bluuebunny/crossref_metadata_2025 huggingface dataset:
Release of calcium ions linked to the activation of potassium conductance in a caffeine‐treated sympathetic neurone.
Authors: Kuba K
Published: December 2014

1. The mechanism of spontaneous and rhythmic hyperpolarizations which occur in bullfrog sympathetic ganglion cells under the effect of caffeine (2‐‐10 mM) were further analysed. 2. Intracellular injection of EGTA blocked generation of caffeine hyperpolarizations (C‐hyperpolarizations): this confirmed the previous conclusion (Kuba & Nishi, 1976) that these hyperpolarizations are caused by rhythmic increases in the K+ conductance (GK) of the membrane as a result of rises in free intracellular Ca2+. 3. The amplitude and duration of a C‐hyperpolarization induced by an action potential was a function of the time since the previous one; the longer the interval, greater the area. 4. The relationship between the product of the amplitude and duration of a C‐hyperpolarization and the preceding interval depended on external Ca2+; when this was low the relationship shifted, so as to indicate an involvement of a Ca2+ accumulating process in the generation mechanism of C‐hyperpolarizations. 5. A rapid lowering of temperature triggered the generation of a C‐hyperpolarization before appearance of a rhythmic one. There seemed to be no threshold temperature for the effect of such a cold shock; cooling from any temperature within a certain range (10‐‐25 degrees C) by more than a few degrees was effective. 6. The rapid cooling effect was observed even in a Ca2+‐free Mg2+ solution. 7. Dantrolene Na increased the interval between rhythmic C‐hyperpolarizations or blocked them, but affected less those triggered by an action potential or cold shock. 8. Intracellular injection of Ca2+ triggered the generation of a C‐hyperpolarization before the appearance of a rhythmic one. 9. The latency of the generation of an action potential‐evoked C‐hyperpolarization was dependent on the preceding interval; the shorter the interval, the longer the latency. There was a refractory period for induction of an action potential‐induced C‐hyperpolarization. 10. The interval between rhythmic C‐hyperpolarizations was increased by a small or moderate membrane hyperpolarization (5‐‐20 mV) and decreased by a larger hyperpolarization; the refractory period of an action potential‐induced C‐hyperpolarization was similarly increased and then decreased by progressive membrane hyperpolarization. 11. These results suggest that rhythmic increases in the GK under the effect of caffeine are due to oscillations of the intracellular Ca2+ concentration and that there may be Ca storage sites in the bullfrog sympathetic ganglion cell which are comparable to the sarcoplasmic reticulum in the skeletal muscle fibre.
A sodium‐indpendent low affinity transport system for neutral amino acids in rabbit ileal mucosa.
Authors: Paterson J Y , Sepúlveda F V , Smith M W
Published: December 2014

1. The kinetic parameters for serine, alanine and methionine uptake by rabbit ileal mucosa have been determined in the absence of Na. 2. Uptake of all three amino acids took place through a single mediated system. The apparent Km values of serine, alanine and methionine for this system were equal to their respective apparent K1 values (approximately 89, 75 and 23 mM respectively). 3. Autoradiography was used to measure the cellular location of alanine uptake by rabbit ileum. Approximately 80% of the total uptake took place in the upper third of each villus. This uptake was reduced by 75% either by removal of Na or addition of serine. The proportional distribution of Na‐dependent and Na‐independent alanine uptakes along the villus was found to be equal. 4. The kinetic properties of the low affinity uptake mechanism for neutral amino acids, seen in the absence of Na, were virtually identical with those of one of the uptake mechanisms seen previously in the presence of Na. 5. The low affinity uptake mechanism appears to be Na‐independent. It is suggested that the Na‐coupled uptake of amino acid takes place through the high affinity system.
The actions of dopamine and of sulpiride on regional blood flows in the rat kidney.
Authors: Chapman B J , Horn N M , Munday K A , Robertson M J
Published: December 2014

1. Blood flow was measured in the renal cortex and medulla of anaesthetized rats by the hydrogen washout method. The effects of dopamine infusion were measured. 2. Low doses of dopamine (20 and 65 n‐mole.kg‐1.min‐1) caused only small increases in renal blood flow, and a higher dose (200 n‐mole.kg‐1.min‐1) caused vasoconstriction. After alpha‐blockade with phenoxybenzamine (9 mumole.kg‐1), all doses of dopamine caused vasodilatation in the cortex and medulla of the kidney. 3. This dopamine‐induced renal vasodilatation was almost abolished by sulpiride (0.7 mumole.kg‐1.min‐1), but was only slightly attenuated by propranolol (10 mumole.kg‐1). 4. Sulpiride did not significantly alter the renal blood flow responses to noradrenaline or isoprenaline, or the blood pressure responses to histamine, acetylcholine, 5HT, noradrenaline and isoprenaline. 5. In normal rats, infusion of sulpiride generally caused a reduction in renal cortical blood flow. This response showed a positive correlation with the initial blood pressure. 6. It is concluded that there are specific dopamine receptors in the renal vasculature of the rat, and that dopamine may play a role in the normal control of renal blood flow.
Swelling studies of bovine corneal stroma without bounding membranes.
Authors: Elliott G F , Goodfellow J M , Woolgar A E
Published: December 2014

1. The swelling characteristics of demembranated bovine corneal stroma were studied as a function of time and of the pH and ionic strength of the bathing solution. 2. Compared with other pH values, the stroma swelled least near pH 4. 3. In the pH range 6‐‐10, increasing the pH resulted in an increase both in the rate of swelling and in the hydration reached in a given time. 4. At pH 2 and 4, a final constant value of hydration was attained. At higher pH values no such equilibrium was attained when the hydration of the tissue was followed for at least 100 hr. 5. The swelling at high pH values was consistent with the hypothesis that the Donnan‐osmotic contribution is the major component of the swelling pressure. 6. The ionic strength dependence was complex. There was a general decrease of swelling with increase in the ionic strength (mu) until around mu = 0.1. The swelling at mu = 0.15 was greater than at mu = 0.1 and mu = 0.25. 7. The results were interpreted on the assumption that the Donnan‐osmotic effect is the major component of the swelling pressure.
A study of the role of renal nerves in the renal responses to 60° head‐up tilt in the anaesthetized dog
Authors: DiBona G. F. , Johns E. J.
Published: December 2014

1. Renal responses to 10 min of 60° head‐up tilt were measured in anaesthetized dogs in which renal perfusion pressure was maintained at a relatively constant value.

2. Tilting was associated with a fall in systemic blood pressure and an increase in heart rate. Renal blood flow and glomerular filtration rate remained constant while there was a significant decrease in both absolute and fractional excretion of sodium.

3. Animals which had undergone acute renal denervation were tilted. The cardiovascular responses were similar to intact animals. A fall in renal blood flow was observed but the glomerular filtration rate was maintained at a steady value during tilting. The decreased renal tubular excretion of sodium measured in intact animals was abolished.

4. Alpha‐adrenergic blockade of the kidney was achieved by infusion of phentolamine into the renal artery. Tilting of these animals caused cardiovascular changes similar to those observed in control animals but renal blood flow, glomerular filtration rate and sodium handling remained unchanged.

5. Animals in which both carotid sinuses had been acutely denervated were tilted. Systemic blood pressure fell as in intact animals, but the rise in heart rate was significantly less. Renal blood flow, glomerular filtration rate and the rate of sodium excretion were unchanged.

6. A 10 min period of 60° head‐up tilt in anaesthetized dogs resulted in an unchanged renal blood flow and glomerular filtration rate which was associated with a decrease in both fractional excretion of sodium and sodium excretion. The renal sympathetic nerves were shown to be responsible for these changes in tubular sodium handling which appeared to exert their action via renal tubular α‐adrenergic receptors. This activation of the renal nerves appeared to be mediated by the carotid sinus baroreceptor reflex.
Dorsal root vasodilatation in cat skeletal muscle.
Authors: Hilton S M , Marshall J M
Published: December 2014

1. A study has been made, in the cat anaesthetized with chloralose, of the effects of antidromic stimulation of dorsal roots L6‐S1 on the blood flow through the gastrocnemius muscle. 2. Stimulation of the peripheral ends of the ligated dorsal roots with current pulses of 0.3‐0.5 msec duration and at intensities most effective in activating the smaller afferent fibres, for periods of 15‐20 sec, produced a 50‐60% increase in muscle vascular conductance which was slow in onset and long outlasted the stimulus. 3. This muscle vasodilatation could be evoked in the paralysed animal and was unaffected by guanethidine or atropine. It was, however, greatly reduced or even abolished by the prostaglandin synthetase inhibitors, indomethacin or acetylsalicylic acid, in doses which had no effect on the dilatation produced by a local injection of acetylcholine or the functional hyperaemia induced by muscle contraction. 4. It is concluded that activity in the smaller myelinated or unmyelinated afferent fibres of skeletal muscle produces an increase in muscle blood flow which is mediated, at least in part, by prostaglandins locally synthesized within the muscle.
On the release of transmitter at normal, myasthenia gravis and myasthenic syndrome affected human end‐plates.
Authors: Cull‐Candy S G , Miledi R , Trautmann A , Uchitel O D
Published: December 2014

1. Transmitter release has been studied at normal, myasthenia gravis (m.g.) and myasthenic syndrome (m.s.) affected human end‐plates. At normal and diseased end‐plates evoked transmitter release is Poisson for a mean quantal content, m less than ten. 2. The relation between log m and log [Ca]o, at normal and m.g. end‐plates is linear, with a slope of 3.3‐3.4. The value of m at m.g. end‐plates is about five times larger than normal, below Ca 0.7 mM (Mg, 2mM). This difference in m is reduced at higher Ca levels. 3. The slope of the relation between log m.e.p.p. frequency and log [K]o is similar at normal and m.g. end‐plates. Over its linear portion the relationship has a slope of approximately 6. 4. Fluctuations in the latency of evoked transmitter release were compared at normal and m.g. nerve terminals. At normal end‐plates the probability of release reaches a peak about 0.3‐0.4 msec after unitary e.p.p.s of the shortest latency and returns to zero about 1.0 msec after the peak. At m.g. end‐plates the distribution of latencies shows less uniformity. 5. At m.s. end‐plates m is approximately 5 in normal Ringer solution (2 mM‐Ca, 1 mM‐Mg). The relation between log m and log [Ca]o is linear, with a slope of 1.0‐1.5. The K dependence of m.e.p.p. frequency appears reduced at m.s. end‐plates. 6. Assuming a co‐operative mechanism for transmitter release at normal human motor nerve terminals, the dissociation constant for the Ca complex is about 1.6X10(‐3) M and the dissociation constant for the Mg complex is about 1.0X10(‐3) M. 7. It is concluded that the presynaptic changes, at m.g. end‐plates, are not the primary cause of the defect in nerve muscle transmission. At m.s. end‐plates the presynaptic changes are sufficient to account for failure in transmission. Possible mechanisms for the abnormalities in transmitter release are considered.
Transmitter induced calcium entry across the post‐synaptic membrane at frog end‐plates measured using arsenazo III.
Authors: Miledi R , Parker I , Schalow G
Published: December 2014

1. The Ca2+ influx occurring across the post‐synaptic membrane during transmitter action was studied at the frog neuromuscular junction, using the Ca sensitive dye arsenazo III to monitor the resulting changes in free myoplasmic Ca2+ concentration. 2. Calibration experiments showed a linear relationship between the amount of Ca2+ injected by ionophoresis into a muscle fibre, and the peak size of the arsenazo light absorbance record. 3. Ionophoretic application of acetylcholine (ACh) to voltage clamped end‐plates gave rise to an arsenazo signal. The size of this response varied with the Ca2+ concentration in the bathing solution. 4. The arsenazo light response increased in size steeply, and non‐linearly, with hyperpolarization of the end‐plate membrane, even when the end‐plate current increased approximately linearly with hyperpolarization. The voltage dependence of the light response could be fitted well by an exponential with a voltage constant of 28 mV. Changes in Ca2+ concentration of the bathing medium had little effect on this relationship. 5. At end‐plates bathed in isotonic CaCl2 solution the voltage dependence of both the arsenazo light response, and the end‐plate current showed a closely similar, non‐linear relationship. 6. Addition of 12 mM‐Co2+ to a bathing solution initially containing 12 mM‐Ca2+ substantially reduced the size of the arsenazo light response, and the voltage dependence of this response became more linear. 7. Arsenazo light responses were also recorded in response to transmitter release evoked by nerve stimulation. The size of the nerve evoked light response showed a non‐linear voltage dependence, whilst the end‐plate current was a linear function of membrane potential.
The passive membrane properties and excitatory junction potentials of the guinea pig deferens.
Authors: Bywater R A , Taylor G S
Published: December 2014

1. Electrotonic potentials were recorded from the superficial smooth muscle cells of the guinea‐pig vas deferens using the method of Abe & Tomita (1968), in response to low‐amplitude, long‐duration (greater than or equal to 2 sec) pulses. 2. Averaging techniques were used to increase the signal/noise ratio, and the intracellularly recorded electrotonic potentials were corrected for extracellular voltage drop across the bath series resistance. 3. Since the length of tissue in the stimulating and recording compartments affects the time course of electrotonic potentials (see Appendix and Bywater & Redman, 1978) the passive membrane properties were measured with known amounts of tissue in these two compartments. 4. The length constant (lambda) was 0.86 mm and the membrane time constant (tau m) 270 msec. 5. Excitatory junction potentials (e.j.p.s) were recorded and averaged in response to field stimulation of intact branches of the hypogastric nerve. The mean time constant of the exponential decay phase of the e.j.p. (288 msec) was similar to the membrane time constant (tau m = 270 msec). 6. As the e.j.p.s showed little change in amplitude or time constant of decay when recorded up to several millimetres from the stimulating electrode it was assumed that the tissue was isopotential during the e.j.p., and an estimate was made of the time course of the underlying junctional current. 7. The estimated time course of the junctional current during an e.j.p. was similar to the observed time course of a spontaneous junction potential (s.e.j.p.). 8. As the time course of the junctional current during an s.e.j.p.is similar to the time course of the potential change it is likely that the factors which determine the time current underlying the s.e.j.p. also determine the time course of the e.j.p. current.
Dendritic trees and cutaneous receptive fields of adjacent spinocervical tract neurones in the cat.
Authors: Brown A G , Rose P K , Snow P J
Published: December 2014

1. The relationship between the dendritic trees and the receptive fields of adjacent spinocervical tract neurones were studied using the intracellular injection of horseradish peroxidase in chloralose‐anaesthetized, paralysed, cats. 2. Fourteen pairs of neurones were successfully stained and the receptive fields of twelve pairs were also defined. Five of the pairs were ‘rostrocaudal pairs’, i.e. in line within +/‐ 50 micrometer of each other in the rostrocaudal axis of the cord. Nine of the pairs were ‘mediolateral pairs’, i.e. in line within +/‐ 50 micrometer of each other in the mediolateral axis of the cord. 3. For twelve pairs of stained neurones, for which the receptive fields were described, a correspondence was found between the organization of their dendritic trees and their receptive fields. 4. All five rostrocaudal pairs of neurones had interdigitating dendritic trees together with overlapping receptive fields. 5. Of the seven mediolateral pairs, four had receptive fields which overlapped and interdigitating dendritic trees. The remaining three had separate receptive fields and non‐interdigitating dendritic trees. 6. The results are discussed in relation to previous work on the columnar organization of the receptive fields of s.c.t. neurones and the columnar organization of hair follicle afferent fibre terminals in the spinal cord. The hypothesis is advanced that the receptive fields of most s.c.t. neurones are defined by their connexions with hair follicle afferent fibres such that along the mediolateral axis spatial separation of the dendritic trees of s.c.t. neurones is crucial for receptive field separation.
Intracellular pH in early Xenopus embryos: its effect on current flow between blastomeres.
Authors: Turin L , Warner A E
Published: December 2014

1. Electrophysiological techniques were used to monitor the flow of electric current from one cell to the next in Xenopus laevis embryos between the 4‐cell and early blastula stages of development. Intracellular pH and blastocoel pH were determined using pH‐sensitive micro‐electrodes. 2. The resting intracellular pH was 7.74+/‐0.02 (S.E. of mean, n = 29); there were no systematic differences between developmental stages. Blastocoel cavity pH was 8.4+/‐0.06 (S.E. of mean, n = 10). The intracellular buffer value was 18 m‐equiv. H+/pH unit per litre. 3. In embryos treated with bicarbonate buffered Holtfreter solution equilibrated with 100% CO2 the intracellular pH fell to 6.3+/‐0.17 (S.D., n = 8). The membrane potential fell and the input resistance increased. The size of the effect on membrane potential and input resistance varied. 4. From the 32‐cell stage onwards current flow from one cell to the next was abolished when the intracellular pH fell to below 6.5; the effect was rapid in onset and completely reversible. At cleavage stages of development lowering intracellular pH with CO2 had no effect on current flow from cell to cell. 5. The relationship between intracellular pH and current flow from cell to cell was sigmoid and covered between 0.2 and 0.4 pH units. The pH at which current flow was completely abolished ranged from 6.85 to 6.4. 6. Alterations in extraembryonic pH over the range 5.8‐7.5 had no effect on any parameter measured. 7. We conclude that lowering the intracellular pH increases the resistance of both non‐junctional junctional membranes. The data do not allow us to extract the pH junctional conductance relationship. 8. Variations in intracellular pH may provide a useful tool for the study of the functional role of direct cell to cell communication in both adult organs and early embryos.
The effects of vanadate on the fluxes of sodium and potassium ions through the sodium pump
Authors: Beaugé L. A. , Cavieres J. J. , Glynn I. M. , Grantham J. J.
Published: December 2014

1. The effects of sodium orthovanadate on the fluxes of sodium and potassium (or rubidium) ions through the sodium pump have been investigated in intact human red cells and in resealed ghosts prepared from them. Sodium—potassium exchange, potassium—potassium exchange, pump reversal, sodium—sodium exchange and uncoupled sodium efflux have each been studied.

2. When intact human red cells were incubated in high‐sodium media containing vanadate in low concentrations, inhibition of potassium or rubidium influx was marked only if the potassium or rubidium concentration in the medium was sufficiently high to cause nearly maximal influx in the absence of vanadate. The absence of inhibition at lower potassium or rubidium concentrations cannot be explained by supposing that the onset of inhibition by vanadate is slower in these conditions.

3. Lowering the extracellular sodium concentration, or raising the vanadate concentration, decreased the minimum concentration of extracellular potassium or rubidium at which inhibition by vanadate was detected.

4. Experiments on potassium influx into intact red cells treated with the ionophore A23187 showed that magnesium ions act at intracellular sites to promote inhibition by vanadate.

5. Measurements of potassium efflux from intact red cells incubated in high‐sodium media, with or without potassium, showed that potassium—potassium exchange was inhibited by vanadate at low concentrations whereas reversal of the pump was not.

6. Measurements of sodium efflux from intact red cells or resealed ghosts incubated in high‐sodium media, with or without potassium, showed that vanadate had little or no effect on sodium—sodium exchange at concentrations at which sodium—potassium exchange was markedly reduced. Much higher concentrations of vanadate did cause partial inhibition of sodium—sodium exchange.

7. Experiments to determine whether vanadate in low concentrations inhibited uncoupled sodium efflux were inconclusive, but suggested that the flux was inhibited. Measurements of the ATP hydrolysis that is thought to be associated with the uncoupled sodium efflux showed that this hydrolysis was strongly inhibited.

8. The different effects of vanadate on the different fluxes are discussed, and related to the way in which vanadate is thought to act on the sodium pump.
Lateral contacts and interactions of horizontal cell dendrites in the retina of the larval tiger salamander
Authors: Lasansky A.
Published: December 2014

1. The contacts of horizontal cell dendrites with processes of other second order neurones were studied at the level of the electron microscope in serial sections of the salamander retina. Intracellular recordings of the responses to light of horizontal and bipolar cells were used to investigate the possible significance of some of the morphological findings.

2. Horizontal cell dendrites make close membrane appositions (gap junctions) with one another and are post‐synaptic to bipolar cell dendrites at presumed chemical synapses. On the other hand, there is no clear evidence that horizontal cell dendrites are presynaptic to any other neuronal processes at the outer plexiform layer, so that the output connexions of horizontal cell bodies remain a matter of speculation.

3. It is suggested that the bipolar cell input and the gap junctions between dendrites contribute, respectively, depolarizing and hyperpolarizing components to the responses of horizontal cell bodies to surround illumination. In addition, the facilitatory effect of central illumination on the surround response of horizontal cell bodies may result, although perhaps only partly, from observed properties of the surround response of bipolar cells.

4. In the course of these observations, bipolar cells were found to be presynaptic at the outer plexiform layer not only to horizontal cell dendrites, but also to other bipolar cells, horizontal cell axon terminals and certain processes belonging to an as yet unidentified neurone.
The spinal cord ventral root: an afferent pathway of the hind‐limb pressor reflex in cats.
Authors: Longhurst J C , Mitchell J H , Moore M B
Published: December 2014

1. In anaesthetized cats the sciatic nerve was cut and the central end was stimulated at a high frequency and voltage. This caused an increase in arterial blood pressure and a rise in heart rate. The pressure response was diminished by dorsal root section but not completely eliminated until ventral root section (L4‐S3). The tachycardia response was abolished by dorsal root section alone. 2. In other cats capsaicin was injected intra‐arterially into the hind limb, causing elevations in both blood pressure and heart rate. Similar to the sciatic nerve stimulation experiments, the pressor response was principally reduced by dorsal root section but was further significantly decreased by ventral root section (L1‐S3). The rise in heart rate was prevented by dorsal root section alone. 3. It is concluded that, in cats, the afferent pathway of the pressor response to sciatic nerve stimulation and to hind‐limb capsaicin injection are conducted principally in the dorsal roots but also to a small extent in the ventral roots of the spinal cord. Although the tachycardia response appears to be conducted only through the dorsal roots, it is possible that at lower resting heart rates and by stimulation of a large population of the unmyelinated skeletal muscle afferents, the ventral root is a functional pathway.
Slow inward barium current and contraction on frog single muscle fibres.
Authors: Potreau D , Raymond G
Published: December 2014

1. Excitation‐contraction coupling process in isolated frog muscle fibres, under conditions which allow the development of a Ba permeability, has been investigated by the simultaneous recording of electrical and mechanical activity. 2. The sustained contraction elicited by a long lasting Ba action potential depends on two mechanisms. The first is potential dependent, the second which is inhibited by MnCl2 (10 mM), depends on the inward flux of Ba ions. 3. The relationship observed between the inward IBa and the peak tension resembles that which has been observed between ICa and the contraction on other muscular structures. 4. The relative tension progressively declines as the intracellular Ba concentration increases and the contractility ends after a series of depolarizing pulses (or Ba action potentials). This indicates that the Ba ions which enter the cell release Ca ions and replace them in the intracellular storage sites. 5. Following a pretreatment with caffeine, the inward IBa fails to induce a contraction. Moreover a muscle which has been loaded with barium until the contraction ceases, does not develop a contracture in presence of caffeine. These results show that the Ba induced Ca release is located at the level of the sarcoplasmic reticulum. 6. Calculations show that the amount of Ba ions necessary to abolish the contractility corresponds to the maximum ability of the sarcoplasmic reticulum for Ca binding. 7. Almost all the inward flux of Ba ions and the contraction are abolished by glycerol‐treatment which suggests that the coupling occurs at the T‐system level. The results are discussed in regard to the technical limitations of the voltage‐clamp method.
The acetylcholine channel open time in chick muscle is not decreased following innervation.
Authors: Schuetze S M
Published: December 2014

1. The mean channel open time (tau) of ACh receptors was measured in chick muscles at various stages of development. Tau was estimated by analysing ACh induced current fluctuations recorded extracellularly from small (ca. 20 micrometers2) membrane patches. 2. At random sites on uninnervated, embryonic chick muscle fibres in vitro, tau was relatively long‐‐4 msec at 23 degrees C. 3. Estimates of tau at synaptic sites on embryonic myotubes innervated in vitro were identical to estimates at extrasynaptic sites on the same fibres. Both were comparable to estimates on uninnervated myotubes. 4. Synaptic currents at cultured junctions decayed slowly as simple exponentials. The decay time constants were never shorter than the mean channel open time measured by fluctuation analysis. 5. In anterior latissimus dorsi and intercostal muscle fibres of 4‐ to 18‐week posthatched chicks, fluctuation analysis and synaptic current decays indicate that the channel open time of mature chick endplate receptors is as long as that of embryonic synaptic receptors in vitro. Apparently, tau remains prolonged throughout the maturation of chick neuromuscular junctions.
The action of somatostatin on neurones of the myenteric plexus of the guinea‐pig ileum.
Authors: Katayama Y , North R A
Published: December 2014

1. Intracellular recordings were made from neurones in ganglia of the myenteric plexus of the guinea‐pig ileum. 2. Somatostatin (10‐300 nM) was applied to the neurones by adding it to the perfusing solution or by ejecting it (charges up to 500 nC) from an ionophoresis electrode onto the soma membrane. 3. By both methods of application, somatostatin either hyperpolarized or depolarized a proportion of neurones. Depolarizing responses were more often observed with ionophoretic application, and hyperpolarizing responses were more often observed with application by perfusion. Both responses were preserved in solutions containing zero Ca and elevated (6 mM) Mg. Some cells were both hyperpolarized and depolarized, depending on the method of administration. 4. The depolarizing responses to somatostatin were associated with an increase in cell input resistance; they became larger with membrane depolarization and smaller with membrane hyperpolarization, and reversed in polarity at a potential close to the potassium equilibrium potential. The hyperpolarizing responses to somatostatin were accompanied by a fall in cell input resistance.
Delayed development of amiloride‐sensitive sodium transport in lamb distal colon.
Authors: Hills F , James P S , Paterson J Y , Smith M W
Published: December 2014

1. Na transport has been measured in vitro across distal colons taken from fetal and early post‐natal lambs. 2. The mucosal to serosal Na flux fell by half during the first three weeks of post‐natal life. Similar falls were recorded for measured short‐circuit current and open‐circuit voltage. The net transport of Na, measured isotopically at all stages of development, corresponded approximately to that calculated from measurements of short‐circuit current. 3. The serosal to mucosal flux of Na was approximately half the mucosal to serosal flux at all stages in development. 4. Amiloride affected neither the short‐circuit current nor the mucosal to serosal flux of Na measured during the first five days of post‐natal life. The short‐circuit current of an increasing proportion of distal colons (30‐70%) began to show some sensitivity to amiloride during the second to third week of post‐natal life. Sensitivity of the short‐circuit to inhibition by amiloride appeared to be fully developed in the 8‐week‐old lamb colon. 5. The serum concentration of aldosterone was high at birth. It then fell rapidly to levels approaching those found in fetuses in the last week of pregnancy. The serum concentration of cortisol was two orders of magnitude higher than for aldosterone. Changes in cortisol concentration during development paralleled those for aldosterone. 6. There appears to be no aldosterone‐induced change in Na transport across lamb distal colon during the first week of post‐natal development. Comparisons are made between this situation and that found in the neonatal pig, where aldosterone acts to increase Na reabsorption immediately after birth. Possible reasons for this species difference are discussed.
The contrast sensitivity of cat retinal ganglion cells at reduced oxygen tensions.
Authors: Enroth‐Cugell C , Goldstick T K , Linsenmeier R A
Published: December 2014

1. These experiments were done to investigate the effect of various degrees of hypoxia on the function of retinal ganglion cells (recorded in the optic tract) and on retinal oxygen tension. 2. The contrast sensitivity of the centre of X and Y cells, the surround of X cells and the non‐linear subunits of Y cells were measured separately by choosing appropriate spatial and temporal parameters of a sinusoidal grating pattern. 3. Retinal oxygen tension was measured with a bipolar polarographic oxygen electrode positioned in the vitreous humor close to the retina. 4. The time course of changes in ganglion cell sensitivity and retinal oxygen tension was similar. However, oxygen tension frequently overshot the prehypoxic value at the end of hypoxia, while sensitivity did not. 5. The cat retina was rather resistant to hypoxia. Contrast sensitivity and mean firing rate did not change provided the arterial oxygen tension was above about 35 mmHg, but usually dropped precipitously at lower arterial values. 6. The apparent reason for this resistance is that retinal oxygen tension was well regulated, falling only 0.14 mmHg per mmHg of arterial oxygen tension for arterial values above about 35 mmHg, which corresponds to a retinal oxygen tension of about 10 mmHg. Retinal oxygen tension decreased more sharply (0.62 mmHg per mmHg) at lower values of arterial oxygen tension, where sensitivity also decreased. 7. The centre, surround and subunits reacted similarly to hypoxia. This suggests that lateral pathways (i.e. surround) and pathways which might be expected to use more synapses than the centre (i.e. surround and subunits) are not more susceptible to hypoxia.
Sarcomere length‐tension relations of frog skinned muscle fibres at lengths above the optimum.
Authors: Julian F J , Moss R L
Published: December 2014

1. Single twitch fibres were dissected from anterior tibial muscles of the frog, Rana pipiens, and were then either chemically or mechanically skinned. Short segments of the skinned fibres were transferred to an experimental chamber and mounted between a force transducer and a stationary wire. 2. The average sarcomere length was determined from light photomicrographs of the segments obtained during activation and while relaxed. Activations were maximal, in solutions of pCa 5.49 and at 5 degrees C. Fibre segments having regions in which the striation pattern was highly non‐uniform were rejected. 3. The relationship between tension and average sarcomere length was determined for sarcomere lengths between 2.1 and 3.8 micrometer. Tension always decreased when sarcomere length was increased above about 2.2 micrometer. Tension plotted against over‐all average sarcomere length lay above data obtained from living fibres by Gordon, Huxley & Julian (1966a, b). 4. Good agreement with living fibre results was found when tension was plotted against the shortest average sarcomere length within a portion of the segment. 5. These findings indicate that sarcomere length non‐uniformities greatly influence the shape of the sarcomere length‐tension relation in skinned fibres at long lengths. In addition, no evidence was found for a length‐dependent influence of calcium on tension development at long lengths during maximal activation.
Effect of glycerol treatment on the calcium current of frog skeletal muscle.
Authors: Siri L N , Sánchez J A , Stefani E
Published: December 2014

1. Current and voltage clamp experiments were carried out on frog skeletal muscle fibres. For voltage clamp, the three micro‐electrode technique near the fibre end was used. 2. Calcium spikes and currents were recorded in TEA sulphate saline. The addition of 400 mM‐glycerol did not appreciably modify them. 3. Muscle fibers were detubulated with the glycerol method. They showed sodium propagating action potentials, with sodium and potassium currents of expected amplitudes. 4. Calcium spikes and currents were reduced or abolished in detubulated muscle fibres. 5. An analysis of fibre capacitance showed a linear correlation between the remaining ICa and the degree of electric discontinuity between the transverse tubular system and the surface membrane. 6. These results indicate that ICa is mainly located in the transverse tubular system. This localization is compatible with some role during mechanical activation.
The interaction of sodium and calcium ions at the cell membrane and the control of contractile strength in frog atrial muscle.
Authors: Chapman R A , Tunstall J
Published: December 2014

1. The relationship between [Na]o and the contracture tension, developed by isolated frog trabeculae, has been investigated in the presence of different levels of bathing K and Ca ions and after experimental manoeuvres likely to increase [Na]i. 2. Raising [K[o, [Ca]o or [Na]i all increase the strength of the contractures induced by lowering the bathing [Na] except when the [Na]o is close to zero, suggesting that the Ca‐Na exchange depends on membrane potential or [K]o. 3. The experimental data have been compared to the predictions of three relatively simple models of Ca‐Na exchange in the membrane, where [Ca]i depends on the [K]o either directly or by way of its effect on the membrane potential and tension varies according to a second order relationship with [Ca]i. 4. The only scheme to fit all the experimental data satisfactorily is one which assumes an exchange of one Ca ion for three Na ions across the membrane. This scheme requires that the contractile system has an apparent binding constant for Ca2+, similar to that found with skinned cardiac muscle cells or isolated cardiac myofibrils. In intact muscle, when the [Na]i is close to that measured experimentally, the model predicts that tension should vary with the [Ca]o2, 1/[Na]o4, and the [Ca]/[Na]o2 ratio.
Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices.
Authors: Llinás R , Sugimori M
Published: December 2014

1. The electrical activity of Purkinje cells was studied in guinea‐pig cerebellar slices in vitro. Intracellular recordings from Purkinje cell somata were obtained under direct vision, and antidromic, synaptic and direct electroresponsiveness was demonstrated. Synaptic potentials produced by the activation of the climbing fibre afferent could be reversed by direct membrane depolarization. 2. Input resistance of impaled neurones ranged from 10 to 19 M omega and demonstrated non‐linearities in both hyperpolarizing and depolarizing directions. 3. Direct activation of a Purkinje cell indicated that repetitive firing of fast somatic spikes (s.s.) occurs, after a threshold, with a minimum spike frequency of about 30 spikes/sec, resembling the ‘2‐class’ response of crab nerve (Hodgkin, 1948). 4. As the amplitude of the stimulus was increased, a second form of electroresponsiveness characterized by depolarizing spike bursts (d.s.b.) was observed and was often accomppanied by momentary inactivation of the s.s. potentials. Upon application of tetrodotoxin (TTX) or removal of Na+ ions from the superfusion fluid, the s.s. potentials were abolished while the burst responses remained intact. However, Ca conductance blockers such as Co, Cd, Mn and D600, or the replacement of Ca by Mg, completely abolish d.s.b.s. 5. If Ca conductance was blocked, or Ca removed from the superfusion fluid without blockage of Na conductance, two types of Na‐dependent electroresponsiveness were seen: (a) the s.s. potentials and (b) slow rising all‐or‐none responses which reached plateau at approximately ‐15 mV and could last for several seconds. These all‐or‐none Na‐dependent plateau depolarizations outlasted the stimulus and were accompanied by a large increase in membrane conductance. Within certain limits the rate of rise and amplitude of the plateau were independent of stimulus strength. The latency, however, was shortened as stimulus amplitude was increased. These potentials were blocked by TTX or by Na‐free solutions. 6. Substitution of extracellular Ca by Ba or intracellular injection of tetraethylammonium generated prolonged action potentials lasting for several seconds and showing a plateau more ositive than those obtained in norrmal circumstances by either non‐inactivating Na or Ca currents. 7. Spontaneous firing of the Purkinje cell was characterized by burst‐like activity consisting of both s.s. and d.s.b. responses. Addition of TTX to the bath left the basic spontaneous activity and its frequency unaltered, indicating tha Ca spiking and Ca‐dependent K conductance changes are the main events underlying this oscillatory behaviour. 8...
Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibres.
Authors: Colatsky T J
Published: December 2014

1. Voltage clamp studies of the excitatory sodium current, INa, were carried out in rabbit cardiac Purkinje fibres using th two‐micro‐electrode technique. Previous work has shown the rabbit Purkinje fibre to have relatively simple morphology (Sommer & Johnson, 1968) and electrical structure (Colatsky & Tsien, 1979a) compared to other cardiac preparations. 2. Non‐uniformities in membrane potential were kept small by reducing the size of INa to less than 50 microA/cm2 of total membrane surface area through prepulse inactivation or removal of external sodium, Nao. Temporal resolution was improved by cooling to 10‐26 degrees C. These adjustments did not greatly alter the measured properties of the sodium channel. 3. Under these conditions, sodium currents were recorded satisfying a number of criteria for adequate voltage control. Direct measurement of longitudinal non‐uniformity using a second voltage electrode showed only small deviations at the time of peak current. 4. The properties of the sodium channel were examined using conventional protocols. Both peak sodium permeability, PNa, and steady‐state sodium inactivation, h infinity, showed a sigmoidal dependence on membrane potential. PNa rose steeply with small depolarizations, increasing roughly e‐fold per 3.2 mV, and reaching half‐maximal activation at ‐30 +/‐ 2 mV. The h infinity ‐V curve had a midpoint of ‐74.9 +/‐ 2 mV and a reciprocal slope of 4.56 +/‐ 0.13 mV at temperatures of 10‐19.5 degrees C, and showed a dependence on temperature, shifting to more negative potentials with cooling (approximately 3 mV/10 degrees C). Recovery of INa from inactivation in double pulse experiments followed a single exponential time course with time constants of 108‐200 msec at 19 degrees C for holding potentials near ‐80 mV. No attempt was made to describe the activation kinetics because of uncertainties about the early time course of the current. 5. These data predict a maximum duration for INa of less than 1‐2 msec and a maximum peak current density of about 500 microA/cm2 under physiological conditions, i.e. 37 degrees C and 150 mM‐Nao. This current magnitude is sufficient to discharge the membrane capacitance at rates comparable to those measured experimentally (311 +/‐ 27 V/sec, Colatsky & Tsien, 1979a). 6. The limitations of the method are discussed. The major problem is the longitudinal cable delay which limits the speed of voltage control. This makes it difficult to separate the activation of INa from the decay of the capacity transient for potentials positive to ‐15 mV. 7. It is concluded that the approach described is valid for measurements of sodium currents in the potential range where action potentials are initiated, making it possible to study cardiac sodium channels in an adult mammalian preparation which is free of enzymatic treatment.
Effects of various gastrointestinal peptides on parietal cells and endocrine cells in the oxyntic mucosa of rat stomach.
Authors: El Munshid H A , Håkanson R , Liedberg G , Sundler F
Published: December 2014

1. The effects of secretin, glucagon, cholecystokinin‐pancreozymin (CCK‐PZ), gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP), somatostatin, neurotensin and enkephalin on basal, pentagastrin‐ and histamine‐stimulated gastric acid secretion were investigated in the conscious fistula rat. 2. Glucagon and GIP were ineffective inhibitors of basal and pentagastrin‐stimulated secretion. CCK‐PZ stimulated acid secretion at a low dose level but at higher doses it inhibited both pentagastrin‐ and histamine‐induced secretions. VIP was ineffective at low doses and at high doses its action was complicated by reflux of stimulated pancreatic and intestinal secretions into the stomach. Met‐enkephalin inhibited histamine‐ but not pentagastrin‐stimulated secretion. Neurotensin inhibited the response to pentagastrin but had no effect on histamine‐stimulated secretion. Secretin and somatostatin were potent inhibitors of basal and pentagastrin‐stimulated acid secretion with little or no effect on the response to histamine. 3. At doses completely inhibitory to pentagastrin‐stimulated secretion secretin and somatostatin did not block the mobilization of gastric mucosal histamine by pentagastrin, although somatostatin caused partial competitive inhibition at lower doses of pentagastrin. Thus secretin and somatostatin inhibited pentagastrin‐induced secretion neither by blocking gastric mucosal histamine mobilization nor by abolishing the direct action of histamine on the parietal cell ‐‐ findings which are inconsistent with the proposed role of histamine as the mediator of the action of gastrin on the parietal cell.
Reduced inhibition during epileptiform activity in the in vitro hippocampal slice.
Authors: Dingledine R , Gjerstad L
Published: December 2014

1. Intracellular recordings were made from CA1 pyramidal cells in the hippocampal slice in vitro. The responses to orthodromic and antidromic activation and to ionophoretically applied GABA were studied. 2. The epileptogenic agent sodium benzyl penicillin reduced the recurrent i.p.s.p. evoked by subthreshold antidromic stimulation. Reversal potential studies of the i.p.s.p. and resistance measurements showed that this reduction was mainly due to a decrease in i.p.s.p. conductance. 3. Penicillin also reduced the conductance and associated membrane potential changes induced by ejecting GABA near the soma or into the apical dendritic region. 4. The mixed e.p.s.p.‐i.p.s.p. evoked by orthodromic stimulation was converted to a pure depolarizing potential as the i.p.s.p. was blocked. Concurrently the probability of discharge to a constant orthodromic stimulus was increased. Similar changes were seen in a low chloride solution. 5. The time course of the reduction of inhibition was similar to that of the enhanced orthodromic response seen after penicillin treatment. 6. We conclude that reduction of postsynaptic inhibition is partly responsible for the increased probability of orthodromic discharge caused by penicillin. The longer latency all‐or‐nothing burst seen in some cells, however, seems to require an additional mechanism, although reduced inhibition may facilitate the triggering of this burst.
Suppression of fever in rabbits by a protein synthesis inhibitor, anisomycin.
Authors: Cranston W I , Hellon R F , Townsend Y
Published: December 2014

1. The protein synthesis inhibitor, anisomycin, was given into the cerebral ventricles of rabbits as a priming dose followed by a continuous infusion. Doses of 100, 200 and 300 microgram followed by infusions at 100, 200 and 300 microgram/hr inhibited the incorporation of [14C] leucine into hypothalamic protein by over 90%. 2. Injection and infusion of anisomycin (300 microgram) suppressed the febrile response to leucocyte (endogenous) pyrogen given into the ventricles (I.C.V.) or I.V. 3. Dialysis experiments showed that anisomycin did not combine irreversibly with leucocyte pyrogen. 4. Anisomycin did not interfere with thermoregulation in a cold environment. 5. It is concluded that pyrogenesis may involve a step which is dependent on synthesis of hypothalamic protein with a rapid turnover.