Myofascial force transmission: muscle relative position and length determine agonist and synergist muscle force.

Equal proximal and distal lengthening of rat extensor digitorum longus (EDL) were studied. Tibialis anterior, extensor hallucis longus, and EDL were active maximally. The connective tissues around these muscle bellies were left intact. Proximal EDL forces differed from distal forces, indicating myofascial force transmission to structures other than the tendons. Higher EDL distal force was exerted (ratio approximately 118%) after distal than after equal proximal lengthening. For proximal force, the reverse occurred (ratio approximately 157%). Passive EDL force exerted at the lengthened end was 7-10 times the force exerted at the nonlengthened end. While kept at constant length, synergists (tibialis anterior + extensor hallucis longus: active muscle force difference approximately -10%) significantly decreased in force by distal EDL lengthening, but not by proximal EDL lengthening. We conclude that force exerted at the tendon at the lengthened end of a muscle is higher because of the extra load imposed by myofascial force transmission on parts of the muscle belly. This is mediated by changes of the relative position of most parts of the lengthened muscle with respect to neighboring muscles and to compartment connective tissues. As a consequence, muscle relative position is a major codeterminant of muscle force for muscle with connectivity of its belly close to in vivo conditions.     

Muscle oxygen consumption,determined by NIRS,in relation to external force and EMG

Local oxygen consumption in a muscle (VO(2)) can be determined by near infrared spectroscopy (NIRS). In principle it should be possible to use this measure to validate musculoskeletal models. However, the relationship between VO(2) and external force, or between VO(2) and surface EMG, as a measure for muscle activity, is hardly known. The aim of this study was: (1) to evaluate the characteristics of the relationship between VO(2) and external moments and (2) to determine whether differences exist between the EMG-moment relationship and the VO(2)-moment relationship. Subjects (n=5) were asked to perform isometric contractions exerting combinations of elbow flexion and pro/supination moments at force levels up to 70% of their maximum. Simultaneous surface-EMG and NIRS measurements were performed on the m. biceps breve (BB) and the m. brachioradialis (BR). A linear relationship was found between EMG and VO(2). For the BB VO(2) and EMG were linearly related to both the flexion moment and the pro/supination moment. However, for the BR only a linear relationship with flexion moment was found. As expected, based on the findings above, the relationship between VO(2) and elbow flexion moment can be described by a linear equation, under the conditions of this study (isometric, and force levels up to 70%). These findings suggest that load sharing is independent of force level and that next to EMG, VO(2) can be used for the validation of musculoskeletal models.     

The relative changes in isometric force and work during fatigue and recovery in isolated toad sartorius muscle

Toad sartorius muscle was subjected to sinusoidal varying length changes at 2 Hz to measure work. Both isometric tetanic force and work per cycle were measured before, during, and after a 3-min fatigue. Both isometric tetanic force and positive work, the work done by the muscle during the shortening part of the cycle, rapidly decreased in parallel in the first 40 s of fatigue. Thereafter, force continued to decrease, but at a slower rate, to about 10% of prefatigue values, whereas positive work levelled off at about 30% of prefatigue values. Negative work, the work done on the muscle during the lengthening part of the cycle, increased during fatigue to the extent that net work became negative. This was due to a prolonged relaxation, which resulted in active force still being generated while the muscle was being stretched. Work and force recovered at about the same rate. Isometric force measurements alone do not give any clear indication that net work will be negative under a particular set of experimental conditions.     

Muscle soreness-induced reduction in force generation is accompanied by increased nitric oxide content and DNA damage in human skeletal muscle

We examined the effect of exercise-induced muscle soreness on maximal force generation, tissue nitric oxide (NO) and 8-hydroxydeoxyguanosine (8-OHdG) content in human skeletal muscle. Female volunteers were assigned to control (C) and muscle soreness (MS) groups (n = 6 in each). MS group performed 200 eccentric muscle actions of the rectus femoris to induce muscle soreness. Maximal force generation was measured 24 h before and after exercise in both groups. Needle biopsy samples were assayed for NO content with electron spin resonance spectroscopy after ex vivo spin trapping, and 8-OHdG content were measured with an enzyme-linked immuno assay. Maximal force decreased by 11+/-5.4% (p < .05) 24 h after exercise in MS group. Muscle soreness increased NO and 8-OHdG contents from their control values of 0.39+/-0.08 arbitrary units and 0.035+/-0.004 pmol/micromol DNA to 0.96+/-0.05 (p < .05) arbitrary units and 0.044+/-0.005 (p < .05) pmol/micromol DNA, respectively. This is the first demonstration that muscle soreness-induced decrease in maximal force generation is a result of an increase in muscular NO content and associated with enhanced formation of 8-OHdG in human skeletal muscle.     

Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity

We investigated the influence of telomere proximity and composition on the expression of an EGFP reporter gene in human cells. In transient transfection assays, telomeric DNA does not repress EGFP but rather slightly increases its expression. In contrast, in stable cell lines, the same reporter construct is repressed when inserted at a subtelomeric location. The telomeric repression is transiently alleviated by increasing the dosage of the TTAGGG repeat factor 1 (TRF1). Upon a prolongated treatment with trichostatin A, the derepression of the subtelomeric reporter gene correlates with the delocalization of HP1α and HP1β. In contrast, treating the cells with 5 azacytidin, a demethylating agent, or with sirtinol, an inhibitor of the Sir2 family of deacetylase, has no apparent effect on telomeric repression. Overall, position effects at human chromosome ends are dependent on a specific higher-order organization of the telomeric chromatin. The possible involvement of HP1 isoforms is discussed.     

Muscle force depends on the amount of transversal muscle loading

Skeletal muscles are embedded in an environment of other muscles, connective tissue, and bones, which may transfer transversal forces to the muscle tissue, thereby compressing it. In a recent study we demonstrated that transversal loading of a muscle with 1.3 N cm⁻² reduces maximum isometric force (F_im) and rate of force development by approximately 5% and 25%, respectively. The aim of the present study was to examine the influence of increasing transversal muscle loading on contraction dynamics.     

Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content.

The purpose of this investigation was to validate that in vivo measurement of skeletal muscle attenuation (MA) with computed tomography (CT) is associated with muscle lipid content. Single-slice CT scans performed on phantoms of varying lipid concentrations revealed good concordance between attenuation and lipid concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1 g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The test-retest coefficient of variation for two CT scans performed in six volunteers was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the methodological variability is low. Lean subjects had significantly higher (P < 0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU) and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2 diabetic subjects had lower MA values that were not different from obese nondiabetic subjects. There was also good concordance between MA in midthigh and midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r = 0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients with Type 2 diabetes mellitus, reduced MA was associated with increased muscle fiber lipid content determined with histological oil red O staining (P = -0.43, P < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in percutaneous biopsy specimens from vastus lateralis was also associated with MA (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in vivo determined by CT is related to its lipid content and that this noninvasive method may provide additional information regarding the association between muscle composition and muscle function.     

Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy

This study evaluated the hypothesis that, due to functional and structural differences, the apparent elastic modulus and viscous behavior of cardiac and skeletal muscle and vascular endothelium would differ. To accurately determine the elastic modulus, the contribution of probe velocity, indentation depth, and the assumed shape of the probe were examined. Hysteresis was observed at high indentation velocities arising from viscous effects. Irreversible deformation was not observed for endothelial cells and hysteresis was negligible below 1 μm/s. For skeletal muscle and cardiac muscle cells, hysteresis was negligible below 0.25 μm/s. Viscous dissipation for endothelial and cardiac muscle cells was higher than for skeletal muscle cells. The calculated elastic modulus was most sensitive to the assumed probe geometry for the first 60 nm of indentation for the three cell types. Modeling the probe as a blunt cone–spherical cap resulted in variation in elastic modulus with indentation depth that was less than that calculated by treating the probe as a conical tip. Substrate contributions were negligible since the elastic modulus reached a steady value for indentations above 60 nm and the probe never indented more than 10% of the cell thickness. Cardiac cells were the stiffest (100.3±10.7 kPa), the skeletal muscle cells were intermediate (24.7±3.5 kPa), and the endothelial cells were the softest with a range of elastic moduli (1.4±0.1 to 6.8±0.4 kPa) depending on the location of the cell surface tested. Cardiac and skeletal muscle exhibited nonlinear elastic behavior. These passive mechanical properties are generally consistent with the function of these different cell types.     

The vector of jaw muscle force as determined by computer-generated three dimensional simulation: a test of Greaves' model

We present results from a detailed three-dimensional finite element analysis of the cranium and mandible of the Australian dingo (Canis lupus dingo) during a range of feeding activities and compare results with predictions based on two-dimensional methodology [Greaves, W.S., 2000. Location of the vector of jaw muscle force in mammals. Journal of Morphology 243, 293-299]. Greaves showed that the resultant muscle vector intersects the mandible line slightly posterior to the lower third molar (m3). Our work demonstrates that this is qualitatively correct, although the actual point is closer to the jaw joint. We show that it is theoretically possible for the biting side of the mandible to dislocate during unilateral biting; however, the bite point needs to be posterior to m3. Simulations show that reduced muscle activation on the non-biting side can considerably diminish the likelihood of dislocation with only a minor decrease in bite force during unilateral biting. By modulating muscle recruitment the animal may be able to maximise bite force whilst minimising the risk of dislocation.     

The relative position of RyR feet and DHPR tetrads in skeletal muscle

In skeletal muscle, L-type calcium channels (or dihydropyridine receptors, DHPRs) are coupled functionally to the calcium release channels of the sarcoplasmic reticulum (or ryanodine receptors, RyRs) within specialized structures called calcium release units (CRUs). The functional linkage requires a specific positioning of four DHPRs in correspondence of the four identical subunits of a single RyR type 1. Four DHPRs linked to the four binding sites of the RyR1 cytoplasmic domain (or foot), define the corners of a square, constituting a tetrad. RyRs self-assemble into ordered arrays and by associating with them, DHPRs also assemble into ordered arrays. The approximate location of the four DHPRs relative to the four identical subunits of a RyR-foot can be predicted on the basis of the relative position of tetrads and feet within the arrays. However, until recently one vital piece of information has been lacking: the orientation of the two arrays relative to one another. In this work we have defined the relative orientation of the RyR and DHPR arrays by directly superimposing replicas of rotary shadowed images of rows of feet, obtained from isolated SR vesicles, and replicas of tetrad arrays obtained by freeze-fracture. If the orientation for the two sets of images is carefully maintained, the superimposition provides specific constraints on the DHPR-RyR relative position.     

A mathematical model for predicting relative muscle force with a perturbation analysis of selected muscle parameters

A mathematical model is presented that predicts relative muscle forces using a minimum of experimentally derived input data. Tests of this model against literature values for maximum muscle force of four cat hindlimb muscles show a maximum error of only 5%. A perturbation analysis using this model demonstrates its sensitivity and applicability, as well as the congruence between this model and previous theoretical discussions of muscle function.     

The relative position of EDL muscle affects the length of sarcomeres within muscle fibers: experimental results and finite-element modeling

BACKGROUND: Effects of extramuscular connective tissues on muscle force (experimentally measured) and lengths of sarcomeres (modeled) were investigated in rat. It was hypothesized that changes of muscle-relative position affect the distribution of lengths of sarcomeres within muscle fibers. METHOD OF APPROACH: The position of extensor digitorum longus muscle (EDL) relative to intact extramuscular connective tissues of the anterior crural compartment was manipulated without changing its muscle-tendon complex length. RESULTS: Significant effects of EDL muscle relative position on proximal and distal EDL forces were found, indicating changes of extramuscular myofascial force transmission. EDL isometric force exerted at its proximal and distal tendons differed significantly. Finite-element modeling showed that the distribution of lengths of sarcomeres is altered by changes of muscle-relative position. CONCLUSIONS: It is concluded that forces exerted on a muscle via extramuscular myofascial pathways augment distributions of lengths of sarcomeres within that muscle.     

Human skeletal muscle carnitine palmitoyltransferase I activity determined in isolated intact mitochondria

This study was designed to compare theactivity of skeletal muscle carnitine palmitoyltransferase I (CPT I) intrained and inactive men (n = 14) andwomen (n = 12). CPT Iactivity was measured in intact mitochondria, isolated from needlebiopsy vastus lateralis muscle samples (~60 mg). The variability ofCPT I activity determined on two biopsy samples from the same leg onthe same day was 4.4, whereas it was 7.0% on two biopsy samples fromthe same leg on different days. The method was sensitive to the CPT Iinhibitor malonyl-CoA (88% inhibition) and therefore specific for CPTI activity. The mean CPT I activity for all 26 subjects was 141.1 ± 10.6 µmol · min¹ · kgwet muscle (wm)¹ and wasnot different when all men vs. all women (140.5 ± 15.7 and 142.2 ± 14.5 µmol · min¹ · kgwm¹, respectively) were compared. However, CPT Iactivity was significantly higher in trained vs. inactive subjects forboth men (176.2 ± 21.1 vs. 104.1 ± 13.6 µmol · min¹ · kgwm¹) and women (167.6 ± 14.1 vs. 91.2 ± 9.5 µmol · min¹ · kgwm¹). CPT I activity was also significantly correlatedwith citrate synthase activity (all subjects,r = 0.76) and maximal oxygen consumption expressed in milliliters per kilogram per minute (all subjects, r = 0.69). Theresults of this study suggest that CPT I activity can be accurately andreliably measured in intact mitochondria isolated from human musclebiopsy samples. CPT I activity was not affected by gender, and higheractivities in aerobically trained subjects appeared to be the result ofincreased mitochondrial content in both men and women.

     

Continuous percutaneous measurement by laser-Doppler flowmetry of skeletal muscle microcirculation at varying levels of contraction force determined electromyographically

Microcirculation in the upper portion of the trapezius muscle was measured percutaneously by continuous laser-Doppler flowmetry (LDF) during two 10-min series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Stepwise increased contraction was induced by keeping the arms straight and elevated at 30, 60, 90 and 135°, which was repeated with a 1-kg load carried in each hand. Thereafter, fatigue and recovery were recorded while the subject kept her arms straight and elevated at 45° carrying the 1-kg hand load as long as possible, followed by rest with arms hanging and no load. A group of 16 healthy women of different ages was studied. Signal processing was done on line using a 386 SX computer. The LDF- and root-mean-square (rms) EMG signals were normalized. Spectrum analyses of EMG mean power frequency (MPF) and median spectrum frequency were performed. The rms-EMG increased significantly with an increase in the calculated shoulder torque (r=0.75). Accumulated local fatigue was indicated by a decrease in MPF with increased shoulder angle and added load (r = –0.54). Blood flow increased with increased shoulder angle (r=0.82, with hand loadr=0.62) and with increased shoulder torque (r=0.72), and also showed a significant increase with increased EMG activity (r=0.74). The LDF showed a negative correlation to MPF (r= –0.67), with increased values when MPF was lowered. During the endurance test, a moderate increase of LDF occurred which reached its maximum during the 1st min of recovery. Then, a slow return to the base level was recorded. The ability to increase the flow in the microcirculation with increasing muscle load was not diminished with age.     

Invasion of drug and pesticide resistance is determined by a trade-off between treatment efficacy and relative fitness

Drug and pesticide resistance are among the most pressing problems facing public, animal and plant health today. In order to design effective resistance management strategies it is imperative to identify criteria for the invasion of resistant forms. Two key determinants of the ability of a resistant pest or pathogen to invade are any inherent fitness costs to the resistant subpopulation, and the effect of treatment on the sensitive and resistant subpopulations. For two generic classes of model which encompass many of the standard models in this field, we summarize relative fitness and treatment efficacy via two simple parameters, and demonstrate that invasion of resistance depends critically on a trade-off between them. Thresholds for invasion are derived when the effect of treatment is a constant reduction in the life-history parameters of the pathogen, and when treatment efficacy varies periodically with the repeated application and subsequent decay of the chemical.     

Skeletal muscle performance determined by modulation of number of myosin motors rather than motor force or stroke size

Skeletal muscle can bear a high load at constant length, or shorten rapidly when the load is low. This force-velocity relationship is the primary determinant of muscle performance in vivo. Here we exploited the quasi-crystalline order of myosin II motors in muscle filaments to determine the molecular basis of this relationship by X-ray interference and mechanical measurements on intact single cells. We found that, during muscle shortening at a wide range of velocities, individual myosin motors maintain a force of about 6 pN while pulling an actin filament through a 6 nm stroke, then quickly detach when the motor reaches a critical conformation. Thus we show that the force-velocity relationship is primarily a result of a reduction in the number of motors attached to actin in each filament in proportion to the filament load. These results explain muscle performance and efficiency in terms of the molecular mechanism of the myosin motor.     

Regulation of catch muscle by twitchin phosphorylation: effects on force, ATPase, and shortening.

Recent experiments on permeabilized anterior byssus retractor muscle (ABRM) of Mytilus edulis have shown that phosphorylation of twitchin releases catch force at pCa > 8 and decreases force at suprabasal but submaximum [Ca2+]. Twitchin phosphorylation decreases force with no detectable change in ATPase activity, and thus increases the energy cost of force maintenance at subsaturating [Ca2+]. Similarly, twitchin phosphorylation causes no change in unloaded shortening velocity (Vo) at any [Ca2+], but when compared at equal submaximum forces, there is a higher Vo when twitchin is phosphorylated. During calcium activation, the force-maintaining structure controlled by twitchin phosphorylation adjusts to a 30% Lo release to maintain force at the shorter length. The data suggest that during both catch and calcium-mediated submaximum contractions, twitchin phosphorylation removes a structure that maintains force with a very low ATPase, but which can slowly cycle during submaximum calcium activation. A quantitative cross-bridge model of catch is presented that is based on modifications of the Hai and Murphy (1988. Am. J. Physiol. 254:C99-C106) latch bridge model for regulation of mammalian smooth muscle.