bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the strength of common input to human motoneurons from the cross‐correlogram.
Authors: Nordstrom M A , Fuglevand A J , Enoka R M
Published: December 2014

1. The relationship between the motor unit discharge pattern (rate and variability) and synchronization of motor unit pairs was studied in the first dorsal interosseus muscle of human subjects. In separate trials of up to 4 min duration, subjects voluntarily controlled the mean discharge rate of an identified motor unit at one of several prescribed rates (range 7.5‐17.5 Hz). 2. The effect of discharge rate on the synchronous peak in the cross‐correlogram was examined in eighty motor unit pairs from six subjects. Five commonly used synchronization indices were used to quantify synchrony in the cross‐correlograms constructed from different discharge‐rate trials. For each synchronization index, the apparent magnitude of synchrony increased at lower motor unit discharge rates. The synchronization indices were not equally sensitive to discharge rate; increases in the different indices ranged from 72 to 494% between the highest and lowest discharge rates. 3. A model of the membrane potential trajectory underlying rhythmic motoneuron discharge was used to explain the observed increase in the magnitude of the synchronization indices at lower discharge rates. The essential feature of this model is that the probability of a common‐input EPSP causing a synchronous discharge in two motoneurons is independent of discharge rate. This means that the number of synchronous action potentials in excess of chance in any trial depends on the properties of the common‐input EPSPs and the duration of the trial, but is not related to motor unit discharge rates. The model also demonstrated that when the excess synchronous counts are normalized to motor unit discharge rate, or baseline counts in the histogram (as in the conventional synchronization indices), the magnitude of the index increases when the motor unit discharge rates are low. 4. The strength of common input to motoneurons could be misinterpreted if conventional synchronization indices are used because of discharge‐rate effects. The model was used to derive an index of the strength of common input to motoneurons (CIS) that was independent of motor unit discharge rate. CIS is the frequency of synchronous action potentials in the motor unit pair in excess of those expected due to chance (calculated during periods of tonic discharge in both units). The mean CIS in first dorsal interosseus motor unit pairs ranged from 0.052 to 1.005 extra synchronous action potentials per second across subjects. 5. Discharge variability was correlated with each of the synchronization indices and the CIS.(ABSTRACT TRUNCATED AT 400 WORDS)
Physiological evidence for a slow K+ conductance in human cutaneous afferents.
Authors: Taylor J L , Burke D , Heywood J
Published: December 2014

1. The depression in axonal excitability that follows short trains of impulses (H1) may lead to spike frequency adaptation to a sustained stimulus, and has been attributed to a slow K+ conductance. The present experiments sought indirect evidence for slow K+ channels at the node of Ranvier of human cutaneous afferents based on the demonstration of post‐tetanic changes in excitability typical of H1. 2. The excitability changes in low‐threshold cutaneous afferents in the digital nerves of the index finger were explored using a submaximal test pulse conditioned by trains of supramaximal stimuli, containing up to 100 impulses. Changes in the amplitude of the compound sensory action potential set up by a constant test stimulus were used as a measure of the changes in excitability. These changes in amplitude were paralleled by inverse changes in latency. 3. When the conditioning stimulus was a single supramaximal pulse, excitability was enhanced at conditioning‐test intervals of 4‐40 ms, with a peak at 6‐8 ms. When the conditioning stimulus consisted of a train of ten pulses delivered at 200 Hz, the recovery cycle was dominated by subnormality that was maximal at 20 ms and subsided gradually over 50 ms. 4. The post‐train depression in excitability increased as the number of pulses in the conditioning train increased to ten but changed little with further increases in train duration. The degree of depression increased with the pulse frequency within the train. Cooling the hand from a skin temperature of 35 to 25 degrees C slowed the recovery processes but did not alter the magnitude of the post‐train depression. 5. These characteristics are typical of the H1 phase of post‐tetanic depression in axonal excitability. The extent of the depression in excitability suggests, first, that there may be a significant K+ conductance at the nodes of human cutaneous afferents and, secondly, that H1 may play a significant role in limiting repetitive discharge in normal and pathological afferents.
Vibrotactile sensitivity of slowly adapting type I sensory fibres associated with touch domes in cat hairy skin.
Authors: Vickery R M , Gynther B D , Rowe M J
Published: December 2014

1. Recordings were made from single slowly adapting type I (SAI) afferent fibres associated with touch domes in the cat hairy skin. Controlled vibratory stimuli were used first, to characterize the precision with which these SAI afferents reflect the temporal aspects of vibrotactile stimuli, and second, to determine whether earlier disparate reports of SAI responsiveness to vibration may be attributable to highly specific stimulus requirements. 2. Eighteen SAI fibres from femoral cutaneous nerve branches were examined; each was associated with one to three touch domes. SAI responses to both steps and sinusoidal vibration (1‐1.5 s in duration) were affected profoundly by both probe size and position. Punctate stimulus probes (250 microns) produced much higher response levels and steeper stimulus‐response relations than those elicited with large (2 mm) probes, probably on account of focal distortion created within the dome by the smaller probes. SAI sensitivity to vibration was also affected markedly by the amplitude of any pre‐indentation on which the vibration was superimposed; sensitivity was much lower when the pre‐indentation exceeded 100 microns, in particular with larger stimulus probes. 3. Measures of both vibration sensitivity and the precision of impulse patterning demonstrated that, if appropriate stimulus parameters are chosen, the SAI fibres can respond to 1 s trains of vibration (amplitude < or = 100 microns) in a tightly phase‐locked, 1:1 manner for frequencies up to 500 Hz. At frequencies from approximately 100‐500 Hz the SAI fibres displayed broad 1:1 plateaus, where their response rate remained constant over a range of amplitudes, and phased‐locking was tightest. Responses remained phase‐locked up to 1000 Hz, but could not follow the vibration with a 1:1 pattern above 500 Hz. 4. The results demonstrate that with appropriate stimulus parameters, touch dome‐associated SAI fibres are capable of signalling vibrotactile information over a similar bandwidth of frequencies as do Pacinian sensory fibres. The variability in past reports of SAI vibration sensitivity may relate principally to differences in stimulus conditions. However, in view of the SAI capacity for responding to vibration with temporally precise, patterned activity, it appears that their reported failure to contribute to vibrotactile sensibility must be attributed to limitations imposed in the central processing of SAI signals.
Inward current caused by sodium‐dependent uptake of GABA in the crayfish stretch receptor neurone.
Authors: Kaila K , Rydqvist B , Pasternack M , Voipio J
Published: December 2014

A two‐microelectrode current‐voltage clamp and Cl(‐)‐selective microelectrodes were used to examine the effects of gamma‐aminobutyric acid (GABA) on membrane potential, current and intracellular Cl‐ activity (aiCl) in the crayfish stretch receptor neurone. All experimental solutions were CO2‐HCO3‐ free. 2. GABA (500 microM) produced a mono‐ or biphasic depolarization (amplitude < or = 10 mV), often with a prominent initial depolarizing component followed by a transient shift to a more negative level. In some neurones, an additional depolarizing phase was seen upon washout of GABA. Receptor desensitization, being absent, played no role in the multiphasic actions of GABA. 3. The pronounced increase in membrane conductance evoked by GABA (500 microM) was associated with an increase in aiCl which indicates that the depolarizing action was not due to a current carried by Cl‐ ions. 4. The currents activated by GABA under voltage clamp conditions were inwardly directed when recorded at the level of the resting membrane potential, and they often revealed a biphasic character. The reversal potential of peak currents activated by pulses of 500 microM‐GABA (EGABA) was 9‐12 mV more positive than the reversal potential of the simultaneously measured net Cl‐ flux (ECl). ECl was 2‐7 mV more negative than the resting membrane potential. 5. EGABA (measured using pulses of 500 microM‐GABA) was about 10 mV more positive than the reversal potential of the current activated by 500 microM‐muscimol, a GABA agonist that is a poor substrate of the Na(+)‐dependent GABA uptake system. 6. In the absence of Na+, the depolarization and inward current caused by 500 microM‐GABA were converted to a hyperpolarization and to an outward current. Muscimol produced an immediate outward current both in the presence and absence of Na+. 7. Following block of the inhibitory channels by picrotoxin (100‐200 microM), the depolarizing effect of 500 microM‐GABA was enhanced and the transient hyperpolarizing shifts were abolished. 8. In the presence of picrotoxin, GABA (> or = 2 microM) produced a concentration‐dependent monophasic inward current which had a reversal potential of +30 to +60 mV. This current was inhibited in the absence of Na+ and by the GABA uptake blocker, nipecotic acid. Unlike the channel‐mediated current, the picrotoxin‐insensitive current was activated without delay also at low (2‐10 microM) concentrations of GABA.(ABSTRACT TRUNCATED AT 400 WORDS)
Synaptically triggered action potentials begin as a depolarizing ramp in rat hippocampal neurones in vitro.
Authors: Hu G Y , Hvalby O , Lacaille J C , Piercey B , Ostberg T , Andersen P
Published: December 2014

1. During just‐suprathreshold synaptic activation of CA1 pyramidal cells in rat hippocampal slices in vitro the action potential begins as a slow depolarizing ramp, superimposed on the underlying EPSP and forming an integral part of the action potential. We call this ramp a synaptic prepotential (SyPP). 2. In order to examine the SyPP, a procedure for subtraction of the underlying EPSP was necessary. Because action potentials were only elicited by a subset of EPSPs with larger than average amplitude, a subtraction of the mean subthreshold EPSP would not give valid results. Instead, an EPSP to be subtracted was selected from an assemblage of subthreshold EPSPs, so that its amplitude matched the initial part of the spike‐generating EPSP. 3. Virtually all action potentials started with a SyPP. Using an amplitude criterion of 1 S.D. of the mean of the matching subthreshold EPSPs, just‐suprathreshold EPSPs gave prepotentials in 72‐100% of all action potentials from fifteen randomly selected cells. With a criterion of 2 S.D.S, the frequency of occurrence ranged from 36 to 100%. 4. With a constant stimulus strength, there was a certain variability of the spike latencies. Shorter latency spikes had steeper, but smaller SyPPs than later spikes, suggesting that the slope of SyPP influenced the timing of the cell discharge. 5. The SyPP was best fitted by a single, exponentially rising curve, and was both smaller and slower than the large amplitude action potential. Its amplitude was 1‐6 mV and the time constant 1‐5 ms, which was 10‐50 times slower than that of the upstroke of the action potential. 6. A properly timed hyperpolarizing current pulse could block the large amplitude action potential, thereby unmasking the SyPP as an initial depolarizing ramp. 7. The SyPP was more sensitive than the large amplitude action potential to intracellular injection of QX‐314, a lidocaine derivative. At the concentrations used (10 or 30 mM) no detectable changes were seen in the large amplitude action potential. 8. Droplet application of a specific N‐methyl‐D‐aspartate receptor antagonist, DL‐2‐amino‐5‐phosphonovaleric acid (1 mM), reduced both the EPSP and the firing probability, but did not change the SyPP. 9. The SyPP amplitude and time course depended upon the membrane potential at which the cell was activated. Depolarization enhanced and prolonged the SyPP, while hyperpolarization gave opposite effects. In part, the depolarization‐induced amplitude increase could be attributed to membrane accommodation. 10. Antidromically evoked action potentials never started with a prepotential.(ABSTRACT TRUNCATED AT 400 WORDS)
Calcium release from separate receptor‐specific intracellular stores induced by histamine and ATP in a hamster cell line.
Authors: Den Hertog A , Hoiting B , Molleman A , Van den Akker J , Duin M , Nelemans A
Published: December 2014

1. The specificity of intracellular Ca2+ stores to Ca(2+)‐mobilizing agonists was studied in DDT1 MF‐2 vas deferens cells of the Syrian hamster. 2. Application of histamine (100 microM) or ATP (100 microM) to the DDT1 MF‐2 cells caused an initial increase of intracellular Ca2+ followed by a lower phase as measured by using Indo‐1 as fluorescent probe at 22 degrees C. The basal Ca2+ level (146 nM) was enhanced to 309 nM by histamine and to 379 nM by ATP. 3. A transient rise in intracellular Ca2+ lasting for about 2 min was measured in the presence of histamine or ATP in the absence of extracellular Ca2+. The basal Ca2+ level (78 nM) was increased to 128 nM by histamine and to 145 nM by ATP. 4. A transient hyperpolarization was elicited in single cells as measured with microelectrodes by both agonists under Ca(2+)‐free conditions with a similar time course as the change in internal Ca2+. The hyperpolarization observed in the presence of histamine amounted to 23 mV and 31 mV with ATP. The histamine‐induced responses were abolished by the H1 histaminoceptor antagonist mepyramine (10 microM) and the responses evoked by ATP were blocked by the P2 purinoceptor antagonist suramin (300 microM). 5. A second internal Ca2+ response could only be evoked under Ca(2+)‐free conditions by applying a higher agonist concentration or after replenishing the intracellular stores with Ca2+ from the extracellular space. 6. A second addition of an optimal concentration (100 microM) of the agonist to the cells under Ca(2+)‐free conditions did not evoke mobilization of internal Ca2+ or hyperpolarization, but resulted in a rise of the cellular inositol (1,4,5)‐trisphosphate content (Ins(1,4,5)P3) as determined by a radioligand binding assay. 7. The cells responded to both agonists (100 microM) with a transient Ca2+ response if successively applied at a maximal effective concentration (100 microM) under Ca(2+)‐free conditions. 8. Simultaneous stimulation of H1 histaminoceptors and P2 purinoceptors resulted in the absence of external Ca2+ in an additional increase in internal Ca2+ represented by the amplitude and area of the response and in an increased response area of the hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Transduction mechanism for glutamate‐induced potassium current in neurones of the mollusc Planorbarius corneus.
Authors: Bolshakov VYu  , Gapon S A , Magazanik L G
Published: December 2014

1. The potassium currents evoked by glutamate agonists on isolated and identified neurones of molluscan pedal ganglia were investigated using the voltage clamp technique. 2. Glutamate responses were not modified by increasing intracellular cyclic nucleotide concentrations (treatment with 8‐Br‐cAMP, 8‐Br‐cGMP, forskolin and/or the phosphodiesterase inhibitor isobutylmethylxantine, IBMX), whereas inward‐going currents induced by the nucleotides were observed. It follows that glutamate currents are independent of intracellular cyclic nucleotide control. 3. Protein kinase C activation with phorbol esters or oleoylacetylglycerol induced a slowly developing outward current and reduced glutamate response amplitude. Staurosporine itself did not affect the glutamate responses but completely prevented the effects of phorbol esters and oleoylacetylglycerol. This indicated that protein kinase C was not involved in the transduction mechanism for the potassium component of the glutamate response. 4. The possible involvement of inositol‐1,4,5‐trisphosphate seems to be improbable because the glutamate responses were independent of intracellular calcium concentration. Intracellular injection of calcium buffer BAPTA, failed to affect any of the glutamate currents, although it effectively blocked the after‐hyperpolarization following directly evoked action potentials. 5. Nordihydroguaiaretic acid (NDGA) and indomethacin, inhibitors of the lipoxygenase and cyclo‐oxygenase pathways of arachidonic acid metabolism, correspondingly, did not change the glutamate responses of these neurones. 6. The failure to demonstrate the involvement of any known secondary messenger systems in glutamate response transduction favours two assumptions: (1) the receptor‐G protein complex controls the potassium channel directly; or (2) some still unknown transduction system is used.
Calcium homeostasis in the outer segments of retinal rods from the tiger salamander.
Authors: Lagnado L , Cervetto L , McNaughton P A
Published: December 2014

1. The processes regulating intracellular calcium in the outer segments of salamander rods have been investigated. The main preparation used was the isolated rod loaded with the Ca(2+)‐sensitive photoprotein aequorin, from which outer segment membrane current and free [Ca2+]i could be recorded simultaneously. Two other preparations were also used: outer segment membrane current was recorded from intact, isolated rods using a suction pipette, and from detached outer segments using a whole‐cell pipette. 2. Measurements of free intracellular [Ca2+] in Ringer solution were obtained from two aequorin‐loaded rods. Mean [Ca2+]i in darkness was 0.41 microM, and after a bright flash [Ca2+]i fell to below detectable levels ( < 0.3 microM). No release of intracellular Ca2+ by a bright flash of light could be detected ( < 0.2 microM). 3. Application of the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine (IBMX) caused an increase in the size of the light‐sensitive current and a rise in [Ca2+]i, but application of IBMX either when the light‐sensitive channels had been closed by a bright light or in the absence of external Ca2+ caused no detectable rise in [Ca2+]i. It is concluded that IBMX increases [Ca2+]i by opening light‐sensitive channels, and does not release Ca2+ from stores within the outer segment. 4. Removal of external Na+ caused a rise in [Ca2+]i to around 2 microM and completely suppressed the light‐sensitive current. 5. The Na(+)‐Ca2+, K+ exchange current in aequorin‐loaded rods was activated in first‐order manner by internal free calcium, with a mean Michaelis constant, KCa, of 1.6 microM. 6. The KCa of the Na(+)‐Ca2+, K+ exchange was increased by elevating internal [Na+]. 7. The Michaelis relation between [Ca2+]i and the activity of the Na(+)‐Ca2+, K+ exchange was used to calculate the change in [Ca2+]i occurring during the response to a bright light. In aequorin‐loaded rods in Ringer solution the mean change in free [Ca2+]i after a bright flash was 0.34 microM. In these rods 10% of the dark current was carried by Ca2+. 8. Most of the calcium entering the outer segment was taken up rapidly and reversibly by buffer systems. The time constant of equilibration between free and rapidly bound Ca2+ was less than 20 ms. No slow component of calcium uptake was detected. 9. Two components of calcium buffering could be distinguished in the outer segments of aequorin‐loaded rods.(ABSTRACT TRUNCATED AT 400 WORDS)
Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat.
Authors: Cazalets J R , Sqalli‐Houssaini Y , Clarac F
Published: December 2014

1. The role of serotonin (5‐HT) and excitatory amino‐acids (EAAs) in the activation of the neural networks (i.e. the central pattern generators) that organize locomotion in mammals was investigated in an isolated brainstem‐spinal cord preparation from the newborn rat. 2. The neuroactive substances were bath applied and the activity of fictive locomotion was recorded in the ventral roots. 3. Serotonin initiated an alternating pattern of right and left action potential bursts. The period of this rhythm was dose dependent, i.e. it decreased from around 10 s at 2 x 10(‐5) M to 5 s at 10(‐4) M. The effects of serotonin were blocked by a 5‐HT1 antagonist (propranolol) and by 5‐HT2 antagonists (ketanserin, cyproheptadine, mianserin). 5‐HT3 antagonists were ineffective. The effects of methoxytryptamine, a non‐selective 5‐HT agonist, mimicked the 5‐HT effects. 4. The endogenous EAAs, glutamate and aspartate, also triggered an alternating rhythmic pattern. Their effects were blocked by 2‐amino‐5‐phosphonovaleric acid (AP‐5; a N‐methyl‐D‐aspartate (NMDA) receptor blocker) and 6,7‐dinitro‐quinoxaline‐2,3‐dione (a non‐NMDA receptor blocker). 5. Several EAA agonists (N‐methyl‐D,L‐aspartate (NMA) and kainate) initiated rhythmic activity. The period of the induced rhythm (from 3 to 1 s) was similar with both of these substances but in a range of concentrations which was ten times lower in the case of kainate (10(‐6) to 5 x 10(‐6) M) than in that of NMA (10(‐5) to 4 x 10(‐5) M). alpha‐Amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and quisqualate occasionally triggered some episodes of fictive locomotion with a threshold at 6 x 10(‐7) and 10(‐5) M, respectively.
Properties of supraoptic magnocellular neurones isolated from the adult rat.
Authors: Oliet S H , Bourque C W
Published: December 2014

1. Magnocellular neurosecretory cells (MNCs) were isolated from the supraoptic nucleus of adult Long‐Evans rats using an enzymatic procedure. Immunocytochemical staining with antibodies against vasopressin and oxytocin revealed that MNCs can be identified by size. The membrane properties of these cells were examined at 32‐34 degrees C using intracellular recording methods. 2. Isolated MNCs displayed a mean (+/‐ S.E.M.; n = 109) resting membrane potential of ‐64.1 +/‐ 1.0 mV, an input resistance of 571 +/‐ 34 M omega, and a time constant of 8.7 +/‐ 0.4 ms. Measurements of specific resistivity and input capacitance revealed that the soma of these cells accounts for a mere 20% of their total somato‐dendritic membrane in situ. 3. Voltage‐current relations measured near ‐60 mV were linear negative to spike threshold. From more hyperpolarized membrane potentials, voltage responses to depolarizing current steps displayed transient outward rectification and delayed impulse discharge. 4. Action potentials (76.6 +/‐ 0.9 mV) triggered from an apparent threshold of ‐59.3 +/‐ 0.1 mV broadened progressively at the onset of spontaneous or current‐evoked spike trains. Steady‐state spike duration increased as a logarithmic function of firing frequency with a maximum near 25 Hz. These effects were abolished in Ca(2+)‐free solutions. 5. In all cells, evoked spike trains were followed by a prolonged Ca(2+)‐sensitive after‐hyperpolarization. In contrast, only a small proportion (16%) of MNCs displayed spontaneous bursting activity or depolarizing after‐potentials following brief current‐evoked bursts. 6. Isolated MNCs responded to amino acids (glutamate and GABA) and to the neuropeptide cholecystokinin, indicating that receptors for these neurotransmitters are expressed postsynaptically by MNCs and are retained following dissociation. 7. Increasing the osmolality of the superfusing solution by 5‐30 mosmol kg‐1 caused a membrane depolarization associated with a decrease of input resistance and accelerated spontaneous spike discharge in each of thirty‐six MNCs tested. Current‐clamp analysis suggested that these responses resulted from the activation of a cationic conductance. Excitatory effects of hyperosmolality were not observed in non‐magnocellular neurones (n = 6).
Effects of perchlorate on excitation‐contraction coupling in frog and crayfish skeletal muscle.
Authors: Györke S , Palade P
Published: December 2014

1. The effects of perchlorate on various aspects of excitation‐contraction coupling in frog and crayfish skeletal muscle have been examined in optical and electrophysiological experiments on voltage‐clamped cut muscle fibres. 2. In the frog, perchlorate shifted the voltage dependence of charge movement and consequent sarcoplasmic reticulum (SR) Ca2+ release, but it had little effect on the slow inward calcium current. 3. In the crayfish, perchlorate had little effect on either calcium currents or the SR Ca2+ release that contributes to myoplasmic Ca2+ elevations. 4. Two alternative explanations for these results are discussed. There may be two functional types of dihydropyridine receptors, those (perchlorate sensitive) that communicate with the ryanodine receptor via charge movement and those (perchlorate insensitive) that function solely as Ca2+ entry points. Alternatively, the results would be consistent with two separate voltage sensors on each dihydropyridine receptor, only one of which is perchlorate sensitive.
Ionic mechanisms mediating 5‐hydroxytryptamine‐ and noradrenaline‐evoked depolarization of adult rat facial motoneurones.
Authors: Larkman P M , Kelly J S
Published: December 2014

1. The actions of 5‐hydroxytryptamine (5‐HT) and noradrenaline (NA) on the membrane properties of facial motoneurones in slices from the adult rat brainstem in vitro were examined using intracellular recording techniques. 2. In voltage clamp recording, hyperpolarizing voltage steps (> 20 mV), from holding potentials at or close to the resting potential, induced a slowly activating, voltage‐dependent inward current possessing properties similar to the hyperpolarization‐activated current (Ih) seen in other cell types. From tail current analysis two groups of facial motoneurones can be distinguished in terms of the activation range for Ih, one with a half‐maximal activation at ‐81 mV and the other at ‐94 mV but with similar shapes. 3. 5‐HT (120/126) and NA (21/21) depolarized facial motoneurones. The reversal potentials (Em) obtained from peak voltage amplitude I‐V plots in varying extracellular potassium concentrations suggested mechanisms involving a decrease in K+ conductance. 4. Under voltage clamp, close to the resting potential, both 5‐HT (39/41) and NA (13/13) evoked inward currents. 5. I‐V plots and plots of 5‐HT‐sensitive current at different membrane potentials, obtained from currents evoked by voltage steps and measured before the development of Ih (instantaneous current), indicated that the 5‐HT‐evoked inward current was predominately associated with a decrease in conductance but with a range of reversal potentials for 5‐HT (E5‐HT) from close to, to much more negative than the reversal potential for a potassium conductance (EK). In some cases no change or increases in instantaneous conductance were observed. 6. Steady‐state I‐V relationships and plots of 5‐HT‐sensitive current, measured after development of Ih, indicated a 5‐HT‐associated conductance increase with a time and voltage dependence close to that of Ih, which could be abolished by extracellular caesium (2‐5 mM). 7. The NA‐evoked inward current was always associated with a decrease in conductance. Instantaneous and steady‐state I‐V relationships as well as plots of NA‐sensitive current indicated a reversal potential at EK. 8. The activation curve for Ih was shifted to more positive potentials in the presence of 5‐HT. The time constant for activation of Ih showed a similar shift. 9. 5‐Carboxamidotryptamine (5‐CT), a 5‐HT receptor agonist, was selective for the enhancement of Ih and only evoked an inward current when the holding potential was within the activation range of Ih.(ABSTRACT TRUNCATED AT 400 WORDS)
The classification of afferents from muscle spindles of the jaw‐closing muscles of the cat.
Authors: Taylor A , Durbaba R , Rodgers J F
Published: December 2014

1. The effects of the muscle‐depolarizing drug succinylcholine (SCh) on the stretch responses of jaw‐closer muscle spindle afferents were studied in the anaesthetized cat. Using ramp and hold stretches repeated every 6 s the basic measurements made were: initial frequency (IF), peak frequency (PF) and static index (SI), the frequency 0.5 s after the end of the ramp of stretch. Derived from these were: dynamic difference (DD) = PF‐IF, dynamic index (DI) = PF‐SI and static difference (SD) = SI‐IF. Increases in these measures caused by a single I.V. dose of SCh (200 micrograms kg‐1) are symbolized by the prefix delta. 2. In a population of 234 units, delta DD and delta IF were each distributed bimodally, but were uncorrelated, thus defining four subgroups. 3. delta DD was argued to be an index of the effect of bag1 intrafusal fibre contraction and delta IF to be an index of the effect of bag2 fibre contraction. On this basis it is proposed that units can be divided into four groups according to the predominant influences of the bag1, bag2 and chain fibres as b1c (6.8%), b1b2c (22.2%), b2c (54.3%) or c (16.7%). 4. Testing with sine wave stretches at 1 Hz showed that changes in mean frequency and amplitude of response caused by SCh correlated with delta IF and delta DD respectively, but separated groups of units much less effectively than did ramp and hold testing. 5. Evidence is presented to indicate that the control value of DD in passive spindles does not relate to the potential strength of bag1 fibre effects in fully activated spindles. The bag1 fibre appears to contribute little to responses of spindle afferents in the passive state. DD is superior to DI as a measure of bag1 effects. 6. Conduction velocity was unimodally distributed in masseter spindle afferents and was not correlated with delta DD or delta IF and was therefore of no value in classifying them. 7. Neither the threshold of afferents to quick transient stretch nor the coefficient of variation of interspike intervals provided any significant additional help in classification. 8. The unexpectedly high proportion of units of b2c type is thought to include primaries lacking appreciable bag1 fibre contacts and secondaries with more or less substantial bag2 contracts.
The effect of succinylcholine on cat gastrocnemius muscle spindle afferents of different types.
Authors: Taylor A , Rodgers J F , Fowle A J , Durbaba R
Published: December 2014

1. A population of 269 gastrocnemius muscle spindle afferents have been studied in anaesthetized cats for the effects of succinylcholine (SCh) on their response to ramp and hold stretches repeated every 6 s. The effectiveness and reliability of the SCh test was improved by prior stimulation of the muscle at 10 Hz for 30 s to increase the blood flow. 2. Responses have been assessed from averaged cycle histograms before and after a single I.V. dose of SCh of 200 micrograms kg‐1. As for previous studies of jaw muscle spindles the basic measurements were initial frequency (IF), peak frequency (PF) and static index (SI), the frequency 0.5 s after the end of the ramp of stretch. Dynamic difference (DD = PF‐IF), dynamic index (DI = PF‐SI) and static difference (SD = SI‐IF) were derived from these and increases caused by SCh indicated by the prefix delta. 3. delta DD and delta IF were each distributed bimodally and since they were uncorrelated formed the basis for a four‐way classification. Since delta DD can be attributed to activation of bag1 (b1) intrafusal fibres and delta IF to bag2 (b2) fibres, while all afferents receive input from chain (c) fibres it is proposed as with the jaw spindles that the classes correspond to predominant influence from b1c, b1b2c, b2c and c intrafusal fibres. 4. The proportion of units in the different groups were similar to those in the jaw muscles except for there being very few b1c type in gastrocnemius. 5. Conduction velocity was bimodally distributed with the best dividing line at 63.2 m s‐1. The b1b2c units were all, save one, in the fast group, while the b2c units were equally divided between fast and slow. 6. Mean control values for DD did not differ between the b1b2c and the b2c groups, which is taken to indicate that the b1 fibre does not contribute significantly to the dynamic stretch response of spindles with no intrafusal contraction. 7. The results emphasize the importance of recognizing that some apparently primary afferents lack b1 fibre influence, while many secondaries have marked b2 fibre influence. 8. The importance of the SCh classification is discussed in relation to the identification of fusimotor effects on spindle discharge and in relation to studies of central connectivity.
Responses of laryngeal receptors to intralaryngeal CO2 in the cat.
Authors: Bartlett D , Knuth S L
Published: December 2014

1. We recorded afferent activities of single fibres in the superior laryngeal nerves of decerebrate or anaesthetized, paralysed cats while 3, 5 and 10% CO2 was added to a constant flow of warm, humidified air through the isolated upper airway. 2. Fifty‐three receptors with discharge frequencies modulated by intralaryngeal CO2 were studied. Of these, forty‐eight showed CO2‐induced attenuation of their firing rates. Pulses of 3, 5 or 10% CO2, alternating with air at intervals ranging from 1.5 to 60 s, also diminished the discharge frequencies. This diminution was greater with higher CO2 concentrations and longer pulse durations. 3. Five of the fifty‐three receptors were stimulated by intralaryngeal CO2. The discharge frequencies of these units increased slowly and by only a few impulses per second during CO2 exposure. 4. Thirty‐four of the CO2‐sensitive receptors were tested with other stimuli, including water, saline, positive and negative intralaryngeal pressures and cold air. The responses to these stimuli varied among receptors, but many of the units that reduced their frequencies with intralaryngeal CO2 were consistently stimulated by positive and/or negative intralaryngeal pressures. 5. Thirty‐six of the receptors were anatomically located by probing the upper airway. Twenty‐six were in the larynx, and ten were in the rostral trachea, within 5 mm of the cricoid cartilage. 6. The results, which are directly applicable to the investigation of reflex responses reported in the preceding paper, indicate that the predominant initial response to intralaryngeal CO2 under the conditions of these studies is attenuation of laryngeal receptor activity.
Calcium‐induced calcium release in crayfish skeletal muscle.
Authors: Györke S , Palade P
Published: December 2014

1. Cut crayfish skeletal muscle fibres were mounted in a triple Vaseline‐gap voltage clamp with the Ca(2+)‐sensing dye Rhod‐2 allowed to diffuse in via the cut ends. Ca2+ currents across the surface/T‐tubule membranes (ICa) were recorded simultaneously with changes in myoplasmic Ca2+ concentration (Ca2+ transients). 2. Excitation‐contraction coupling in crayfish skeletal muscle fibres is abolished when calcium in the extracellular solution is replaced by Mg2+. 3. The amplitude of the Ca2+ transients elicited by voltage clamp pulses closely followed the amplitude of the peak calcium currents recorded simultaneously across the surface/T‐tubule membranes. This included decreases in both parameters as the pulse potential approached ECa (reversal potential for Ca2+), as well as secondary Ca2+ transients accompanying large tail calcium currents occurring upon repolarization from very large depolarizations. 4. A large contribution of sarcoplasmic reticulum (SR) Ca2+ release to the Ca2+ transients was revealed by a large decrease in the transient caused by the calcium‐induced calcium release (CICR) blockers procaine and tetracaine. 5. Short pulses which interrupted the calcium current while SR Ca2+ release was in progress at high rates caused the Ca2+ transient to stop rising nearly immediately after the end of the pulse in most fibres. In about 15% of the fibres the Ca2+ transients continued to rise, albeit at a slower rate, for 10‐20 ms after the end of the pulse, as if released Ca2+ was able to elicit some further Ca2+ release from the SR for a while. 6. Even with fibres displaying little sign of continued release after termination of short pulses under control conditions, procaine accelerated the decay of Ca2+ transients elicited by short pulses, indicating that continued release was taking place even as the transient was declining. 7. These results suggest that CICR in crayfish fibres is more closely controlled by a small entry of Ca2+ via surface/T‐tubule membrane Ca2+ current than by a larger amount of Ca2+ released from the SR. The limited positive feedback of released Ca2+ on further Ca2+ release allows CICR to remain graded (according to ICa) rather than all‐or‐none.
Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes.
Authors: Shimoni Y , Banno H , Clark R B
Published: December 2014

1. Transient outward potassium currents (I(t)) were compared in single cardiac myocytes obtained from normal and hyperthyroid rabbits. Currents were recorded using the suction electrode whole‐cell voltage clamp technique. 2. In ventricular myocytes from hyperthyroid animals (at 22 degrees C and a stimulation rate of 0.2 Hz), I(t) was 4‐ to 5‐fold larger than in normal myocytes, in a potential range of ‐20 to +60 mV. As in normal myocytes, I(t) in hyperthyroid myocytes was calcium insensitive, and was more than 90% suppressed by 2 mM 4‐aminopyridine. 3. The increase in I(t) was observed over a wide range of stimulation rates, even at rates sufficiently slow to enable complete reactivation of the I(t) channels. However, there was a major change in the rate dependence of I(t) in hyperthyroid myocytes, with significant I(t) current still present at rates (e.g. 1‐2 Hz) at which it is normally completely suppressed. 4. The augmentation of I(t) in the hyperthyroid myocytes could not be accounted for by changes in the voltage dependence or the kinetics of channel activation or inactivation. There was no change in the reversal potential of I(t), implying no change in the selectivity of the channel. 5. Single‐channel activity was recorded using the cell‐attached mode of recording. In myocytes from hyperthyroid rabbit we observed the following: (a) active patches (often containing two channels) were obtained more frequently in comparison to control; (b) the unitary conductance of the channel was the same; (c) single‐channel openings persisted at high stimulation rates. 6. In contrast to hyperthyroid ventricular cells, I(t) in atrial cells from the same hearts was not substantially changed. 7. The rate dependence of I(t) in atrial cells was also unaffected by hyperthyroidism, in contrast to the large changes observed in ventricular cells. Thus, in atrial cells from hyperthyroid hearts the current was totally suppressed at rates of 1‐2 Hz, as in euthyroid conditions. 8. Single‐channel recordings in the cell‐attached mode showed a unitary conductance similar to that found in normal atrial cells. Channel activity was suppressed at 2 Hz, in contrast to hyperthyroid ventricular cells. 9. In conclusion, I(t) is drastically changed in hyperthyroid rabbit ventricle cells. The changes are in the magnitude of the macroscopic current and its rate dependence. Since the unitary conductance is unchanged (and the peak open probabilities are normally high at positive membrane potential(s) the number of active channels in the membrane must be increased. In atrial cells from the same hyperthyroid hearts no changes are apparent.(ABSTRACT TRUNCATED AT 400 WORDS)
Presynaptic histamine H1 and H3 receptors modulate sympathetic ganglionic synaptic transmission in the guinea‐pig.
Authors: Christian E P , Weinreich D
Published: December 2014

1. To study the effects of histamine on the efficacy of sympathetic ganglionic synaptic transmission, extracellular recordings of the postganglionic compound action potential (CAP) and intracellular recordings of excitatory postsynaptic potentials (EPSPs) elicited by preganglionic electrical stimulation were obtained from isolated guinea‐pig superior cervical ganglia (SCG). 2. In different preparations, superfusion with histamine (0.1‐100 microM) either potentiated or depressed the postganglionic CAP elicited by electrical stimulation of the cervical sympathetic trunk (0.2‐3.0 Hz). The direction of response produced by histamine did not depend on stimulation frequency or histamine concentration; potentiation and depression both showed concentration dependence over the range of histamine concentrations tested. 3. Experiments employing a variety of histamine receptor agonists or antagonists revealed that histamine‐induced potentiation of the postganglionic CAP could be attributed to histamine H1 receptor activation, and depression to H3 receptor activation. 4. Histamine similarly potentiated or depressed the intracellularly recorded EPSP. However, these opposite effects occurred at different synapses. In agreement with the studies on the postganglionic CAP, histamine H1 antagonists prevented histamine‐induced potentiation of the EPSP and H3 receptor antagonists prevented histamine‐induced depression. 5. Direct quantal analyses of histamine‐induced synaptic potentiation and depression were implemented to determine the pre‐ and postsynaptic components of these effects. Quantal size was estimated by measuring the amplitude of spontaneous miniature EPSP amplitudes. Histamine‐induced potentiation and depression of the evoked EPSP were found to be accompanied by increased or decreased quantal content respectively, and unchanged quantal size, providing evidence that presynaptic mechanisms were involved in mediating both effects. 6. Some guinea‐pigs were actively sensitized to ovalbumin. Subsequent exposure of the isolated SCG from these animals to the sensitizing antigen produced changes in the EPSP amplitude that correlated significantly to the response produced by exogenously applied histamine at the same synapse. 7. The correspondence between the effects of specific antigen challenge and exogenous histamine on evoked EPSPs at a synapse provides evidence that endogenous histamine released during an immunological response to antigen challenge can activate histamine H1 and H3 receptors to modulate synaptic efficacy in sympathetic ganglia.
The cardiovascular, endocrine and renal response of tetraplegic and paraplegic subjects to dietary sodium restriction.
Authors: Sutters M , Wakefield C , O'Neil K , Appleyard M , Frankel H , Mathias C J , Peart W S
Published: December 2014

1. The effects of change from a high to low sodium diet upon renal sodium and water excretion and hormone responses were studied in patients with dissociated sympathetic control (DS, tetraplegic) and controls with sympathetic control largely intact (IS, paraplegic). 2. Total and fractional urinary sodium excretion fell in response to sodium restriction in both groups, but the fall in fractional sodium excretion was greater in the DS group compared with the IS group (DS, 1.34 +/‐ 0.12 to 0.42 +/‐ 0.05%; IS, 0.96 +/‐ 0.08 to 0.52 +/‐ 0.06%). 3. Supine mean arterial pressure fell during the low salt period in the DS group (80.2 +/‐ 2.7 to 74.4 +/‐ 2.3 mmHg) but was unaffected by salt restriction in the IS group (101 +/‐ 2.3 to 98.8 +/‐ 2.7 mmHg). In the DS group, creatinine clearance remained constant throughout the low salt period (103.7 +/‐ 7.9 to 98.3 +/‐ 9.7 ml min‐1), but fell during salt restriction in the IS group (101.4 +/‐ 8.5 to 83.2 +/‐ 5 ml min‐1). 4. Plasma renin activity was lower during salt loading in DS subjects but increased more rapidly and to higher levels in response to salt restriction (DS, 1021 +/‐ 142 to 4439 +/‐ 355; IS, 1765 +/‐ 269 to 3683 +/‐ 465 pg angiotensin I ml‐1 h‐1). Plasma atrial natriuretic peptide concentration was higher in the DS group during salt loading and salt restriction (DS, 37.6 +/‐ 5.6 to 22 +/‐ 3.8; IS, 20.2 +/‐ 2.3 to 11 +/‐ 1.6 pg ml‐1).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro.
Authors: Mo Z L , Katafuchi T , Muratani H , Hori T
Published: December 2014

1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1.1 +/‐ 0.1 spikes/s (mean +/‐ S.E.M.). 2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97%) were excited by 10(‐6) M AVP with an increase in firing rate from the basal level of 1.1 +/‐ 0.1 to a maximum of 2.5 +/‐ 0.2 spikes/s. There was a dose‐dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10(‐10) M. The remaining six neurones were not affected by application of AVP. 3. Application of oxytocin (OXT, 10(‐6) M) increased the firing rate of all thirty‐eight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low‐Ca2+ or Ca(2+)‐free‐high‐Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes. 4. The AVP‐induced excitatory responses were completely but reversibly blocked by the V1‐type receptor antagonists, [1‐(beta‐mercapto‐beta, beta‐cyclopentamethylene‐propionic acid), 2‐(O‐methyl)tyrosine]‐arginine vasopressin (d(CH2)5Tyr(Me)AVP) (n = 5) and Phaa‐D‐Tyr(Et)Phe‐Gln‐Asn‐Lys‐Pro‐Arg‐NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly‐NH2d(CH2)5[Tyr‐(Me)2Thr4]ornithine vasotocin, which suppressed the OXT‐induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10(‐6) M) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1.0 +/‐ 0.1 to a maximum of 1.8 +/‐ 0.2 spikes/s (n = 60). The effect of AII was completely abolished by an AII receptor antagonist, [Sar1,Ile8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on AII concentration in all of eleven neurones tested. The threshold concentration was assumed to be about 10(‐9) M. The activity of 5 (3%) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII.(ABSTRACT TRUNCATED AT 400 WORDS)