Skeletal muscles present a non-cross-bridge increase in sarcomere stiffness and tension on Ca(2+) activation, referred to as static stiffness and static tension, respectively. It has been ...hypothesized that this increase in tension is caused by Ca(2+)-dependent changes in the properties of titin molecules. To verify this hypothesis, we investigated the static tension in muscles containing different titin isoforms. Permeabilized myofibrils were isolated from the psoas, soleus, and heart ventricle from the rabbit, and tested in pCa 9.0 and pCa 4.5, before and after extraction of troponin C, thin filaments, and treatment with the actomyosin inhibitor blebbistatin. The myofibrils were tested with stretches of different amplitudes in sarcomere lengths varying between 1.93 and 3.37 μm for the psoas, 2.68 and 4.21 μm for the soleus, and 1.51 and 2.86 μm for the ventricle. Using gel electrophoresis, we confirmed that the three muscles tested have different titin isoforms. The static tension was present in psoas and soleus myofibrils, but not in ventricle myofibrils, and higher in psoas myofibrils than in soleus myofibrils. These results suggest that the increase in the static tension is directly associated with Ca(2+)-dependent change in titin properties and not associated with changes in titin-actin interactions.
Obscurin is a giant sarcomeric protein expressed in striated muscles known to establish several interactions with other proteins of the sarcomere, but also with proteins of the sarcoplasmic reticulum ...and costameres. Here, we report experiments aiming to better understand the contribution of obscurin to skeletal muscle fibers, starting with a detailed characterization of the diaphragm muscle function, which we previously reported to be the most affected muscle in obscurin (Obscn) KO mice. Twitch and tetanus tension were not significantly different in the diaphragm of WT and Obscn KO mice, while the time to peak (TTP) and half relaxation time (HRT) were prolonged. Differences in force-frequency and force-velocity relationships and an enhanced fatigability are observed in an Obscn KO diaphragm with respect to WT controls. Voltage clamp experiments show that a sarcoplasmic reticulum’s Ca2+ release and SERCA reuptake rates were decreased in muscle fibers from Obscn KO mice, suggesting that an impairment in intracellular Ca2+ dynamics could explain the observed differences in the TTP and HRT in the diaphragm. In partial contrast with previous observations, Obscn KO mice show a normal exercise tolerance, but fiber damage, the altered sarcomere ultrastructure and M-band disarray are still observed after intense exercise.
Repetitive or prolonged muscle contractions induce muscular fatigue, defined as the inability of the muscle to maintain the initial tension or power output. In the present experiments, made on intact ...fiber bundles from FDB mouse, fatigue and recovery from fatigue were investigated at 24°C and 35°C. Force and stiffness were measured during tetani elicited every 90 s during the pre-fatigue control phase and recovery and every 1.5 s during the fatiguing phase made of 105 consecutive tetani. The results showed that force decline could be split in an initial phase followed by a later one. Loss of force during the first phase was smaller and slower at 35°C than at 24°C, whereas force decline during the later phase was greater at 35°C so that total force depression at the end of fatigue was the same at both temperatures. The initial force decline occurred without great reduction of fiber stiffness and was attributed to a decrease of the average force per attached crossbridge. Force decline during the later phase was accompanied by a proportional stiffness decrease and was attributed to a decrease of the number of attached crossbridge. Similarly to fatigue, at both 24 and 35°C, force recovery occurred in two phases: the first associated with the recovery of the average force per attached crossbridge and the second due to the recovery of the pre-fatigue attached crossbridge number. These changes, symmetrical to those occurring during fatigue, are consistent with the idea that, i) initial phase is due to the direct fast inhibitory effect of Pii increase during fatigue on crossbridge force; ii) the second phase is due to the delayed reduction of Ca(2+) release and /or reduction of the Ca(2+) sensitivity of the myofibrils due to high Pii.
When skeletal muscles are stretched during activation in the absence of myosin-actin interactions, the force increases significantly. The force remains elevated throughout the activation period. The ...mechanism behind this non-crossbridge force, referred to as
static tension
, is unknown and generates debate in the literature. It has been suggested that the static tension is caused by Ca
2+
-induced changes in the properties of titin molecules that happens during activation and stretch, but a comprehensive evaluation of such possibility is still lacking. This paper reviews the general characteristics of the static tension, and evaluates the proposed mechanism by which titin may change the force upon stretch. Evidence is presented suggesting that an increase in intracellular Ca
2+
concentration leads to Ca
2+
binding to the PEVK region of titin. Such binding increases titin stiffness, which increases the overall sarcomere stiffness and causes the static tension. If this form of Ca
2+
-induced increase in titin stiffness is confirmed in future studies, it may have large implications for understating of the basic mechanisms of muscle contraction.
Stretching of activated skeletal muscles induces a force increase above the isometric level persisting after stretch, known as residual force enhancement (RFE). RFE has been extensively studied; ...nevertheless, its mechanism remains debated. Unlike previous RFE studies, here the excess of force after stretch, termed static tension (ST), was investigated with fast stretches (amplitude: 3-4% sarcomere length; duration: 0.6 ms) applied at low tension during the tetanus rise in fiber bundles from flexor digitorum brevis (FDB) mouse muscle at 30°C. ST was measured at sarcomere length between 2.6 and 4.4 μm in normal and N-benzyl-p-toluene sulphonamide (BTS)-added (10 μM) Tyrode solution. The results showed that ST has the same characteristics and it is equivalent to RFE. ST increased with sarcomere length, reached a peak at 3.5 μm, and decreased to zero at ∼4.5 μm. At 4 μm, where active force was zero, ST was still 50% of maximum. BTS reduced force by ∼75% but had almost no effect on ST. Following stimulation, ST developed earlier than force, with a time course similar to internal Ca(2+) concentration: it was present 1 ms after the stimulus, at zero active force, and peaked at ∼3-ms delay. At 2.7 μm, activation increased the passive sarcomere stiffness by a factor of ∼7 compared with the relaxed state All our data indicate that ST, or RFE, is independent of the cross-bridge presence and it is due to the Ca(2+)-induced stiffening of a sarcomeric structure identifiable with titin.
Stretching of an activated skeletal muscle induces a transient tension increase followed by a period during which the tension remains elevated well above the isometric level at an almost constant ...value. This excess of tension in response to stretching has been called 'static tension' and attributed to an increase in fibre stiffness above the resting value, named 'static stiffness'. This observation was originally made, by our group, in frog intact muscle fibres and has been confirmed more recently, by us, in mammalian intact fibres. Following stimulation, fibre stiffness starts to increase during the latent period well before crossbridge force generation and it is present throughout the whole contraction in both single twitches and tetani. Static stiffness is dependent on sarcomere length in a different way from crossbridge force and is independent of stretching amplitude and velocity. Static stiffness follows a time course which is distinct from that of active force and very similar to the myoplasmic calcium concentration time course. We therefore hypothesize that static stiffness is due to a calcium-dependent stiffening of a non-crossbridge sarcomere structure, such as the titin filament. According to this hypothesis, titin, in addition to its well-recognized role in determining the muscle passive tension, could have a role during muscle activity.
•Precision in drawing and tracing task does not show correlation between subjects.•Lack of correlation is task dependent and not shape dependent.•Evaluation of fine motor control should include both ...a drawing and a tracing task.
Drawing and tracing tasks, by being relatively easy to execute and evaluate, have been incorporated in many paradigms used to study motor control. While these tasks are helpful when examining various aspects relative to the performance, the relationship in proficiency between these tasks was not evaluated to our knowledge. Seeing that drawing is thought to be an internally cued and tracing an externally cued task, differences in performances are to be expected. In this study, a quantitative evaluation of the precision of circle drawing and tracing, and spiral tracing was made on 150 healthy subjects. Our results show that, while precision is correlated when repeating drawing circles, tracing spirals, or tracing circles as well as between tracing spirals and tracing circles; there is no correlation when subjects performed drawing circles and tracing spirals or between drawing and tracing of circles. These results suggest that this lack of correlation is task dependent and not shape dependent. We suggest that the evaluation of fine motor control should include both a tracing and a drawing task, taking in consideration the precision in each task. We believe that this approach could help not only to evaluate fine motor control more accurately, but also to identify subjects who are more reliant on either internal or external cueing and to what extent.
The mechanism of force enhancement during lengthening was investigated on single frog muscle fibres by using fast stretches
to measure the rupture tension of the crossbridge ensemble. Fast stretches ...were applied to one end of the activated fibre
and force responses were measured at the other. Sarcomere length was measured by a striation follower device. Fast stretching
induced a linear increase of tension that reached a peak and fell before the end of the stretch indicating that a sudden increase
of fibre compliance occurred due to forced crossbridge detachment induced by the fast loading. The peak tension (critical
tension, P c ) and the sarcomere length needed to reach P c (critical length, L c ) were measured at various tensions during the isometric tetanus rise and during force enhancement by slow lengthening. The
data showed that P c was proportional to the tension generated by the fibre under both isometric and slow lengthening conditions. However, for
a given tension increase, P c was 6.5 times greater during isometric than during lengthening conditions. Isometric critical length was 13.04 ± 0.17 nm
per half-sarcomere (nm hs â1 ) independently of tension. During slow lengthening critical length fell as the force enhancement increased. For 90% enhancement,
L c reduced to 8.19 ± 0.039 nm hs â1 . Assuming that the rupture force of the individual crossbridge is constant, these data indicate that the increase of crossbridge
number during lengthening accounts for only 15.4% of the total force enhancement. The remaining 84.6% is accounted for by
the increased mean strain of the crossbridges.
The Muscle Shortening Maneuver (MSM) is derived from Feldman's λ model of motor control, and seems to induce a more balanced agonist- antagonist-muscular action. The hypothesized mechanism of action ...is a modulation of the Tonic Stretch Reflex Threshold (TSRT). We designed a pilot, randomized trial aimed to explore the mechanisms of action of the technique. An ancillary objective was to research the implementation of the MSM as a stroke rehabilitation intervention.
A sample of 10 participants with chronic stroke was enrolled and randomly assigned to MSM (n, 5) or conventional physical therapy (CPT) (n, 5) treatments. The TSRTs were assessed by the Montreal Spasticity Measure device. A selection of clinical and instrumental outcome measures was taken to investigate function and activity levels. Data were collected at baseline, end-of-treatment, and one month after the end-of-treatment.
No adverse events were observed. In both between- and within-group post-treatment assessments, in the affected ankle the MSM group showed decreased TSRTs of the plantar flexor, increased strength of the dorsiflexor and active range of motion; also, the time needed to perform the Timed Up and Go test decreased. No changes were evident across assessments in the CPT group.
The MSM seems able to modulate the TSRTs in individuals with stroke. Although with the limitations due to the pilot design, the variation in participants' responses appear to be promising. Many methodological issues have to be clarified and specified conceiving the progression toward a confirmatory trial.
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