Reflex activation of locust flight motoneurones by proprioceptors responsive to muscle contractions

 This report investigates the reflex activation of locust flight motoneurones following their spiking activity. As shown elsewhere, an electrical stimulus applied to a flight muscle produces multiple waves of delayed excitation in wing elevator and depressor motoneurones. Nerve ablation experiments show that this response is initiated by the mechanical movement of the stimulated muscle, and not the antidromic spike evoked in the motoneurone. The delayed excitation still occurs in the absence of inputs from the wing receptor systems, and also when all other sources of afferent feedback are abolished, excepting thoracic nerve 2. Following complete deafferentation, spikes in flight motoneurones had no influence on other flight motoneurones. Numerous afferents in the purely sensory nerve 2 are excited by flight muscle contractions. The responses are consistent for repeated contractions of the same muscle, but differ when other muscles are stimulated. During tethered flight, changes in the activation of single flight muscles are reflected in changes of the nerve 2 discharge pattern. Electrical stimulation of this nerve causes delayed excitation of flight motoneurones, and can initiate flight activity. It is suggested that internal proprioceptors, such as those associated with nerve 2, will contribute to shaping the final motor output for flight behaviour. Accepted: 24 April 1996     

Metabolic properties of human acetylcholine receptors can be characterized on cultured human muscle

Experiments examining acetylcholine receptor (AChR) metabolism in tissue culture have hitherto been limited to animal systems. For many studies, the human AChR on human skeletal muscle provides a more physiologic target. However, previous studies suggested that the levels of AChR produced on cultured human muscle were inadequate for metabolic studies. We demonstrate here that the metabolism of human acetylcholine receptors can be analysed on pure human muscle fibers that develop in tissue culture. Degradation of AChR follows first-order kinetics and is inhibited 85% by leupeptin, demonstrating that proteolysis of human AChR occurs in the lysosome. New AChR continue to appear on the cell surface for 3 h in the presence of cycloheximide, indicating the existence of a pool of intracellular AChR destined for the cell membrane. This pool is equivalent to approximately one-third of the AChR present on the surface of the cell. At any given time, the rate of AChR accumulation on the cell surface can be quantitatively accounted for by the rates of synthesis and degradation. Our results demonstrate that studies on the effects of hormones, neurotoxins or antibodies from patients with autoimmune neuromuscular diseases are now possible with human AChR which develop on intact human muscle myotubes formed in tissue culture.     

Selective fatigue of fast motor units after electrically elicited muscle contractions.

The aim of the present study was to elucidate the electrophysiological manifestations of selective fast motor unit (MU) activation by electrical stimulation (ES) of knee extensor muscles. In six male subjects, test contraction measurement at 40% maximal voluntary contraction (MVC) was performed before and at every 5 min (5, 10, 15 and 20 min) during 20-min low intensity intermittent exercise of either ES or voluntary contractions (VC) at 10% MVC (5-s isometric contraction and 5-s rest cycles). Both isolated intramuscular MU spikes obtained from three sets of bipolar fine-wire electrodes and surface electromyogram (EMG) were simultaneously recorded and were analyzed by means of a computer-aided intramuscular spike amplitude-frequency analysis and frequency power spectral analysis, respectively. Results indicated that mean MU spike amplitude, particularly those MUs with relatively large amplitude, was significantly reduced while those MUs with small spike amplitude increased their firing rate during the 40% MVC test contraction after the ES. This was accompanied by the increased amplitude of surface EMG (rmsEMG). However, no such significant changes in the intramuscular and surface EMGs were observed after VC. These findings indicated differential MU activation patterns in terms of MU recruitment and rate coding characteristics during ES and VC, respectively. Our data strongly suggest the possibility of "an inverse size principle" of MU recruitment during ES.     

Trunk muscle reflexes are elicited by small continuous perturbations in healthy subjects and patients with low-back pain

Low-back pain (LBP) has been recognized as the leading cause of disability worldwide. Lumbar instability has been considered as an important mechanism of LBP and one potential contributor to lumbar stability is trunk muscle reflex activity. However, due to the differences in experimental paradigms used to quantify trunk mechanics and trunk reflexes it remains unclear as to what extent the reflex pathway contributes to overall lumbar stability. The goal of this work was to determine to what extent reflexes of various trunk muscles were elicited by the small continuous perturbations normally used to quantify trunk mechanics. Electromyographic (EMG) activity was measured bilaterally from 3 trunk extensor muscles and 3 trunk flexor muscles at four epochs: 25–50 ms, 50–75 ms, 75–100 ms and 100–125 ms following each perturbation. Reflex activity was seen in all muscles as 34 of the 48 muscle-epoch combinations showed a significant reflex response to either perturbations in the forward or backward direction. However, the reflex EMG activity did not correlate with mechanical estimates of the reflex response. Thus, even though reflexes are indeed elicited by the small perturbations used to quantify trunk mechanics, their exact contribution to overall lumbar stability remains unknown.     

HCV infective virions can be carried by human platelets

It has been previously demonstrated that platelets (PLTs) can bind and transport HIV-1 infectious virions. Hepatitis C virus (HCV)-HIV-1 co-infection occurs frequently among users of illicit intravenous drugs, thereby increasing the severity of HIV disease and the evolution towards chronic active hepatitis and hepatocellular carcinoma of HCV-related hepatitis. In the present study we investigated whether or not PLTs can carry HCV, and studied the binding mechanisms. Purified PLTs, obtained from healthy donors, HCV negative and HIV negative, were adsorbed with HCV-containing serum and then employed to infect a THP-1 monocytoid cell line. Replication of HCV was observed as shown by positivity for the E2 antigen within THP-1 cells, by indirect immunofluorescence; moreover, HCV-RNA was detected in supernatants of THP-1 cells at day 7 post-incubation with HCV-adsorbed PLTs. The binding of HCV to PLTs seems to involve fibronectin (FN), as already shown in the case of HIV-1. Indeed, treatment with RGD (Gly-Arg-Gly-Asp-Ser), the key oligopeptide of FN binding, inhibits the ability of HCV to be carried by PLTs in infective forms; the same phenomenon occurs with Mabs to FN. Moreover the infection of THP-1 cells seems to increase FN surface expression, as demonstrated by immunofluorescence tests.     

Influence of a valgus knee brace on muscle activation and co-contraction in patients with medial knee osteoarthritis

The purpose of this study was to analyse the effect of a valgus knee orthosis designed for patients with knee osteoarthritis on the electromyographic activity (EMG) of seven muscles of the lower limb during gait. Twelve patients with medial knee osteoarthritis walked on a treadmill in three different conditions: without orthosis, with a knee orthosis in 4° valgus adjustment and with an orthosis in a neutral flexible adjustment. Root-mean-square (RMS) was analysed in each condition during a 150 ms pre-activation phase and during the stance phase of gait, which was divided in four sub-phases. In addition, co-contraction ratios (CCRs) were calculated between extensor/flexor, medial/lateral muscles and between agonist and antagonist muscle pairs. Significant decreases in muscle activity and CCRs were observed with the use of the knee orthosis in both adjustments compared to the condition without orthosis. Using the valgus brace, medial/lateral CCR decreased significantly during the late stance and the flexor/extensor CCR decreased significantly during the loading phase and late stance. Decreases of muscle pairs CCRs were observed with the neutral flexible adjustment. The results support the theory of a possible beneficial effect of knee braces in reducing knee loading by decreasing muscle activation and co-contraction levels, which could contribute to decelerate disease progression in patients with knee osteoarthritis.     

Repeated contractions alter the geometry of human skeletal muscle.

The aim of this study was to investigate the effect of repeated contractions on the geometry of human skeletal muscle. Six men performed two sets (sets A and B) of 10 repeated isometric plantarflexion contractions at 80% of the moment generated during plantarflexion maximal voluntary contraction (MVC), with a rest interval of 15 min between sets. By use of ultrasound, the geometry of the medial gastrocnemius (MG) muscle was measured in the contractions of set A and the displacement of the MG tendon origin in the myotendinous junction was measured in the contractions of set B. In the transition from the 1st to the 10th contractions, the fascicular length at 80% of MVC decreased from 34 +/- 4 (means +/- SD) to 30 +/- 3 mm (P < 0.001), the pennation angle increased from 35 +/- 3 to 42 +/- 3 degrees (P < 0.001), the myotendinous junction displacement increased from 5 +/- 3 to 10 +/- 3 mm (P < 0.001), and the average fascicular curvature remained constant (P > 0.05) at approximately 4.3 m(-1). No changes (P > 0.05) were found in fascicular length, pennation angle, and myotendinous junction displacement after the fifth contraction. Electrogoniometry showed that the ankle rotated by approximately 6.5 degrees during contraction, but no differences (P > 0.05) were obtained between contractions. The present results show that repeated contractions induce tendon creep, which substantially affects the geometry of the in-series contracting muscles, thus altering their potential for force and joint moment generation.     

The influence of knee varus and valgus on quadriceps muscle activity changes induced by stretching and kneeling

This study aimed to determine the influence of knee varus (VARUS) and valgus (VALGUS) on the differences in individual quadriceps muscle (QM) activity during knee extension maximum voluntary isometric contractions (MVICs) and sit/stand transitions and on the changes in individual QM activity during sit/stand transitions after QM stretching and kneeling. Ten young healthy males each with VARUS and VALGUS were included. The electromyography signals of the vastus medialis (VM), vastus lateralis, and rectus femoris were recorded during sit/stand transitions before and after rest, stretching, and kneeling and during knee extension MVICs after rest. The individual muscle-to-total muscle activity ratio was assessed. The VARUS group exhibited a significantly higher VM muscle activity ratio in the sit-to-stand and stand-to-sit tasks than in knee extension MVICs (p = 0.004 and p = 0.044, respectively) and a tendency that the VM muscle activity ratio increased in the sit-to-stand task after stretching (p = 0.051), whereas the VALGUS group exhibited no significance. Individuals with VARUS required high VM muscle activity ratios during sit/stand transitions. Future studies should be conducted to determine whether habitual sit-to-stand exercises after QM stretching are effective in preventing knee medial osteoarthritis development in individuals with VARUS.     

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle.

Prostaglandins are known to be involved in the regulation of local blood flow within human skeletal muscles during exercise, and the concentration of prostaglandins increases locally and systemically in response to exercise. The systemic release of prostaglandins can be inhibited by oral intake of nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled. Microdialysis enables determination of local concentrations of water-soluble substances within the tissue. In the present study, the microdialysis method was used to infuse NSAIDs locally into human skeletal muscles producing a local block of prostaglandin formation. In addition, the graded blockade at various distances from the infusion site within the muscle during rest, exercise and recovery was determined. Microdialysis was performed in thigh muscles (vastus lateralis muscle) in six healthy men. One of the microdialysis catheters was used to block prostaglandin synthesis by infusion of the NSAID indomethacin. Additional catheters were placed 1 and 4 cm away from the infusion and in the contralateral leg (working control). Following 2 h of rest, the subjects performed 200 maximal eccentric contractions with each leg followed by 3 h of rest. The study revealed that infusion of NSAID reduced local prostaglandin E(2) concentration by approximately 30-50% (4 cm away from the infusion) and 85% (1 cm away from the infusion) compared with the contralateral (unblocked) thigh muscle. In conclusion, the present study shows that infusion of NSAIDs into human muscle via microdialysis catheters results in a graded blockade of prostaglandin synthesis.     

Characteristics of human knee muscle coordination during isometric contractions in a standing posture: The effect of limb task

Different functional roles for the hands have been demonstrated, however leg control is not as well understood. The purpose of the present study was to evaluate bilateral knee neuromuscular control to determine if the limb receiving greater attention would have more well-tuned control compared to an unattended limb. Surface electrodes were placed on seven muscles of each limb, before standing on two force platforms. Visual feedback was given of the forces and moments of the “focus limb,” but not the “unattended limb.” Static isometric forces were matched with their focus limb, requiring their unattended limb to push in the opposite direction, using a combination of forward–backward–medial–lateral shear forces while muscle activity was collected bilaterally. There was a significant main effect for limb task (p = 0.02), with the medial hamstrings being more specific (p = 0.001) while performing the unattended limb and the lateral hamstring being more well-tuned (p = 0.007) while performing the focus limb task. The focus limb’s medial and lateral gastrocnemius were principally active in the forwards direction, but only the unattended limb’s lateral gastrocnemius was active in the backwards direction. Findings suggest unique neuromuscular control strategies are used for the legs depending on limb task.     

Strategies of muscular support of varus and valgus isometric loads at the human knee

In this paper we studied how subjects activate their muscles in response to static varus and valgus loads at the knee. The muscles' contributions to the external moments were estimated using an EMG driven biomechanical model of the knee. The individual muscle activation and loading patterns were examined to identify the strategies that the nervous system uses to support varus and valgus knee moments. It was found that the (1) co-contraction of the hamstrings and quadriceps, and (2) activation of the gracilis and tensor fascia lata increased with the increasing magnitude of the varus and valgus moments. These 2 activation patterns provided positive support of valgus and varus loads at the knee The sartorius appears to be activated to provide positive support of valgus loads at the knee, whereas during varus moments this muscle increases the varus load on the knee, i.e. provides negative support. Generally, the hamstrings and quadriceps co-contraction contributed to most of the muscular support of the varus and valgus moments. In addition, co-contraction supported 11-14% of the external moment in pure varus and pure valgus respectively. It appears that there are activation strategies with the specific purpose to support varus and valgus moments, albeit small, which suggest dual goals of the neuromotor system during the support of varus and valgus moments.     

The mode of myofibril remodelling in human skeletal muscle affected by DOMS induced by eccentric contractions

Myofibrillar Z-disc streaming and loss of the desmin cytoskeleton are considered the morphological hallmarks of eccentric contraction-induced injury. The latter is contradicted by recent studies where a focal increase of desmin was observed in biopsies taken from human muscles with DOMS. In order to determine the effects of eccentric contraction-induced alterations of the myofibrillar Z-disc, we examined the distribution of alpha-actinin, the Z-disc portion of titin and the nebulin NB2 region in relation to actin and desmin in DOMS biopsies. In biopsies taken 2-3 days and 7-8 days after exercise, we observed a significantly higher number of fibres showing focal areas lacking staining for alpha-actinin, titin and nebulin than in biopsies taken from control or 1 h after exercise. None of these proteins were part of Z-disc streamings but instead they were found in distinct patterns in areas characterised by altered staining for desmin and actin. These were preferentially seen in regions with increased numbers of sarcomeres in parallel myofibrils. We propose that these staining patterns represent different stages of sarcomere formation. These findings therefore support our previous suggestion that muscle fibres subjected to eccentric contractions adapt to unaccustomed activity by the addition of new sarcomeres.     

Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain. However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional mitochondria and that the level of ROS production is higher in young compared to aged muscle. Accordingly, we could not find any increase in oxidative modification of proteins in muscle from elderly donors. However, the accumulation of lipofuscin was identified as a robust marker of human muscle aging. The data support a model, where ROS-induced molecular damage is continuously removed, preventing the accumulation of dysfunctional mitochondria despite ongoing ROS production.     

Repetitive eccentric muscle contractions increase torque unsteadiness in the human triceps brachii

Torque steadiness and low-frequency fatigue (LFF) were examined in the human triceps brachii after concentric or eccentric fatigue protocols. Healthy young males (n = 17) performed either concentric or eccentric elbow extensor contractions until the eccentric maximal voluntary torque decreased to 75% of pre-fatigue for both (concentric and eccentric) protocols. The number of concentric contractions was greater than the number of eccentric contractions needed to induce the same 25% decrease in eccentric MVC torque (52.2 ± 2.9 vs. 41.5 ± 2.1 for the concentric and eccentric protocols, respectively, p < .01). The extent of peripheral fatigue was ～12% greater after the concentric compared to the eccentric protocol (twitch amplitude), whereas LFF (increase in double pulse torque/single pulse torque), was similar across protocols. Steadiness, or the ability for a subject to hold a submaximal isometric contraction, was ～20 % more impaired during the Ecc protocol (p = .052). Similarly, the EMG activity required to hold the torque steady was nearly 20% greater after the eccentric compared to concentric protocol. These findings support that task dependent eccentric contractions preferentially alter CNS control during a precision based steadiness task.     

Nonisometric behavior of fascicles during isometric contractions of a human muscle

Fascicle length, pennation angle, and tendonelongation of the human tibialis anterior were measured in vivo byultrasonography. Subjects (n = 9) wererequested to develop isometric dorsiflexion torque gradually up tomaximal at the ankle joint angle of 20° plantarflexion from theanatomic position. Fascicle length shortened from 90 ± 7 to 76 ± 7 (SE) mm, pennation angle increased from 10 ± 1 to 12 ± 1°, and tendon elongation increased up to 15 ± 2 mm with gradedforce development up to maximum. The tendon stiffness increased withincreasing tendon force from 10 N/mm at 0-20 N to 32 N/mm at240-260 N. Young's modulus increased from 157 MPa at 0-20 Nto 530 MPa at 240-260 N. It can be concluded that, in isometriccontractions of a human muscle, mechanical work, some of which isabsorbed by the tendinous tissue, is generated by the shortening ofmuscle fibers and that ultrasonography can be used to determine thestiffness and Young's modulus for human tendons.