bluuebunny/crossref_metadata_2025 huggingface dataset:
A non‐linear voltage dependent charge movement in frog skeletal muscle.
Authors: Chandler W K , Rakowski R F , Schneider M F
Published: December 2014

1. Voltage‐clamp experiments were carried out using the three microelectrode technique. Using this method membrane current density at V1 is proportional to deltaV( = V2 ‐ V1) where V1 and V2 are voltages at distances 1 and 21 from the end of a fibre. Voltage dependent sodium currents were blocked by tetrodotoxin, potassium by tetraethylammonium ions and rubidium. Contraction was blocked by adding sucrose, 467 mM. 2. The current deltaV (control) associated with a positive voltage step from a hyperpolarized conditioning voltage to the holding potential, ‐80 mV, showed two components, a capacitative transient which decayed rapidly and a maintained steady level...
Effects of glycerol treatment and maintained depolarization on charge movement in skeletal muscle.
Authors: Chandler W K , Rakowski R F , Schneider M F
Published: December 2014

1. Voltage‐clamp experiments were carried out using the techniques described in the preceding paper. 2. In one series of experiments an attempt was made to disrupt the T‐system with glycerol treatment. Muscles were soaked in Ringer + 400 mM glycerol for 1 hr at room temperature, transferred to Ringer + 5 mM calcium + 5 mM magnesium for 20‐30 min, and then cooled to around 2 degrees C and placed in an isosmotic test solution containing tetrodotoxin for electrical measurements. 3. The density of charge seen in isosmotic tetraethylammonium (TEA) solution with strong depolarization, normalized according to fibre capacitance, was decreased by glycerol treatment to about one third the amount seen in untreated hypertonic fibres. 4. An analysis of fibre capacitance revealed that only 0‐4 of the tubular capacitance was removed by this particular glycerol procedure. If the density of charge with respect to capacitance is corrected for this decrease in capacitance, the results indicate that glycerol treatment removed or immobilized 0‐77 of the charge initially present. Thus the effect of glycerol treatment to reduce charge does not depend entirely on disrupting the electrical continuity of the T‐system. 5. The effects of maintained depolarization were studied using a TEA Ringer made hypertonic with sucrose. When the voltage was changed from ‐80 to ‐21 mV the measurable charge movement declined exponentially to zero with a time constant of 13‐24 sec. On repolarization the process recovered exponentially to the initial level with a time constant of 21‐53 sec. 6. Experiments were also carried out using a sodium Ringer made hypertonic with sucrose. For small depolarizations only charge movement currents were seen, whereas for large depolarizations large delayed ionic currents, presumably carried by potassium, were observed. With moderate depolarizations in the range V = ‐40 to ‐30 mV, both components were of comparable magnitude. 7. A plot of the fractional charge movement (Q/Qmax) vs. V fitted at moderate depolarizations is similar to that of n infinity vs. V fitted at larger depolarizations. Values of n infinity were obtained by fitting the delayed ionic current to n4(V ‐ VK). For voltages between ‐40 and ‐30 mV the time constant for charge tauQ was always less than taun; values of taun/tauQ varied from 1‐6 to 4‐3. 8. Glycerol treatment had little if any effect on the kinetics of delayed rectifier currents. Values of gK measured in isosmotic solution following glycerol were about one third the values obtained in untreated fibres in a hypertonic solution (osmolality three times normal). The threefold difference in gK is probably due to a similar difference in internal potassium concentration. 9. These results and others are difficult to reconcile with the idea that the charge movement process acts as a gate for potassium channels. It seems more likely that charge movement is a step in the activation of contraction.
Charge movement in the membrane of striated muscle.
Authors: Adrian R H , Almers W
Published: December 2014

1. Non‐linear polarization currents apparently due to permanent dipoles or mobile charges in the membrane can be measured by appropriate comparison of the transient currents required to produce small and large steps of membrane potential. Integration of these transient polarization currents estimates the charge transfer associated with the movement of membrane dipoles or charges. 2. Depolarization from ‐100 to 0 mV requires a charge transfer of 35 nC/muF in addition to the charge transfer predicted by linear extrapolation of the charge required for a small depolarization from ‐100 mV. Depolarizations of varying size give a charge‐voltage relation which is sigmoid saturating beyond o mV and with a midpoint at about ‐50 mV. The ratnged depolarization reduces or removes charge movement detected by comparing currents for small and large voltage steps from ‐100 mV (Charge 1). However in depolarized fibres comparison of currents from a small potential step at +40 mV and a large hyperpolarizing potential step from ‐20 mV reveals large movements of a second charge (Charge 2). Movement of Charge 2 is less steeply dependent on voltage than movement of Charge 2 both in magnitude and in rate. 4. In size and voltage dependence these two kinds of charge movement correspond to measured voltage dependence of capacity in normally polarized and depolarized fibres (Adrian & Almers, 1976).
The effects of lithium and sodium on the potassium conductance of snail neurones.
Authors: Partridge L D , Thomas R C
Published: December 2014

1. The iontophoretic injection of lithium into snail neurones reversibly increased the resting relative potassium permeability (PK). 2. Long exposures to snail Ringer containing 25 mM‐Li and correspondingly reduced Na also caused an increase in PK. This did not occur with Ringer in which the same reduction of Na was made by replacing it with Tris. 3. Replacement of part of the Ringer Na by either Li or Tris led to proportional decreases in internal Na. 4. Injecting large quantities of Na into ouabain‐treated cells caused effects similar to those of Li injection. Without ouabain, Na injection stimulated the electrogenic Na pump. 5. A number of tests failed to produce any clear evidence that intracellular Ca was involved in the response to Li.
The contractile state of rabbit papillary muscle in relation to stimulation frequency.
Authors: Edman K A , Jóhannsson M
Published: December 2014

1. The relationship between active force and stimulation frequency (0‐25‐5/sec) was studied at 36‐37 degrees C in isolated papillary muscles of the rabbit. 2. The muscle's force producing capability at a given frequency was determined as the isometric twitch response to a test stimulus that was applied at various times after a priming period. The optimum contractile response was obtained at an interval of 0‐8 sec between the test pulse and the last stimulus of the priming period. 3. The optimum contractile response exceeded the steady‐state twitch amplitude at all stimulation frequencies higher than 1/sec. While the steady‐state twitch resonse declined at frequencies higher than 4/sec, the optimum contractile response was steadily increased as the stimulation frequency was raised. 4. The optimum contractile response was also determined after priming the muscle with a sinusoidal a.c. pulse (field strength, 10 V (r.m.s.)/cm; frequency, 20 c/s; duration, 2‐5 sec). The optimum contractile response obtained after a.c. stimulation was 2‐2 times greater than the maximal steady‐state response. Its absolute value was 67‐3+/‐6‐1 mN/mm2 (mean +/‐S.E. of mean, n = 6). 5. The twitch potentiation produced by priming the muscle at a given frequency decayed exponentially in two phases after optimum contractile response had been attained. The time constants of the two phases, determined after a.c. stimulation, were 2‐6+/‐0‐8 (n = 4) and 92‐0+/‐13‐3 sec (n = 7), respectively. 6. The optimum contractile response determined at various stimulation frequencies was linearly related to the fraction of time during which the cell membrane was depolarized (beyond ‐40 mV) by the action potentials. 7. The results are interpreted in terms of a two‐component model of the metabolism of activator calcium in the excitation‐contraction coupling.
Membrane currents of the tunicate egg under the voltage‐clamp condition.
Authors: Okamoto H , Takahashi K , Yoshii M
Published: December 2014

1. Ionic currents of the egg membrane of a certain tunicate. Halocynthia roretzi Drashe, were studied by the voltage‐clamp technique. 2. The membrane depolarization beyond ‐55mV in standard artificial sea water induced mainly transient inward current and slight outward currents, when the holding potential was kept at ‐99 mV. 3. The transient inward current was composed of two components; the major one showed a faster time course, a more negative critical level of about ‐55 mV, and a reversal potential around +60 mV and the minor one showed a slower time course, a less negative critical level o ‐10 mV, and no definite reversal potential. 4. The major component became maximum at about ‐25 mV with the peak time of 6‐9 msec at 15 degrees C, and the maximum currents ranged from 0‐5 to 1‐5 X 10(‐5) A/cm2. 5. The major component of the inward current was abolished by the replacement of Na with choline or Tris or Cs ions, while it was almost unaltered by the replacement with Li. The minor component was independent of Na concentration in the external solution. 6. The major component showed the activation and inactivation identical with those of Na current of other excitable membranes. A conditioning depolarization over ‐90 mV inactivated the Na current and the half inactivation of the major inward current was obtained by a conditioning pulse to ‐56 mV, when the pulse duration was 400 msec and the temperature was at 15 degrees C. 7. The time course of the Na current was formulated with m and h parameters in the following equations: (see article). 8. The kinetic parameters taum and tauh of egg Na current were calculated and compared with those of the squid axon. The potential dependence of taum and tauh was almost identical with that of the axon, but the absolute values of both taum and tauh were ten‐ to twentyfold larger than those of the axon in any range of the membrane potential. 9. The temperature depdence of the kinetic parameters taum, tauh and of the chord conductance gNa was studied. The Q10's for taum and tauh were both 4‐0, while the Q10 for gNa was 2‐0 in the temperature range from 5 to 20 degrees C. 10. The outward and inward rectifying conductances of egg membrane were remarkably activated at the potential level above +100 mV and below ‐70 mV respectively in standard artificial sea water. Both increased currents were subsequently subject to inactivation. 11. It was suggested that Na, Ca, K inward rectifying and K outward rectifying conductances all exist separately in the egg cell membrane and the Na current was essentially identical with that through the Na channel in other excitable membranes.
Effects of glucose on 45Ca2+ uptake by pancreatic islets as studied with the lanthanum method.
Authors: Hellman B , Sehlin J , Täljedal I B
Published: December 2014

1. Fluxes of 45Ca2+ were studied in pancreatic islets from non‐inbred ob/ob‐mice. Because La3+ blocked the transmembrane fluxes of 45Ca2+ in islet cells, incubations aimed at measuring glucose‐induced changes of the intracellular Ca2+ were ended by washing the islets with 2 mM‐La3+ for 60 min. 2. Uptake of 45Ca2+ progressed for 2 hr; the intracellular concentration of exchangable Ca2+ was about 7 m‐mole/kg dry wt., as estimated from the isotope distribution at apparent equilibrium in islets exposed to 3 mM D‐glucose. Raising the D‐glucose concentration to 20 mM enhanced the 45 Ca2+ uptake whether or not the islets had first been equilibrated with the isotope. The stimulatory effect of D‐glucose was observed in Tris buffer containing no anions but Cl‐ as well as in polyanionic bicarbonate buffer. The effect could not be reproduced with equimolar L‐glucose. 3. The rate of 45Ca2+ release was the same whether the islets had been pre‐loaded in the presence of 3 or 20 mM D‐glucose. Thus the 45Ca2+ that had been taken up in response to 20 mM D‐glucose appeared to be released much more slowly than the bulk of intracellular 45Ca2+. The release of 45Ca2+ was not significantly influenced by D‐glucose during the release period. Incubation for 30 min was require for half of the radioactivity to be released. 4. The rates of insulin secretion were about the same in uni‐anionic Tris buffer as in polyanionic bicarbonate buffer. A marked insulin secretory response to 20 mM D‐glucose was observed in either buffer. 5. It is concluded that 20 mM D‐glucose causes a net uptake of Ca2+ from the extracellular fluid into the interior of the beta‐cells. This uptake is probably not regulated at the level of the plasma membrane but more likely reflects an increased affinity of some intracellular phase or compartment for the ion. Because the observed uptake and release of intracellular 45Ca2+ are slow processes in comparison with the rapid effects of extracellular Ca2+ on insulin secretion, insulin secretion may also depend on a more superficial and La3+‐displacable Ca2+ pool.
Developmental aspects of potassium flux and permeability of the embryonic chick heart.
Authors: Carmeliet E E , Horres C R , Lieberman M , Vereecke J S
Published: December 2014

1. The rate coefficient of 42K efflux, the transmembrane potential, the intracellular concentrations of Na and K and the volume/surface area have been measured in embryonic chick hearts of different ages. 2. With respect to age, the rate coefficient for 42K efflux was minimal for preparations from 6‐8 day old embryos, and distinctly higher values were obtained for the hearts of 3‐5 and 18‐20 days. With respect to the effect of external K concentration (Ko), all age groups showed a five‐ to sevenfold increase in rate coefficient between 2‐5 and 140 mM‐Ko. The effect of Ko was found to be indepedent of extracellular Na, except in the 18‐20 day hearts bathed in K‐free solution. 3. Intracellular concentrations of K and Na were found to decrease, membrane potential to increase with age. The volume/surface area measured by stereologic and morphometric techniques did not change with age. 4. The permeability coefficient for K (PK), calculated from the absolute K flux and the measured membrane potentials, was fairly constant for a given age between 2‐5 and 20 mM‐Ko. In K‐free solution, PK was markedly reduced (factor 4). At a given Ko, PK increased twofold between 6‐8 and 18‐20 days while PNa remained relatively constant.
The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium‐free ringer solution and re‐incubated at 37 degrees C in the presence of external potassium.
Authors: Law R O
Published: December 2014

1. The cells in slices cut from the renal outer medulla of normally hydrated adult rats were loaded with Na and depleted of K by incubation for up to 100 min in cold iso‐osmolal K‐free Ringer containing 180 mM‐Na. There was a continuous net cellular water loss during this time; an inverse linear relationship existed between water content and intracellular Na concentration. 2. The original intracellular Na and K concentration were restored following 60 min re‐incubation in warm Ringer (37 degrees C) containing 5‐9 mM‐K. Restoration of cellular water content was incomplete after re‐incubation for up to 120 min. 3. During incubation in cold K‐free Ringer the presence of 1 mM ouabain did not affect cellular Na uptake or K and water loss. Ethacrynic acid, 1 mM, completely blocked cellular Na uptake and water loss, without affecting the intracellular K concentration at 100 min. When ouabain and ethacrynic acid were present together water loss was also prevented but intracellular Na concentration rose slightly by 100 min. 4. During re‐incubation in warm K‐containing Ringer 1 mM ouabain inhibited Na extrusion completely for up to 60 min while only partially preventing K uptake and further depressing the level of cellular hydration. Ouabain in the presence of 1 mM ethacrynic acid had similar effects on intracellular Na and K concentrations, but raised the level of intracellular water above that of cells in control slices. 5. Ethacrynic acid alone, 1 mM, did not interfere with Na extrusion or K uptake, but also raised intracellular water above control values. 6. The results obtained are discussed in relation to (a) the nature of the preparation used, (b) the possible membrane transport processes occurring and their known or suggested sensitivity to ouabain and ethacrynic acid, (c) the mechanisms which may be responsible for cell volume maintenance in the medulla.
The effect of acetzolamide on Ion transport across isolated sheep rumen epithelium.
Authors: Emanović D , Harrison F A , Keynes R D , Rankin J C
Published: December 2014

1. The net fluxes of sodium and chloride from the lumen to the blood side of isolated sheep rumen epithelium were reduced by treatment of both sides of the epithelium with acetazolamide. 2. The changes in the net fluxes of sodium and chloride were significantly correlated and showed recovery after removal of acetazolamide. 3. The net flux of potassium from blood to lumen side of the epithelim was not affected by treatment with acetazolamide. 4. It is suggested that acetazolamide blocks coupled sodium and chloride transport which may be mediated through 'low‐activity' carbonic anhydrase enzymes.
A diurnal rhythm in the absorption of glucose and water by isolated rat small intestine.
Authors: Fisher R B , Gardner M L
Published: December 2014

1. Glucose and water absorption by isolated small intestine from rats which have had unrestricted access to food is 50‐60% higher at night than during the daytime. 2. When the feeding time is restricted to 06.00‐09.00 hr G.M.T. glucose and water absorption rates in the period from 3 to 7 hr after withdrawal of food are almost as high as the rates observed at night‐time in the animals with unrestricted feeding. 3. These changes in absorption rates appear to be associated with feeding time and not with the pattern of illumination.
Cortical suppression of the ritino‐collicular pathway in the monocularly deprived cat.
Authors: Berman N , Sterling P
Published: December 2014

1. In nine cats monocularly deprived from birth, the responses of single neurones in the superior colliculus contralateral to the deprived eye were studied. 2. In six animals most units could be driven by visual stimuli only through the ipsilateral (experienced) eye despite the fact that this colliculus receives a major input from the contralateral (deprived) retina. 3. Immediately following removal of visual cortex, including areas 17, 18 and 19, the collicular units could be driven by the deprived eye. 4. We conclude that the cortex must exert a powerful suppression of the retino‐collicular input, and we argue that this suppression occurs in normal as well as in monocularly deprived animals. 5. In three animals the retinal input from the deprived eye was not suppressed but instead dominated many collicular celld, apparently to the exclusion of the cortical input from the experienced eye.
Lateral geniculate relay of slowly conducting retinal afferents to cat visual cortex.
Authors: Cleland B G , Levick W R , Morstyn R , Wagner H G
Published: December 2014

1. Lateral geniculate neurones of the cat were studied in terms of the latency for activation by local electrical stimulation of the retina, the latency of electrical activation from the visual cortex and properties of receptive fields. Most of the units were relay cells (antidromic activation from visual cortex) but a small proportion were trans‐synaptically activated from the cortex. The latter group included units with on‐off, on‐centre or off‐centra receptive fields. 2. Direct activation of lateral geniculate neurones from local electrical stimulation of retinal ganglion cells or their axons in the retina was identified by the sharpness of timing of the elicited impulses. This procedure revealed the existence of slowly conducting axons relaying in the lateral geniculate nucleus. 3. The distribution of latencies for direct activation from the retina was bimodal with an extended tail of long values. It is similar to the distribution of antidromic latencies of retinal ganglion cells following stimulation of the optic tract. 4. There was a tendency for geniculate neurones with fast input from the retina to have fast axons to the visual cortex and correspondingly for medium‐speed and slow input. 5. The previous classification of geniculate receptive fields into sustained and transient types was extended to include commonly encountered 'brisk' and uncommonly encountered 'sluggish' varieties of each. The extension was based on visual properties and latency for direct electrical activation from the retina. Units with receptive fields differing from the familiar on‐centre or off‐centre concentric pattern were encountered rarely; they included colour‐coded fields, local‐edge‐detectors and one edge‐inhibitory off‐centre type.
Ionic currents in the guinea‐pig taenia coli.
Authors: Inomata H , Kao C Y
Published: December 2014

Short segments of portions of taenia coli of the guinea‐pig averaging 54 mum X 219 mum X ca. 200 mum have been studied by a double sucrose‐gap voltage‐clamp technique. 2. The average total capacitance was 0‐4 muF, corresponding to approximately 10(4) cells, if a specific membrane capacitance of 3 muF/cm2 were assumed. 3. A significant resistance, averaging 11‐4omega, was in series with the membrane, and seriously limited the accuracy of the voltage control possible. 4. On depolarization, an early transient inward current was followed by a late maintained outwary current. 5. The late current was carried mainly by K+, because its direction could be reversed if the preparation were first depolarized in isotonic K2SO4 and held back to the original resting potential. 6. After appropriate corrections for residual capacitative and leakage currents, a reversal potential for the late current (Eb) was determined to be 15‐20 mV more negative than the natural resting potential. It was not affected by the amplitude or the duration of the activating voltage step, but could be changed by prolonged applications of holding current. 7. At rest, the ratio of PNa:PK was 0‐16:1; for Eb it was 0‐05:1. 8. The reversal potential for the transient early inward current (Ea) averaged 22 mV in Krebs‐bicarbonate solution, but was shifted to about 35 mV when the late current was first suppressed with tetraethylammonium ion. The shift suggested that there was some overlap of the early and late currents. 9. Reduction of [Na+]o to 50% of normal, or replacement of all Na+ with dimethyldiethanol ammonium ion and choline ion, failed to cause any significant shifts in the reversal potential of the early current or reduce the magnitude of the early current. 10. Reduction of [Ca2+]o to 0‐25 or 0‐1 of the normal caused shifts of the Ea toward the negative and reductions in the early current. These changes can occur without changes in the maximum chord conductance of the early current, such as might happen in ordinary Krebs‐bicarbonate solution, or in preparations which had been depolarized by prior treatment with isotonic K2SO4 and then held back to the original membrane voltage. 11. Increase of [Ca2+]o to 5 times normal increased the early inward current, and the maximum chord conductances of the early and late currents, but did not shift the Ea. 12. In preparations pretreated with TEA, increasing [Ca2+]o to 5 times normal shifted Ea toward 45 mV. 13. The various observations are interpreted to mean that the early current in the taenia coli is carried principally by influx of Ca2+, and not by Na+.
Characteristics of the rectifying properties of the sino‐atrial node cell of the rabbit.
Authors: Seyama I
Published: December 2014

After confirming the region of the sino‐atrial (S‐A) node by its characteristic action potential, man‐made strands including the pacemaker region of the rabbit heart were prepared and simple cable theory analysis performed. The estimated gamma was 828 mum in Tyrode. 2. The single sucrose gap method was employed to conduct both the current‐clamp experiment and the voltage‐clamp experiment. In both methods outward‐going and inward‐going rectification were observed. 3. The existence of a positive after‐potential in the case of the current‐clamp experiment and of an outward current tail in the case of the voltage‐clamp experiment after cessation of cathodal pulses suggests that the outward‐going rectification is due to the increase of K conductance. 4. The slowly developed inward‐going rectification was always accompanied with a decrease of membrane resistance. It is unlikely that change in K conductance is solely responsible for this rectification. Discussion was made of the possibility that changes in both Na and Cl conductance together with K conductance might be involved.
Characteristics of the entry process for sodium in transporting epithelia as revealed with amiloride.
Authors: Cuthbert A W , Shum W K
Published: December 2014

1. The permeation of sodium ions trhough the mucosal surface of frog skin epithelium at different transepithelial potentials has been investigated using the blocking drug amiloride. 2. An increase in serosal negativity in voltage‐clamped skins was associated with an increase in the absolute amount of inhibition caused by a fixed concentration of amiloride. Hyperpolarizing or depolarizing skins with respect to the short‐circuited condition did not affect the apparent affinity of amiloride for the entry sites. 3. When skins were voltage clamped at ‐50 mV (serosa negative) the specific binding of amiloride to sodium entry sites was increased by 77% compared to the short‐circuited condition. Skins clamped at +50 mV had only 72% of the specific binding found in short‐circuited skins. Experiments with a second blocking drug, triamterene, indicated that the extra binding sites appearing at ‐50mV were similar to those found under short‐circuit conditions. The appearance and disappearance of binding sites may reflect changes in cell volume. 4. The findings suggest that the increased sodium current which flows when skins are clamped at ‐50 mV results from an increase in the number of entry sites, and perhaps also to a voltage sensitive increase in flux through each entry site.
The role of carbonic anhydrase inhibitors on anion permeability into ox red blood cells.
Authors: Cousin J L , Motais R
Published: December 2014

1. Organic anion permeability in ox red blood cell was measured by studying steady‐state self‐exchange of oxalate, chosen as a prototypical substrate of the organic anion transport system previously described; chloride self‐exchange measured the inorganic anion permeability. 2. Carbonic anhydrase inhibitors of the sulphonamide class inhibit both organic anion self‐exchange (A‐/A‐) and chloride self‐exchang (CL‐/CL‐) although carbonic anhydrase plays no role in these exchanges. These results confirm the conclusions already published that sulphonamides can act directly on the cellular membrane as specific inhibitors of anion transport. 3. There is a correlation between the chemical structure of the sulphonamides and their capacity for inhibiting transmembrane anionic exchange. It is of significance that N‐sulphamyl substitution, which abolishes the carbonic anhydrase inhibitory potency, does not destroy anionic inhibitory capacity and may even increase it. 4. For each sulphonamide the capacities for inhibiting chloride transport and oxalate transport are strictly identical. Inhibition appears non‐competitive. 5. The temperature sensitivity of oxalate self‐exchange is exactly the same as that of chloride self‐exchange. From this, and from the nature of their inhibition by sulphonamides, it is proposed that chloride and organic anions share the same transport mechanism. 6. In the light of the present results the chloruretic action of sulphonamides in various tissues, in particular the kidney, is discussed.
The excretion of urea by dogs following a meat meal.
Authors: O'Connor W J , Summerill R A
Published: December 2014

1. After a meal of meat (10g/kg), urea excretion in dogs increased by about 200%, plasma urea by 60% and exogenous creatinine clearance by 40% in comparison with control experiments. 2. Urea, given by stomach tube in doses producing the same increase in plasma urea, caused urea excretion to increase by only 90%, with no increase in creatinine clearance. With the increased glomerular filtration rate after meat there was added excretion of urea. 3. In control experiments and after urea, the rate of excretion of urea was directly proportional to plasma urea. The ratio urea clearance/creatinine clearance, was 0‐45. 4. After meat, urea clearance increased more than creatinine clearance, the ratio increasing to 0‐55, i.e. a smaller fraction of the filtered urea was re‐absorbed after meat. 5. After meat, 10g/kg, the rate of urea production rose to 230‐600 mumole/min for 4‐6 hr.
The study of (Methyl‐3H)decamethonium dichloride incorporation into normal and dystrophic mouse muscle.
Authors: Marusyk H , Monckton G
Published: December 2014

1. (Methyl‐3H)decamethonium dichloride was injected intravenously into the tail vein of dystrophic and normal mice of the Bar Harbour strain 129 ReJ/dy in paralysing doses. 2. Scintillation counts were made of 1 mm sections of diaphragm and tibialis anterior which showed a normal distribution of tritiated decamethonium in the dystrophic animals. 3. Intraperitoneal injections of L‐(gamma‐3H)leucine were made into dystrophic and normal mice. Examination of diaphragm and tibialis anterior by scintillation counting showed the abnormal uptake typical of dystrophic involvement of murine muscle. 4. The normal distribution of (methyl‐3H)decamethonium dichloride uptake by the dystrophic muscle does not support the concept of active denervation in this disease.
Renal handling of phenol red. II. The mechanism of substituted phenolsulphophthalein (PSP) dye transport in rabbit kidney tubules in vitro.
Authors: Sheikh M I
Published: December 2014

1. The uptake of various substituted phenolsulphophthalein dyes by cortical slices of rabbit kidney has been studied in detail in order to obtain more information on the secretory system for organic anions. 2. The rate of initial uptake of dyes and the accumulation after incubation for 2 hr under aerobic conditions increased in the order: phenol red (PR) greater than bromophenol blue (BPB) greater than bromocresol green (BCG) greater than bromothymol blue (BTB), while the reverse order of uptake was observed under anaerobic conditions. There was no difference between the uptake of BTB under aerobic and anaerobic conditions. 3. The accumulation of dyes under anaerobic conditions could be accounted for by binding to tissue constituents. In comparison with PR (Sheikh, 1972), the substituted dyes were found to interact extensively with the 700 G (cell membranes) and cytosol fractions of renal homogenates. 4. Low concentrations of the substituted dyes efficiently inhibited the accumulation of rho‐aminohippurate (PAH). The concentration of dye resulting in 50% inhibition of PAH accumulation (KI) agreed well with concentrations estimated to sustain 50% of maximal dye transport (KM). On this basis the affinity of the dyes for the transport system increases in the order: PR less than BPB less than BCG less than BTB. 5. Probenecid, 2,4‐dinitrophenol, PAH, octanoate and succinate affected to a smaller extent the uptake and binding of BPB and BCG by renal tissue than that previously shown for PR (Sheikh, 1972). No inhibitory effect of these substances on the accumulation of BTB by kidney tissue was observed. 6. The binding of PSP dyes by phospholipid vesicles (liposomes) and a representative binding protein, human serum albumin, exhibited close similarity to that of binding by renal tissue. Partition experiments involving octanol‐water phases indicated that the hydrophobicity of the dyes increased in the order: PR less than BPB less than BCG less than BTB. 7. The results indicate that BTB, despite its inhibitory potency, is not transported by the organic anion system. BPB and BCG are transported to a lesser extent, and interact more strongly with the transport system than does PR. It is suggested that the substituted dyes by virtue of hydrophobic interaction with the transport system reduce the movement of the mobile part of the transport system.
Calcium‐dependent potassium exchange in human red cell ghosts.
Authors: Simons T J
Published: December 2014

1. The properties of the Ca‐dependent K transport system of human red cell ghosts have been examined under equilibrium exchange conditions. 2. K transport is stimulated half‐maximally by about 0‐4muM‐Ca2i+ or 5muM‐Sr2i+, but much higher concentrations of Ba2i+ give only slight stimulation. Mg is a weak antagonist to Ca. 3. The free Ca2+ concentration in human red cells is estimated to be below 0‐25muM. 4. The curve relating the rate of K transport to the intracellular Ca2+ concentration is complicated and suggests that internal Ca acts at three or more sites. 5. K, Rb and possibly Cs ions are transported by the Ca‐dependent system. Under comparable conditions the relative rates are 1(K):1‐5(Rb): less than 0‐05(Cs). 6. No Ca‐dependent transport of Na, Li or choline could be detected. If Na is transported, it must be at less than 1/40 of the rate of K. 7. The rate of K transport is almost linearly related to the K concentration in the 0‐200 mM range, but the curve is sigmoid close to the origin. 8. Intracellular, but not extracellular Na inhibits K transport, in a way that suggests competition with K at more than one site. 9. These results suggest that the transport system has a complex mechanism.
A study of the transport and permeability properties of the guinea‐pig amniotic membrane.
Authors: North P M , Segal M B
Published: December 2014

1. The simultaneous measurement of the two‐way sodium flux across the in vitro amniotic epithelium did not reveal a preferential active movement of sodium in either direction. The amnion is thus unlikely to be the site of formation of amniotic fluid. 2. The permeability of the amniotic epithelium to some non‐electrolytes has been measured with isotopes and was found to be generally low in relation to the thinness of the tissue. The permeability to non‐electroytes would appear to be depebility to sodium and to non‐electrolytes was found to vary with gestational age. The amnion from animals of 61‐70 days' gestation was markedly more permanent than those at 50‐60 days (term 70 days).
The time‐dependent and dose‐dependent effects of caffeine on the contraction of the ferret heart
Authors: Chapman R. A. , Léoty C.
Published: December 2014

1. Trabeculae isolated from ferret heart and from other mammalian hearts have been mounted in a way that enables the tension generated to be measured while the composition of the bathing fluid is rapidly altered.

2. Application of caffeine to these trabeculae initiates a rapid transient contracture and depresses the strength of regularly evoked heart beats.

3. The strength of the contractures, the rate of tension development and the rate of spontaneous relaxation are all increased by raising the concentration of the applied caffeine.

4. The strength of the caffeine contracture is relatively unaffected by changes in the bathing Na+, K+ or Ca2+ concentrations, but is reduced by exposure to the free‐base form of local anaesthetics.

5. Lowering of the temperature has complex effects on the amplitude of the caffeine contracture due to the differing temperature sensitivities of the contraction and spontaneous relaxation.

6. Following a caffeine contracture, a period of perfusion by caffeinefree solution is required before a full‐sized contracture can be evoked by the re‐application of caffeine. This re‐priming of the caffeine contracture has a sigmoidal time course that can be fitted by a two compartment model. The rate constants of the filling of each of the compartments can be obtained analytically, and are found to be increased by raising the extracellular calcium concentration, [Ca]o, by stimulating the preparation or by raising the temperature. Reducing the [Na]o or raising the [K]o has little effect on these processes.

7. The presence of traces of caffeine in the perfusing fluid between the conditioning and test challenges with the caffeine contracture solution reduces the extent of the re‐priming without much affecting its rate.

8. The behaviour of several model systems have been compared with that of the heart with the aid of an analogue computer. A four compartment closed system has been found to simulate the results presented in this paper.

9. It appears that caffeine has its effects by acting to increase the rate of release of activator calcium from one part of a non‐homogeneous intracellular relaxing system present within the mammalian heart, which is likely to be the sarcoplasmic reticulum.
ATP hydrolysis associated with an uncoupled sodium flux through the sodium pump: evidence for allosteric effects of intracellular ATP and extracellular sodium
Authors: Glynn I. M. , Karlish S. J. D.
Published: December 2014

1. A method has been developed for regenerating [γ32P]ATP of constant specific activity within resealed red cell ghosts, and for measuring its hydrolysis. The method may be used to follow the hydrolysis of ATP at concentrations down to 1 μ
M, and for periods long enough for the ATP at these very low concentrations to turn over several hundred times.

2. Using this method we have been able to show that the ‘uncoupled’ efflux of Na caused by the Na pump when resealed red cell ghosts are incubated in (Na + K)‐free media is associated with a hydrolysis of ATP. The stoicheiometry is roughly 2‐3 Na ions expelled per molecule of ATP hydrolysed.

3. Measurements of ATP hydrolysis and Na efflux as functions of intracellular ATP concentration have shown that uncoupled Na efflux, and its associated ATP hydrolysis, are saturated at intracellular ATP concentrations in the region of 1 μ
M.

4. Measurement of ATP hydrolysis as a function of ATP concentration in resealed ghosts incubated in a K‐containing medium gave a complicated activation curve suggesting the involvement of high‐affinity (Km ca. 1 μ
M) and low‐affinity (Km ca. 100 μ
M) sites.

5. When resealed ghosts containing about 1 μ
M‐ATP were incubated in a Na‐free or in a high‐Na medium, the addition of K to the medium reduced the rate of ouabain‐sensitive ATP hydrolysis.

6. Ouabain‐sensitive ATP hydrolysis in resealed ghosts incubated in K‐free choline media was inhibited by external Na at low concentrations (Ki < 1 m
M), but this inhibition was reversed as the external Na concentration was further increased.

7. The results show that uncoupled Na efflux may be thought of as the transport mode associated with Na‐ATPase activity, just as Na‐K exchange is the transport mode associated with (Na + K)‐ATPase activity. The significance of the differences between uncoupled Na efflux and Na‐ATPase activity, on the one hand, and Na—K exchange and (Na + K)‐ATPase activity, on the other, is discussed.
Impedance components in longitudinal direction in the guinea‐pig taenia coli.
Authors: Ohba M , Sakamoto Y , Tokuno H , Tomita T
Published: December 2014

1. When the tissue impedance of the guinea‐pig taenia coli was measured across a 2 mm sucrose gap in a longitudinal direction, the impedance locus could be fitted by two different circular arcs. Their characteristic frequencies were about 0‐6 and 240 Hz after 60 min superfusion with sucrose solution. From the effects of changing the width of sucrose gap and of transection of tissue, and also from taking the difference between impedances measured at two distances, it was concluded that the low‐frequency locus corresponds to the transverse impedance of the plasma membrane and the high‐frequency locus to the longitudinal tissue impedance. 2. A change in the longitudinal tissue impedance was measured during superfusion with sucrose solution, using a frequency range between 5 Hz and 10 kHz. The admittance decreased with time of superfusion and this time course could be expressed by the sum of three exponential terms. The fastest component, having a time constant of 1‐3 min at 10 kHz, was interpreted to correspond to a process of wash‐out of extracellular medium. 3. Admittances at zero and infinite frequencies were obtained from the impedance locus. The decrease in these admittances with the time was analysed and the values at the start of washing were obtained by extrapolating the admittance change to zero time. 4. From these values it was estimated that the myoplasmic resistance was 214 omega cm, the junctional resistance 372 omega cm, and the junctional capacity 3‐1 muF/cm at 25 degrees C. In these calculations the equivalent circuit of tissue was assumed to be expressed by two components in series: one for the myoplasmic resistance and the other for the junction which has the junctional resistance and capacity in parallel. 5. After 90 min superfusion with sucrose solution, the total tissue impedance measured at zero frequency was increased from 586 to 3034 omega cm. In the total impedance the myoplasmic resistance was increased from 214 to 914 omega cm and the junctional resistance from 372 to 2120 omega cm. Thus, the change in junctional resistance was greater than that in myoplasmic resistance during superfusion of sucrose solution.
A study of peripheral input to and its control by post‐ganglionic neurones of the inferior mesenteric ganglion.
Authors: Szurszewski J H , Weems W A
Published: December 2014

1. Intracellular recordings were made, in vitro, from neurones of guinea‐pig inferior mesenteric ganglia (IMG) attached, via the lumbar colonic nerves, to segments of distal colon. 2. 'Spontaneous' synaptic input from colonic afferent fibres was observed in 79% of the neurones tested. In any given preparation, the level and pattern of this synaptic input to different neurones varied considerably. 3. Superfusion of colonic segments with drugs (papaverine, isoprenaline, and adenosine triphosphate) which reduce colonic motility decreased colonic afferent input to IMG neurones. 4. Superfusion of colonic segments with acetylcholine or stimulation of pelvic nerves, both of which increase colonic motility, increased colonic afferent input to IMG neurones. 5. Superfusion of colonic segments with either atropine or tubocurarine reduced the level of 'spontaneous', colonic afferent input. However, distension of these relaxed segments increased the colonic afferent input. 6. Repetitive stimulation of preganglionic inputs to the IMG inhibited afferent input from drug relaxed segments of colon that were moderately distended by the injection of air into the lumen. Superfusion of the colon with phentolamine blocked this inhibition. 7. The results of this study suggest that IMG neurones receive afferent input from mechanoreceptors located in the distal colon and that the mechanosensitivity of this afferent pathway is in part controlled by efferent noradrenergic neurones of the IMG. The IMG‐colon neural circuitry can therefore be considered to form a feed‐back control system which participates in the regulation of colonic motility.
Further studies of the potential‐dependence of the sodium‐induced membrane current in snail neurones.
Authors: Kononenko N I , Kostyuk P G
Published: December 2014

1. The potential‐dependence of the membrane current induced by intracellular injections of sodium ions was studied on giant neurones of the snail Helix pomatia. This current decreases with membrane hyperpolarization at room temperature and can be reversed at sufficiently negative holding potentials. The same injections at 7 degrees C, as well as injections of lithium or potassium ions do not induce membrane currents and do not increase membrane conductance. 2. An increase in the amount of injected sodium changes the potential‐dependence of the induced membrane currents. Small injections (about 1 muC) induce a current that does not depend upon the membrane potential. Further increase in the injection size not only increases the induced current but also enhances its potential‐dependence and often reveals the existence of a reversal potential. The latter reaches ‐60 to ‐65 mV with large sodium injections. 3. An increase in extracellular potassium concentration from 4 to 8 mM shifts the reversal potential 17 mV in the depolarizing direction, and a decrease from 4 to 2 mM shifts it 14 mV in the hyperpolarizing direction. Replacement of potassium by rubidium or elimination of sodium ions from the outside solution, does not affect the induced current or its potential‐dependence. 4. The coefficient of electrogenicity (the ratio between the amount of charge transferred by the sodium‐induced membrane current and the amount brought into the cell during the injection) increases with an increase in the injection size if the membrane potential is clamped near the resting potential level. This relation is reversed when the holding potential is ‐80 mV. The reversal takes place at holding potentials near ‐60 mV. 5. 10 mM TEA does not affect the induced current and its potential‐dependence. 6. It is suggested that the potential‐dependence of the sodium‐induced membrane current is a result of a specific increase in the membrane potassium conductance that is coupled with high activity of the sodium pump.
Prolonged inactivation of cortical pyramidal tract neurones in cats by distension of the carotid sinus
Authors: Coleridge Hazel M. , Coleridge John C. G. , Rosenthal Fred
Published: December 2014

1. We have investigated the effects of stimulating carotid sinus baroreceptors upon the activity of single cortical pyramidal tract cells (PT‐cells) in anaesthetized cats.

2. Extracellular potentials were recorded from PT‐cells, which were driven orthodromically (1/sec) by stimulating thalamic nuclei (N. ventralis lateralis, N. ventralis posterolateralis) or afferent nerves in the contra‐lateral forepaw. Baroreceptors were stimulated by inflating small balloons placed in the bifurcations of one or both common carotid arteries.

3. Distension of the carotid sinus caused a prolonged depression of the orthodromically evoked discharge of eighteen of thirty‐two PT‐cells, the effect ranging from a 15% reduction in firing to complete cessation of activity (average reduction, 39%). The depression of firing outlasted the period of balloon inflation by an average of 85 sec; in some experiments inhibition persisted for as long as 2‐3 min.

4. Inflation of the balloon caused a reflex fall in arterial pressure (mean decrease, 29 mmHg), pressure reverting to the control level as soon as the balloon was deflated. Single fibre recording from the carotid sinus nerve confirmed that stimulation was confined to baroreceptors and that carotid chemoreceptors were unaffected by balloon distension.

5. Depression of PT‐cell activity could not be explained simply by a fall in cerebral blood flow resulting from the reflex fall in arterial blood pressure. When a comparable or greater degree of hypotension was produced by bleeding or peripheral vagal stimulation, PT‐cell firing fell in a third of experiments but reverted immediately to the control level when arterial pressure was restored. Thus some factor other than a decrease in cerebral perfusion pressure was responsible for the prolonged inhibition evoked by carotid sinus distension.

6. Our results are consistent with the hypothesis that baroreceptor input to the reticular formation exerts an ascending influence on cortical mechanisms, with prolonged inhibitory effects comparable to those previously demonstrated at spinal level.