Muscle shortening velocity depends on tissue inertia and level of activation during submaximal contractions.
ABSTRACT: In order to perform external work, muscles must do additional internal work to deform their tissue, and in particular, to overcome the inertia due to their internal mass. However, the contribution of the internal mass within a muscle to the mechanical output of that muscle has only rarely been studied. Here, we use a dynamic, multi-element Hill-type muscle model to examine the effects of the inertial mass within muscle on its contractile performance. We find that the maximum strain-rate of muscle is slower for lower activations and larger muscle sizes. As muscle size increases, the ability of the muscle to overcome its inertial load will decrease, as muscle tension is proportional to cross-sectional area and inertial load is proportional to mass. Thus, muscles that are larger in size will have a higher inertial cost to contraction. Similarly, when muscle size and inertial load are held constant, decreasing muscle activation will increase inertial cost to contraction by reducing muscle tension. These results show that inertial loads within muscle contribute to a slowing of muscle contractile velocities (strain-rates), particularly at the submaximal activations that are typical during animal locomotion.
Project description:At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O2 to the mitochondria. Accordingly, intracellular O2 tension (PmbO2) markedly declines in order to increase muscle O2 uptake (mVO2). However, whether the change in PmbO2 during muscle contraction modulates mVO2 and whether the O2 release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O2 saturation of Mb (SmbO2) and PmbO2 kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min × 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the VmO2peak significantly increased by 32%. Although the PmbO2 during muscle contraction did not affect the increased mVO2 in endurance-trained muscle, the O2 release rate from Mb increased because of the increased Mb concentration and faster decremental rate in SmbO2 at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster VO2 kinetics in endurance-trained muscle.
Project description:We evaluated whether the central nervous system (CNS) chooses muscle activations not only to achieve behavioral goals but also to minimize stresses and strains within joints. We analyzed the coordination between quadriceps muscles during locomotion in rats before and after imposing a lateral force on the patella. Vastus lateralis (VL) and vastus medialis (VM) in the rat produce identical knee torques but opposing mediolateral patellar forces. If the CNS regulates internal joint stresses, we predicted that after imposing a lateral patellar load by attaching a spring between the patella and lateral femur, the CNS would reduce the ratio between VL and VM activation to minimize net mediolateral patellar forces. Our results confirmed this prediction, showing that VL activation was reduced after attaching the spring whereas VM and rectus femoris (RF) activations were not significantly changed. This adaptation was reversed after the spring was detached. These changes were not observed immediately after attaching the spring but only developed after 3-5 days, suggesting that they reflected gradual processes rather than immediate compensatory reflexes. Overall, these results support the hypothesis that the CNS chooses muscle activations to regulate internal joint variables.
Project description:Most striated muscles generate steady contractile tension when activated, but some preparations, notably cardiac myocytes and slow-twitch fibers, may show spontaneous oscillatory contractions (SPOC) at low levels of activation. We have provided what we believe is new evidence that SPOC is a property of the contractile system at low actin-myosin affinity, whether caused by a thin-filament regulatory system or by other means. We present a quantitative single-sarcomere model for isotonic SPOC in skeletal muscle with three basic ingredients: i), actin and myosin filaments initially in partial overlap, ii), stretch activation by length-dependent changes in the lattice spacing, and iii), viscoelastic passive tension. Modeling examples are given for slow-twitch and fast-twitch fibers, with periods of 10 s and 4 s respectively. Isotonic SPOC occurs in a narrow domain of parameter values, with small minimum and maximum values for actin-myosin affinity, a minimum amount of passive tension, and a maximum transient response rate that explains why SPOC is favored in slow-twitch fibers. The model also predicts the contractile, relaxed and SPOC phases as a function of phosphate and ADP levels. The single-sarcomere model can also be applied to a whole fiber under auxotonic and fixed-end conditions if the remaining sarcomeres are treated as a viscoelastic load. Here the model predicts an upper limit for the load stiffness that leads to SPOC; this limit lies above the equivalent loads expected from the rest of the fiber.
Project description:The intracellular Ca(2+) concentration ([Ca(2+)](i)) in skeletal muscles must be rapidly regulated during the excitation-contraction-relaxation process. However, the signalling components involved in such rapid Ca(2+) movement are not fully understood. Here we report that mice deficient in the newly identified PtdInsP (phosphatidylinositol phosphate) phosphatase MIP/MTMR14 (muscle-specific inositol phosphatase) show muscle weakness and fatigue. Muscles isolated from MIP/MTMR14(-/-) mice produced less contractile force, had markedly prolonged relaxation and showed exacerbated fatigue relative to normal muscles. Further analyses revealed that MIP/MTMR14 deficiency resulted in spontaneous Ca(2+) leakage from the internal store - the sarcoplasmic reticulum. This was attributed to decreased metabolism (dephosphorylation) and the subsequent accumulation of MIP/MTMR14 substrates, especially PtdIns(3,5)P(2) and PtdIns (3,4)P(2). Furthermore, we found that PtdIns(3,5)P(2) and PtdIns(3,4)P(2) bound to, and directly activated, the Ca(2+) release channel (ryanodine receptor 1, RyR1) of the sarcoplasmic reticulum. These studies provide the first evidence that finely controlled PtdInsP levels in muscle cells are essential for maintaining Ca(2+) homeostasis and muscle performance.
Project description:Skeletal muscle adapts to different patterns of motor nerve activity by alterations in gene expression that match specialized properties of contraction, metabolism, and muscle mass to changing work demands (muscle plasticity). Calcineurin, a calcium/calmodulin-dependent, serine-threonine protein phosphatase, has been shown to control programs of gene expression in skeletal muscles, as in other cell types, through the transcription factor nuclear factor of activated T cells (NFAT). This study provides evidence that the function of NFAT as a transcriptional activator is regulated by neuromuscular stimulation in muscles of intact animals and that calcium influx from the transient receptor potential (TRPC3) channel is an important determinant of NFAT activity. Expression of TRPC3 channels in skeletal myocytes is up-regulated by neuromuscular activity in a calcineurin-dependent manner. These data suggest a mechanism for cellular memory in skeletal muscles whereby repeated bouts of contractile activity drive progressively greater remodeling events.
Project description:The objective was to better understand how a series compliance alters contraction kinetics and power output of muscle to enhance the work done on a load. A mathematical model was created in which a gravitational point load was connected via a linear spring to a muscle (based on the contractile properties of the sartorius of leopard frogs, Rana pipiens). The model explored the effects of load mass, tendon compliance, and delay between onset of contraction and release of the load (catch) on lift height and power output as measures of performance. Series compliance resulted in increased lift height over a relatively narrow range of compliances, and the effect was quite modest without an imposed catch mechanism unless the load was unrealistically small. Peak power of the muscle-tendon complex could be augmented up to four times that produced with a muscle alone, however, lift height was not predicted by peak power. Rather, lift height was improved as a result of the compliance synchronizing the time courses of muscle force and shortening velocity, in particular by stabilizing shortening velocity such that muscle power was sustained rather than rising and immediately falling. With a catch mechanism, enhanced performance resulted largely from energy storage in the compliance during the period of catch, rather than increased time for muscle activation before movement commenced. However, series compliance introduced a trade-off between work done before versus after release of the catch. Thus, the ability of tendons to enhance locomotor performance (i.e. increase the work done by muscle) appears dependent not only on their established role in storing energy and increasing power, but also on their ability to modulate the kinetics of muscle contraction such that power is sustained over more of the contraction, and maximizing the balance of work done before versus after release of a catch.
Project description:No effective treatment exists for patients with X-linked myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1?4 and Mtm1 p.R69C mice model severely and moderately symptomatic XLMTM, respectively, due to differences in the degree of myotubularin deficiency. Contractile function of intact extensor digitorum longus (EDL) and soleus muscles from Mtm1?4 mice, which produce no myotubularin, is markedly impaired. Contractile forces generated by chemically skinned single fiber preparations from Mtm1?4 muscle were largely preserved, indicating that weakness was largely due to impaired excitation contraction coupling. Mtm1 p.R69C mice, which produce small amounts of myotubularin, showed impaired contractile function only in EDL muscles. Short-term replacement of myotubularin with a prototypical targeted protein replacement agent (3E10Fv-MTM1) in Mtm1?4 mice improved contractile function and muscle pathology. These promising findings suggest that even low levels of myotubularin protein replacement can improve the muscle weakness and reverse the pathology that characterizes XLMTM.
Project description:Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measurement, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (P max), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power generation during concentric contractions in the extensor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P 0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, <50 %, respectively). Mice at other ages (5-32 months) were also tested for regression modeling. We hypothesized and found that power decreased with age not only at P max but also over the load range. Importantly, we found greater age-associated deficits in both power and velocity when the muscles were contracting concentrically against heavy loads (>50 % P 0). The shape of the force-velocity curve also changed with age (a/P 0 increased). In addition, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.
Project description:Engineered skeletal muscles are inferior to natural muscles in terms of contractile force, hampering their potential use in practical applications. One major limitation is that the extracellular matrix (ECM) not only impedes the contraction but also ineffectively transmits the forces generated by myotubes to the load. In the present study, ECM remodelling improves contractile force in a short time, and a coordinated, combined electrical and mechanical stimulation induces the desired ECM remodelling. Notably, the application of single and combined stimulations to the engineered muscles remodels the structure of their ECM networks, which determines the mechanical properties of the ECM. Myotubes in the tissues are connected in parallel and in series to the ECM. The stiffness of the parallel ECM must be low not to impede contraction, while the stiffness of the serial ECM must be high to transmit the forces to the load. Both the experimental results and the mechanistic model suggest that the combined stimulation through coordination reorients the ECM fibres in such a way that the parallel ECM stiffness is reduced, while the serial ECM stiffness is increased. In particular, 3 and 20 minutes of alternating electrical and mechanical stimulations increase the force by 18% and 31%, respectively.
Project description:Duchenne Muscular Dystrophy is a genetic disease caused by the lack of the protein dystrophin. Dystrophic muscles are highly susceptible to contraction-induced injury, and following contractile activity, have disrupted plasma membranes that allow leakage of calcium ions into muscle fibers. Because of the direct relationship between increased intracellular calcium concentration and muscle dysfunction, therapeutic outcomes may be achieved through the identification and restriction of calcium influx pathways. Our purpose was to determine the contribution of sarcolemmal lesions to the force deficits caused by contraction-induced injury in dystrophic skeletal muscles. Using isolated lumbrical muscles from dystrophic (mdx) mice, we demonstrate for the first time that poloxamer 188 (P188), a membrane-sealing poloxamer, is effective in reducing the force deficit in a whole mdx skeletal muscle. A reduction in force deficit was also observed in mdx muscles that were exposed to a calcium-free environment. These results, coupled with previous observations of calcium entry into mdx muscle fibers during a similar contraction protocol, support the interpretation that extracellular calcium enters through sarcolemmal lesions and contributes to the force deficit observed in mdx muscles. The results provide a basis for potential therapeutic strategies directed at membrane stabilization of dystrophin-deficient skeletal muscle fibers.