bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of carbon dioxide on the tonic and the rhythmic discharges of expiratory bulbospinal neurones.
Authors: Bainton C R , Kirkwood P A
Published: December 2014

1. Extracellular micro‐electrodes were used to measure the responses of expiratory bulbospinal neurones to CO2 in anaesthetized, paralyzed cats, ventilated with O2. Simultaneous measurements were made of phrenic nerve and intercostal nerve filament discharges. 2. Hypocapnia produced tonic activity in some of the expiratory neurones and in expiratory filaments but rendered the phrenic and inspiratory filaments silent. 3. A graded excitatory effect of CO2 on tonic activity of both the neurones and the filaments was seen which progressed smoothly and continuously to rhythmic activity as CO2 was increased and to zero as CO2 was decreased. 4. Increases in blood pressure produced effects which were opposite to those produced by CO2, and which had a faster time course. 5. The CO2 response curves of those units showing tonic activity were indistinguishable from the CO2 response curves of those which did not. 6. A mid line lesion in the medulla interrupted inspiratory activity, converting activity of expiratory bulbospinal neurones from periodic to ionic firing patterns. 7. Following such lesions the CO2 threshold for rhythmic excitation of medullary neurones was elevated and the slopes of their CO2 response curves were reduced. 8. These findings fully confirm the hypothesis put forward by Bainton, Kirkwood & Sears (1978b) that bulbospinal respiratory neurones convey both tonic and rhythmic excitation to spinal respiratory motoneurones and that the rhythmic excitation of expiratory muscles derives from a period inhibition of expiratory bulbospinal neurones which are subjected to a tonic CO2 dependent excitation which is continuously variable over the physiological range.
The effects of calcium deprivation upon mechanical and electrophysiological parameters in skeletal muscle fibres of the frog.
Authors: Lüttgau H C , Spiecker W
Published: December 2014

1. The effects of Ca2+ deprivation upon mechanical and electrophysiological parameters of single muscle fibres from the m. semitendinosus and the m. iliofibularis of the frog were investigated. 2. When the external free Ca concentration was reduced in steps of one order of magnitude from 10(‐3) to 10(‐9) M, using up to 10 mM‐EGTA and in the presence of 3 mM‐Mg2+, the maximum force of K contractures declined by 5‐15%, the plateau of maximum force shortened, and in most cases the phase of spontaneous relaxation lengthened. 3. In Ringer solution containing 10(‐9) M‐Ca2+ and 1 mM‐Mg2+ 85% of maximum tetanic force could be maintained for at least 15 sec (5 Hz; 3 degrees C). 4. The reduction of external Ca2+ from 10(‐3) to 10(‐9) M and its replacement by Mg2+ induced a 20‐30 mV shift towards more negative potentials of the ‘steady state’ inactivation curve (which relates maximum force upon full depolarization to the logarithm of the K concentration or the corresponding membrane potential during the conditioning period). 5. The same alteration in concentrations of divalent cations caused little or no change in the shape and potential dependence of the activation curve (which relates maximum force to the logarithm of the external K concentration of the corresponding membrane potential). 6. The threshold potential for the onset of delayed rectification (point voltage clamp) and that for the initiation of an action potential did not change when external Ca2+ was reduced to 10(‐9) M and replaced by Mg2+. 7. When the concentration of EGTA2‐ was increased to 80 mM (in the presence of 5 mM‐Mg2+) twitch height dropped to very small values within a few minutes. However, tetanic force (50 Hz) reaching 20‐85% of the original value could still be induced after 1 hr in high EGTA2‐. 8. The experiments show that external Ca2+ acts upon excitation‐contraction coupling mainly by impeding ‘inactivation'. A hypothesis is proposed in which the plateau of maximum force during a contracture is the consequence of a regenerative Cai2+‐dependent shift of the inactivation curve towards more positive potentials.
Changes in recurrent inhibition during voluntary soleus contractions in man studied by an H‐reflex technique.
Authors: Hultborn H , Pierrot‐Deseilligny E
Published: December 2014

1. The recurrent inhibition, brought about by a conditioning H‐reflex discharge, was estimated in human subjects by the amplitude of a test H‐reflex involving only the soleus motoneurones which fired in response to the conditioning volley. The modifications of the recurrent inhibition during contraction were evaluated by comparing the amplitude of the test H‐reflex to a reference H‐reflex. Both reflexes experienced the excitation underlying the voluntary contraction, but only the test H‐reflex was subjected to the recurrent inhibition evoked by the conditioning H‐reflex discharge. 2. Distinct differences were observed between the modifications of the test reflex and those of the reference H‐reflex during both tonic and phasic voluntary contractions. Evidence is presented that these differences were due to changes in the amount of recurrent inhibition elicited by the conditioning discharge. 3. The changes in recurrent inhibition were studied while the subjects performed voluntary tonic contractions of various forces. The weakest contractions were accompanied by a decrease in the size of the test reflex. With greater contraction forces, there was no longer an inhibition of the test reflex, but instead a facilitation which grew continuously with increased contraction forces. The test reflex could eventually exceed the reference H‐reflex amplitude at the strongest contractions. This is taken to indicate that the recurrent inhibition following the conditioning discharge was progressively decreasing, as the contraction force increased. 4. During ramp contractions, whatever the contraction velocity, the time courses of the variations of the test and reference H reflexes were almost inverse. Evidence is presented that these differential time courses were due to changes in the amount of recurrent inhibition elicited by the conditioning discharge. 5. The possibility of occlusion in the recurrent pathway ;as considered and it was concluded that the decrease in the recurrent inhibition elicited by the conditioning discharge was essentially due to an inhibitory control (spinal and/or suprasegmental) acting on Renshaw cells. This inhibition of Renshaw cells eventually counteracts the increasing excitatory inputs (resulting from the voluntary motor discharge) which they receive via motor axon collaterals during increasing tonic contractions and throughout ramp contractions. 6. The functional significance of the Renshaw cell inhibition during voluntary contraction is discussed in relation to the inhibition exerted through the recurrent pathway on both motoneurones and Ia inhibitory interneurones. It is suggested that the depression of Renshaw cell activity could play an important role during voluntary movements by favouring reciprocal Ia inhibition.
Estimates of cable parameters in lamprey spinal cord neurones.
Authors: Christensen B N , Teubl W P
Published: December 2014

1. Two micro‐electrodes were used to penetrate giant interneurones in the isolated lamprey spinal cord. A brief (50‐‐100 microsec) current pulse was applied to one electrode while the other recorded the voltage transient response. 2. A formal analysis of the voltage transient was achieved by the simplifying reduction of each neurone. Somas were treated as a parallel combination of resistance and capacitance. Dendrite trees were reduced to an equivalent cylinder (Rall, 1959). 3. The voltage transients were analysed according to the procedure suggested by Jack & Redman (1971b) to estimate the cable parameters governing the passive propagation of transmembrane potentials. Membrane time constant (tau m), dendritic to soma conductance ratio (rho 00), and electrotonic length (L) of the equivalent cylinder were estimated from these data. 4. In thirty‐two interneurones it was possible to determine the membrane time constant, but rho 00 and L were determined in only twenty‐two. 5. For the twenty‐two neurones in which all cable parameters were estimated, the electrotonic length of the equivalent cylinder was similar to that found for cat spinal motoneurones (1‐‐2 space constants). 6. Simulations of the voltage transient using the Rall model of the motoneurone as developed by Jack & Redman (1971b) resulted in a voltage response which closely ditted the experimental data. 7. These results suggest that the Rall model of the motoneurone accurately describes the propagation of passive transmembrane potentials in lamprey spinal cord neurones. It is further concluded that the time constant for soma and dendritic membrane is similar in these neurones.
Calcium and receptor regulation of radiosodium uptake by dispersed rat parotid acinar cells.
Authors: Landis C A , Putney J W
Published: December 2014

1. Dispersed rat parotid acinar cells were used to study the effects of secretagogues on 22Na uptake. 2. Carbachol stimulated 22Na uptake, and caused a net gain in total Na and a loss in total K. These effects were accentuated in the presence of 10(‐3) M‐ouabain. 3. Substance P, epinephrine and phenylephrine also stimulated 22Na uptake while isoproterenol and angiotensin II did not. 4. The 22Na uptake due to carbachol was inhibited by atropine, procaine or CoCl2; the response to Substance P was inhibited by CoCl2 only. 5. Extracellular Ca was required for stimulation of 22Na uptake by carbachol. Strontium but not Ba could substitute for Ca in supporting 22Na uptake. 6. Uptake of 22Na was stimulated by the divalent cationophore, A‐23187, and Ca was required for this effect. 7. It is concluded that activation of Ca influx by muscarinic, alpha‐adrenergic or peptide agonists triggers, among other effects, an increased membrane permeability to Na.
Anion exchange and volume regulation during metabolic blockade of renal cortical slices.
Authors: Pine M B , Rhodes D , Thorp K , Tsai Y
Published: December 2014

1. The development of swelling of rat and guinea‐pig renal cortical slices was studied after metabolic blockade (hypoxia plus glycolytic blockade with iodo‐acetic acid) and/or exposure to ‘isotonic’ high potassium, no sodium solution. 2. Swelling was greater after exposure to oxygenated high potassium solution than after metabolic blockade in physiologic Krebs‐Henseleit solution. Swelling was reduced after metabolic blockade in high potassium solution compared to incubation in oxygenated high potassium solution. Increasing periods of transient metabolic blockade in Krebs‐Henseleit solution progressively blunted swelling when slices were subsequently incubated in oxygenated high potassium solution. 3. Metabolic blockade in Krebs‐Henseleit solution resulted in marked reductions in potassium and increases in sodium. Incubation in high potassium solution resulted in marked increases in potassium and similar low levels of sodium regardless of associated interventions. Metabolic blockade in both media resulted in significantly greater increases in renal cortical chloride than in monovalent cations (potassium plus sodium). Incubation in oxygenated high potassium solution was associated with similar increases in renal cortical chloride and total monovalent cations. 4. Renal cortical losses of solids and protein and increases in renal cortical inulin space were greater after metabolic blockade than after incubation under oxygenated conditions regardless of the incubation media. 5. These data support the conclusion that during metabolic blockade there is a significant replacement of larger intracellular anions by extracellular chloride. The loss of osmotically active intracellular anions limits the increase in renal cortical volume during metabolic inhibition and exposure to high potassium solution.
Selective antagonism of amino acid‐induced and synaptic excitation in the cat spinal cord.
Authors: Davies J , Watkins J C
Published: December 2014

1. The effects of D‐alpha‐aminoadipate (DalphaAA), D‐alpha‐aminosuberate (DalphaAS) and other excitatory amino acid antagonists have been compared on the excitatory responses of neurones of the cat spinal cord to acetylcholine, a range of glutamate‐related amino acids and stimulation of appropriate excitatory synaptic pathways. The ionophoretic technique was used for administration of excitants and antagonists. 2. DalphaAA and DalphaAS had little or no effect on acetylcholine‐induced excitation of Renshaw cells. Responses of either Renshaw cells or dorsal horn neurones in the spinal cord to excitatory amino acids were depressed in the order: N‐methyl‐D‐aspartate (NMDA), L‐homocysteate, D‐glutamate, ibotenate greater than D‐homocysteate, L‐aspartate, D‐aspartate greater than L‐glutamate, kainate and quisqualate. 3. These effects are consistent with the existence of different excitatory amino acid receptors, one type being sensitive to the actions of the antagonists, and activated predominantly by the NMDA group of excitants, with other receptors being relatively insensitive to DalphaAA and DalphaAS and activated predominantly by quisqualate and kainate. On this hypothesis, many amino acids are assumed to have mixed actions on DalphaAA‐sensitive and ‐insensitive receptors. 4. 2‐Amino‐4‐phosphonobutyrate (2APB) and L‐glutamic acid diethyl ester (GDEE) produced different patterns of antagonism of excitatory amino acid‐induced responses from those observed with DalphaAA and DalphaAS. Neither substance was as potent as DalphaAA or DalphaAS as an excitatory amino acid antagonist. 5. Both DalphaAA and DalphaAS selectively antagonized synaptic excitation of Renshaw cells evoked by dorsal root stimulation without affecting cholinergic excitation of these cells evoked by ventral root stimulation. These latter responses were selectively antagonized by dihydro‐beta‐erythroidine (DHbetaE). DalphaAA also antagonized synaptic excitation of unidentified dorsal horn neurones of the spinal cord evoked by dorsal root stimulation. Neither GDEE (particularly) nor 2APB were as effective as DalphaAA or DalphaAS as depressants of synaptic excitation. 6. Taken in conjunction with the results of in vitro studies on the specificity of action of Dalpha¿ and related substances, these observations suggest that certain synaptic excitations in the spinal cord are mediated by an excitatory amino acid transmitter, and that this transmitter interacts with receptors which are activated selectively by NMDA, less selectively by other amino acids, including L‐aspartate, and probably only slightly by quisqualate, kainate and (exogenous) L‐glutamate.
Fluctuations of Pa, CO2 with the same period as respiration in the cat.
Authors: Lewis G , Ponte J , Purves M J
Published: December 2014

1. A CO2 sensor using mass spectrometry is described. It responds linearly to O2 and CO2 with a time constant of 0.5 sec: it is not affected by pressure or flow in the physiological range: its temperature coefficient is 4 mm Hg PCO2 per degree C at 37 degrees C. 2. When this sensor and its through flow cuvette were placed in a common carotid artery‐to‐jugular vein loop in anaesthetized cats breathing spontaneously or being ventilated artificially, fluctuations of Pa, CO2 which had the same period as respiration were readily observed. 3. The amplitude of these fluctuations varied inversely with respiratory frequency being less than 1.5 mmHg Pa, CO2 in the range of normal respiratory frequencies in the cat, 25‐‐35 min‐1. The amplitude also varied with the mixed venous‐to‐end tidal CO2 difference which was altered either by giving the cat CO2 to inhale or infusing CO2 intravenously. 4. We have concluded that these fluctuations of Pa, CO2 are unlikely to provide a significant drive to ventilation at normal respiratory frequencies but they may provide a signal that gas exchange in the lung is less than optimal.
The effects of hypoglycaemia on cerebral blood flow and metabolism in the new‐born calf.
Authors: Gardiner R M
Published: December 2014

1. The effects of insulin hypoglycaemia on cerebral blood flow and metabolism have been examined in unanaesthetized, unrestrained calves between 1 and 26 days after birth. 2. Cerebral blood flow was measured with an inert gas technique using molecular hydrogen, and cerebral metabolism was quantified by determination of arterio‐cerebral venous (A‐‐V) concentration differences for oxygen, glucose, lactate, pyruvate, acetoacetate, beta‐D‐hydroxybutyrate and ammonia. 3. During normoglycaemia the mean (A‐‐V) difference for glucose was close to one sixth that of oxygen, on a molar basis. A small net loss of pyruvate from the brain was found, but there was no significant (A‐‐V) difference for lactate. Arterial concentrations of acetoacetate and beta‐D‐hydroxybutyrate were low, and no utilization of ketone bodies by the brain was demonstrated. 4. Moderate hypoglycaemia (arterial plasma glucose concentration 1‐‐2 m‐mole/l.) had no measurable effect on either cerebral blood flow or metabolism. 5. During profound hypoglycaemia (arterial plasma glucose concentration less than 1.0 m‐mole/l.) cerebral glucose uptake was sufficient to account for only 56% of the cerebral oxygen consumption. Cerebral oxygen consumption fell in comatose animals, but increased during hypoglycaemic convulsions, as did cerebral blood flow. 6. In day‐old calves hypoglycaemia was associated with a rise in blood lactate concentration and uptake of lactate by the brain. 7. A net loss of ammonia by the brain was observed during hypoglycaemia in calves at all ages examined. The loss was greater in convulsing than in comatose animals.
Reflex excitation of antral motility induced by gastric distension in the ferret.
Authors: Andrews P L , Grundy D , Scratcherd T
Published: December 2014

1. In the urethane anaesthetized ferret gastric inflation with 50 ml. 0.9% NaCl at a rate of 10 ml./min evoked large gastric contractions. The threshold of intragastric pressure required to elicit the reflex was 3.1 +/‐ 0.5 cmH2O. 2. The response was enhanced by splanchnic nerve section and markedly reduced by bilateral cervical vagotomy, indicating that both afferent and efferent limbs of the reflex were in the vagus nerves. 3. By using a transected stomach it was shown that distension of the corpus evoked contractions of the antrum that were abolished by vagotomy. 4. The reflex activation of antral motility by vagal afferents with receptive fields in the corpus may play a physiological role in gastric emptying.
Voltage, temperature and ionic dependence of the slow outward current in Aplysia burst‐firing neurones.
Authors: Johnston D
Published: December 2014

1. The slow outward current in Aplysia burst‐firing neurones was studied under voltage‐clamp conditions. This current, designated Iso, was measured as the incremental outward tail current following small depolarizing commands. 2. Iso was shown to be a pure K+ current, probably activated by the influx of Ca2+ during the depolarizing command (Johnston, 1976). For small depolarizations, the peak conductance was about 10(‐7) mhos. 3. The rate of decay of Iso could be fit by a single exponential and was voltage‐dependent, increasing with depolarization. 4. The decay rate of Iso was also temperature‐dependent, with a Q10 of about 3. The peak conductance, however, was much less temperature‐sensitive, with a Q10 of about 1.5. 5. The voltage dependence of decay rate suggested either the presence of a voltage‐dependent Ca2+ pump or that the change in intracellular calcium concentration was not the rate‐limiting step in the decay of Iso.
Potential clamp analysis of membrane currents in rat myelinated nerve fibres.
Authors: Brismar T
Published: December 2014

1. Large myelinated nerve fibres were isolated from rats and the membrane action potential was recorded in single nodes of Ranvier. Potential clamp experiments were performed at 24 degrees C and in one fibre also at 33 degrees C. 2. Positive potential steps were associated with an initial, mainly Na carried, current with an equilibrium potential (Ue) of 40 +/‐ 13 mV. The INa vs. U curve showed rectification at large positive potentials. 3. The Na permeability (PNa) curve was characteristically S‐shaped with a half value at ‐48 +/‐ 6 mV and a ceiling value of 3.7 +/‐ 0.7 cm.sec‐1.10(‐3). PNa as defined by the constant field equation accounted for the rectification of the INa/U curve. 4. The potential and time dependence of the rapid inactivation (h) process was described quantitatively in terms of its steady state (h infinity) vs. U curve and its rate constants (alpha h and beta h) vs. U curves. h infinity (U = ‐80 mV) was 0.68 +/‐ 0.09. 5. The delayed currents were small and the ionic specificity of the delayed permeability changes was not identified. Tentatively calculated PK at large potentials was 0.21 +/‐ 0.06 cm.sec‐1.10(‐3). The leak conductance (gL) was 130 +/‐ 33 mS.cm‐2. 6. A temperature rise in one experiment from 24 to 33 degrees C increased the rate constants (alpha h and beta h), but did not significantly change the size of the delayed currents. 7. INa was completely blocked by 25 nM‐TTX in the outside solution. External application of 5 mM‐TEA only slowly and incompletely blocked the small delayed currents. This effect was not fully reversible. 8. A comparison with frog fibres showed that the node in rat fibres had (a) a lower Ue of the initial current (probably because of a lower Na selectivity of the channel for the initial current), (b) approximately equal max. peak PNa, (c) about 10 mV negatively shifted PNa vs. U and h infinity vs. U curves, (d) quantitatively similar relations between rate constants of inactivation (alpha h and beta h) and U at 20‐‐24 degrees C, (e) PK that was 1/5 of PK in frog fibres, (f) 4‐‐5 times larger leak conductance, (g) membrane action potentials of smiliar amplitude and duration.
Summation of rod signals within the receptive field centre of cat retinal ganglion cells.
Authors: Enroth‐Cugell C , Harding T H
Published: December 2014

1. The processing of rod signals within the receptive field centre of cat retinal ganglion cells was investigated in two spot summation experiments by using the analytical methods of response and sensitivity summation. 2. The rod system was isolated by presenting test stimuli of short wave‐length light against either a completely dark background or a dim background of long wave‐length light. 3. Stimulus‐‐response curves were obtained for two small, square‐wave modulated test spots applied at points in the receptive field centre of equal sensitivity. The test spots were presented either singly or simultaneously. 4. In the absence of surround antagonism, the flux required to evoke a weak criterion response was the same whether the spots were presented singly or together. However, the flux required to evoke larger responses was typically half as great when the two spots were delivered together as it was when either was presented alone. 5. Over a moderate response range, the magnitude of response to the two test spots presented together equalled the algebraic sum of the two responses to the test spots presented alone. However, for responses of large magnitude, the algebraic sum was larger. 6. Permitting the surround to contribute substantially to the cell's response changed the outcome of the two spot summation experiment. 7. The data are consistent with a three stage model of signal processing within the receptive field centre: an early compressive power law transformation (within each sub‐area) of illuminance into a neural signal which is followed by linear summation of sub‐area signals and then a second compressive transformation.
Renal function in conscious rats after indomethacin. Evidence for a tubular action of endogenous prostaglandins.
Authors: Haylor J , Lote C J
Published: December 2014

1. Conscious rats, with implanted carotid arterial cannulae, received a saline infusion (5.8 ml./hr) via a tail vein for a 6 hr period. The urinary excretion of water, sodium, potassium, urea and the osmolal output were monitored, together with the systemic blood pressure. Glomerular filtration rate (inulin clearance) and effective renal plasma flow (p‐aminohippurate clearance) were also measured. Four hours after the start of the infusion, indomethacin (10 mg/kg body weight) in buffered saline, or buffered saline alone, was administered via the tail vein. 2. Following indomethacin administration, urine flow, sodium output and osmolal output were markedly reduced (P less than 0.01). However, there were no measurable changes in the systemic blood pressure, glomerular filtration rate, or effective renal plasma flow. 3. It is concluded that the changes in urinary excretion observed after indomethacin are not dependent on changes in effective renal plasma flow or glomerular filtration, and it is suggested that indomethacin inhibits the synthesis of endogenous prostaglandins which directly influence renal tubular function.
Prostaglandin synthesis and renal function in man.
Authors: Haylor J
Published: December 2014

1. Experiments were performed to determine the changes in renal function which occur following prostaglandin synthetase inhibition in healthy conscious humans. It was hoped that such experiments could provide information on the mechanism by which renal prostaglandin synthesis influences urinary excretion. 2. In water‐diuretic male subjects (receiving a slow saline infusion) the renal excretion of sodium and water was reduced following I.V. acetylsalicylic acid (1 g) administration, while the effective renal plasma flow (p‐aminohippurate clearance), and glomerular filtration rate (inulin clearance) remained unaltered. 3. In normally hydrated female subjects on an unrestricted diet, the mean urinary prostaglandin E output was 8.5 ng/hr. The renal excretion of sodium, water and urinary prostaglandin E were significantly reduced (P less than 0.05) following oral acetylsalicylic acid (1.2 g) administration. 4. In normally hydrated female subjects on an unrestricted diet the renal excretion of sodium and water was reduced following oral paracetamol (1.5 g) administration. 5. It is concluded that following renal prostaglandin synthetase inhibition in conscious humans, the excretion of sodium and water can be reduced without measurable changes in the glomerular filtration rate or effective renal plasma flow. It is suggested that in conscious healthy humans, the kidney may continually synthesize prostaglandin which might help to maintain sodium and water excretion by a direct action on the renal tubule without influencing renal blood flow. The relevance of this hypothesis to the intrarenal location of prostaglandin synthetase is discussed.
Visual pigments of rods and cones in a human retina.
Authors: Bowmaker J K , Dartnall H J
Published: December 2014

1. Microspectrophotometric measurements have been made of the photopigments of individual rods and cones from the retina of a man. The measuring beam was passed transversely through the isolated outer segments. 2. The mean absorbance spectrum for rods (n = 11) had a peak at 497.6 +/‐ 3.3 nm and the mean transverse absorbance was 0.035 +/‐ 0.007. 3. Three classes of cones were identified. The long‐wave cones ('red' cones) had a lambda max of 562.8 +/‐ 4.7 nm (n = 19) with a mean transverse absorbance of 0.027 +/‐ 0.005. The middle‐wave cones ('green' cones) had a lambda max of 533.8 +/‐ 3.7 nm (n = 11) with a mean transverse absorbance of 0.032 +/‐ 0.007. The short‐wave cones ('blue' cones) had a lambda max of 420.3 +/‐ 4.7 nm (n = 3) with a mean transverse absorbance of 0.037 +/‐ 0.011. 4. If assumptions are made about the length of cones and about pre‐receptoral absorption, it is possible to derive psychophysical sensitivities for the cones that closely resemble the appropriate pi mechanisms of W. S. Stiles. 5. If assumptions are made about the length of rods and about pre‐receptoral absorption, however, the psychophysical sensitivity derived for the rods is considerably broader than the C.I.E. scotopic sensitivity function.
Spontaneous fluctuations of potassium channels in the apical membrane of frog skin.
Authors: Van Driessche W , Zeiske W
Published: December 2014

1. The previously demonstrated K+‐dependent short‐circuit current through the skin of frog species Rana temporaria (Zeiske & Van Driessche, 1979), bathed with mucosal K+‐ and serosal Na+‐Ringer solution, was investigated with current‐fluctuation analysis. 2. The current‐noise spectra were recorded in the frequency range from 1 to 800 Hz and showed a Lorentzian component with a mean plateau value S0 = (1.50 +/‐ 0.05).10(‐20) A2.s.cm‐2 and a corner frequency of fc=(81.0 +/‐ 3.4)Hz(n=14). 3. S0 increased with mucosal K+ concentration, [K]o, while fc remained almost unchanged. A decrease in S0 was observed when serosal Na+ was replaced by K+. 4. Mucosal Cs+ (10 mM) depressed, reversibly, the K+‐dependent current noise to the level of the background noise. Moreover, a linear decrease in fc with increasing Cs+ concentration was observed. 5. Among the other tested alkali cations, Rb+ was the only blocker though less potent than Cs+. Tetraethylammonium, 4‐aminopyridine, 2.4.6‐triaminopyrimidine and amiloride had no effect. 6. Alterations in the transcellular transport of Na+ contained in a mucosal solution with high [K]o resulted in significant changes in K+ current noise. 7. The current‐fluctuation intensities decreased with increasing contact time to high [K]o; these changes were concomitant with the previously reported time dependence of the short‐circuit current (Zeiske & Van Driessche, 1979). 8. The K+‐dependent fluctuations are thought to originate from K+‐selective pathways in the apical cell membranes. The description of the K+‐current noise by a single Lorentzian suggests that the "K+ channels" switch randomly between an open and closed state. 9. Assuming a two state model for the channel‐kinetics, the single channel current i and the channel density M were calculated as i=(0.37 +/‐ 0.05)pA and M=(0.53 +/‐ 0.08) mu‐2 (n=13).
Induction of action potentials in cultured slow muscle fibres of the frog.
Authors: Cull‐Candy S G , Miledi R , Uchitel O D
Published: December 2014

1. Slow muscle fibres of the frog were maintained in a simple organ culture system for up to 28 days at 18 degrees C. Slow fibres cultured for one week resembled innervated fibres in their lack of ability to generate an action potential. 2. By 10 days a few fibres had acquired the action potential mechanism and in muscles cultured for 28 days all slow fibres examined were capable of generating action potentials most of which reached or exceeded 0 mV membrane potential. 3. Slow muscle fibres which were denervated for two weeks in vivo retained their ability to generate overshooting action potentials after 4 weeks of culture. Thus, in the culture system described, slow muscle fibres are capable of developing action potentials and the action potential mechanism in these fibres remains for at least one month in culture.
The time course of sodium inactivation in squid giant axons.
Authors: Gillespie J I , Meves H
Published: December 2014

1. The time course of Na inactivation was studied in intact and perfused squid giant axons under voltage‐clamp conditions. 2. The pulse programme consisted of a conditioning pulse of varying duration, followed after an interval of 3‐8 msec by test pulse. The measurements were done in sea water with 1/3 or 1/5 of the normal Na concentration. In most experiments a 100 microseconds conditioning pulse was sufficient to reduce INa peak elicited by the test pulse. In some experiments even a 50 microseconds conditioning pulse produced a clear reversible decrease of INa peak. We conclude that the upper limit for an initial delay in the development of inactivation is 50‐100 microseconds; this applies to temperatures between 0 and 13 degrees C and membrane potentials between ‐40 and 15 mV. The decrease of INa peak with increasing duration of the conditioning pulse was consistent with an exponential decay starting at 50 or 100 microseconds. 3. With large Na currents in full Na sea water the time course of inactivation became sigmoid. This is attributed to a long‐lasting tail of inward current which follows the conditioning pulse and produces a voltage drop across the series resistance. 4. If the conditioning pulse and the test pulse were not separated by an interval, INa peak showed a sigmoid dependence on the duration of the conditioning pulse. This phenomenon is predicted by the equations of Hodgkin & Huxley (1952) as first pointed out by Kniffki, Siemen & Vogel (1978). With sufficiently strong conditioning pulses INa peak could even increase in size.
Cerebral energy metabolism in diving and non‐diving birds during hypoxia and apnoeic asphyxia.
Authors: Bryan R M , Jones D R
Published: December 2014

1. Cerebral energy metabolism during apnoeic asphyxia and steady‐state hypoxia was compared in ducks and chickens; ducks tolerate apnoeic asphyxia 3‐8 times longer than chickens. 2. Fluctuations in the reduced form of respiratory chain nicotinamide adenine dinucleotide (NADH) were monitored from the left cerebral hemisphere by a noninvasive fluorometric technique and used as an indicator of mitochondrial hypoxia. NADH fluorescence was expressed in aribtrary units (a.u.) where 100 a.u. was defined as the fluorescence change from normoxia to anoxia. Electroencephalogram (e.e.g.) and surface Po2 were recorded from the right hemisphere. 3. After 1 min of asphyxia NADH fluorescence increased by 37 a.u.+/‐3.60 S.E. of mean (n=54) in paralysed chickens and 8 a.u.+/‐1.41 (n=55) in aralysed ducks. After 2 min the fluorescence increased by only 15 a.u.+/‐1.95 in ducks. 4. Both species showed an isoelectric e.e.g. when fluorescence increased by approximately 35 a.u., indicating that anaerobic ATP production in ducks did not maintain brain function (e.e.g.) for a greater accumulation of respiratory chain NADH. 5. At a given decrease in tissue Po2 ducks and chickens showed the same level of NADH increase, indicating that both species are equally dependent on tissue Po2 for the maintenance of redox state. 6. We conclude that biochemical adjustment which enhance anaerobic ATP production and/or prolong oxidative phosphorylation during progressive hypoxia are not responsible for increased cerebral tolerance to apnoeic asphyxia in the duck.
The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour.
Authors: Bradbury M W , Cole D F
Published: December 2014

1. The jugular lymphatic trunks were cannulated in anaesthetized rabbits and cats. Over 6‐8 hr, the mean lymph flow was 2.3 microliters min‐1 in the rabbit (one side only) and 5.0 microliters min‐1 in the cat (sum of both sides). 2. After a single injection of radio‐iodinated albumin into a lateral cerebral ventricle without significant rise in pressure, a mean of 14.4% of the radioactivity was recovered in deep cervical lymph of one side in the rabbit and of 12.9% in that of both sides in the cat. 3. During slow infusion of [125I]albumin and fluorescent dextran of 150,000 mol. wt. into a lateral ventricle of the cat at 20 microliters min‐1, radioactivity and fluorescence reached plateaus in deep cervical lymph at 47.4 and 50.0% of their concentrations in cisternal c.s.f. respectively. 4. No significant radioactivity, other than from blood, was detected in superficial cervical lymph after intraventricular injection of radio‐iodinated albumin in the cat. 5. No significant radioactivity, other than from blood, was detected in deep cervical lymph of the rabbit or in deep and superficial cervical lymph of the cat within 6 hr after injection of radio‐iodinated albumin into the aqueous humour or orbital fat. 6. Gradients of radioactivity in tissues within the orbit suggested that there is a small flow of c.s.f., 0.05‐0.15 microliters min‐1 in the rabbit, passing centrifugally along the subarachnoid space of the optic nerve, through the posterior part of the globe and into the orbital tissue. Also a small proportion of aqueous humour, 1‐2% or more, drains through the anterior sclera into the surrounding tissue. 7. A substantial quantity of cerebrospinal fluid drains into the deep cervical lymphatic system of the rabbit, 30% or more, and of the cat, 10‐15% or more. The small component of aqueous humour drainage passing through the wall of the glove does not enter cervical lymph within 6 hr, if at all.
The equilibrium between different conformations of the unphosphorylated sodium pump: effects of ATP and of potassium ions, and their relevance to potassium transport
Authors: Beaugé L. A. , Glynn I. M.
Published: December 2014

1. Changes in the intrinsic fluorescence of Na, K‐ATPase protein have been used to monitor the interconversion of E1 (low fluorescence) and E2 (high fluorescence) forms of the unphosphorylated enzyme.

2. In media lacking sodium and nucleotides, 1 m
M‐potassium was sufficient to convert practically all of the enzyme into the E2 form. In media containing 1 m
M‐potassium, 1 m
M‐EDTA, and no sodium or magnesium, the addition of ATP, or its β, γ‐imido or methylene analogues, converted the enzyme back into the E1 form. The relation between nucleotide concentration and the fraction of the enzyme that was in the E1 form could be described by a rectangular hyperbola, with a K½ of about 15 μ
M for ATP, 65 μ
M for adenylyl‐imidodiphosphate (AMP‐PNP) and 180 μ
M for adenylyl (β, γ‐methylene)‐diphosphonate (AMP‐PCP). ADP also converted the enzyme back into the E1 form, with a K½ of about 25 μ
M, but the relation between concentration and fraction converted was not well described by a rectangular hyperbola.

3. In similar media containing 50 m
M‐potassium, much higher concentrations of ATP were required to convert the enzyme back into the E1 form, and the conversion was probably incomplete.

4. If we assume that ATP and potassium ions affect each other's binding solely by altering the equilibrium between E1 and E2 forms of the enzyme, we are able to conclude (i) that potassium ions bind to the E1 form with a moderately low affinity, (ii) that, in the absence of nucleotides, the equilibrium between E1K and E2K is poised strongly in favour of E2K, (iii) that the binding of ATP to a low‐affinity site alters the equilibrium constant for the interconversion of E1K and E2K by two to three orders of magnitude, so that, at saturating levels of ATP, the equilibrium is probably slightly in favour of E1K, and (iv) that in sodium‐free, potassium‐containing media, ATP will appear to bind to the enzyme more tightly than would be expected from the dissociation constant of the E2K. ATP complex.

5. The pattern of the equilibrium constants for the various reactions between E1, E2, ATP and potassium is compatible with the hypothesis that the ATP‐accelerated conversion of E2K into E1K, and the subsequent release of potassium ions from low‐affinity inward‐facing sites, are part of the normal sequence of events during potassium influx in physiological conditions.
Paired‐pulse and frequency facilitation in the CA1 region of the in vitro rat hippocampus
Authors: Creager Robert , Dunwiddie Thomas , Lynch Gary
Published: December 2014

1. Several types of facilitation of evoked synaptic responses were investigated in the CA1 region of the in vitro rat hippocampus. Homosynaptic paired‐pulse facilitation and heterosynaptic frequency facilitation were characterized and found to be differentiable processes on the basis of several characteristics.

2. Paired‐pulse facilitation, which occurs when the same input is stimulated twice in rapid succession, is manifested as an increase in both the extracellularly recorded population spike and the field e.p.s.p., and is specific to the set of afferents excited by the first impulse. Responses to other excitatory afferents show no facilitation by a heterosynaptic conditioning pulse.

3. At intervals less than 200 msec, the degree of facilitation produced by a preceding impulse appears to decline as a first order exponential function of time. Facilitation is increased by lowering calcium or raising magnesium concentrations in the bathing medium, with no apparent change in the time constant of the decay process.

4. The phenomenon that has sometimes been termed frequency facilitation, and which occurs during the early phase of repetitive stimulation, appears to be an extension of paired‐pulse facilitation. It is seen as an increase in amplitude of both the e.p.s.p. and population spike in response to stimulation of homosynaptic inputs, can be predicted with fair accuracy by assuming that the residual paired‐pulse facilitation produced by each impulse adds linearly with that from previous impulses, and is affected by calcium and magnesium ions in the same manner as is paired‐pulse facilitation. These two types of facilitation, which apparently share a common mechanism, are termed synaptic or primary facilitation.

5. Another type of facilitation, which we suggest might more properly be called frequency facilitation, develops slowly during the course of repetitive stimulation. It is the result of an increase in cell firing in response to any excitatory input, either homo‐ or heterosynaptic, at time points at which the field e.p.s.p. is typically depressed.

6. Increases in the potassium concentration of the perfusion medium produce effects similar to those observed with frequency facilitation; stimulation‐evoked increases in the extracellular concentration of this ion are hypothesized to underlie this type of generalized facilitation.
Effects of autonomic stimulation on the release of vasoactive intestinal peptide from the gastrointestinal tract in the calf
Authors: Bloom S. R. , Edwards A. V.
Published: December 2014

1. The effects of autonomic stimulation on the release of vasoactive intestinal peptide (VIP) from the gastrointestinal tract have been investigated in adrenalectomized claves 2‐5 weeks after birth.

2. Stimulation of the peripheral ends of the splanchnic nerves (10 Hz for 10 min) caused a small fall in the concentration of VIP in portal and arterial plasma, together with a rise in the concentration in intestinal lymph. None of these changes achieved statistical significance.

3. The effects of stimulation of the peripheral ends of the thoracic vagi, below the heart (10 Hz for 10 min), were found to depend in part upon the integrity of the splanchnic sympathetic innervation. A substantial rise in the concentration of VIP in intestinal lymph occurred whether or not the splanchnic nerves had been cut whereas an associated rise in arterial plasma VIP was only observed in calves in which the splanchnic nerves had been sectioned.

4. The rise in the concentration of VIP in intestinal lymph, in response to vagal stimulation, was unaffected by concomitant stimulation of the splanchnic nerves, although the associated rise in arterial plasma VIP concentrations was suppressed. The response was also found to be resistant to atropine.

5. The minimum estimated concentration of VIP in the extracellular fluid of the gastrointestinal tract was estimated to be about 60 p‐mole/l. at rest and to rise by 70‐120 p‐mole/l. in response to vagal stimulation.

6. Intravenous infusions of VIP at a dose of 50 ng kg−1 min−1 (16 p‐mole kg−1 min−1), which raised the minimum estimated concentration of VIP in the gastro‐intestinal tract to the highest range encountered during stimulation, produced no significant changes in the concentrations of glucose, insulin, pancreatic glucagon or pancreatic polypeptide in the arterial plasma.

7. It is concluded that a small amount of VIP is released from the gastrointestinal tract in response to vagal stimulation. In contrast, release of VIP is unaffected by stimulation of the splanchnic nerves except in so far as the rate at which the peptide passes into the circulation is reduced by adrenergic vasoconstriction.
The effects of alimentary infusions of glucose, amino acids, or neutral fat on meal size in hungry pigs.
Authors: Stephens D B
Published: December 2014

1. Young growing pigs trained to press a panel in order to obtain delivery of small quantities of food were adapted to eating all their food during one readily measured meal per day. 2. Twenty‐nine pigs were surgically fitted with an exteriorized cannula connected to either (a) the stomach or (b) the duodenum. 3. Two pigs were each fitted with two cannulae in the duodenum which were exteriorized and connected outside the body. Food was then shunted so as to pass along outside the body from the pyloric region of the duodenum to the lower part of the duodenum via the tube connecting the exteriorized cannulae. 4. While feeding, the pigs were given 250 ml. infusions of solutions of (1) 0.9% saline or (2) 15% glucose into either the stomach or the duodenum. Similar volumes of amino acids or 15% neutral fat were infused into the duodenum. 5. The infusions lasted about 3 min and were started 2‐3 min after the beginning of a meal. 6. Control meals without infusions took 30‐40 min. The 15% intraduodenal glucose infusions consistently produced a suppression of eating 15‐20 min after the end of the infusion. 7. Infusions of 0.9% saline, of 10% amino acid or of 15% neutral fat did not reduce significantly the intake of food or the duration of the meal. 8. It was not clear how the glucose solution was able to suppress appetite. The possible existence of a specific glucose receptor is discussed.
The nature of the atrial receptors responsible for a reflex decrease in activity in renal nerves in the dog
Authors: Linden R. J. , Mary D. A. S. G. , Weatherill D.
Published: December 2014

1. In dogs anaesthetized with chloralose, distension of small balloons in the pulmonary vein—atrial junctions and left atrial appendage, to stimulate left atrial receptors, caused a reduction in activity in efferent renal nerves. This response was maintained during distension of the balloons for 30 min periods.

2. In a second group of dogs, cooling the cervical vagi in steps reduced the magnitude of the response in renal nerves. In seven dogs, the response in fourteen preparations of renal nerves was slightly reduced with the vagi at 18 °C and markedly reduced or abolished at 12 °C. The effect of cooling the vagi was the same as the previously shown effect of cooling on the increase in activity in myelinated afferent vagal fibres during similar stimulation of atrial receptors.

3. In a third group of dogs, the cervical vagi were cooled to 9 °C. In six dogs, fifty‐four preparations of renal nerves showed no significant response to distension of the balloons.

4. In a fourth group of dogs, both vagi were sectioned in the neck. In three dogs, twenty‐four preparations of renal nerves then showed no response to distension of the balloons.

5. It is concluded that the reduction in activity in efferent renal nerves during distension of small balloons in the pulmonary vein—atrial junctions and left atrial appendage involves only atrial receptors discharging into myelinated vagal fibres.
Vasoactive intestinal peptide in relation to atropine resistant vasodilatation in the submaxillary gland of the cat.
Authors: Bloom S R , Edwards A V
Published: December 2014

1. Release of VIP from the submaxillary gland, in response to stimulation of the chorda tympani, and its vasodilator action at the site of release have been investigated in anaesthetised cats. 2. Chorda stimulation at 20 Hz produced an abrupt rise in the concentration of VIP in the submaxillary venous effluent plasma, accompanied by a substantial increase in submaxillary blood flow, in the presence or absence of atropine. 3. Intra‐arterial infusions of VIP which reproduced the rise in submaxillary venous plasma concentration that occurred during chorda stimulation at 20 Hz, also produced a rise in submaxillary blood flow of the same order of magnitude. 4. Direct comparison of the responses of the submaxillary vasculature to intraarterial infusions of VIP, ACh and bradykinin showed that the vasodilator potency of VIP far exceeded that of either of the other agonists. 5. Intra‐arterial infusion of ACh, sufficient to elicit a maximal submaxillary vasodilator response, caused no detectable release of VIP from the gland. 6. The results are discussed in relation to the proposition that VIP is released from post‐ganglionic parasympathetic neurones, in the submaxillary gland of the cat, and acts, as a transmitter, to cause vasodilatation, which is resistant to atropine.