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1.
  • Edman, Paul, et al. (författare)
  • Synchronous oscillations of length and stiffness during loaded shortening of frog muscle fibres
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 534:2, s. 553-563
  • Tidskriftsartikel (refereegranskat)abstract
    • A study was made of the damped oscillations in fibre length that are observed when isolated muscle fibres from the frog are released during the plateau of an isometric tetanus to shorten against a constant load (force clamp recording) near the isometric level (temperature, 1.0-11.0 C; initial sarcomere length, 2.25 m). 2. The oscillatory length changes of the whole fibre were associated with similar length changes of marked consecutive segments along the fibre. The segmental length changes were initially in synchrony with the whole-fibre movements but became gradually more disordered. At the same time the length oscillation of the whole fibre was progressively damped. 3. The fast length step that normally occurs at the outset of the load-clamp manoeuvre was essential for initiating the oscillatory behaviour. Accordingly, no length oscillation occurred when the load clamp was arranged to start as soon as the selected tension level was reached during the rising phase of the tetanus. 4. The instantaneous stiffness was measured as the change in force that occurred in response to a high-frequency (2-4 kHz) length oscillation of the fibre. During the load-clamp manoeuvre, when the tension was kept constant, the stiffness underwent periodic changes that correlated well in time with the damped oscillatory changes in fibre length. However, there was a phase shift between the stiffness oscillation and the oscillation of shortening velocity, the latter being in the lead of the stiffness response by 21.4 0.8 ms (n = 19) at 1.8 0.1 C . 5. A mechanism is proposed to explain the oscillatory behaviour of the muscle fibre based on the idea that the quick length step at the outset of the load clamp leads to synchronous activity of the myosin cross-bridges along the length of the fibre.
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2.
  • Enevoldsen, L.H., et al. (författare)
  • The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 536:3, s. 871-877
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Adrenaline-stimulated lipolysis in adipose tissue may increase with training. The rate-limiting step in adipose tissue lipolysis is catalysed by the enzyme hormone-sensitive lipase (HSL). We studied the effect of exercise training on the activity of the total and the activated form of HSL, referred to as HSL (DG) and HSL (TG), respectively, and on the concentration of HSL protein in retroperitoneal (RE) and mesenteric (ME) adipose tissue, and in the extensor digitorum. longus (EDL) and soleus muscles in rats. 2. Rats (weighing 96 + 1 g, mean +/- S.E.M.) were either swim trained (T, 18 weeks, n = 12) or sedentary (S, n = 12). Then RE and ME adipose tissue and the EDL and soleus muscles were incubated for 20 min with 4.4 muM adrenaline. 3. HSL enzyme activities in adipose tissue were higher in T compared with S rats. Furthermore, in RE adipose tissue, training also doubled HSL protein concentration (P < 0.05). In ME adipose tissue, the HSL protein levels did not differ significantly between T and S rats. In muscle, HSL (TG) activity as well as HSL (TG)/HSL (DG) were. lower in T rats, whereas HSL (DG) activity did not differ between groups. Furthermore, HSL protein concentration in muscle did not differ between T and S rats (P > 0.05). 4. In conclusion, training increased the amount of HSL and the sensitivity of HSL to stimulation by adrenaline in intra-abdominal adipose tissue, the extent of the change differing between anatomical locations. In contrast, in skeletal muscle the amount of HSL was unchanged and its sensitivity to stimulation by adrenaline reduced after training.
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3.
  • Axelson, Hans W, et al. (författare)
  • Human motor control consequences of thixotropic changes in muscular short-range stiffness
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 535:Pt 1, s. 279-288
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary aim of the present study was to explore whether in healthy subjects the muscle contractions required for unrestrained voluntary wrist dorsiflexions are adjusted in strength to thixotropy-dependent variations in the short-range stiffness encountered in measurements of passive torque resistance to imposed wrist dorsiflexions.After a period of rest, only the first movement in a series of passive wrist dorsiflexions of moderate amplitude exhibited clear signs of short-range stiffness in the torque response. During analogous types of voluntary movements, the extensor EMG during the first movement after rest showed a steep initial rise of activity, which apparently served to compensate for the short-range stiffness.The passive torque resistance to minute repetitive wrist dorsiflexions (within the range of short-range stiffness) was markedly reduced after various types of mechanical agitation. During analogous low-amplitude voluntary wrist dorsiflexions the extensor EMG signals were weaker after than before agitation.Mechanical agitation also led to enhancement of passive dorsiflexion movements induced by weak constant torque pulses. In an analogous way, the movement-generating capacity of weak voluntary extensor activations (as determined by EMG recordings) was greatly enhanced by mechanical agitation.The signals from a force transducer probe pressed against the wrist flexor tendons - during passive wrist dorsiflexions - revealed short-range stiffness responses which highly resembled those observed in the torque measurements, suggesting that the latter to a large extent emanated from the stretched, relaxed flexor muscles. During repetitive stereotyped voluntary wrist dorsiflexions, a close correspondence was observed between the degree of short-range stiffness as sensed by the wrist flexor tension transducer and the strength of the initial extensor activation required for movement generation.The results provide evidence that the central nervous system in its control of voluntary movements takes account of and compensates for the history-dependent degree of inherent short-range stiffness of the muscles antagonistic to the prime movers.
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4.
  • Edin, Benoni B (författare)
  • Cutaneous afferents provide information about knee joint movements in humans.
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 531:Pt 1, s. 289-297
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Neurophysiological evidence that afferent information from skin receptors is important for proprioception has been gathered mainly in experiments relating to the human hand and finger joints. To investigate if proprioceptive information is also provided by skin mechanoreceptor afferents from skin areas related to large joints of postural importance, microneurography recordings were obtained in humans from skin afferents in the lateral cutaneous femoral nerve to study their responses to knee joint movements. 2. Data were collected from 60 sequentially recorded afferents from slowly (n = 23) and fast (n = 6) adapting low-threshold mechanoreceptors, hair follicle receptors (n = 24), field receptors (n = 1) and C mechanoreceptors (n = 6). Fascicular recordings showed that the lateral cutaneous femoral nerve supplies extensive areas of the thigh: from 5-10 cm below the inguinal ligament down to below and lateral to the knee joint; accordingly, the afferents originated in receptors located in wide areas of the human thigh. 3. All afferents from fast and slowly adapting low-threshold mechanoreceptors, as well as C mechanoreceptors, responded to manually applied skin stretch. In contrast, the same stimulus elicited, at most, feeble responses in hair follicle receptors. 4. Qualitative and quantitative analyses of the responses of a subset of afferents revealed that in particular slowly adapting afferents effectively encode both static and dynamic aspects of passively imposed knee joint movements. 5. It was concluded that receptors in the hairy skin of humans can provide high-fidelity information about knee joint movements. A previously undefined type of slowly adapting receptor (SA III) seemed particularly suited for this task whereas this does not seem to be the case for either hair follicle receptors or C mechanoreceptors.
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5.
  • Gladden, M. H., et al. (författare)
  • Coupling between serotoninergic and noradrenergic neurones and γ-motoneurones in the cat
  • 2000
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 527, s. 213-223
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Noradrenaline is known to suppress transmission from group II muscle afferents when locally applied to γ-motoneurones, and serotonin (5-HT) facilitates the transmission. The purpose of this investigation was to search for evidence of monoaminergic innervation of γ-motoneurones. 2. Eight γ-motoneurones were labelled with rhodamine-dextran, and 50 μm thick sagittal sections of the spinal cord containing them were exposed to antibodies against dopamine β-hydroxylase (DBH) and 5-HT. All the cells were directly and/or indirectly excited by muscle group II afferents from the muscle they innervated and/or other muscles. 3. Appositions between monoaminergic fibres and the labelled somata and dendrites were located with three-colour confocal laser scanning microscopy by examining series of optical sections at 1 or 0·5 μm intervals. 4. DBH and 5-HT varicosities formed appositions with the somata and dendrites of all the γ-motoneurones. The mean packing densities for 5-HT (1·12 ± 0·11 appositions per 100 μm2 for somata and 0·91 ± 0·07 per 100 μm2 for dendrites) were similar to the densities of contacts reported for α-motoneurones. Monoaminergic varicosities in apposition to dendrites greatly outnumbered those on the somata. 5. The density of DBH appositions was consistently lower - corresponding means were 53% and 62% of those for 5-HT on the somata and dendrites, respectively. 6. It is concluded from an analysis of the distribution and density of varicosities in apposition to the γ-motoneurones compared with the density in the immediate surround of the dendrites that there is indeed both a serotoninergic and noradrenergic innervation of γ-motoneurones.
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  • Mekjavic, I.B., et al. (författare)
  • Motion sickness potentiates core cooling during immersion in humans
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 535:2, s. 619-623
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The present study tested the hypothesis that motion sickness affects thermoregulatory responses to cooling in humans. 2. Ten healthy male volunteers underwent three separate head-out immersions in 28 degrees C water after different preparatory procedures. In the 'control' procedure immersion was preceded by a rest period. In the 'motion sickness' procedure immersion was preceded by provocation of motion sickness in a human centrifuge. This comprised rapid and repeated alterations of the gravitational (G-) stress in the head-to-foot direction, plus a standardized regimen of head movements at increased G-stress. In the 'G-control' procedure, the subjects were exposed to similar G-stress, but without the motion sickness provocation. 3. During immersion mean skin temperature, rectal temperature, the difference in temperature between the forearm and 3rd digit of the right hand (DeltaT(forearm-fingertip)), oxygen uptake and heart rate were recorded. Subjects provided ratings of temperature perception, thermal comfort and level of motion sickness discomfort at regular intervals. 4. No differences were observed in any of the variables between control and G-control procedures. In the motion sickness procedure, the DeltaT(forearm-fingertip) response was significantly attenuated, indicating a blunted vasoconstrictor response, and rectal temperature decreased at a faster rate. No other differences were observed. 5. Motion sickness attenuates the vasoconstrictor response to skin and core cooling, thereby enhancing heat loss and the magnitude of the fall in deep body temperature. Motion sickness may predispose individuals to hypothermia, and have significant implications for survival time in maritime accidents.
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  • Tonkonogi, Michail, et al. (författare)
  • Mitochondrial function and antioxidative defence in human muscle : effects of endurance training and oxidative stress.
  • 2000
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 528 Pt 2, s. 379-88
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of endurance training on oxidative phosphorylation and the susceptibility of mitochondrial oxidative function to reactive oxygen species (ROS) was investigated in skeletal muscle of four men and four women. Mitochondria were isolated from muscle biopsies taken before and after 6 weeks of endurance training. Mitochondrial respiration was measured before and after exposure of mitochondria to exogenous ROS (H2O2 + FeCl2). Endurance training increased peak pulmonary O2 uptake (VO2,peak) by 24 % and maximal ADP-stimulated mitochondrial oxygen consumption (state 3) by 40% (P<0.05). Respiration in the absence of ADP (state 4), the respiratory control ratio (RCR = state 3/state 4) and the ratio between added ADP and consumed oxygen (P/O) remained unchanged by the training programme. Exposure to ROS reduced state 3 respiration but the effect was not significantly different between pre- and post-training samples. State 4 oxygen consumption increased after exposure to ROS both before (+189 %, P< 0.05) and after training (+243 %, P<0.05) and the effect was significantly higher after training (P<0.05, pre- vs. post-training). The augmented state 4 respiration could in part be attenuated by atractyloside, which indicates that ADP/ATP translocase was affected by ROS. The P/O ratio in ROS-treated mitochondria was significantly lower (P<0.05) compared to control conditions, both before (-18.6+/-2.2 %) and after training (-18.5+/-1.1%). Muscle activities of superoxide dismutase (mitochondrial and cytosolic), glutathione peroxidase and muscle glutathione status were unaffected by training. There was a positive correlation between muscle superoxide dismutase activity and age (r = 0.75; P<0.05; range of age 20-37 years), which may reflect an adaptation to increased generation of ROS in senescent muscle. The muscle glutathione pool was more reduced in subjects with high activity of glutathione peroxidase (r = 0.81; P<0.05). The influence of short-term training on mitochondrial oxygen consumption has for the first time been investigated in human skeletal muscle. The results showed that maximal mitochondrial oxidative power is increased after endurance training but that the efficiency of energy transfer (P/O ratio) remained unchanged. Antioxidative defence was unchanged after training when expressed relative to muscle weight. Although this corresponds to a reduced antioxidant protection per individual mitochondrion, the sensitivity of aerobic energy transfer to ROS was unchanged. However, the augmented ROS-induced non-coupled respiration after training indicates an increased susceptibility of mitochondrial membrane proton conductance to oxidative stress.
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  • Yu, M, et al. (författare)
  • Marathon running increases ERK1/2 and p38 MAP kinase signalling to downstream targets in human skeletal muscle.
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 536:Pt 1, s. 273-82
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. We tested the hypothesis that long-distance running activates parallel mitogen-activated protein kinase (MAPK) cascades that involve extracellular signal regulated kinase 1 and 2 (ERK1/2) and p38 MAPK and their downstream substrates. 2. Eleven men completed a 42.2 km marathon (mean race time 4 h 1 min; range 2 h 56 min to 4 h 33 min). Vastus lateralis muscle biopsies were obtained before and after the race. Glycogen content was measured spectrophotometrically. ERK1/2 and p38 MAPK phosphorylation was determined by immunoblot analysis using phosphospecific antibodies. Activation of the downstream targets of ERK1/2 and p38 MAPK, MAPK-activated protein kinase-1 (MAPKAP-K1; also called p90 ribosomal S6 kinase, p90rsk), MAPK-activated protein kinase-2 (MAPKAP-K2), mitogen- and stress-activated kinase 1 (MSK1) and mitogen- and stress-activated kinase 2 (MSK2) was determined using immune complex assays. 3. Muscle glycogen content was reduced by 40 +/- 6 % after the marathon. ERK1/2 phosphorylation increased 7.8-fold and p38 MAPK phosphorylation increased 4.4-fold post-exercise. Prolonged running did not alter ERK1/2 and p38 MAPK protein expression. The activity of p90rsk, a downstream target of ERK1/2, increased 2.8-fold after the marathon. The activity of MAPKAPK-K2, a downstream target of p38 MAPK, increased 3.1-fold post-exercise. MSK1 and MSK2 are downstream of both ERK1/2 and p38 MAPK. MSK1 activity increased 2.4-fold post-exercise. MSK2 activity was low, relative to MSK1, with little activation post-exercise. 4. In conclusion, prolonged distance running activates MAPK signalling cascades in skeletal muscle, including increased activity of downstream targets: p90rsk, MAPKAP-K2 and MSK. Activation of these downstream targets provides a potential mechanism by which exercise induces gene transcription in skeletal muscle.
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  • Pinniger, G J, et al. (författare)
  • H-reflex modulation during passive lengthening and shortening of the human triceps surae.
  • 2001
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 534:Pt 3, s. 913-23
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The present study investigated the effects of lengthening and shortening actions on H-reflex amplitude. H-reflexes were evoked in the soleus (SOL) and medial gastrocnemius (MG) of human subjects during passive isometric, lengthening and shortening actions performed at angular velocities of 0, +/-2, +/-5 and +/-15 deg s(-1). 2. H-reflex amplitudes in both SOL and MG were significantly depressed during passive lengthening actions and facilitated during passive shortening actions, when compared with the isometric H-reflex amplitude. 3. Four experiments were performed in which the latencies from the onset of movement to delivery of the stimulus were altered. Passive H-reflex modulation during lengthening actions was found to begin at latencies of less than 60 ms suggesting that this inhibition was due to peripheral and/or spinal mechanisms. 4. It is postulated that the H-reflex modulation seen in the present study is related to the tonic discharge of muscle spindle afferents and the consequent effects of transmission within the Ia pathway. Inhibition of the H-reflex at less than 60 ms after the onset of muscle lengthening may be attributed to several mechanisms, which cannot be distinguished using the current protocol. These may include the inability to evoke volleys in Ia fibres that are refractory following muscle spindle discharge during rapid muscle lengthening, a reduced probability of transmitter release from the presynaptic terminal (homosynaptic post-activation depression) and presynaptic inhibition of Ia afferents from plantar flexor agonists. Short latency facilitation of the H-reflex may be attributed to temporal summation of excitatory postsynaptic potentials arising from muscle spindle afferents during rapid muscle lengthening. At longer latencies, presynaptic inhibition of Ia afferents cannot be excluded as a potential inhibitory mechanism.
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26.
  • Tonkonogi, Michail, et al. (författare)
  • Mitochondrial oxidative function in human saponin-skinned muscle fibres : effects of prolonged exercise.
  • 1998
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 510 ( Pt 1), s. 279-86
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The influence of prolonged exhaustive exercise on mitochondrial oxidative function was investigated in ten men. 2. Muscle biopsies were taken before and after exercise and mitochondrial respiration investigated in fibre bundles made permeable by pretreatment with saponin. 3. After exercise, respiration in the absence of ADP increased by 18 % (P < 0.01), but respiration at suboptimal ADP concentration (0.1 mM) and maximal ADP-stimulated respiration (1 mM ADP) remained unchanged. 4. In the presence of creatine (20 mM), mitochondrial affinity for ADP increased markedly and respiration at suboptimal ADP concentration (0.1 mM) was similar (pre-exercise) or higher (post-exercise; P < 0.05) than with 1 mM ADP alone. The increase in respiratory rate with creatine was correlated to the relative type I fibre area (r = 0.84). Creatine-stimulated respiration increased after prolonged exercise (P < 0.01). 5. The respiratory control index (6.8 +/- 0.4, mean +/- s.e.m.) and the ratio between respiration at 0.1 and 1 mM ADP (ADP sensitivity index, 0.63 +/- 0.03) were not changed after exercise. The sensitivity index was negatively correlated to the relative type I fibre area (r = -0.86). 6. The influence of exercise on muscle oxidative function has for the first time been investigated with the skinned-fibre technique. It is concluded that maximal mitochondrial oxidative power is intact or improved after prolonged exercise, while uncoupled respiration is increased. The latter finding may contribute to the elevated post-exercise oxygen consumption. The finding that the sensitivity of mitochondrial respiration for ADP and creatine are related to fibre-type composition indicates intrinsic differences in the control of mitochondrial respiration between fibres.
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27.
  • Walsh, B, et al. (författare)
  • The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle.
  • 2001
  • Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 537:Pt 3, s. 971-8
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The role of phosphorylcreatine (PCr) and creatine (Cr) in the regulation of mitochondrial respiration was investigated in permeabilised fibre bundles prepared from human vastus lateralis muscle. 2. Fibre respiration was measured in the absence of ADP (V(0)) and after sequential additions of submaximal ADP (0.1 mM ADP, V(submax)), PCr (or Cr) and saturating [ADP] (V(max)). 3. V(submax) increased by 55 % after addition of saturating creatine (P < 0.01; n = 8) and half the maximal effect was obtained at 5 mM [Cr]. In contrast, V(submax) decreased by 54 % after addition of saturating phosphorylcreatine (P < 0.01; n = 8) and half the maximal effect was obtained at 1 mM [PCr]. V(max) was not affected by Cr or PCr. 4. V(submax) was similar when PCr and Cr were added simultaneously at concentrations similar to those in muscle at rest (PCr/Cr = 2) and at low-intensity exercise (PCr/Cr = 0.5). At conditions mimicking high-intensity exercise (PCr/Cr = 0.1), V(submax) increased to 60 % of V(max) (P < 0.01 vs. rest and low-intensity exercise). 5. Eight of the subjects participated in a 16 day Cr supplementation programme. Following Cr supplementation, V(0) decreased by 17 % (P < 0.01 vs. prior to Cr supplementation), whereas ADP-stimulated respiration (with and without Cr or PCr) was unchanged. 6. For the first time evidence is given that PCr is an important regulator of mitochondrial ADP-stimulated respiration. Phosphorylcreatine decreases the sensitivity of mitochondrial respiration to ADP whereas Cr has the opposite effect. During transition from rest to high-intensity exercise, decreases in the PCr/Cr ratio will effectively increase the sensitivity of mitochondrial respiration to ADP. The decrease in V(0) after Cr supplementation indicates that intrinsic changes in membrane proton conductance occur.
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  • Alsted, Thomas J., et al. (författare)
  • Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle
  • 2013
  • Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 591:20, s. 5141-5155
  • Tidskriftsartikel (refereegranskat)abstract
    • In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride lipase (ATGL) and HSL collectively account for approximate to 98% of the TG hydrolase activity in mouse skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.
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  • Alstermark, Bror, et al. (författare)
  • The lateral reticular nucleus : a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.
  • 2013
  • Ingår i: Journal of Physiology. - : Wiley-Blackwell. - 0022-3751 .- 1469-7793. ; 591:22, s. 5453-5458
  • Tidskriftsartikel (refereegranskat)abstract
    • The lateral reticular nucleus (LRN) is a major precerebellar centre of mossy fibre information to the cerebellum from the spinal cord that is distinct from the direct spinocerebellar paths. The LRN has traditionally been considered to provide the cerebellum with segregated information from several spinal systems controlling posture, reaching, grasping, locomotion, scratching and respiration. However, results are presented that show extensive convergence on a majority of LRN neurons from spinal systems. We propose a new hypothesis suggesting that the LRN may use extensive convergence from the different input systems to provide overview and integration of linked motor components to the cerebellum. This integrated information is sent in parallel with the segregated information from the individual systems to the cerebellum that finally may compare the activity and make necessary adjustments of various motor behaviours.
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  • Apps, Richard, et al. (författare)
  • Gating of cutaneous input to cerebellar climbing fibres during a reaching task in the cat
  • 1997
  • Ingår i: Journal of Physiology. - 1469-7793. ; 502:Pt 1, s. 203-214
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Task-dependent modulation of cutaneous input to climbing fibres projecting to the C1, C2 and C3 zones in the cerebellar paravermal lobule V was investigated in awake cats during performance of a reaching task. 2. Climbing fibre responses resulting from low intensity (non-noxious) electrical stimulation of the ipsilateral superficial radial nerve were recorded as extracellular field potentials in the cerebellar cortex using chronically implanted microwires. 3. Response size, measured as the time-voltage integral of the evoked field potential, was assessed during three phases of the reaching movement, reaction, reach and grasp, and compared with the response size at rest. 4. At C1 and C3 zone recording sites response size was usually reduced during the task (7/10 sites). The reduction was most pronounced in the grasp phase, occasionally accompanied by a smaller reduction in the reach and reaction phases. In one case an enhancement was found in the reach phase. 5. Response size was also modulated during the task at four of six C2 zone recording sites. However, the results were mixed. In three cases the modulation resembled the pattern at C1/C3 sites with the responses being reduced in the grasp phase accompanied on occasion by a lesser reduction in the reach phase. In the remaining case there was an enhancement during grasp. In this case and one other there was also an enhancement during the reaction phase. 6. The findings indicate significant gating of cutaneous input to climbing fibres projecting to the C1, C2 and C3 zones during reaching movements, while the variability between recording sites suggests functional differences, both between and within zones.
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  • Arheden, Håkan, et al. (författare)
  • Cross-bridge behaviour in skinned smooth muscle of the guinea-pig taenia coli at altered ionic strength
  • 1988
  • Ingår i: Journal of Physiology. - 1469-7793. ; 403, s. 539-558
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The effects of varied levels (25-300 mM) of ionic strength on mechanical properties and ATP hydrolysis rate of chemically skinned guinea-pig taenia coli fibres were investigated. 2. The tension development following activation by calcium (pCa 4 8), and relaxation following removal of calcium (pCa 9), were slower in 25 mm compared to 150 mm ionic strength. In fibres activated by thiophosphorylation of myosin light chains, by exposure to ATP-y-S, the tension development was rapid and independent of ionic strength. 3. The maximal shortening velocity (Vmax) was obtained from force-velocity relations determined by the quick-release method. The rate of ATP hydrolysis (JATP) was determined by measurement of pyruvate released from phosphoenolpyruvate (PEP). In order to obtain maximal Vmax and JATP at a Mg-ATP concentration of 1 mm, an ATP regenerating system was required. In thiophosphorylated fibres 2 mmphosphocreatine (PCr) or 3-2 mM-PEP were adequate for maximal Vmax and JATP respectively. In calcium-activated fibres 5 mM-PCr was required for maximal Vmax. 4. The isometric force of thiophosphorylated fibres showed a biphasic dependence on ionic strength with a maximum at 90 mm. Vmax was essentially unchanged between 50 and 200 mm ionic strength. At 25 mm ionic strength, isometric force and Vmax were decreased by, respectively, about 15 and 25%. At 250 mM ionic strength, isometric force and Vmax were decreased by, respectively, 47 and 33 %. 5. Vm.x decreased with decreasing [Mg-ATP]. At [Mg-ATP] less than 0 1 mm there was no difference in Vmax between 35 and 150 mM ionic strength. At 250 mM ionic strength Vmax was lower than that at 150 mm at all [Mg-ATP]. 6. JATP during contraction in thiophosphorylated fibres at 35, 150 and 250 mm ionic strength was respectively, 0-62, 0-98 and 0-93 ,umol g-1 min-'. The energetic tension cost (JATP/force) increased with ionic strength. 7. The force response to a quick stretch was investigated in the relaxed, contracted and rigor states at 25, 150 and 250 mm ionic strength. Stiffness in the relaxed state increased with speed of stretch and was higher the lower the ionic strength. In the contracted and rigor states, stiffness was also affected by ionic strength, but the relative effect in the contracted state was small. 8. The effects of ionic strength on the behaviour of the skinned smooth muscle fibre may involve an influence on the filament system, but are also compatible with an increased binding of smooth muscle myosin to actin at low ionic strength. The results from activated and rigor muscle suggest that ionic strength does not exclusively affect kinetics of rapid cross-bridge equilibria but may also influence mechanical properties of attached cross-bridge states.
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  • Arheden, Håkan, et al. (författare)
  • Force response to rapid length change during contraction and rigor in skinned smooth muscle of guinea-pig taenia coli
  • 1991
  • Ingår i: Journal of Physiology. - 1469-7793. ; 442, s. 601-630
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Mechanical transients in fibre bundles of skinned smooth muscle of guinea-pig taenia coli at 21-22 degrees C were investigated by recording tension responses to length changes of up to 9%, complete within 0.3 ms. 2. The length-force relationship, recorded continuously during rapid stretch of a Ca(2+)-activated contracted muscle, was linear up to at least 2.5 times the isometric force, corresponding to a stretch of about 1%. The slope of the relationship (stiffness) increased with the velocity of stretch. 3. During rapid release (about 120 muscle lengths s-1) the length-force relationship was linear down to about 50% of the initial isometric force, reached at about 80 microseconds after the beginning of the release. At lower force the length-force relationship was concave upwards. The linear portion extrapolated to zero force at about -0.008 muscle lengths. In large releases the length-force plot approached the force baseline under an acute angle, and negative force was transiently exerted. 4. When the muscle was stretched back to the initial length after a shortening step, force transiently rose above the isometric force, but decayed back within a few milliseconds. Stiffness at the time of restretch was compared with that in the initial shortening step by plotting force vs. length, and was found to be decreased to 63% within 0.3 ms of a step to zero force. Stiffness decreased further with time at zero force, and after 256 ms was about 29% of the isometric value. 5. In rigor, caused by the introduction of ATP-free solution during the plateau of isometric contraction, fibre tension decreased to about 30% of the active tension, whereas stiffness relative to force increased; 82% of the initial stiffness in rigor was detected in a restretch immediately after a shortening step, decreasing to 59% at 256 ms. When the fibre was activated at suboptimal [Ca2+] to cause the same force as in rigor, stiffness was lower than in rigor and decreased more after a release. 6. After completion of a release-stretch cycle, stiffness was rapidly restored to the same value as in isometric contraction. Test stretches at different points in time after completion of the cycle revealed that most of the stiffness had been restored within 1 ms of the restretch, occurring concomitantly with a decay in force.7. The shape of the length-force relationship during a release was analysed using a model consisting of a linear (cross-bridge) elasticity in series with an exponential (passive) elasticity and assuming no detachment of cross-bridges during release. In rigor the exponential element contributed 40% of the total compliance of the fibre. The model, although closely fitting the data, could not account for the results using an exponential elasticity with unaltered properties during activation at optimal and suboptimal [Ca2"] and in rigor. 8. The results suggest rapid detachment of some of the attached cross-bridges during and after a shortening step to slack length. Detachment of strongly bound cross-bridges may occur during a restretch, if it causes a strain on the attached crossbridges exceeding their working range. During the restretch, and on return to isometric contraction after the restretch, cross-bridges rapidly reattach in strongly bound configurations.
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40.
  • Arner, Anders, et al. (författare)
  • Effects of calcium and substrate on force-velocity relation and energy turnover in skinned smooth muscle of the guinea-pig
  • 1985
  • Ingår i: Journal of Physiology. - 1469-7793. ; 360, s. 347-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Mechanical properties and rate of ATP breakdown (JATP) have been determined in the chemically skinned guinea-pig taenia coli at 22 degrees C. The influence of varied [Ca2+], [Mg ATP] and muscle length were investigated. The shortening response after a step decrease in force (isotonic quick release) was highly curvilinear in the first 100-200 ms. This effect was shown to be a time-dependent response to the force step and not primarily caused by the shift along the length-force relation associated with shortening. Maximal shortening velocity (Vmax) decreased gradually following the release. At pCa (= -log [Ca2+]) 4.5, Vmax at 20 and 1000 ms after release was 0.49 +/- 0.07 and 0.041 +/- 0.004 (mean +/- S.E. of mean, n = 5) lengths s-1 respectively. Unloaded shortening velocity obtained from length steps of different magnitude (slack test) also showed a gradual decrease after the release, consistent with the isotonic release results. Increasing [Ca2+] from the relaxed state at pCa 9 (1 microM-calmodulin present) gave increased isometric force to a maximum at pCa 4.5. Half-maximal response was obtained at pCa 6.1. JATP at maximal force at pCa 4.5 was about 3 times the basal rate at pCa 9. The relation between JATP and force was highly non-linear, with a marked increase in JATP with little alteration in force at the highest [Ca2+]. When force was reduced to zero at pCa 4.5 by shortening the muscle to 0.3 L0 (L0 being the length giving maximal active force), JATP decreased by about 30%. At two levels of [Ca2+] giving similar force (pCa 5.75 and 4.5) the energetic tension cost obtained by length variations was lower at the low [Ca2+]. At pCa 6.0, Vmax and force were decreased to the same extent relative to their values at pCa 4.5. At pCa 5.75, where there was no reduction in force but a 25% decrease in isometric JATP, Vmax was unchanged relative to pCa 4.5. Force, Vmax and JATP were all dependent on [Mg ATP]. Half-maximal response was obtained at 0.1 mM for force and Vmax, and at 0.5 mM for JATP. The results are discussed in relation to a possible influence of both Ca2+ and Mg ATP on kinetic properties of the cross-bridge cycle.
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41.
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42.
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43.
  • Baczyk, Marcin, et al. (författare)
  • Presynaptic actions of transcranial and local direct current stimulation in the red nucleus
  • 2014
  • Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 592:Pt 19, s. 4313-28
  • Tidskriftsartikel (refereegranskat)abstract
    • The main aim of the present study was to examine to what extent long-lasting subcortical actions of transcranial direct current stimulation (tDCS) may be related to its presynaptic actions. This was investigated in the red nucleus, where tDCS was recently demonstrated to facilitate transmission between interpositorubral and rubrospinal neurons. Changes in the excitability of preterminal axonal branches of interpositorubral neurons close to rubrospinal neurons were investigated during and after tDCS (0.2 mA) applied over the sensorimotor cortical area in deeply anaesthetized rats and cats. As a measure of the excitability, we used the probability of antidromic activation of individual interpositorubral neurons by electrical stimuli applied in the red nucleus. Our second aim was to compare effects of weak (≤1 μA) direct current applied within the red nucleus with effects of tDCS to allow the use of local depolarization in a further analysis of mechanisms of tDCS instead of widespread and more difficult to control depolarization evoked by distant electrodes. Local cathodal polarization was found to replicate all effects of cathodal tDCS hitherto demonstrated in the rat, including long-lasting facilitation of trans-synaptically evoked descending volleys and trisynaptically evoked EMG responses in neck muscles. It also replicated all effects of anodal tDCS in the cat. In both species, it increased the excitability of preterminal axonal branches of interpositorubral neurons up to 1 h post-tDCS. Local anodal polarization evoked opposite effects. We thus show that presynaptic actions of polarizing direct current may contribute to both immediate and prolonged effects of tDCS. © 2014 The Physiological Society.
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44.
  • Bannatyne, B A, et al. (författare)
  • Excitatory and inhibitory intermediate zone interneurons in pathways from feline group I and II afferents: differences in axonal projections and input.
  • 2009
  • Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 587:Pt 2, s. 379-99
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to compare properties of excitatory and inhibitory spinal intermediate zone interneurons in pathways from group I and II muscle afferents in the cat. Interneurons were labelled intracellularly and their transmitter phenotypes were defined by using immunocytochemistry. In total 14 glutamatergic, 22 glycinergic and 2 GABAergic/glycinergic interneurons were retrieved. All interneurons were located in laminae V-VII of the L3-L7 segments. No consistent differences were found in the location, the soma sizes or the extent of the dendritic trees of excitatory and inhibitory interneurons. However, major differences were found in their axonal projections; excitatory interneurons projected either ipsilaterally, bilaterally or contralaterally, while inhibitory interneurons projected exclusively ipsilaterally. Terminal projections of glycinergic and glutamatergic cells were found within motor nuclei as well as other regions of the grey matter which include the intermediate region, laminae VII and VIII. Cells containing GABA/glycine had more restricted projections, principally within the intermediate zone where they formed appositions with glutamatergic axon terminals and unidentified cells and therefore are likely to be involved in presynaptic as well as postsynaptic inhibition. The majority of excitatory and inhibitory interneurons were found to be coexcited by group I and II afferents (monosynaptically) and by reticulospinal neurons (mono- or disynaptically) and to integrate information from several muscles. Taken together the morphological and electrophysiological data show that individual excitatory and inhibitory intermediate zone interneurons may operate in a highly differentiated way and thereby contribute to a variety of motor synergies.
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45.
  • Barker, D., et al. (författare)
  • Identification of intrafusal muscle fibres activated by single fusimotor axons and injected with fluorescent dye in cat tenuissimus spindles.
  • 1978
  • Ingår i: The Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 275, s. 149-165
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Intrafusal muscle fibres of cat tenuissimus spindles have been injected with the fluorescent dye Procion Yellow and identified histologically after recording their changes in membrane potential during 1/sec stimulation of single static or dynamic gamma axons. 2. Thirteen intrafusal muscle fibres innervated by static gamma axons were identified as eight bag2 and five chain fibres. The fact that none proved to be a bag1 fibre is not regarded as significant, for reasons given in the Discussion. 3. In one spindle Procion Yellow was injected into two intrafusal muscle fibres activated by the same static gamma axon; they were identified as a bag2 and a chain fibre. 4. Nine intrafusal muscle fibres innervated by dynamic gamma axons were identified as seven bag1 fibres, one bag2 fibre, and one long chain fibre. 5. In one spindle two bag fibres were injected, one activated by a dynamic gamma axon, the other by a static gamma axon; the former proved to be a bag1 fibre, the latter a bag2 fibre. 6. Stimulation of static gamma axons elicited junctional potentials in seven bag2 fibres and one damaged chain fibre, and action potentials in one bag2 and four chain fibres. In the whole sample of impaled intrafusal muscle fibres (identified and unidentified) activated by static axons, junctional potentials were recorded from twenty‐three (62.2%), and action potentials from fourteen (37.8%). Stimulation of dynamic gamma axons always elicited junctional potentials. 7. In a number of instances it was possible to examine the ultrastructure of motor endings belonging to the stimulated gamma axon. The myoneural junctions of trail endings supplied by static gamma axons to bag2 and chain fibres were both smooth and folded; the deepest and most regular folding occurred on chain fibres. The terminals of p2 plates supplied to bag1 fibres by dynamic gamma axons had smooth myoneural junctions. © 1978 The Physiological Society
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46.
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47.
  • Bass, Joseph J., et al. (författare)
  • The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor in vivo
  • 2021
  • Ingår i: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 599:3, s. 963-979
  • Tidskriftsartikel (refereegranskat)abstract
    • KEY POINTS:Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy.Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged.In response to VDR-KD mitochondrial function and related gene-set expression is impaired.In vitro VDR knockdown induces myogenic dysregulation occurring through impaired differentiation.These results highlight the autonomous role the VDR has within skeletal muscle mass regulation.Objective: Vitamin-D deficiency is estimated to affect ∼40% of the world's population and has been associated with impaired muscle maintenance. Vitamin-D exerts its actions through the Vitamin-D-receptor (VDR), the expression of which was recently confirmed in skeletal muscle, and its down-regulation is linked to reduced muscle mass and functional decline. To identify potential mechanisms underlying muscle atrophy, we studied the impact of VDR knockdown (KD) on mature skeletal muscle in vivo, and myogenic regulation in vitro in C2C12 cells.Methods: Male Wistar rats underwent in vivo electrotransfer (IVE) to knock down the VDR in hind-limb tibialis anterior (TA) muscle for 10 days. Comprehensive metabolic and physiological analysis was undertaken to define the influence loss of the VDR on muscle fibre composition, protein synthesis, anabolic and catabolic signalling, mitochondrial phenotype, and gene expression. Finally, in vitro lentiviral transfection was used to induce sustained VDR-KD in C2C12 cells to analyse myogenic regulation.Results: Muscle VDR-KD elicited atrophy through a reduction in total protein content, resulting in lower myofibre area. Activation of autophagic processes was observed, with no effect upon muscle protein synthesis or anabolic signalling. Furthermore, RNA-Seq analysis identified systematic down-regulation of multiple mitochondrial respiration related protein and genesets. Finally, in vitro VDR-knockdown impaired myogenesis (cell cycling, differentiation and myotube formation).Conclusion: Taken together, these data indicate a fundamental regulatory role of the VDR in the regulation of myogenesis and muscle mass; whereby it acts to maintain muscle mitochondrial function and limit autophagy.
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48.
  • Bengtsson, Per, et al. (författare)
  • Inhibition of acid formation and stimulation of somatostatin release by cholecystokinin-related peptides in rabbit gastric glands
  • 1989
  • Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 419, s. 765-774
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The purpose of the present study was to investigate the role of somatostatin in the inhibition of acid production induced by caerulein and cholecystokinin (CCK) in isolated rabbit gastric glands. Acid production was estimated by the aminopyrine technique.2. Exogenous somatostatin 14 and somatostatin 28 (10(-7) M) reduced to a similar extent the aminopyrine uptake produced by 5 x 10(-5) M-histamine during the course of 40 min incubation.3. Significant inhibition of histamine-stimulated aminopyrine accumulation occurred at a somatostatin 14 concentration of 10(-9) M.4. Caerulein and CCK octapeptide (10(-13)-10(-7) M) were found to release somatostatin from isolated gastric glands in a dose-dependent manner. The dose-response relationships for somatostatin release and inhibition of aminopyrine uptake were similar. Thus, the half-maximal dose approximations for somatostatin release and inhibition of aminopyrine uptake were 0.5 and 1.4 x 10(-9) M respectively for CCK octapeptide and 0.9 and 2.5 x 10(-11) M for caerulein. Heptadecapeptide gastrin proved to be a very poor releaser of somatostatin in the system used. The CCK octapeptide-induced somatostatin release was time dependent and the concentrations of somatostatin that accumulated in the incubation medium were similar to those of exogenous somatostatin that were needed to evoke inhibition.5. The present results support the concept that cholecystokinin inhibits gastric acid secretion by releasing somatostatin from endocrine-like cells in the gastric mucosa. It is suggested that cholecystokinin-related peptides may play a physiological role in inhibiting gastric acid secretion. A similar role for gastrin is not supported by the present study.
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49.
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50.
  • Bergquist, Filip, 1970, et al. (författare)
  • Role of the commissural inhibitory system in vestibular compensation in the rat.
  • 2008
  • Ingår i: The Journal of physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 586:Pt 18, s. 4441-52
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the role of the vestibular commissural inhibitory system in vestibular compensation (VC, the behavioural recovery that follows unilateral vestibular loss), using in vivo microdialysis to measure GABA levels in the bilateral medial vestibular nucleus (MVN) at various times after unilateral labyrinthectomy (UL). Immediately after UL, in close correlation with the appearance of the characteristic oculomotor and postural symptoms, there is a marked increase in GABA release in the ipsi-lesional MVN. This is not prevented by bilateral flocculectomy, indicating that it is due to hyperactivity of vestibular commissural inhibitory neurones. Over the following 96 h, as VC occurs and the behavioural symptoms ameliorate, the ipsi-lesional GABA levels return to near-normal. Contra-lesional GABA levels do not change significantly in the initial stages of VC, but decrease at late stages so that when static symptoms have abated there remains a significant difference between the MVNs of the two sides. We also investigated the role of the commissural inhibition in Bechterew's phenomenon, by reversibly inactivating the intact contra-lesional labyrinth in compensating animals through superfusion of local anaesthetic on the round window. Transient inactivation of the intact labyrinth elicited the lateralized behaviour described by Bechterew, but did not alter the GABA levels in either MVN, suggesting the involvement of distinct cellular mechanisms. These findings indicate that an imbalanced commissural inhibitory system is a root cause of the severe oculomotor and postural symptoms of unilateral vestibular loss, and that re-balancing of commissural inhibition occurs in parallel with the subsequent behavioural recovery during VC.
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