bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sarcomere length dependence of the rate of tension redevelopment and submaximal tension in rat and rabbit skinned skeletal muscle fibres
Authors: McDonald Kerry S. , Wolff Matthew R. , Moss Richard L. 
Published: September 2004

We examined the hypothesis that in skeletal muscle the steep relationship between twitch tension and sarcomere length (SL) within the range 2.30 to 1.85 μm involves SL‐dependent alterations in the rate of tension development.
In skinned preparations of both rat slow‐twitch and rabbit fast‐twitch skeletal muscle fibres the rate of tension redevelopment (ktr) at 15°C was reduced at short SL (∼2.00/μm) compared with a longer SL (∼2.30 μm). In submaximally activated fibres, the decrease in ktr over this range of lengths was greater in fast‐twitch fibres (38% reduction) than in slow‐twitch fibres (14% reduction).
Ca2+ sensitivity of tension, as assessed as the pCa (−log[Ca2+]) for half‐maximal activation, or pCa50, decreased to a greater extent in rabbit fast‐twitch skeletal muscle fibres than in slow‐twitch fibres from both rabbit and rat when SL was reduced from ∼2.30 to ∼1.85 μm. The ΔpCa50 over this SL range was 0.24 ± 0.07 pCa units in fast‐twitch fibres from rabbit psoas muscle. The ΔpCa50 for slow‐twitch fibres from rabbit and rat soleus muscle was 0.08 ± 0.02 and 0.10 ± 0.04 pCa units, respectively.
Osmotic compression of both slow‐twitch and fast‐twitch fibres at a SL of 2.00 μm increased ktr to values similar to those obtained at a SL of 2.30 μm in the absence of dextran. This result indicates that the slower rate of tension redevelopment at short SL is due in large part to the increase in interfilament lattice spacing associated with shorter SL.
Taken together, these results suggest that length dependence of twitch tension is, in part, due to length dependence of isometric cross‐bridge interaction kinetics, an effect that is mediated by length‐dependent changes in interfilament lattice spacing.
Rhythmic bursting of pre‐ and post‐inspiratory neurones during central apnoea in mature mice
Authors: Paton Julian F. R. 
Published: September 2004

Stimulation of pulmonary vagal C fibres (PCFs) inhibits inspiration but the response pattern of respiratory rhythm‐generating neurones is unknown. This study provides the first description of the effects of PCF stimulation on six different types of respiratory neurones located in the ventrolateral medulla of the mature mouse.
Studies were performed in both urethane‐anaesthetized (1.5 g kg−1 I.P.) mature mice and in an arterially perfused working heart‐brainstem preparation (WHBP). In both preparations the respiratory motor pattern of phrenic and recurrent laryngeal nerves were comparable. Stimulation of PCFs, using phenylbiguanide (2–5 μg) injected into the right atrium, evoked a similar respiratory and cardiac response pattern in both anaesthetized and perfused mice, which included: (i) a significant prolongation of the inter‐inspiratory interval; (ii) an increase in the duration and amplitude of post‐inspiratory (ii) activity; and (iii) an atropine‐sensitive bradycardia (50–260 beats min−1).
In the WHBP, PCF stimulation evoked a depolarization (11 ± 1 mV) and high frequency tonic discharge (up to 64 Hz) in ten out of twenty‐one PI neurones. During the PCF‐induced prolongation of PI activity all other PI neurones (n= 11), as well as pre‐inspiratory neurones (PreI; n= 11), displayed oscillations in membrane potential and/or rhythmic bursting at a similar frequency of 0.7‐1.0 Hz. Other respiratory neurones recorded, including stage II expiratory neurones (n= 7), early‐ (n= 6), ramp‐ (n= 16) and late‐inspiratory neurones (n= 4), ceased firing rhythmically during PCF stimulation.
The firing behaviour of PI and PreI neurones was assessed after switching to a low Ca2+ (0.2 mm)‐high Mg2+ (5.25 mm) perfusate to block synaptic transmission in the WHBP. In the absence of synaptic transmission, PreI neurones (n= 7/8) continued to discharge rhythmically, whereas all other respiratory cell types (including PI neurones, n= 5) fired tonically.
In conclusion, stimulation of PCFs elicits a reflex‐evoked prolongation of the PI phase of the respiratory cycle and excitation of PI neurones including rhythmic discharging. It is suggested that this rhythmic bursting depends on inhibitory connections from PreI neurones. The functional significance of these central ‘apnoeic rhythms’ are discussed.
Rhythmic motor activity and interlimb co‐ordination in the developing pouch young of a wallaby (Macropus eugenii)
Authors: Ho Stephen M. 
Published: September 2004

The forelimb motor behaviour of developing wallaby was studied. A clock‐like alternating movement was reactivated whenever the animal was removed from the pouch.
Forelimb stepping frequency increased during the first 3 weeks of development, while the phase relationship remained constant. Forelimb activity could be affected by altering the afferent feedback from the contralateral limb, or an increase in ambient temperature.
In vitro experiments were performed using an isolated brainstem‐spinal cord preparation from animals up to 6 weeks postnatal. Fictive locomotor activity could be evoked by electrical stimulation or bath‐applied NMDA (< 10 μm).
Bath‐applied strychnine (10‐25 μm) and bicuculline (10‐50 μm) disrupted the phase relationship between motor pools, while rhythmic motor discharge remained in the absence of these inhibitory pathways.
The present findings indicate that the pattern generator that underlies the robust forelimb movement during the first journey to the pouch is retained for different motor functions during in‐pouch development. The neural network that underlies such behaviour can be divided into two major components, a rhythm generator within each hemicord, and a pattern co‐ordinating pathway which involve both glycinergic and GABAergic interneurones.
Novel glutamate‐ and GABA‐independent synaptic depolarization in granule cells of guinea‐pig hippocampus
Authors: Forti Matteo , Michelson Hillary B. 
Published: September 2004

Dual intracellular recordings of granule cells, hilar interneurons and CA3 pyramidal cells were performed in transverse slices of guinea‐pig hippocampus. At resting membrane potential, in the presence of 4‐aminopyridine, ionotropic glutamate receptor antagonists and the GABAA receptor antagonist bicuculline, granule cells showed spontaneous, large amplitude depolarizations correlated with synchronous bursting activity of interneurons.
Under these conditions, pyramidal cells exhibited large amplitude monophasic GABAB inhibitory postsynaptic potentials (IPSPs) synchronous with the GABAergic interneuron burst discharges. The granule cells also received a GABAB input, which was evident only when the neurons were depolarized by DC injection. The GABAB receptor antagonist CGP 55845A (CGP) blocked the GABAB IPSPs in both pyramidal cells and granule cells; however, the depolarizing potential in granule cells was unaffected by the drug.
The granule cell depolarization in the presence of CGP was monophasic and exhibited linear voltage dependence with a reversal potential around −40 mV, suggesting that it was generated by a synaptic input activating a mixed cationic current.
The granule cell depolarization was abolished following the addition of tetrodotoxin to the bath. In addition, perfusing the slice with a low Ca2+‐containing solution (0.5 mm Ca2+–10 mm Mg2+) also abolished the granule cell depolarization, confirming the synaptic origin of the event.
(S)‐Methyl‐4‐carboxyphenylglycine, l‐(+)‐2‐amino‐3‐phosphonopropionic acid, propranolol and atropine did not affect the granule cell depolarization, indicating that metabotropic glutamate receptors,β‐adrenergic receptors and muscarinic cholinergic receptors were not involved in generating the granule cell depolarizing synaptic response.
These findings indicate that, in the absence of both glutamatergic and GABAergic inputs, synchronous interneuronal activity can produce a depolarizing synaptic response in granule cells. The neurochemical responsible for the depolarization is currently under investigation.
Characterization of the inward current induced by metabotropic glutamate receptor stimulation in rat ventromedial hypothalamic neurones
Authors: Lee K. , Boden P. R. 
Published: September 2004

Whole‐cell patch clamp recordings were made from rat ventromedial hypothalamic neurones in slices of brain tissue in vitro. Bath application of 50 μm (1S, 3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD) depolarized all neurones tested by activation of an inward current of approximately 55 pA at −60 mV.
The inward current elicited by 1S,3R‐ACPD was unaffected by K+ channel blockade with external Cs+, Ba2+ or TEA. However, the current was significantly reduced by replacement of the external NaCl with either Tris‐HCl or LiCl.
The 1S,3R‐ACPD‐induced current was reduced by the heavy metal ions Ni2+ or La3+ and also by the Na+–Ca2+ exchange current inhibitor 3′,4′‐dichlorobenzamil.
The effects of 1S,3R‐ACPD were mimicked by the group I metabotropic agonist 3,5‐dihydroxyphenylglycine (DHPG) but not by the group III selective agonist, l‐2‐amino‐4‐phosphonobutanoate (l‐AP4). Furthermore, the effects of 1S,3R‐ACPD were inhibited by the metabotropic antagonists α‐methyl‐4‐carboxyphenylglycine (MCPG) and 1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) but not by the presynaptic metabotropic receptor antagonists α‐methyl‐4‐phosphonophenylglycine (MPPG) or α‐methyl‐4‐tetrazolylphenylglycine (MTPG).
Photorelease of caged GDPβS inside neurones irreversibly blocked the 1S,3R‐ACPD‐induced current whilst photolysis of caged GTPγS inside neurones irreversibly potentiated this current.
The PLC inhibitor U‐73122 significantly reduced the size of the inward current induced by 1S,3R‐ACPD. This effect was not mimicked by the inactive analogue U‐73343.
Flash photolysis of the caged calcium chelator diazo‐2 inside neurones diminished the response to 1S,3R‐ACPD.
It is concluded that group I metabotropic glutamate receptors depolarize neurones in the VMH by activation of a Na+–Ca2+ exchange current through a G‐protein coupled increase in intracellular Ca2+.
Distribution of sarcomere length and intracellular calcium in mouse skeletal muscle following stretch‐induced injury
Authors: Balnave C. D. , Davey D. F. , Allen D. G. 
Published: September 2004

The effect on sarcomere organization of stretching intact single skeletal muscle fibres by 50% of their optimum length (Lo) during ten consecutive short tetani was investigated. Stretch reduced tetanic force to 36 ± 4% of the pre‐stretch condition. Sarcomere organization was analysed using both electron and confocal microscopy. For confocal microscopy the striation pattern was examined by fluorescently staining F‐actin with rhodamine–phalloidin.
Electron microscopy revealed that fibres which had been stretched during contraction contained areas of severe sarcomere disorganization, as well as adjacent sarcomeres of normal appearance.
Confocal images of stretched fibres, which had been fixed and stained with rhodamine–phalloidin, showed focal regions of overstretched sarcomeres and regions where sarcomeres of adjacent myofibrils were out of alignment with each other. Analysis of all sarcomeres along the length of fibres showed regions of sarcomere inhomogeneity were distributed throughout the fibre length and cross‐section.
Fibres were microinjected with the fluorescent [Ca2+]i indicator fura‐2 before being stretched. Conventional wide‐field fluorescence imaging microscopy showed that the tetanic [Ca2+]i was reduced after stretching but remained uniformly distributed.
This study confirms the finding that stretch‐induced muscle injury has components caused by disorganization of the myofibrillar array and by failure of tetanic Ca2+ release. The structural damage is spatially heterogeneous whereas the changes in Ca2+ release appear to be spatially homogeneous.
Changes in initiation of orienting gaze shifts after muscimol inactivation of the caudal fastigial nucleus in the cat
Authors: Goffart Laurent , Pélisson Denis 
Published: September 2004

The production of a goal‐directed saccadic gaze shift involves the specification of movement amplitude and direction, and the decision to trigger the movement. Behavioural and neurophysiological data suggest that these two functions involve separate processes which may interact.
The medio‐posterior cerebellar areas are classically assigned a major contribution to the control of saccade metrics, and previous cerebellar lesion studies have revealed marked dysmetria of visually triggered gaze shifts. In contrast, these studies did not provide evidence for a cerebellar role in saccadic initiation.
In the present study, we investigated in the head‐unrestrained cat the deficits in both the initiation and the metrics control of saccadic gaze shifts following pharmacological inactivation of the caudal part of the fastigial nucleus (cFN).
After cFN inactivation, latencies for contraversive gaze shifts increased to about 137 ± 28 % of normal, and latencies for ipsiversive gaze shifts decreased to about 84 ± 8 % of normal. Similar changes in head movement latency were observed, such that the temporal coupling between eye and head components remained largely unaffected.
Contraversive gaze shifts were more hypometric as their latency increased. In contrast, the degree of hypermetria in ipsiversive gaze shifts was unrelated to latency.
These results suggest a functional role of the medio‐posterior cerebellum in gaze shift initiation and in storing information about the target location and/or the desired gaze shift amplitude.
Differing effects of histamine and serotonin on microvascular permeability in anaesthetized rats
Authors: Michel C. C. , Kendall S. 
Published: September 2004

We have investigated simultaneous changes in the hydraulic permeability (Lp) and the retention of perfusate macromolecules in single mesenteric venules of anaesthetized rats during perfusion with either histamine or serotonin.
The venules were microperfused in situ. Retention of macromolecules was assessed from the effective oncotic pressure (σΔπ) exerted by the perfusate across the vessel walls. Lp and σΔπ were estimated by the red cell microperfusion technique.
Perfusion with histamine (at concentrations between 16 μm and 3.26 mm) and serotonin (at concentrations between 26 μm and 1.3 mm) transiently increased Lp and reduced σΔπ Maximal changes were seen at 6–9 min with histamine and at 3 min with serotonin.
Maximal increases in Lp were greater with histamine (approximately 3 ‐fold) than with serotonin (1.5‐ to 2‐fold). Serotonin, however, decreased σΔπ from a baseline of 14–15 cm H2O to one of 6–7 cm H2O whereas the fall of σΔπ with histamine was only from 14–15 cm H2O to 10–11 cm H2O.
The data are consistent with the hypothesis that serotonin increases permeability by inducing openings in the venular endothelium which do not retain macromolecules. If histamine also increases permeability by gap formation, these gaps are able to retain macromolecules to a significant extent.
Dynamics of viscoelastic properties of rat cardiac sarcomeres during the diastolic interval: involvement of Ca2+
Authors: Stuyvers Bruno D. M. Y. , Miura Masahito , Keurs Henk E. D. J. ter 
Published: September 2004

Cardiac sarcomere stiffness was investigated during diastole in eighteen trabeculae dissected from the right ventricle of rat heart. The trabeculae were stimulated at 0.5 Hz, in a modified Krebs–Henseleit solution (pH, 7.4; 25 °C). Sarcomere length (SL) was measured using high resolution (±2 nm) laser diffraction techniques. Force (F) was measured with a silicon strain gauge.
SL increased exponentially (amplitude, 25 ± 9 nm; n= 5) throughout diastole. This increase occurred even at slack SL, showing that this phenomenon was due to an internal expansion. The majority of the muscles showed discrete spontaneous fluctuations of SL (amplitude < 20 nm) starting ∼l s after the end of the twitch.
The intracellular free Ca2+ concentration ([Ca2+]i) was measured from the fluorescence of microinjected fura‐2 salt in seven trabeculae under the same experimental conditions. [Ca2+]i continuously declined (from 240 to 90 nm) during diastole following a monoexponential time course (time constant, 210–325 ms).
The stiffness of the sarcomere was evaluated at 10, 30, 50, 70 and 90% of diastole using bursts (30 ms) of 500 Hz sinusoidal perturbations of muscle length (amplitude of SL oscillations < 30 nm). At 1 mm external Ca2+ concentration ([Ca2+]o), the average stiffness modulus (Mod) increased from 9.3 ± 0.6 to 12 ± 0.6 mN mm−2μm1 (n= 18; P < 0.05), while the average phase shift (Ф) between F and SL signals decreased from 84 ± 3 to 73 ± 4 deg (n= 18; P < 0.05) between 10 and 90% during diastole. The increase in Mod and the decrease in Ф reversed when spontaneous activity occurred. When [Ca2+]0 was raised to 2 mm, the stiffness time course reversed approximately 450 ms earlier, simultaneously with the occurrence of spontaneous activity.
Our results show that diastole is only an apparent steady state and suggest that the structural system responsible for the viscoelastic properties of the sarcomere is regulated by [Ca2+]i in the submicromolar range. Different possible origins of the dynamic changes in viscoelasticity during diastole are discussed.
Age‐related functional changes of the glutamate receptor channels in rat Meynert neurones
Authors: Akaike Norio , Rhee Jeong‐Seop 
Published: September 2004

The developmental changes of glutamate receptors (GluRs) in acutely dissociated rat Meynert neurones were investigated using the conventional whole‐cell and nystatin perforated patch recording modes under voltage‐clamp conditions.
The neurones became less responsive to N‐methyl‐d‐aspartic acid (NMDA) with age, most dramatically between 1 day and 2 weeks, while the responses to kainic acid (KA) and l‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) gradually increased. The metabotropic GluR response appeared a few days after birth, but thereafter no further change was observed.
The decrease in the NMDA response during postnatal development was due to an abrupt reduction in the number of receptors without affecting the affinity, voltage‐dependent Mg2+ blockade or high Ca2+ permeability (Pca/PCs≈ 7.0).
P
ca/PCs in the presence of KA decreased from 2.8 in the 1‐day‐old (1D) rat neurones to 1.1 and 0.44 in the 2‐week‐old (2W) and 6‐month‐old (6M) rat neurones, respectively. The concentration–response relationship for KA shifted to the left with age. The KA response was not affected by NS‐102, a KA‐selective antagonist, thus indicating that the increased affinity of the receptor for the ligand resulted from the change in the AMPA receptor channel subunits.
The AMPA response in the presence of 10−4 M cyclothiazide showed a change in the inward rectifying current–voltage relationship with age. The KA response was strongly cross‐desensitized by the addition of AMPA and was also blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), whereas a rapid desensitization of the AMPA response was removed in a concentration‐dependent manner by cyclothiazide. These results indicate that the non‐NMDA receptor channels are assembled from the subunits of the AMPA receptor family without the GluR‐2 subunit, thus resulting in a high Ca2+ permeability.
The l‐glutamate (Glu)‐induced responses were more sensitive to dl‐2‐amino‐5‐phosphonopentanoic acid (APV) in the 1D rat neurones than in the adult rat neurones.
Both NMDA and KA raised the intracellular Ca2+ concentration ([Ca2+]i) in all neurones of 1D, 2W and 6M rats, though the charybdotoxin‐sensitive Ca2+‐activated K+ current (IK(ca)) did not appear in the 1D rat neurones. An age‐related prolongation of both IK(Ca) decay and [Ca2+]i clearance was also seen after the removal of KA.
It was thus concluded that the age‐related changes of ionotropic receptors appear to play a key role in the activities of immature and mature rat Meynert cholinergic neurones. The KA‐induced IK(Ca), which developed with ageing, may thus function as one of the negative feedback systems, and thereby prevent excess cell excitation and neural damage, especially in adult rats.
Ionic currents during sustained pacemaker activity in rabbit sino‐atrial myocytes
Authors: Zaza Antonio , Micheletti Maria , Brioschi Angelica , Rocchetti Marcella 
Published: September 2004

The contribution of various ionic currents to diastolic depolarization (DD) in rabbit sino‐atrial myocytes was evaluated by the action potential clamp technique. Individual currents were identified, during sustained pacemaking activity reproduced under voltage clamp conditions, according to their sensitivity to supecific channel blockers.
The current sensitive to dihydropyridines (DHPs), blockers of L‐type Ca2+ current (ICa,L), was small and outward during most of DD. Diastolic DHP‐sensitive current was affected by changes in the driving force for K+, but it was insensitive to E‐4031, which blocks the current termed IK,r; it was abolished by cell dialysis with a Ca2+ chelator.
The current sensitive to 2 mm Cs+ (ICs), a blocker of hyperpolarization‐activated current (If), was inward during the whole DD and it was substantially larger than the net inward current flowing during this phase. However, diastolic IK,r, identified in the same cells as the current sensitive to the blocker E‐4031, exceeded ICs 2‐fold.
These findings suggest that: (a) Ca2+ influx during the pacemaker cycle increases a K+ conductance, thus inverting the direction of the net current generated by L‐type Ca2+ channel activity during DD; (b) the magnitude of If would be adequate to account fully for DD; however, the coexistence of a larger IK,r suggests that other channels besides If contribute inward current during this phase.
Anaplerotic processes in human skeletal muscle during brief dynamic exercise
Authors: Gibala Martin J. , MacLean Dave A. , Graham Terry E. , Saltin Bengt 
Published: September 2004

This study examined changes in tricarboxylic acid cycle intermediates (TCAIs) in human skeletal muscle during 5min of dynamic knee extensor exercise (∼80% of maximum workload) and following 2 min of recovery.
The sum of the seven measured TCAIs (ΣTCAIs) increased from 1.10 ± 0.08mmol (kg dry weight)−1 at rest to 3.12 ± 0.24, 3.86 ± 0.35 and 4.33 ± 0.30 mmol (kg dry weight)−1after 1, 3 and 5 min of exercise, respectively (P≤ 0.05). The ΣTCAIs after 2 min of recovery (3.74 ± 0.43 mmol (kg dry weight)−1) was not different compared with 5 min of exercise.
The rapid increase in ΣTCAIs during exercise was primarily mediated by large changes in succinate, malate and fumarate. These three intermediates accounted for > 90 % of the net increase in ΣTCAIs during the first minute of contraction.
Intramuscular alanine increased after 1 min of exercise by an amount similar to the increase in the ΣTCAIs (2.33 mmol (kg dry weight)−1) (P≤ 0.05). Intramuscular pyruvate was also higher (P≤0.05) during exercise, while intramuscular glutamate decreased by ∼50% within 1 min and remained low despite an uptake from the circulation (P≤ 0.05).
The calculated net release plus estimated muscle accumulation of ammonia after 1 min of exercise (∼60 μmol (kg wet weight)−1) indicated that only a minor portion of the increase in ΣTCAIs could have been mediated through the purine nucleotide cycle and/or glutamate dehydrogenase reaction.
It is concluded that the close temporal relationship between the increase in ΣTCAIs and changes in glutamate, alanine and pyruvate metabolism suggests that the alanine amino‐transferase reaction is the most important anaplerotic process during the initial minutes of contraction in human skeletal muscle.