bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitive osmometer function of juxtaglomerular cells in vitro.
Authors: Frederiksen O , Leyssac P P , Skinner S L
Published: December 2014

The rate of renin release from viable juxtaglomerular cells was studied during prolonged superfusion of isolated rat renal glomeruli with Ringer solutions of differing osmolarities. 2. Reduction in osmolarity from 305 to 285 m‐osmole/l. by lowering sucrose concentration caused renin release rate to double. A rise in osmolarity of 30 m‐osmole/l. by raising sucrose concentration halved release rate. 3. The response to osmolarity was graded. During the first 30 min following a 20 m‐osmole/l. decrease in osmolarity, 1‐57 +/‐ 0‐22% (S.E. of mean) of cellular renin content was released; three times this amount was released with a decrease of 50 m‐osmole/l. The effect persisted at lower release rates for 60‐90 min. 4. The juxtaglomerular cells were four to five times more sensitive to changes in osmolarity through sucrose than sodium chloride concentration. Changes in potassium chloride concentration (7‐57 mM) had little effect. 5. Sodium chloride had no direct ionic effect on renin release outside its osmotic properties. 6. The findings support a previous proposal that the rate of renin release in vitro relates directly to the volume of the juxtaglomerular cell. The hypothesis is developed that a similar mechanism may underlie renin secretion in vivo.
Voltage‐clamp analysis of transmembrane ionic currents in guinea‐pig myometrium: evidence for an initial potassium activation triggered by calcium influx.
Authors: Vassort G
Published: December 2014

Voltage‐clamp analysis of ionic transmembrane currents in very small strands of guinea‐pig myometrium was carried out with a double sucrose‐gap technique. It was found that the electrical activity, consisting of a spike followed by a long plateau, is controlled by, at least, four ionic conductances. (1) A fast inward current is responsible for the spike generation. Its low equilibrium potential accounts, partly, for the low amplitude of the spike. (2) The fast inward current is antagonized by an early outward current which occurs almost simultaneously. This fast outward current is blocked by TEA. Its reversal potential is about ‐95 mV. A tenfold increase in the external K‐concentration shifts the reversal potential by 50 mV. Thus, it is concluded that the initial outward current is carried by K+. (3) A slow current, whose reversal potential ranges from ‐40 to ‐10 mV, is responsible for the negative after‐potential. Cl‐depletion (to one‐ninth) does not modify this current while Na‐depletion (to one‐ninth) decreases its reversal potential by about 20 mV. (4) A late current which shows delayed rectification is elicited by long pulses. Its analysis is made difficult by the change mainly of the K‐equilibrium potential suggesting accumulation of K+ outside the cell membrane. (5) The availability of the inward current and of the slow current, determined in TEA solution, shows that both currents are half‐inactivated by a 8 mV conditioning depolarization. Using a slope factor of ‐2‐5 or ‐3 the availability curve fits the experimental values. In normal solution, the availability curve of the initial current appears complex in the hyperpolarization range. The fast outward current, which is partly inactivated at the resting potential, is restored by conditioning hyperpolarization and then antagonizes the Ca inward current more. (6) It is concluded that the fast K‐current controls the spike generation and accounts for the fast repolarization of the spike. The fast and transient increase in K‐conductance may be the result of a momentary local increase in Ca concentration at the internal surface of the membrane.
Post‐natal developmental changes in the length‐tension relationship of cat papillary muscles.
Authors: Davies P , Dewar J , Tynan M , Ward R
Published: December 2014

The length‐tension relationship and the effect of paired electrical stimulation were studied in right ventricular papillary muscles obtained from cats. The animals were divided into three age groups: neonatal kittens, less than 24 hr of age; infant kittens, 16‐‐18 days of age; and adult cats. 2. The muscles were electrically driven to contract isometrically using field stimulation at 10‐‐20% above the threshold valus. 3. At Lmax the neonatal preparations produced significantly less developed (active) tension than did the adult preparations. The resting tension at Lmax was significantly greater in the neonatal preparations than in the adult ones. The infant group occupied an intermediate position between the two other groups. 4. The response to paired electrical stimulation was less in the neonatal group than in either the infants or the adults. 5. It is concluded that post‐natal developmental changes occur in the contractile properties of the myocardium of the cat.
Avian febrile response.
Authors: D'Alecy L G , Kluger M J
Published: December 2014

The febrile response of the pigeon (Columba livia) was characterized for comparison with our present day understnading of mammalian fever. 2. When injected with live Pasteurella multocida the birds became febrile and died. 3. Varying doses of dead bacteria produced a complex dose‐dependent febrile response. 4. Antipyretics effectively attenuated the febrile response to dead bacteria. 5. The similarities of reptilian, avian and mammalian fever suggest a common origin and perhaps a similar adaptive role of fever in increasing host survival during bacterial infection.
Axoplasm chemical composition in Myxicola and solubility properties of its structural proteins.
Authors: Gilbert D S
Published: December 2014

The chemical composition of axoplasm extracted from the giant axon of Myxicola infundibulum has been analysed, and some of the factors which disperse its gel structure have been identified. 2. The axoplasm contains about 3‐6% protein, and 0‐12% lipid. It is isosmotic with sea water and has a pH near 7‐0. 3. Inorganic ions in extracted axoplasm include: Na+, 13m‐mole/kg wet wtl; K+, 280; Cl‐, 24; Ca2+, 0‐3; Mg2+, 3. 4. Free organic ions in axoplasm include: gly, 180 m‐mole/kg wet st.; cysteic acid, 120; asp, 75; glu, 10; ala, 7; tau, 5; thr, 2; gln and ser, trace; homarine, 63; isethionate, 0. 5. The gel structure is dispersed by solutions containing 1‐‐10 mM‐Ca2+, because this ion activates an endogenous protease. The gel can also be dispersed without proteilysis by solutions containing 0‐5 M‐KCl, or 0‐5 M guanidine hydrochloride, or 3‐5 M urea, all of which break down neurofilaments. 6. It is argued that many aspects of the composition and dispersal properties of Myxicola axoplasm are similar to those in other axons.
Graded activation of myofibrils and the effect of diameter on tension development during contractures in isolated skeletal muscle fibres.
Authors: Gonzalez-serratos H
Published: December 2014

If the space constant of the T‐system (lambdaT) its not large in comparison with the radius (a) of a muscle fibre, different levels of depolarization should activate different proportions of the cross‐section. This possibility was tested in isolated muscle fibres with isotonic and isometric K contractures. 2. During isonic contractures with more than 40 mM‐K, wavy myofibrils appeared in the centre of the fibre. The sarcomere spacings (s) of the wavy myofibrils, measured parallel to the long axis of the myofibrils, were 1‐9‐1‐95 mum. However, the superficial myofibrils could shorten to or below s=1‐5 mum without becoming wavy. 3. In the same muscle fibre where myofibrils became wavy during K contractures, no waviness appeared during repetitive electric stimulation in normal Ringer (50 shocks/sec, 12 degrees C), although s decreased below 1‐5 mum. Wavy myofibrils were interpreted as not activated. 4. With isometric contractures it was found that the amount of depolarization needed to obtain maximal tension was smaller for fibres of shorter radius. The degree of depolarization for producing maximal tension is related to a by 6 mV/10mum. 5. These results strongly suggest that in K contractures lambdaT is not large in comparison with a.
Transmembrane exchange of chloride with bicarbonate ion in mammalian red blood cells: evidence for a sulphonamide‐sensitive "carrier".
Authors: Cousin J L , Motais R , Sola F
Published: December 2014

1. It is well known that red blood cells suspended in isotonic NH4Cl solution swell because penetration of NH3 induces a transmembrane exchange between Cl‐o and OH‐i(or HCO3‐i). The rate of swelling thus depends on the speed of the transmembrane exchanges and on the amount of anions available for exchange. 2. It has been demonstrated in experiments carried out in a CO2‐free medium that OH‐ions are poorly permeating whereas the permeability for HCO3‐is very high. Thus the rate of swelling is largely dependent on the intracellular HCO3‐concentration. In this context the well‐known inhibitory effect of sulphonamides upon swelling can be interpreted, and always has been until now, as being due to the inhibitory action of the drug on the intracellular carbonic anhydrase. However, this inhibitory effect could also result from a direct action of the drug on the transmembrane exchange; it would explain why under conditions of total carbonic anhydrase inhibition we have shown that the inhibition of swelling is far from maximal. 3. A direct experimental evidence of such an effect of carbonic anhydrase inhibitors on the transmembrane exchange of Cl‐with HCO3‐ was obtained with benzolamide (Cl 11,366), Cl 13,580 and ethoxzolamide. Surprisingly enough, however, acetazolamide (Diamox) does not affect the transmembrane exchange process. 4. The inhibitory effect of sulphonamides on HCO3‐transport process is discussed in terms of an interaction of the drug with a transport system common to HCO3‐ and organic anions.
The slow wave in the circular muscle of the guinea‐pig stomach.
Authors: Ohba M , Sakamoto Y , Tomita T
Published: December 2014

The slow wave in the circular muscle of guinea‐pig stomach was investigated with the double sucrose‐gap method. 2. The amplitude of the slow wave was reduced by depolarization, and it was increased by a small hyperpolarization (5‐10 mV). With hyperpolarization greater than 15 mV the amplitude decreased, and the slow wave became reduced, and less dependent on polarization. This residual was not abolished by strong hyperpolarizing current pulses. 3. The frequency of the slow waves was not much affected by membrane polarization. The change was only 15‐20% by depolarization or hyperpolarization of 12mV. 4. Rythmic inward currents could be recorded under voltage‐clamp conditions. The frequency of the inward currents was the same as that of the slow wave. The intensity of inward current was little affected by membrane polarization. 5. Lowering the temperature reduced the frequency of the slow wave. The rates of rise and fall of the component which remained during strong hyperpolarization were similarly decreased by lowering the temperature. The Q10 of the frequency was about 2‐7. 6. It is suggested that the slow wave consists of two different components. One is generated by a potential independent process, and triggers the second component which is potential dependent. The first component may be controlled by some metabolic process.
Milk secretion in the rabbit: changes during lactation and the mechanism of ion transport.
Authors: Peaker M , Taylor J C
Published: December 2014

Changes in the yield and composition of milk and in the permeability of the mammary epithelium to labelled disaccharides and ions have been studied during lactation in rabbits of the Dutch breed. 2. Milk yield increased to reach a peak on day 20 of lactation and then declined, but by 30‐32 days the yield was still relatively high. Milk [protein] and [fat] increased in late lactation; [Na] and [Cl] decreased from early to established lactation (11‐14 days) and then increased, whereas milk [K] and [lactose] showed an inverse pattern to that displayed by[Na] and [Cl]. 3. At all stages of lactation [Na] and [Cl] were both inversely related to milk [lactose] while [K] showed a positive correlation. 4. Labelled lactose and sucrose were found to cross the mammary epithelium at all stages but in increased amounts during late lactation. Sucrose entry from blood into milk was positively correlated with milk [Na], and inversely correlated with [K] and [lactose]. 5. The entry of (24)Na and (36)Cl into milk from blood paralleled the changes in milk [Na] and [Cl]. 6. Intracellular ionic composition determined in vitro was similar for [Na] and [K] in both established (11‐14 days) and late (25‐28 days) lactation, but [Cl] was higher in late lactation. 7. Intracellular potentials recorded in vivo were ‐31 mV (mean) and ‐36 mV in established and late lactation respectively. Transepithelial p.d. was close to zero at both stages. 8. It is suggested that ions and lactose and other small molecules can cross the mammary epithelium by a paracellular, as well as by a transcellular route, throughout lactation and that the paracellular pathway is increased in late lactation. 9. The site of the proposed paracellular pathway and the implications of such a pathway's presence on ion transport are discussed, and a scheme is suggested to account for the ionic composition of milk in this species.
Catecholamine release from bovine adrenal medulla in response to maintained depolarization.
Authors: Baker P F , Rink T J
Published: December 2014

Prolonged exposure of venous‐perfused bovine adrenal glands to high K in the presence of external Ca produces a transient increase in catecholamine output that reaches a maximum after about 1 min and then declines with a half‐time of about 1‐2 min. 2. The time course of the transient secretory response to high K does not depend appreciably on the total catecholamine output which indicates that depletion of releasable catecholamine is unlikely to be responsible for the transient nature of the response. 3. Application of 3‐6 mM‐Ba stimulates secretion from a gland after many minutes exposure to high K, when catecholamine output has declined close to resting levels. This provides further evidence that depletion does not play a major role in the transient response and shows that maintained depolarization does not inhibit the secretory mechanism. 4. Exposure to high K solutions in which Ca has been replaced isomotically by Mg does not evoke any catecholamine output. Subsequent application of Ca always elicits some secretion although the size of this response to added Ca declines rapidly during exposure to Ca‐free, high K solutions. The failure of the secretory response in these experiments is more rapid, and earlier in onset than the declining phase of the normal secretory response evoked in the presence of calcium. 5. Pre‐treatment with Ca‐free solutions of intermediate K content reduces the response to subsequent simultaneous application of high K and Ca. There is a roughly sigmoidal relation between the reduction in response and the logarithm of the K concentration used for pre‐treatment. 6. Thin slices of bovine adrenal medulla show qualitatively similar responses on exposure to high K. Examination of the flourescent signal from slices dyed with the potential‐sensitive dye DiS‐C(3)‐(5) suggests that maintained exposure to high K produces a stable depolarization. 7. The most likely explanation for these results is that K‐depolarization first activates and subsequently inactivates a potential‐sensitive Ca permeability channel. This inactivation is time and possibly potential dependent. 8. The effect of high K on calcium movements in medullary slices was examined. Exposure to 72 mM‐K increases (45)Ca uptake, the increase being greatest during the first 10 min. The efflux of Ca is also increased on exposure to high K in the presence of Ca. The net Ca uptake in 72 mM‐K is smaller than the tracer uptake of Ca. These findings indicate that K depolarization stimulates a Ca‐Ca exchange process. They are also consistent with, but do not offer strong positive support for, the idea that K‐depolarization first activates and subsequently inactivates Ca entry. 9. It is suggested that Ca inactivation might play a role in the modulation of neurosecretion and neurotransmitter release by changes in membrane potential.
Effects of physiologic alterations on binomial transmitter release at magnesium‐depressed neuromuscular junctions.
Authors: Branisteanu D D , Miyamoto M D , Volle R L
Published: December 2014

1. Transmitter release from Mg2+‐treated frog neuromuscular junctions can be described by binomial statistics. Good agreement between the observed amplitude‐frequency distribution of e.p.p.s. and that predicted by binomial statistics is observed with relatively low concentrations of Mg2+. Conversely, good agreement is found with Poisson predictions when higher concentrations of Mg2+ are used to depress transmission. 2. Binomial analysis at these junctions shows that Mg2+ reduces quantal content (m), the probability of release (p) and to a lesser extent the available stores of transmitter (n). Raising Ca2+ causes an increase in n and p and a small but significant increase in n. K+ increases m and p but not n. 3. During 'frequency‐facilitation' (1‐6 Hz), e.p.p.s., m and n are increased but p is unaffected. 4. It is concluded that binomial statistics can be used to estimate the quantal parameters of transmitter release and that these parameters can be identified as discrete entities.
Ionic fluxes in rat uterine smooth muscle.
Authors: Hamon G , Papadimitriou A , Worcel M
Published: December 2014

1. The K+, Na+ and Cl‐fluxes from the oestrogen‐stimulated rat uterine smooth muscle were measured using radioactive tracers. 2. The cellular compartment contained a concentration of K+ of 173‐6 mM which exchanged at a rate of 5‐9 x 10(‐12) mol.cm‐2.sec‐1. 3. Cl‐ exchanged at a rate of 6‐9 x 10(‐12) mol.cm‐2.sec‐1 from a cellular compartment having a concentration of 39‐3 mM. 4. The methods used for the evaluation of Na+ movements over‐estimate both influx and efflux values. If an average value of flux of 9‐2 x 10(‐12) mol.cm‐2.sec‐1 is considered we obtain PNa+/PK+ ratios of 2‐4 (‐42 mV) or 1‐3 (‐57‐6 mV), which are too high and do not correspond to electrophysiological evidence. 5. The relative permeabilities PCl‐/PK+ in the case of a membrane potential of ‐42‐0 mV could be 0‐8, or 1‐3 in the case of a membrane potential of ‐57‐6 mV. 6. Both conductances GK+ and GCl‐ seem to play an important role in determining membrane conductance.
Visual identification of two kinds of nerve cells and their synaptic contacts in a living autonomic ganglion of the mudpuppy (Necturus maculosus).
Authors: McMahan U J , Purves D
Published: December 2014

1. Many of the nerve cells comprising the cardiac parasympathetic ganglion of the mudpuppy are spread out in a thin, transparent sheet of tissue, enabling one to see cellular details in living preparations with differential interference contrast optics. The aim of this study was twofold: to establish the morphology of the nerve cells and their synaptic connections by light and electron microscopy, and to determine which aspects of the ganglion's structure could be reliably identified in the living tissue. 2. There are two types of neurones in the ganglion: (a) principal cells that send post‐ganglionic axons to cardiac muscle fibres, and (b) interneurones whose processes are confined to the ganglion. 3. Interneurones are distinguished from principal cells by the presence of numerous granular vesicles seen with the electron microscope, and by intense formaldehyde‐induced fluorescence. The interneurones are thus similar to catecholamine‐containing interneurones in autonomic ganglia of other vertebrates. 4. Principal cells are innervated by processes that terminate mainly on the cell body, forming up to forty‐five synaptic boutons and covering, on the average, 5% of the perikaryal surface. The synaptic terminals are derived from three sources: (a) axons from the vagus nerves, (b) interneurones and (c) other principal cells. Vagal terminals contacting principal cells contain agranular vesicles typical of preganglionic cholinergic endings. At regions of contact between processes of interneurones and principal cells, the interneurones have granular vesicles focused at membrane specializations; in addition there are small areas of close plasma membrane apposition, probably gap junctions. Some of the contacts between principal cells are characterized by gap junctions; others are structurally similar to vagal endings but persist after vagal degeneration. 6. Interneurones are innervated by axons that make contact mainly with their processes. The axon terminals on processes of interneurones contain agranular vesicles similar to vagal terminals on principal cells. 7. In live preparations principal cells are distinguished from interneurones by their size and the appearance of their organelles. Synaptic contacts on principal cells could often be identified and, in some cases, large contacts from interneurones or those from other nearby principal cells could be traced back to their cell bodies of origin. The validity of these identifications was confirmed by subsequent electron microscopic examination of the same cells.
The contractile properties of slow muscle fibres in sheep extraocular muscle.
Authors: Browne J S
Published: December 2014

1. The diameters of nerve fibres in the sheep trochlear nerve were measured and they fell into two distinct groups. 2. Selective stimulation of the small diameter group of nerve fibres gave rise to a slow contraction of the superior oblique muscle which was attributed to multiply innervated muscle fibres. 3. The slow fibre contraction following a single stimulus to the small diameter nerves had a rise time of 20‐50 msec and was 150‐980 mg in size. On repetitive stimulation, a maximum slow fibre contraction was developed at 120‐140 Hz, and maximum velocity of tension development at 170‐200 Hz. 4. The maximum slow fibre tetanic tension was 7‐0‐12‐3 g, which amounted to 5‐3% of the whole muscle tetanic tension, while the maximum contracture following an injection of suxamethonium was 7% of the whole muscle tetanic tension. 5. The slow fibres were very resistant to fatigue and their contraction increased the resistance of the muscle to stretching. 6. Discrepancies from earlier work and the possible significance of the slow fibres are discussed.
The thermoreculatory responses of the galago (Galago crassicaudatus), the baboon (Papio cynocephalus) and the chimpanzee (Pan stayrus) to heat stress.
Authors: Hiley P G
Published: December 2014

1. The thermoregulatory response of the galago, the baboon and the chimpanzee were studied on exposure to dry bulb temperatures of up to 40 degrees C in a temperature controlled room. 2. Heat exposure caused an elevation in the respiratory frequency of all three species. The increase in the galago was significantly greater than that in the baboon and the chimpanzee. 3. Heat exposure also caused an increase in the cutaneous moisture loss of the baboon and the chimpanzee but not in the galago. 4. Rectal temperatures always rose on heat exposure but the animals never become hypethermic. 5. Sweat gland activity in the baboon and the chimpanzee was stimulated by the administration of acetylcholine and was blocked by the administration of atropine. Sympathetic and parasympathetic drugs had no stimulatory effect on the sueat glands of the galago. 6. Local, infra‐red heating of the skin of the galago and the baboon did not stimulate any sweat gland activity. 7. The sweat glands in the galago and the baboon were found to be epitrichial. 8. These findings are discussed in relation to the habitat of each species. They are also compared to thermoregulation in other primate species, especially in relation to the unique nature of thermoregulation in man.
Centrifugal actions on amacrine and ganglion cells in the retina of the turtle.
Authors: Marchiafava P L
Published: December 2014

1. An electrophysiological investigation of efferent synapses in the retina of the turtle was conducted by recording intracellularly from amacrine cells. These cells have been selected because in birds they have been shown to have direct anatomical connexions with centrifugal fibre terminals. 2. Amacrine cells could be easily distinguished from most other retinal cells, except ganglion cells, by their different photo‐responses. Because both amacrine and ganglion cells may generate action potentials they were distinguished by their responses to optic nerve stimulation. 3. The response of ganglion cells to single shock stimulation of the optic nerve consists of an antidromic action potential followed by a late synaptic potential. 4. Cells which did not show antidromic responses but were electrically excitable, by passing direct current through the recording electrode, were considered to be amacrine cells. 5. Amacrine cells generate an e.p.s.p. in response to optic nerve stimulation. An analysis of the e.p.s.p. suggests that it may be due to a single afferent fibre terminating in the proximity of the cell soma. By analogy to the bird, it is concluded that the amacrine cells e.p.s.p.s result from the activation of centrifugal fibres.
Comparison of vasoactive intestinal peptide and secretin in stimulation of pancreatic secretion.
Authors: Konturek S J , Pucher A , Radecki T
Published: December 2014

Pancreatic volume flow as well as bicarbonate and protein secretion have been measured in chronic pancreatic fistula cats and dogs in response to I.V. infusion of VIP and secretin or duodenal perfusion of sodium oleate and HCl solution. 2. VIP and secretin infused I.V. in cats produced superimposable pancreatic dose‐response curves for volume flow and bicarbonate secretion, reaching almost identical observed and maximal calculated outputs with both peptides. In dogs, VIP was shown previously to be a much less effective stimulant of pancreatic secretion than secretin and the maximal observed bicarbonate output in response to VIP was only about 17% of that to secretin (Konturek, Thor, Dembinski & Król, 1975). It is condluded that VIP in cats is a secretin‐like full agonist, whereas in dogs it is a partial agonist of pancreatic bicarbonate secretion. 3. In cats, secretin and VIP showed equal efficacy and their combination exhibited an augmentatory action on pancreatic bicarbonate secretion with additive kinetics, whereas in dogs, VIP was found to have a lower efficacy than secretin and to inhibit competitively secretin‐induced pancreatic secretion. These results might be explained by the interaction of VIP and secretin, two chemically related peptides, on a common receptor site of the exocrine pancreas. 4. Caerulein, an analogue of CCK‐PZ, infused I.V. in cats and dogs caused a negligible pancreatic bicarbonate secretion and a potent dose‐dependent protein secretion. The combination of graded doses of VIP or secretin with a background dose of caerulein resulted in significantly higher bicarbonate and protein outputs than those induced by VIP or secretin alone. 5. Duodenal perfusion of sodium oleate soap in cats and dogs produced pancreatic dose‐response curves for volume flow and bicarbonate output similar to those evoked by VIP in these species. Pancreatic protein secretion in response to luminal oleate was slightly higher than could be accounted for by the action of VIP alone. This might be attributed to the release by oleate not only of endogenous VIP but also CCK‐PZ or to the vago‐vagal reflexes from gut to pancreas. The results of our combined study on cats and dogs suggest the possibility that oleate releases VIP from the gut and that this peptide may play a physiological role in the stimulation of pancreatic secretion.
Estimation of the lifespan of amiloride binding sites in the membranes of toad bladder epithelial cells.
Authors: Cuthbert A W , Shum W K
Published: December 2014

1. Sodium entry sites in the membranes of isolated epithelial cells prepared from bladders of toads (Bufo marinus) have been labelled with amiloride. The number of binding sites remained constant in suspensions for up to 100 hr. 2. In the presence of a protein synthesis inhibitor (cycloheximide, 0‐5 mug/ml.) there was a decline in the density of binding sites was approximately exponential. Regression analysis gave a half‐life of approximately 60 hr. 3. Aldosterone (5 X 10(‐8) M) caused a significant (P less than 0‐001) increase (50%) in the density of amiloride binding sites. Cells which had been treated with aldosterone had populations of binding sites which declined, in the presence of cycloheximide, at rates indistinguishable from those of untreated cells.
Separation of two voltage‐sensitive potassium currents, and demonstration of a tetrodotoxin‐resistant calcium current in frog motoneurones.
Authors: Barrett E F , Barret J N
Published: December 2014

1. Depolarization‐induced voltage and conductance changes were studied in frog montoneurones in isolated, perfused spinal cord slices. Two types of afterhyperpolarization are observed following action potentials in normal Ringer, a fast afterhyperpolarization lastin 5‐10 msec and a slow afterhyperpolarization lasting 60‐200 msec. Both afterhyperpolarizations are mediated by an increased K+ conductance. 2. The slow afterhyperpolarization and conductance increase underlying it are selectively and reversibly inhibited by perfusion with solutions containing low [Ca2+] (less than or equal to 0‐2 nM) or the Ca2+ antagonists Mn2+ (1mM) or Co2+ (5 mM), and are enhanced by perfusion with high [Ca2+]. 3. Addition of 2‐5 mM tetraethylammonium ion (TEA+) to the perfusing solution prolongs the falling phase of the action potential and abolishes the fast afterhyperpolarization, but does not inhibit the slow afterhyperolarization. 4. When the voltage‐dependent Na+ current is blocked by perfusion with TTX (10‐5 M), intracellularly applied depolarizing current steps evoke fast and slow hyperpolarizations with kinetics and pharmacological sensitivities similar to those of the fast and slow afterhyperpolarizations, respectively. The fast hyperpolarization is maximally activated by brief, intense depolarizations, the slow hyperpolarization by prolonged, less intense depolarizations. 5. These pharmacological and kinetic data demonstrate that in frog motoneurones the repolarization‐fast afterhyperpolarization sequence and the slow afterhyperpolarization are produced by different K+ conductance systems. The fast K+ conductance activates rapidly on depolarization, decays rapidly on repolarization, and is TEA+ sensitive, while the slow K+ conducatance activates and decays more slowly and is Ca2+‐dependent. 6. Motoneurones perfused with TEA+ and TEA often show a slow, regenerative depolarizing response to applied depolarizing currents. These regenerative depolarizations are probably produced by an influx of Ca2+, because they persist in isotonic CaCl2 and are blocked by Mn2+ or low [Ca2+]. The Ca2+‐dependence of the slow afterhyperpolarization and the increase in slow afterhyperpolarization magnitude observed following the slow Ca2+ potentials suggest that a depolarization‐evoked Ca2+ influx activates the K+ conductance underlying the slow afterhyperpolarization. 7. Motoneurones in which the slow Ca2+ and K+ conductance systems have been enhanced by high [Ca2+] or blocked by Mn2+ show altered discharge patterns in response to intracellularly applied depolarizing current steps. Perfusion with twice normal [Ca2+] (4 mM) causes montoneurones to discharge more slowly at all current intensities, and reduces the slope of the 'steady‐state' frequency‐current relationship. Mn2+‐perfused motoneurones exhibit fairly normal high‐frequency discharge at the onset of the current step, but unlike normal motoneurones, do not discharge at frequencies below 60/sec...
Post‐tetanic hyperpolarization, sodium‐potassium‐activated adenosine triphosphatase and high energy phosphate levels in garfish olfactory nerve.
Authors: McDougal D B , Osborn L A
Published: December 2014

1. While much is now known about the Na‐K‐ATPase and the posttetanic hyperpolarization of nervous tissue, they have yet to be studied together in the same preparation. 2. The post‐tetanic hyperpolarization was studied in desheathed garfish olfactory nerve. The rate constant of decay of the post‐tetanic hyperpolarization was determined by monitoring difference potentials after stimulation at 1/sec for 2‐3 min. 3. In membrane fractions prepared from these nerves, the ouabain‐sensitive ATPase activity (Na‐K‐ATPase) was determined by spectrophotometric measurements. 4. Both the post‐tetanic hyperpolarization and the Na‐K‐ATPase showed a similar sigmoidal dependence on K+ concentration. The sequence of cation specificities measured at the K‐site of the enzyme was the same as that determined by post‐tetanic hyperpolarization measurements in whole nerve. 5. The rate constants of the enzyme showed a dependence on Na+ concentration that paralleled the way in which the post‐tetanic hyperpolarization rate constants varied as a function of the number of impulses. When Na+ was completely replaced by Li+, neither enzyme activity nor post‐tetanic hyperpolarization could be measured. 6. The pH optimum for enzyme activity was between pH 7‐0 and 7‐8, while the optimal pH for post‐tetanic hyperpolarization was above pH 8‐0. 7. Metabolite levels in preparations of this nerve studied in vitro correspond to levels found in vivo. 8. High energy phosphate levels were measured fluorometrically in extracts of nerve samples that had been stimulated in air at 1/sec for various intervals. 9. During the first 2 min of stimulation, there was a significant accumulation of inorganic phosphate, and the ATP/ADP.Pi ratio dropped appreciably. 10. The accumulation of ATPase products was commensurate with the approach of post‐tetanic hyperpolarization rate constants to their maximum level. This provides direct evidence for an ATPase functioning in active Na+ transport in nerve. 11. The garfish Na‐K‐ATPase is sensitive to the ATP/ADP ratio of the incubating medium, but is relatively insensitive to orthophosphate, Pi. The fall in post‐tetanic hyperpolarization rate constants observed with continued nerve stimulation may have been partially due to the falling ATP/ADP ratio measured in nerve under similar conditions.
Inhibition of in vitro concentrative prostaglandin accumulation by prostaglandins, prostaglandin analogues and by some inhibitors of organic anion transport.
Authors: Bito L Z , Davson H , Salvador E V
Published: December 2014

1. Incubation of rabbit choroid plexus, anterior uvea (iris‐ciliary body complex) or slices of kidney cortex in a medium containing tritium‐labelled prostaglandin F(2alpha) ([3H]PGF(2alpha) or E1 ([3H]PGE1) results in a four‐ to thirteenfold concentrative accumulation of 3H activity. 2. Addition of PGF(2alpha, PGF(1) or PGA(1), any one of five PG analogues or a PG precursor, arachidonic acid, at a concentration of 10(‐4) M reduced the active accumulation of [3H]PGs by 47‐97%. Octanoic acid, at the same concentration, had only a moderate effect on the choroid plexus and no significant inhibitory effect on [3H]PFG(2alpha) accumulation by anterior uvea or kidney cortex. 3. Inhibition was also obtained with 2 mM iodoacetate (under anaerobic conditions) and with 10(‐4) M diploretin phosphate, probenecid, iodipamide, indomethacin or dinitrophenol. Perchlorate (10(‐4) M) and iodide (10(‐4) or 10(‐3) M) had no inhibitory effect while 10(‐4) M p‐aminohippuric acid had a significant inhibitory effect on the kidney cortex at a concentration of 10(‐4) M and on the anterior uvea at 10(‐3) M. 4. It is concluded that the apparent carrier mediated PG transport systems of the choroid plexus, anterior uvea and kidney cortex are not related to the iodide transport system, but may represent a subcomponent of the iodipamide transport system of these tissues. 5. These results suggest that the systemic distribution and the rate of renal excretion of PGs could be altered by high concentrations of PGs, pharmacologically less active PG analogues, some inhibitors of organic acid transport, and by some inhibitors of PG synthesis and PG action.
The cortical visual areas of the sheep.
Authors: Clarke P G , Whitteridge D
Published: December 2014

1. A stereotaxic method for the sheep brain is described. 2. At its widest part the primary visual area (Visual I) of each hemisphere extends approximately 20 mm anteroposteriorly and, when unfolded, approximately 35 mm from side to side. It occupies both walls of the lateral sulcus, and extends medially to the medial wall of the hemisphere and to the depth of the ectolateral sulcus laterally. 3. The most lateral part of the primary visual area includes 10‐15 degrees of the ipsilateral field; the contralateral field is represented to 135 degrees from the mid line. 4. Visual II also includes a strip of ipsilateral representation on its medial edge and extends to the supra‐sylvian sulcus on the lateral surface of the brain. The furthest lateral representation recorded was 130 degrees lateral. 5. Most of both visual areas is concerned with the area centralis and the visual streak. The remainder of the retina has very little cortical representation. 6. Most cells in Visual I are simple with orientational and sometimes directional sensitivity. Some complex and hypercomplex cells have been seen in Visual I, and these predominate in Visual II. Receptive field sizes from 0‐25 to 10 degree were found. Within 15 degrees of the vertical meridian, binocular cells are common in both Visual I and II.
Influence of changes in external potassium and chloride ions on membrane potential and intracellular potassium ion activity in rabbit ventricular muscle
Authors: Fozzard Harry A. , Lee Chin Ok
Published: December 2014

1. The membrane responses of rabbit papillary muscles to rapid changes in [K]o and [Cl]o were measured with open‐tipped micropipettes and with closed micropipettes made from K‐selective glass.

2. The muscle cells behaved primarily as a K electrode, and responses to changes in [K]o with constant [Cl]o or with constant [K]o × [Cl]o were substantially the same.

3. When [Cl]o was changed at a constant [K]o the membrane potentials changed rapidly and symmetrically by a small value and remained constant for 30 min.

4. Measurement of potential with K+‐selective micro‐electrodes in these experiments showed no change in intracellular K activity. In addition to permitting calculation of K permeability, these measurements reassured us that the K+‐selective electrodes were well insulated and not influenced by electrical shunts at the impalement site.

5. Although the membrane response to changes in [Cl]o was small, it was possible to calculate that the permeability ratio (PCl/PK), was 0·11. The Cl and K conductances were about 0·015 mmho/cm2 and 0·09 mmho/cm2 respectively, resulting in a conductance ratio (gCl/gK) of about 0·17.

6. The time course of depolarization by increase in [K]o was rapid (half‐time 5 sec), but repolarization on return to lower [K]o was much slower (half‐time 50 sec). The depolarization time course was easily fitted by the potential change calculated by assuming the need for K diffusion into the extracellular spaces and taking account of the logarithmic relation between membrane potential and [K]o. These calculations did not fit the time course of repolarization, which was slowed in the fashion expected from an inward‐rectifying membrane.

7. The influence of [K]i on membrane potential was investigated by changes in tonicity of the external solution. Hypotonic solution produced a change in intracellular K activity close to that produced by ideal water movement. However, in hypertonic solution, intracellular K activity did not rise as much as predicted, suggesting a change in intracellular activity coefficient.
An in Vitro system for studying insulin release caused by secretory granules‐plasma membrane interaction: definition of the system.
Authors: Davis B , Lazarus N R
Published: December 2014

1. An in vitro system is described in which insulin beta‐granule‐plasma membrane interaction can be studied. 2. The system shows an absolute requirement for physiological amounts of Ca2+ (2 muM) in order for insulin release to proceed. 3. ATP (5 muM) is abot to augment the Ca2+ effect. 4. Glucose (17 mM) alone does not cause insulin release but in the presence of Ca2+ is as effective as ATP. 5. When glucose, ATP and Ca2+ are added together a positive cooperative effect is produced with over 85% of the total insulin, added in the form of beta‐granules, being released into the medium in 10 min. 6. The system responds to tolbutamide, in the presence of Ca2+ and ATP, by releasing insulin. 7. Diazoxide, a potent insulin inhibitor in vivo, demonstrates a similar activity in vitro. 8. Various control experiments utilizing alternative membranes, granules, nucleotides, sugars and phosphorylated intermediates of metabolism have all reinforced the specificity of the release mechanisms. 9. These results demonstrate that the in vitro system mimics responses found in the intact organism and can be utilized to dissect the mechanisms associated with exocytosis of insulin granules. 10. Preliminary experiments utilizing adrenaline granules‐adrenal plasma membranes and pituitary granules‐pituitary plasma membranes suggest that the in vitro system can be extended to all granule secreting processes.
Spontaneous activity in denervated mouse diaphragm muscle.
Authors: Smith J W , Thesleff S
Published: December 2014

Intracellular electrodes were used to study the discrete depolarizations which trigger fibrillation potentials in chronically denervated mouse diaphragm muscles. Provided that the muscles were perfused on both sides spontaneous activity was maintained in vitro. 2. Discrete spontaneous depolarizations, present only in the centre of the muscle, were recorded from the third day of denervation reaching a maximum in prevalence 9‐12 days after sectioning the nerve. These potentials had random occurrence and nearly constant amplitude and frequency within a fibre, dependence of amplitude and frequency on membrane potential, and low temperature dependence. 3. The spontaneous activity was enhanced and could be initiated in previously quiescent fibres by lowering the external Ca concentration. The activity was reduced by increasing external Ca and was abolished at 15mM‐[Ca] 0. Tetrodotoxin (10‐(7)M) blocked spontaneous activity. 4. The spontaneous activity was enhanced by the catecholamines isoprenaline and adrenaline (0.5‐10 mug/ml.). This effect of isoprenaline was accompanied by an increase in the rate of rise and the amount of overshoot of the action potential. 5. Ouabain (10‐(6)‐10‐(4)M) of K+‐free solutions reversibly blocked spontaneous activity. Ouabain (10‐(4)M) reduced the rate of rise and the amount of overshoot of the action potential. 6. Detubulation of muscle fibres with glycerol of the presence of hypertonic solutions abolished spontaneous activity which could not be restarted by reducing Ca or by the addition of isoprenaline. 7. The results support the suggestion that the spontaneous discrete depolarizations which give rise to fibrillation potentials in denervated muscle result from regenerative sodium conductance increases within the transverse tubular system of the muscle fibres. Catecholamines and ouabain could affect this activity either directly, through an action on membrane excitability, or indirectly via the Na+‐K+ pump.
Excitation of phasically firing hypothalamic supraoptic neurones by carotid occlusion in rats.
Authors: Dreifuss J J , Harris M C , Tribollet E
Published: December 2014

1. The activity of supraoptic neurones has been recorded extracellularly during bilateral occlusion of the common carotid arteries in anaesthetized rats. 2. Experiments in lactating rats showed that occlusion liberated sufficient amounts of neurohypophysial hormones to cause a rise in intramammary pressure 15‐25 s after the onset of occlusion. 3. Ninety‐one percent of the phasic neurones (defined as those showing bursts of activity alternating with periods of silence) were activated by carotid occlusion less than 10 s after the onset of occlusion. Most randomly firing neurones were inhibited or were unaffected. 4. The activation of phasic neurones is unlikely to be just a nonspecific effect, because in the same animals, phasic neurones were excited whilst random neurones were not. 5. Moreover, in phasic neurones, statistical analysis shows (a) that the intervals during which an occlusion was performed were significantly shorter than the intervals between spontaneously occurring bursts, and (b) that this activation was followed by a period of reduced firing probability. 6. The results are discussed with reference to the correlation of supraoptic neuronal activity with hormone release. The possibility is considered of relating the tendency of some supraoptic neurones to fire in bursts with the secretion of vasopressin.
Progress of topographic regulation of the visual projection in the halved optic tectum of adult goldfish.
Authors: Yoon M G
Published: December 2014

1. The patterns of re‐established visual projections on to the rostral half‐tectum are studied following excision of the caudal tectum at various intervals after section of either the contralateral optic nerve or the ipsilateral optic tract in adult goldfish. 2. The pattern of a newly restored retinotectal projection depends on the duration of the post‐operative period given to the halved tectum before it is re‐innervated by regenrating optic fibres from the retina. 3. When the duration is such that regenerating optic fibres invade the denervated rostral half‐tectum at about 40 days or longer after excision of the caudal tectum, the remaining half‐tectum is able to accommodate incoming optic fibres not only from the appropriate temporal hemi‐retina but also from the foreign nasal hemiretina in an orderly compressed topographic pattern. 4. If the surgical operations are timed so that the halved tectum receive regenerating optic fibres earlier than 33 days after excision of the caudal tectum, the halved tectum initially accommodates only those optic fibres originating from the temporal half of the retina at this early stage. 5. This normal (uncompressed) pattern of the newly regenerated visual projection, however, eventually changes into an orderly compressed pattern at a later period. Post‐operative dark‐deprivation of the operated fish has no significant effect on the temporal transition. 6. The temporal transition from an initially normal pattern into an orderly compressed pattern may reflect the time course of progressive and systematic changes involved in topographic regulation of the halved tectum into a whole.
Thermoregulation in rabbits during fever.
Authors: Cranston W I , Duff G W , Hellon R F , Mitchell D
Published: December 2014

1. We have studied the effect of fever on the efficacy of the thermoregulatory control system in conscious rabbits. 2. The control system was challenged by a series of systemic thermal loads produced by the intravenous infusion of hot or cold isotonic solutions. The time integral of the consequent upward or downward displacement of brain temperature was used as an index of the response of the control system. Steady‐state fever was induced by intravenous infusion of plasma containing leucocyte pyrogen. 3. With cold loads there was a linear relation between load and response. The regression coefficients were not significantly changed by fever in any of the six rabbits. Wth hot loads given to afebrile rabbits the regression of response on load was generally not statistically significant, but the responses were not demonstrably greater in the febrile state. 4. We were not able to demonstrate impairment in the capacity of the febrile animal to compensate for systemic thermal loads.