimum around the resting potential, and declines with both hyperpolarizing and depolarizing changes. Half‐inactivation occurred with about 9 mV depolarization and 15 mV hyperpolarization. 12. The instantaneous current‐voltage relations of both early and late currents are linear. The chord conductances Ga and GKare similar in form to those in other tissues.