bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium and potassium currents involved in action potential propagation in normal bovine lactotrophs.
Authors: Cobbett P , Ingram C D , Mason W T
Published: December 2014

1. The properties of whole‐cell and single‐channel Na+ and K+ currents in immunocytochemically identified bovine lactotrophs were studied using the patch‐clamp technique. 2. In the whole‐cell, current‐clamp mode, cells had membrane potentials of ‐94.7 +/‐ 6.7 mV and input resistances of 2‐17 G omega. Current‐induced action potentials were recorded with a threshold around ‐35 mV and amplitude of 40‐65 mV. Repetitive firing was not sustained at frequencies greater than 1‐2 Hz without total inactivation. 3. Under voltage clamp, action potentials were shown to be composed of an inward TTX‐sensitive Na+ current and an outward K+ current that was abolished by internal Cs+. 4. The isolated Na+ current had a threshold for activation around ‐35 mV and rapidly inactivated to a steady state during a test voltage pulse. Inactivation was strongly voltage‐dependent, with the Na+ current being half‐inactivated at ‐20 mV. 5. Recovery from inactivation was voltage dependent and at a holding potential of ‐60 mV, 50% reactivation was achieved after 420 ms. The implications of this long reactivation time on sustained action potential frequency are discussed. 6. Single Na+ channel activity was examined with the outside‐out patch configuration and yielded single‐channel conductances of 22.5 pS. Reconstruction of the voltage and time dependence of single‐channel currents provided an accurate picture of the whole‐cell Na+ current. 7. Whole‐cell outward current carried by K+ in the absence of Na+ and Ca2+ had a large conductance, was slowly activated and demonstrated no inactivation. A second, more rapidly activating Ca2+‐dependent K+ current could also be demonstrated. 8. Ensemble analysis of whole‐cell K+ currents in the absence of Ca2+ showed underlying single‐channel amplitudes of 1.2 pA at +10 mV, with the lactotroph having about 350 active channels at this potential. 9. Recordings of single K+ channels also demonstrated two classes of channel: a small (50 pS) voltage‐activated channel and a higher‐conductance (100 pS) Ca2+‐ sensitive channel. 10. Prolactin secretion was shown to be TTX‐insensitive but sensitive to membrane potential, demonstrated as increased release following increased external K+ but not Na+ concentration.(ABSTRACT TRUNCATED AT 400 WORDS)
The role of frequency in the effects of long‐term intermittent stimulation of denervated slow‐twitch muscle in the rat.
Authors: Al-Amood W S , Lewis D M
Published: December 2014

1. Rat soleus muscle was denervated by sciatic transection and electrically stimulated for periods of between 3 and 9 weeks with intermittent 1 s bursts of pulses. Most of the bursts were either repeated every 90 s and pulses within them had frequencies between 10 and 100 Hz, or had a frequency of 50 Hz and were repeated at intervals between 60 and 600 s. Comparisons were made with continuous stimulation at 10 Hz. 2. At the end of the period of stimulation, isometric twitches and tetani were measured and, in a proportion, also isotonic shortening velocity. 3. Isometric twitch duration (contraction and relaxation) decreased with time of stimulation. Very similar effects were seen in all animals in which intermittent stimulation had been used. There was a significant relationship between the change in twitch duration and the frequency used within the bursts of chronic stimulation, with slightly larger effects at frequencies of 40 and 60 Hz. The lowest burst repetition rate produced the largest effects. 4. It was confirmed that similar changes were found in denervated muscles that were not stimulated, although these changes were smaller and developed more slowly. 5. The extreme loss of tetanic tension induced in the muscle by denervation was reduced by chronic stimulation, with no significant difference between different regimes, although there were small differences which showed the same patterns of effectiveness described for twitch durations. 6. Continuous stimulation at 10 Hz maintained the twitch contraction and relaxation phases at the values found 3 weeks after denervation, that is it prevented secondary shortening of the twitch. Continuous stimulation reduced tension loss but was, perhaps, less effective than intermittent stimulation. 7. Twitch‐tetanus ratio increased with denervation with little spontaneous reversal later. Stimulation at all frequencies reduced the ratio, but it did not reach normal values. 8. Isotonic shortening velocity was measured in many of the muscles. Maximum velocity was estimated and normalized by muscle length.(ABSTRACT TRUNCATED AT 400 WORDS)
A gamma‐aminobutyric‐acid‐mediated inhibition of neurones in the nucleus tractus solitarius of the cat.
Authors: Bennett J A , McWilliam P N , Shepheard S L
Published: December 2014

1. Extracellular recordings were made from 123 synaptically activated neurones in the nucleus tractus solitarius of the chloralose‐anaesthetized cat. 2. Ninety‐one neurones were activated by electrical stimulation of cardiac or pulmonary vagal branches and thirty‐two by stimulation of the aortic nerve. 3. Ionophoretic application of GABA abolished or markedly reduced the evoked or spontaneous activity of each neurone tested. These inhibitory effects were antagonized by the simultaneous ionophoretic application of bicuculline. 4. Glycine inhibited the evoked activity of 60% of neurones tested. This inhibition could be antagonized by the simultaneous application of strychnine. 5. Application of bicuculline alone increased the evoked or spontaneous activity of a large proportion of the neurones; strychnine alone had no significant effect on the evoked or spontaneous activity of the neurones. 6. These results are consistent with the hypothesis that GABA acts as an inhibitory transmitter substance within the nucleus tractus solitarius.
The arrhythmogenic transient inward current iTI and related contraction in isolated guinea‐pig ventricular myocytes.
Authors: Fedida D , Noble D , Rankin A C , Spindler A J
Published: December 2014

1. The arrhythmogenic transient inward current, iTI, and contractions were recorded in isolated guinea‐pig ventricular myocytes, after exposure to strophanthidin or low external K+ (0.5 mM), using a single‐microelectrode voltage‐clamp technique and an optical measure of contraction. 2. The inward current, iTI, and after‐contraction occurred on repolarization after a depolarizing pre‐pulse. Longer pre‐pulses to more positive potentials increased the size and reduced the latency of iTI. Oscillatory currents and contractions also occurred during pulses to positive potentials. 3. The voltage dependence of iTI was studied by repolarizing to different potentials after a constant depolarizing pulse. Inward currents preceded after‐contractions at all potentials. The iTI was maximal at about ‐50 mV, diminishing in magnitude at more negative and positive potentials. It remained inward at potentials up to +47 mV. The contraction exhibited a similar voltage dependence. The current‐voltage relation varied in the same cell with longer exposure to glycosides. Thus, the voltage dependence of iTI reflected not only that of an underlying ionic mechanism but also the effects of potential on intracellular Ca2+ oscillations which trigger iTI. 4. Uniformity of internal Ca2+ transients was achieved by clamping to different potentials at the peak of an inward current. The iTI remained inward at positive potentials. An inward tail current, seen on repolarizing during iTI at the end of a depolarizing pre‐pulse, progressively increased at negative potentials. This voltage dependence may be close to that of the Ca2+‐activated inward current responsible for iTI. 5. Replacement of Na+ by Li+ initially increased the magnitude of iTI, but further exposure abolished the inward current, while the after‐contractions continued to increase. The potential dependence of iTI was not affected by exposure to zero Na+. Replacement of Ca2+ by Sr2+ also abolished iTI and the after‐contraction, but the main effect was to slow their occurrence. 6. The voltage dependence of the Ca2+‐activated inward current in guinea‐pig ventricular myocytes leads us to favour electrogenic Na‐Ca exchange current as a major component of iTI, under our experimental conditions.
Cell and luminal activities of chloride, potassium, sodium and protons in the late distal tubule of Necturus kidney.
Authors: Anagnostopoulos T , Planelles G
Published: December 2014

1. Double‐barrelled (selective vs. conventional) microelectrodes were used to assess the steady‐state activities (a) of the ions Cl‐, K+, Na+ and H+ in peritubular blood capillaries (abld) and in cell (acell) and lumen (alum) of the late distal tubule (l.d.t.) of Necturus. 2. a(cell)cl, a(lum)cl and a(bld)cl were 5.5 +/‐ 0.3, 11.8 +/‐ 1.0 and 70.5 +/‐ 0.1 mM, respectively. They were used to compute the chemical potentials for Cl‐ across the three diffusive barriers of the tissue. Basolateral and apical membrane potentials were ‐74.3 +/‐ 1.1 and ‐60.1 +/‐ 2.0 mV, respectively (cell negative); the lumen was thus negative with respect to blood, by 13.6 +/‐ 1.5 mV. The electrochemical potential difference (e.p.d.) for Cl‐ of 42 mV across the apical membrane opposes Cl‐ absorption, implying active apical Cl‐ uptake, since Cl‐ is known to be absorbed in the l.d.t. Basolateral Cl‐ exit is favoured by an e.p.d. of 10 mV. 3. a(cell)K, a(lum)K and a(bld)K were 65.8 +/‐ 0.8, 2.5 +/‐ 0.1 and 2.5 +/‐ 0.1 mm, respectively. The electrochemical distribution of K+ indicates that K+ absorption, if present, proceeds against an adverse apical e.p.d. of 18 mV. Basolateral K+ distribution is close to its electrochemical equilibrium, suggesting high K+ permeability at this membrane. 4. a(cell)Na was 9.0 +/‐ 0.4 mM, a(bld)Na 71.0 +/‐ 0.3 mM, and a(lum)Na was approximated at about 9 mM. Diffusive Na+ entry from lumen to cell is favoured by an e.p.d. close to 65 mV. Basolateral Na+ exit must be active, since it proceeds against an e.p.d. of 130 mV. 5. Cell, luminal and blood pH were 7.14 +/‐ 0.03, 6.52 +/‐ 0.08 and 7.37 +/‐ 0.04, respectively. The luminal electrochemical potential of H+ is higher than that of cell (by 91 mV) and blood (by 34 mV) indicating that proton secretion into the lumen must be active. 6. The e.p.d. of each ion across the epithelium opposes, by its orientation, the established direction of net transepithelial ion transport, suggesting that the shunt pathway may serve only for back‐diffusion.
The action of external tetraethylammonium ions on unitary delayed rectifier potassium channels of frog skeletal muscle.
Authors: Spruce A E , Standen N B , Stanfield P R
Published: December 2014

1. We have used single‐channel recording to investigate the block by extracellular tetraethylammonium ions (TEA+) of delayed rectifier potassium channels of frog skeletal sarcolemma. 2. TEA+ blocks by reducing the apparent amplitude of unitary currents, without detectable increase in open‐level current variance. 3. The block by TEA+ appeared to be 1:1, the fractional current being halved at 5.8 mM and ‐3 mV. The dissociation constant for the block was voltage dependent, increasing e‐fold for a 138 mV depolarization. 4. Activation of delayed rectifier potassium currents is not altered by TEA+. 5. Open times, which in the presence of TEA+ represents bursts of open and blocked events, are not increased by TEA+, indicating that blocked channels are able to close normally.
Calcium currents, charge movement and dihydropyridine binding in fast‐ and slow‐twitch muscles of rat and rabbit.
Authors: Lamb G D , Walsh T
Published: December 2014

1. The Vaseline‐gap technique was used to record slow calcium currents and asymmetric charge movement in single fibres of fast‐twitch muscles (extensor digitorum longus (e.d.l.) and sternomastoid) and slow‐twitch muscles (soleus) from rat and rabbit, at a holding potential of ‐90 mV. 2. The slow calcium current in soleus fibres was about one‐third of the size of the current in e.d.l. fibres, but was very similar otherwise. In both e.d.l. and soleus fibres, the dihydropyridine (DHP), nifedipine, suppressed the calcium current entirely. 3. In these normally polarized fibres, nifedipine suppressed only part (qns) of the asymmetric charge movement. The proportion of qns suppressed by various concentrations of nifedipine was linearly related to the associated reduction of the calcium current. Half‐maximal suppression of both parameters was obtained with about 0.5 microM‐nifedipine. The calcium current and the qns component of the charge movement also were suppressed over the same time course by nifedipine. Another DHP calcium antagonist, (+)PN200/110, was indistinguishable from nifedipine in its effects of suppressing calcium currents and qns. 4. In all muscle types, the total amount of qns in each fibre was linearly related to the size of the calcium current (in the absence of DHP). On average, qns was 3.3 times larger in e.d.l. fibres than in soleus fibres. 5. In contrast to the other dihydropyridines, (‐)bay K8644, a calcium channel agonist, did not suppress any asymmetric charge movement. 6. The potential dependence of the slow calcium current implied a minimum gating charge of about five or six electronic charges. The movement of qns occurred over a more negative potential range than the change in calcium conductance. 7. Experiments on the binding of (+)PN200/110 indicated that e.d.l. muscles had between about 2 and 3 times more specific DHP binding sites than did soleus muscle. 8. These results point to a close relationship between slow calcium channels, the qns component of the charge movement and DHP binding sites, in both fast‐ and slow‐twitch mammalian muscle. qns appears to be part of the gating current of the T‐system calcium channels.
Greater hydrogen ion‐induced depression of tension and velocity in skinned single fibres of rat fast than slow muscles.
Authors: Metzger J M , Moss R L
Published: December 2014

1. The effects of variations in pH between 7.00 and 6.20 on Ca2+ ‐activated tension development and maximum velocity of shortening (Vmax) were examined in skinned single skeletal fibres from rat slow‐twitch soleus and fast‐twitch superficial (s.v.l.) and deep (d.v.l.) regions of the vastus lateralis muscle. 2. At pH 6.50, Vmax was depressed to a similar degree in each of the soleus, d.v.l., and s.v.l. fibres. Lowering pH to 6.20 resulted in a further decline in Vmax in all fibres; however, differences between the slow fibres, identified by SDS‐polyacrylamide gel electrophoresis, and fast fibres were apparent, with soleus retaining a significantly greater proportion of its control Vmax (0.83 +/‐ 0.03 in soleus vs. 0.69 +/‐ 0.03 in s.v.l.; mean +/‐ S.E.M.). 3. Maximum force production decreased significantly as pH was reduced. Peak force at pH 6.50, relative to that at pH 7.00, was significantly greater in soleus (0.80 +/‐ 0.01) than in the s.v.l. (0.75 +/‐ 0.01) fibres. At pH 6.20 these differences between slow and fast fibres were still greater, in that soleus fibres generated significantly greater relative forces (0.73 +/‐ 0.01) than did d.v.l. (0.67 +/‐ 0.02) or s.v.l. (0.63 +/‐ 0.02) fibres. 4. As pH was lowered the tension‐pCa relationship shifted to the right (i.e. to higher [Ca2+]), indicating a reduction in the Ca2+ sensitivity of tension development. The [Ca2+] necessary to achieve half‐maximal tension in both the slow‐ and fast‐twitch fibres increased approximately 5‐fold when pH was lowered from 7.00 to 6.20. Furthermore, in the case of the soleus, the Ca2+ threshold for tension development was 45 times greater at pH 6.20 than at pH 7.00, while in the fast‐twitch fibres, this increase was 4‐fold. 5. Increased [H+] differentially affected the steepness of the tension‐pCa relationship between slow and fast fibres. As pH was lowered, the steepness of the lower portion of the tension‐pCa curve increased in the soleus and decreased in d.v.l. and s.v.l., suggesting that apparent positive co‐operativity of tension development had increased in soleus and decreased in d.v.l. and s.v.l. fibres. 6. These results (1) demonstrate an increased resistance to H+ ion‐mediated contractile dysfunction in slow‐ compared to fast‐twitch single fibres, and (2) support the hypothesis that muscular fatigue resulting from short‐term, intense muscular contraction may in part be related to elevated H+ ion concentration.
Calcium‐activated chloride current in cultured sensory and parasympathetic quail neurones.
Authors: Bader C R , Bertrand D , Schlichter R
Published: December 2014

1. Sensory (trigeminal and dorsal root) and autonomic (ciliary) ganglia from embryonic quail were dissociated and the neurones were grown in tissue culture. 2. Intracellular recordings were made in voltage clamp using patch electrodes and the whole‐cell recording technique. In order to investigate a calcium‐activated chloride current, the sodium and potassium currents were blocked. 3. Depolarizing voltage steps from a holding potential of ‐100 mV to a test potential of +20 mV triggered an early inward and a delayed outward current. The latter persisted as a long‐lasting inward tail current when the membrane was depolarized to ‐100 mV. 4. These currents were all blocked by extracellular cobalt suggesting that they were calcium dependent. During a test depolarization to +20 mV, in the presence of intracellular EGTA (20 mM), the inward current persisted but the outward current was suppressed. EGTA (20 mM) also suppressed the long‐lasting inward tail current at ‐100 mV. This suggested the presence of a calcium‐activated current. 5. The reversal potential of the calcium‐activated current was near the equilibrium potential for chloride ions and was shifted as predicted by the Nernst equation when the extracellular chloride concentration was changed. 6. The calcium‐activated current was partially blocked by adding 4‐acetamido‐4'‐isothiocyanatostilbene‐disulphonic acid (SITS) at a concentration of 1 mM to the external superfusion medium. This effect of a compound known to interfere with chloride channels together with the results of point (5) suggested the existence of a calcium‐activated chloride current (ICl(Ca)). 7. ICl(Ca) could be activated by transient and sustained components of the calcium current present in the cultured neurones. 8. ICl(Ca) was present in 80% of the sensory neurones but only in 10% of the parasympathetic neurones.
Parameters for 3‐O‐methyl glucose transport in human erythrocytes and fit of asymmetric carrier kinetics.
Authors: Baker G F , Widdas W F
Published: December 2014

1. Equilibrium exchanges in the range of 2‐40 mM‐3‐O‐methyl glucose at 16 degrees C suggested that the half‐saturation concentration for exchange was 22 mM and that the maximum velocity (Vmax) was ca. 149 mmol l‐1 min‐1. 2. Initial rates of exchange influx from 1, 2, 4 and 8 mM into 76 mM solution gave a half‐saturation value of 3.6 mM and a Vmax of 122 mmol‐1 min‐1. 3. The non‐transportable inhibitor 4,6‐O‐ethylidene‐alpha‐D‐glucopyranose (ethylidene glucose) acting on the outside of the cells inhibited 3‐O‐methyl glucose exchanges at 16 degrees C with an inhibition constant (KI) of ca. 11 mM. 4. Sen‐Widdas exit experiments gave the half‐saturation for 3‐O‐methyl glucose at 16 degrees C as only ca. 2 mM and the KI for ethylidene glucose as ca. 4 mM. 5. Efflux inhibitions by ethylidene glucose are satisfactorily predicted by the asymmetric carrier kinetics of Regen & Tarpley (1974) when using the parameters derived from the exchange experiments but not with parameters from Sen‐Widdas exits. 6. Uphill transfer by counterflow experiments and Sen‐Widdas exits cannot be fitted by the Regen and Tarpley kinetics (using the same parameters) unless the kinetics are modified to provide for an extra exchange element which replaces some of the net exit component in the equations. 7. At present the modification to the kinetics is only possible in computer simulations and data handling, but with it the fit to experimental results is good. The nature of the modification is described and in the light of it a revised interpretation of the significance of the Km derived from Sen‐Widdas exits is discussed.
Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord‐tail preparation of the newborn rat.
Authors: Otsuka M , Yanagisawa M
Published: December 2014

1. The pharmacological profile of Spantide, [D‐Arg1, D‐Trp7,9, Leu11] substance P, as a substance P (SP) antagonist was examined in isolated spinal cords of newborn rats. Potential changes were recorded extracellularly from a lumbar ventral root (L1‐L5). Application of SP to the perfusion bath with a brief pressure pulse of 0.05‐0.8 s duration produced a dose‐dependent depolarization of the ventral root. Spantide in concentrations of 2‐16 microM depressed the depolarizing responses of the ventral root to SP in a concentration‐dependent manner. The log dose‐response curve of SP was shifted to the right in the presence of 16 microM‐Spantide by log 5. The responses to neurokinin A (NKA) and bombesin were similarly depressed by 16 microM‐Spantide whereas the responses to noradrenaline, gamma‐aminobutyric acid (GABA), neurotensin and thyrotrophin‐releasing hormone were not affected by 16 microM‐Spantide. 2. In an isolated spinal cord‐tail preparation of the newborn rat, brief pulse injection of capsaicin into the perfusion solution of the tail induced a depolarizing response in a lumbar ventral root (L3‐L5). This response probably represents a nociceptive C fibre reflex. 3. The capsaicin‐induced nociceptive reflex was markedly depressed by 16 microM‐Spantide and the reflex recovered its original amplitude and shape 30‐60 min after removal of Spantide. 4. The capsaicin‐induced nociceptive reflex was depressed by morphine (2 microM) and dynorphin (1‐13) (0.2 microM), and these effects were reversed by 1 microM‐naloxone. 5. In an isolated spinal cord preparation of the newborn rat, stimulation of a dorsal root with single or double shocks induced depolarizing responses of slow time course in both ipsilateral and contralateral ventral roots of the same segment. These slow depolarizing responses were also depressed by 16 microM‐Spantide. In contrast the monosynaptic reflex was not affected by 16 microM‐Spantide. 6. The present results suggest that SP and NKA are involved as neurotransmitters in the capsaicin‐induced nociceptive reflex in the isolated spinal cord‐tail preparation of the newborn rat.
Calcium‐activated inward spike after‐currents in bursting neurone R15 of Aplysia.
Authors: Lewis D V
Published: December 2014

1. Slow inward and outward after‐currents follow action potentials in the bursting pacemaker neurone, R 15, of Aplysia californica. These experiments were performed to examine the role of axo‐dendritic calcium influx in activating these after currents. 2. Depolarizing voltage‐clamp commands issued at the soma were used to elicit the after‐currents. The earlier inward depolarizing after‐current of DAC was followed by the hyperpolarizing after‐current or HAC. The DAC and HAC appeared at a threshold following depolarizing commands in normal sea water, presumably due to triggering of action potentials in inadequately space‐clamped axon. In 100 microM‐tetrodotoxin (TTX), the after‐currents were graded, increasing gradually in amplitude with increasing voltage or duration of the command. 3. After‐current amplitudes varied with the holding potential through the range tested, ‐40 to ‐80 mV. DACs were maximum at ‐40 to ‐50 mV and decreased in amplitude with hyperpolarization. HACs were maximum at ‐40 mV and decreased with hyperpolarization to disappear between ‐70 and ‐80 mV. 4. The dependence of after‐currents upon intracellular calcium accumulation during the depolarizing command was tested in several ways. Bathing R15 in 0 Ca2+‐2 mM‐EGTA (ethyleneglycol‐bis‐(beta‐aminoethylether)‐N,N'‐tetraacetic acid) sea water eliminated the after‐currents. Bathing in 1 mM‐Ca2+ sea water reduced the DAC by 76% and the HAC by 87% following 10 ms long depolarizations to +40 mV. Application of Mn2+ (25 mM) or La3+ (5 mM) blocked the after‐currents. Injection of EGTA intracellularly practically eliminated after‐currents. Greatly prolonged depolarizations were required to elicit them after EGTA injection. Substitution of Ba2+ for Ca2+ also eliminated after‐currents. 5. Sodium‐free sea water eliminated the DAC. The HAC following brief (less than 30 ms) depolarizing commands was also eliminated in zero sodium, although longer commands were followed by an outward tail current. 6. Although the after‐currents seemed dependent upon calcium influx, they were not suppressed by depolarizing commands whose voltage exceeded the calcium equilibrium potential at the soma as indicated by suppression of the calcium‐activated potassium current, or IK(Ca), observed during the depolarization. However, if the extracellular calcium was lowered to 1 mM, large depolarizations did suppress the DAC. 7. Dopamine blocked the after‐currents when applied to the axo‐dendritic area but not when applied to the soma. Similarly, synaptic inhibition of long duration blocked the after‐currents.(ABSTRACT TRUNCATED AT 400 WORDS)
Increased tubuloglomerular feed‐back mediated suppression of glomerular filtration during acute volume expansion in rats.
Authors: Davis J M , Häberle D A , Kawata T , Schmitt E , Takabatake T , Wohlfeil S
Published: December 2014

1. Volume expansion is currently believed to change the intrinsic properties of the juxtaglomerular apparatus such that the sensitivity of the tubuloglomerular feedback (TGF) mechanism is reduced, thus allowing glomerular filtration rate, and hence salt and water excretion, to rise. Recent studies conflict with this view and indeed the older literature reveals that the rise in glomerular filtration rate (GFR) under these conditions is far more modest than would be expected if TGF control were eliminated. 2. To investigate this problem, TGF control of filtration rate was examined by measuring single‐nephron glomerular filtration rate (SNGFR) during loop of Henle perfusion at varying rates in rats under control conditions, after acute, moderate (4% of body weight), iso‐oncotic volume expansion and in rats treated with antibodies to atrial natriuretic peptide (ANP) prior to the acute volume expansion. 3. With TGF control of filtration interrupted by filtrate collection from the proximal tubule, SNGFR in the expanded rats was massively increased compared with controls, although SNGFR measured in the distal tubule, and hence with TGF control intact, was only modestly increased, as was whole‐kidney filtration rate. Loop perfusion at increasing rates up to 30 nl min‐1 progressively decreased SNGFR in controls, and in the expanded rats the range over which control was exerted extended up to 60‐80 nl min‐1. For changes in loop flow around the spontaneous operating point, the sensitivity of the TGF mechanism, defined as delta SNGFR/delta loop flow, was similar in both groups. Treatment of rats with ANP antibodies prior to volume expansion substantially blunted the changes in renal salt and water excretion and the increase in SNGFR seen in the absence of loop perfusion. 4. These results are not consistent with a diminution of TGF function after volume expansion, rather with an enhancement. The latter is best accounted for by vasodilation of preglomerular resistance vessels on volume expansion, a result predicted by calculations from a model based on the serial arrangement of preglomerular and TGF‐controlled vascular resistance elements and the established pharmacological actions of ANP.
Human diaphragmatic endurance during different maximal respiratory efforts.
Authors: Gandevia S C , McKenzie D K
Published: December 2014

1. This study assessed human diaphragmatic endurance under two conditions: during maximal inspiratory efforts (with minimal elevation of abdominal pressure) and during maximal expulsive efforts (with minimal elevation of pleural pressure). Performance was compared with that of the flexors of the elbow. 2. In series of eighteen sustained maximal efforts begun near functional residual capacity the decline in trans‐diaphragmatic pressure was significantly greater during the expulsive than the inspiratory efforts (P less than 0.01). Diaphragmatic endurance was greater than that of the flexors of the elbow. 3. Electromyograms recorded during maximal and submaximal expulsive contractions indicated that the relatively rapid decline in abdominal pressure during the series of expulsive contractions reflected fatigue of the diaphragm rather than the abdominal muscles. Supramaximal phrenic nerve stimulation was used to check that complete activation of the phrenic motoneurone pool could be achieved during series of maximal expulsive efforts. 4. It is concluded that the reduced endurance capacity of the diaphragm during expulsive efforts did not reflect peripheral failure of the abdominal muscles or an inability to activate the diaphragm fully during those maximal efforts. 5. The deterioration in diaphragmatic performance when abdominal pressure is elevated may be due to an impairment of muscle perfusion.
Interpretation of [3H]ouabain binding in guinea‐pig ventricular myocardium in relation to sodium pump activity.
Authors: Herzig S , Lüllmann H , Mohr K , Schmitz R
Published: December 2014

1. The attempt was made to analyse the complex [3H]ouabain binding curves obtained in intact cardiac ventricular preparations electrically stimulated at different frequencies. The result of this analysis was used to draw conclusions from the binding curves on the frequency dependence of sodium pump activity. 2. [3H]Ouabain binding to isolated, electrically stimulated (1.5 Hz) ventricular strips of guinea‐pig hearts was investigated. The positive inotropic effects were studied in separate experiments. Specific [3H]ouabain binding barely reached an equilibrium within 3 h of incubation. A binding curve was constructed using the equilibrium values of specific [3H]ouabain binding obtained at different ouabain concentrations. This binding curve revealed a concentration‐proportional component at positive inotropic concentrations and a saturating component at high, toxic concentrations. At very low, inotropically ineffective ouabain concentrations, however, binding values were higher than expected from a linear relationship between ouabain concentration and binding. 3. The peculiar shape of the binding curve could be largely accounted for by a mathematical model, which takes into consideration biochemical properties and physiological regulation of the sodium pump. The model predicts a concentration‐proportional pattern of binding which takes place in the non‐toxic ouabain concentration range. The slope of the concentration‐proportional component of the binding curve should represent a measure of sodium pump activity. 4. Investigation of binding curves at various stimulation frequencies revealed that, as predicted by the model, the slope of the concentration‐proportional component of the binding curves was increased and the maximum non‐toxic equilibrium binding was decreased with increasing beat frequencies. 5. Quantitative evaluation of the binding curves led to the conclusion that sodium pump activity is a linear function of stimulation frequency in guinea‐pig ventricular preparations, the activity in resting preparations amounting to about 15% of the maximum activity. Comparison of the present results with former studies on sodium pump function suggests that [3H]ouabain binding reflects steady‐state sodium pump activity. If the complex pattern of binding curves is taken into consideration, [3H]ouabain binding measurements may serve as a means of studying sodium pump function.
Hyperpolarizing responses to stretch in sensory neurones innervating leech body wall muscle.
Authors: Blackshaw S E , Thompson S W
Published: December 2014

1. The membrane properties, morphology and physiological responses of peripherally located sensory neurones that innervate body wall muscle of the leech Hirudo medicinalis have been investigated using intracellular recording and dye injection techniques. 2. The peripheral neurones and their dendrites were visualized directly in whole mounts of the body wall by intracellular injection of horseradish peroxidase or Lucifer Yellow. They lie along the course of segmental nerves between the layers of longitudinal and oblique body wall muscle and within the sheath of the nerve. They have a distinctive morphology with two expanded, fan‐shaped dendrites arranged in series separated by the cell body and a 300 micron long cylindrical process. Both dendrites are associated with longitudinal muscle of the ventral body wall but with separate bands of muscle fibres. The axons project into the ventral nerve cord and arborize within the ipsilateral half of the segmental ganglion. No processes extend across the mid‐line of the ganglion or enter the connectives to neighbouring ganglia. 3. 'Resting' membrane potentials recorded from the peripheral cell body or from the axon as it entered the segmental ganglion ranged from ‐30 to ‐70 mV. The transmembrane potential recorded depended on the amount by which the body wall was stretched: the most hyperpolarized values were recorded from the most stretched preparations. Although the peripheral cell body can generate overshooting action potentials these are not actively propagated to the CNS. Rather, imposed voltage changes spread decrementally along the axon. Input resistances measured in the cell body ranged from 14 to 26 M omega. The space constant, estimated from the spread of hyperpolarizing current injected into the cell body, was 2.4 mm. 4. The response of the neurones to change in length of the longitudinal muscle recorded from the axon near its terminal arborization within the ventral nerve cord is a graded DC signal: the neurones thus relay information to CNS synapses in analogue form. Spiking activity recorded extracellularly in the anterior segmental nerve root in response to stretch of the body wall is due to activation of touch mechanosensory cells that innervate the skin. 5. Unlike stretch receptors innervating skeletal muscle in vertebrates or arthropods, the leech neurones respond to stretch of the body wall muscle with maintained hyperpolarizing potentials and to release of stretch with depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of pedal rate on respiratory responses to incremental bicycle work.
Authors: Takano N
Published: December 2014

1. The influence of pedal rate on ventilatory response and breathing pattern during cycle exercise was studied in twelve untrained female subjects performing 15 W/min incremental work on a bicycle at 30 and 60 r.p.m. Comparisons were made within the range of aerobic work rate to avoid additional influences of a developing lactic acidosis. 2. At each pedal rate, CO2 excretion (VCO2) increased progressively to a level of 1.2 1/min with incrementally loaded cycling. With increasing VCO2, minute ventilation (VE), respiratory frequency (f), tidal volume (VT) and end‐tidal PCO2 progressively increased. The inspiratory (TI) and expiratory (TE) durations decreased sharply on the transition from rest to unloaded cycling; further decreases occurred during incrementally loaded cycling. 3. Compared to 30 r.p.m., cycle exercise at 60 r.p.m. resulted in greater increases in VE and lower levels of end‐tidal PCO2 at any given levels of VCO2. The greater ventilatory responses were due mostly to greater increases in f, which were in turn due to greater decreases in TE. The decrease in TI during cycling was little affected by changes in pedal rate. 4. The different magnitudes of ventilatory and PCO2 responses under the two pedal rate conditions suggest that neurogenic stimuli, central and/or peripheral in origin, participate in the control of exercise hyperpnoea in the non‐steady‐state phase. The possibility that the ventilatory response to cycle exercise is affected by the way that pedal rate is changed is discussed.
Voltage‐ and calcium‐activated potassium currents in mouse neuroblastoma x rat glioma hybrid cells.
Authors: Brown D A , Higashida H
Published: December 2014

1. Membrane currents were recorded from voltage‐clamped, microelectrode‐impaled cells of the NG108‐15 mouse neuroblastoma x rat glioma clonal cell line, differentiated with prostaglandin E1. 2. A slow outward tail current reversing at post‐pulse potentials between ‐80 and ‐90 mV was evoked by depolarizing pre‐pulses to near 0 mV. The tail current was inhibited by Cd2+ ions (0.2‐1 mM) and hence attributed to activation of a Ca2+‐dependent K+ current by a priming voltage‐activated Ca2+ current. 3. Two components to this tail current could be distinguished pharmacologically: an early (less than or equal to 50 ms) component inhibited by 1‐5 mM‐tetraethylammonium (TEA), and a late component lasting several hundred milliseconds inhibited by apamin (0.1‐0.4 microM) or d‐tubocurarine (0.1‐0.5 mM). 4. Ionophoretic injection of Ca2+ ions evoked a transient outward current with an apparent reversal potential (from ramped current‐voltage curves) of ‐70 mV. This current was succeeded or sometimes replaced by an inward current with an apparent reversal potential between ‐20 and ‐10 mV. 5. The outward current induced by Ca2+ injections was unaffected or partly inhibited by TEA (1‐5 mM), but was strongly inhibited by apamin or d‐tubocurarine. 6. Hyperpolarizing voltage steps from between ‐30 and ‐40 mV induced inward current relaxations reversing at between ‐80 and ‐90 mV. These were considered to result from deactivation of the voltage‐dependent sustained K+ current, IM. 7. Application of methacholine, muscarine or Ba2+ ions produced an inward current, reduced input conductance and reduced IM deactivation relaxations. 8. It is concluded that differentiated NG108‐15 cells possess several of the K+ currents present in sympathetic neurones, including a delayed rectifier current, two species of Ca2+‐activated K+ current and the M‐current.
Gadolinium selectively blocks a component of calcium current in rodent neuroblastoma x glioma hybrid (NG108‐15) cells.
Authors: Docherty R J
Published: December 2014

1. The effect of the lanthanide cation Gd3+ on voltage‐dependent calcium currents in neuroblastoma x glioma (NG108‐15) cells has been studied using a whole‐cell clamp technique. 2. Gd3+ reduced the amplitude of calcium currents. The amount of inhibition produced by Gd3+ was concentration dependent between about 0.5 and 5 microM and reached a maximum at about 10‐20 microM. 3. A proportion of the total calcium current was resistant to blockade by Gd3+. 4. Gd3+‐resistant calcium current consisted of two components: a rapidly inactivating, 'fast' component which was activated at potentials more positive than about ‐45 mV, and a long‐lasting, 'slow' component which was activated at potentials more positive than about ‐10 mV. 5. It was possible to isolate the slow component, in the presence of Gd3+, by selectively inactivating the fast component with a brief depolarizing pre‐pulse. The fast and slow components of current probably reflect the activity of two subpopulations of calcium channels which are resistant to block by Gd3+. 6. In control conditions inactivation of calcium current could be described by the sum of a fast (tau congruent to 40 ms at +10 mV) and a slow (tau congruent to 800 ms at +10 mV) exponential decay plus a constant. Gd3+ selectively blocked the slowly decaying current. 7. The current blocked by Gd3+ was activated at potentials more positive than about ‐35 mV and decayed monoexponentially (tau congruent to 800 ms at +10 mV). 8. It is concluded that under the experimental conditions used in the present study calcium currents recorded in NG108‐15 cells are made up of at least three components which reflect the activity of three distinct subpopulations of calcium channels, one of which is selectively blocked by Gd3+.
Enkephalin hyperpolarizes interneurones in the rat hippocampus.
Authors: Madison D V , Nicoll R A
Published: December 2014

1. Intracellular recordings were made from pyramidal cells and from electrophysiologically identified interneurones in the CA1 region of the hippocampal slice preparation from the rat. 2. Enkephalin blocked the hyperpolarization of pyramidal cells evoked by application of glutamate to synaptically coupled inhibitory interneurones. 3. Enkephalin hyperpolarized interneurones, most probably by increasing potassium conductance; this action was blocked by the opiate antagonist, naloxone. 4. Activation of gamma‐aminobutyric acid(B) receptors with baclofen in interneurones produced a similar hyperpolarization that was resistant to naloxone. 5. In addition to hyperpolarizing interneurones, enkephalin blocked the inhibitory postsynaptic potential recorded in these cells. 6. These results suggest that opiate receptors are selectively localized on inhibitory interneurones in the hippocampus and are coupled to potassium channels. Activation of these receptors causes a disinhibition of both pyramidal cells and inhibitory interneurones.
Transport of thiamine by brush‐border membrane vesicles from rat small intestine.
Authors: Casirola D , Ferrari G , Gastaldi G , Patrini C , Rindi G
Published: December 2014

1. Microvillous vesicles obtained by a Ca2+ precipitation method from the intestine of adult Wistar albino rats were incubated at 25 degrees C with [35S]‐ or [3H]thiamine of high specific activity. 2. The time course of thiamine uptake was not influenced by the presence of Na+ or K+ nor by the absence of alkaline cations in the incubation medium. 3. At concentrations below 1.25 microM, thiamine was taken up mainly by a saturable mechanism with apparent Km = 0.8 microM and Vmax = 0.35 pmol mg protein‐1 4 s‐1. At higher concentrations, a non‐saturable uptake mechanism prevailed. 4. The thiamine taken up was transferred to the intravesicular space. No thiamine phosphoesters could be detected in the vesicles. 5. The vesicular transport of thiamine was inhibited competitively by several thiamine derivatives and structural analogues, including: cold thiamine; thiamine monophosphate (inhibition constant, Ki = 33 microM); pyrithiamine (Ki = 1.7 microM); 2'‐ethylthiamine (Ki = 27 microM); 5‐chloroethylthiamine (Ki = 70 microM): Amprolium (Ki = 55 microM); 4'‐oxythiamine (Ki = 510 microM).
A dynamic analysis of the ventilatory response to carbon dioxide inhalation in man.
Authors: Bertholon J F , Carles J , Eugene M , Labeyrie E , Teillac A
Published: December 2014

1. The dynamics of the ventilatory response to carbon dioxide inhalation were studied in ten healthy young men using four different inspired fractions of carbon dioxide (FI, CO2) in air (0.015, 0.030, 0.045 and 0.060) successively increasing and decreasing stepwise. 2. Seven such different progressions were performed for each subject and each of seven different durations of the steps (t) ranging between 0.1 (i.e. one ventilatory cycle) and 10 min ('steady‐state' conditions). The overall duration of one test (T) was taken as the sum of the seven successive FI, CO2 steps (t) plus one step, t, of air breathing. Thus, the values of T ranged between 0.8 (i.e. eight ventilatory cycles) and 80 min. Three subjects were tested twice. 3. We measured, as a function of T, the magnitude of the loops formed by the curves PA, CO2‐VE and the value of the highest ventilatory response (VE max) to each progression. For all ten subjects, both functions had two maxima, one for T values of 2.6 or 8.0 min and one for T values of 24 or 40 min, and one minimum at T equal to 12 min. 4. The same measurements were made on tidal volume‐response curves (PA, CO2‐VT) and ventilatory frequency‐response curves (PA, CO2‐f) and yielded the same results except for the ventilatory frequency‐response curves, for which we only found a statistically insignificant single maximum for T values of 24 or 40 min. 5. The locations of the maxima in loop magnitude and VE max were similar in duplicate tests in three subjects, whereas the quantitative values of these variables showed wide differences. 6. We compared our results with what is expected from the current linear dynamic model of ventilatory control submitted to the same forcing function: the first maximum in the loop magnitude is predicted by the model, but the second is not. The model shows no peak in the evolution of VE max. 7. We conclude that controlled system dynamics, which are the only ones included in dynamic models of ventilatory control, cannot by themselves account for our observations, and that one should take into consideration the dynamics of the controlling neuronal network.
Activation and blockage of a calcium‐sensitive cation‐selective pathway in the apical membrane of toad urinary bladder.
Authors: Aelvoet I , Erlij D , Van Driessche W
Published: December 2014

1. The properties of cation movements through a previously described Ca2+‐sensitive oxytocin‐stimulated pathway in the apical membrane of the toad urinary bladder were further investigated. 2. In the absence of Ca2+ and other polyvalent cations in the mucosal medium, oxytocin markedly stimulated the flow of current from mucosa to serosa when the major cation in the mucosal solution was any of the following ions: Na+, K+, Rb+, Cs+ or Li+. Analysis of the current noise showed a Lorentzian component associated with the movement of these cations. 3. Ca2+ and other divalent cations in the mucosal solution depressed both the current and the Lorentzian component of the fluctuation spectra. The Michaelis‐Menten constants were 2.5, 10 and 58 mumol/l for Ca2+, Sr2+ and Mg2+ respectively. 4. The dihydropyridine Ca2+ channel blockers nitrendipine (10(‐5) mol/l) and nicardipine (10(‐6) mol/l) inhibited the Ca2+‐sensitive current. 5. Alterations of the mucosal pH showed that the current and the plateau of the Lorentzian component increased by elevating the pH from 6 to 8. The Ca2+‐sensitive current was further stimulated by increasing pH to 9. However, this manoeuvre resulted in the disappearance of the Lorentzian component in the noise spectrum. 6. Increasing either mucosal [Na+] or [K+] up to 115 mmol/l did not lead to saturation of the current passing through the Ca2+‐sensitive channel. In contrast the amiloride‐sensitive channel showed saturating behaviour when mucosal [Na+] was increased; half‐maximum current was reached when mucosal [Na+] was about 15 mmol/l. 7. When a Na+‐free mucosal solution, prepared with either choline or TEA as major cation, was rapidly replaced by a solution with Na+ (115 mmol/l), the current through the Ca2+‐sensitive channel increased rapidly and then remained at a nearly constant level. This behaviour is in contrast with the response of the current through the amiloride‐sensitive pathway. After suddenly increasing mucosal Na+ concentration ([Na+]m), the current through this channel first increased rapidly and then declined to values of nearly 50% of the peak about 10 min after the increase in [Na+]m.(ABSTRACT TRUNCATED AT 400 WORDS)