Stretching human muscles makes them stronger.
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Humans↗
Biomedical subjects
Dilson E Rassier
Publications and source records attributed to Dilson E Rassier.
History-dependence of isometric muscle force: effect of prior stretch or shortening amplitude.
It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.
Animals↗
Prediction of summation in incompletely fused tetanic contractions of rat muscle.
Summation is the accumulating contractile force resulting from sequential activations applied to a muscle without sufficient interval to permit complete relaxation. The purpose of this study was to evaluate summation in the rat medial gastrocnemius muscle, and to determine if the contractile responses during summation could be predicted from the relationship between force and activation pattern. In the first part of this study, the consistency of summation in the rat gastrocnemius muscle was assessed and prediction equations were derived. The second part compared predicted summation with actual contractions obtained in a new set experiments. Summation was assessed by calculation of the contractile response, per stimulation, for up to five stimulating pulses at these frequencies: 20, 40, 60 and 80Hz. This was done by subtraction of the force transient for j-1 pulses of stimulation (where j=1-5 pulses) from the force response with j pulses of stimulation. Each of these force differences was evaluated for peak rate of force development, contraction time and half-relaxation time. Contraction and half-relaxation times changed by only a small magnitude from values obtained for the twitch. Peak rate of force development was proportional to the active force for all force transients obtained by subtraction. The force per activation increased from the first to the fifth stimulus, and was dependent on interpulse delay. In the second series of experiments, the predicted force was related to the actual force for brief tetanic contractions at 40, 50 and 60Hz (r(2)=0.875). These experiments demonstrate that the force response to sequential activations is consistent and predictable. Summation can be predicted, knowing only the amplitude of the twitch contraction and the relationship between delay and force for each activating stimulus.
Animals↗
Modulation of passive force in single skeletal muscle fibres.
In this study, we investigated the effects of activation and stretch on the passive force-sarcomere length relationship in skeletal muscle. Single fibres from the lumbrical muscle of frogs were placed at varying sarcomere lengths on the descending limb of the force-sarcomere length relationship, and tetanic contractions, active stretches and passive stretches (amplitudes of ca 10% of fibre length at a speed of 40% fibre length/s) were performed. The passive forces following stretch of an activated fibre were higher than the forces measured after isometric contractions or after stretches of a passive fibre at the corresponding sarcomere length. This effect was more pronounced at increased sarcomere lengths, and the passive force-sarcomere length relationship following active stretch was shifted upwards on the force axis compared with the corresponding relationship obtained following isometric contractions or passive stretches. These results provide strong evidence for an increase in passive force that is mediated by a length-dependent combination of stretch and activation, while activation or stretch alone does not produce this effect. Based on these results and recently published findings of the effects of Ca2+ on titin stiffness, we propose that the observed increase in passive force is caused by the molecular spring titin.
Animals↗
Relationship between force and stiffness in muscle fibers after stretch.
The purpose of this study was to evaluate the relationship between force and stiffness after stretch of activated fibers, while simultaneously changing contractility by interfering with the cross-bridge kinetics and muscle activation. Single fibers dissected from lumbrical muscles of frogs were placed at a length 20% longer than the plateau of the force-length relationship, activated, and stretched by 5 and 10% of fiber length (speed: 40% fiber length/s). Experiments were conducted with maximal and submaximal stimulation in Ringer solution and with the addition of 2 and 5 mM of the myosin inhibitor 2,3-butanedione monoxime (BDM) to the solution. The steady-state force after stretch of an activated fiber was higher than the isometric force produced at the corresponding length in all conditions investigated. Lowering the frequency of stimulation decreased the force and stiffness during isometric contractions, but it did not change force enhancement and stiffness enhancement after stretch. Administration of BDM decreased the force and stiffness during isometric contractions, but it increased the force enhancement and stiffness enhancement after stretch. The relationship between force enhancement and stiffness suggests that the increase in force after stretch may be caused by an increase in the proportion of cross bridges attached to actin. Because BDM places cross bridges in a weakly bound, pre-powerstroke state, our results further suggest that force enhancement is partially associated with a recruitment of weakly bound cross bridges into a strongly bound state.
Animals↗
Force enhancement and relaxation rates after stretch of activated muscle fibres.
The residual force enhancement following muscle stretch might be associated with an increase in the proportion of attached cross-bridges, as supported by stiffness measurements. In this case, it could be caused by an increase in the attachment or a decrease in the detachment rate of cross-bridges, or a combination of the two. The purpose of this study was to investigate if the stretch-induced force enhancement is related to cross-bridge attachment/detachment kinetics. Single muscle fibres dissected from the lumbrical muscle of frog were place at a length approximately 20% longer than the plateau of the force-length relationship; they were maximally activated, and after full isometric force was reached, ramp stretches were imposed with amplitudes of 5 and 10% fibre length, at a speed of 40% fibre length s(-1). Experiments were performed in Ringer's solution, and with the addition of 2, 5 and 10 nM of 2,3-butanedione monoxime (BDM), a drug that places cross-bridges in a pre-power-stroke, state, inhibiting force production. The total force following stretch was higher than the corresponding force measured after isometric contraction at the corresponding length. This residual force enhancement was accompanied by an increase relaxation time. BDM, which decreases force production during isometric contractions, considerably increased the relative levels of force enhancement. BDM also increased relaxation times after stretch, beyond the levels observed during reference contractions in Ringer's solution, and beyond isometric control tests at the corresponding BDM concentrations. Together, these results support the idea that force enhancement is caused, at least in part, by a decrease in cross-bridge detachment rates, as manifested by the increased relaxation times following fibre stretch.
Analysis of Variance↗
Active force inhibition and stretch-induced force enhancement in frog muscle treated with BDM.
There is evidence that the stretch-induced residual force enhancement observed in skeletal muscles is associated with 1) cross-bridge dynamics and 2) an increase in passive force. The purpose of this study was to characterize the total and passive force enhancement and to evaluate whether these phenomena may be associated with a slow detachment of cross bridges. Single fibers from frog lumbrical muscles were placed at a length 20% longer than the plateau of the force-length relationship, and active and passive stretches (amplitudes of 5 and 10% of fiber length and at a speed of 40% fiber length/s) were performed. Experiments were conducted in Ringer solution and with the addition of 2, 5, and 10 mM of 2,3-butanedione monoxime (BDM), a cross-bridge inhibitor. The steady-state active and passive isometric forces after stretch of an activated fiber were higher than the corresponding forces measured after isometric contractions or passive stretches. BDM decreased the absolute isometric force and increased the total force enhancement in all conditions investigated. These results suggest that total force enhancement is directly associated with cross-bridge kinetics. Addition of 2 mM BDM did not change the passive force enhancement after 5 and 10% stretches. Addition of 5 and 10 mM did not change (5% stretches) or increased (10% stretches) the passive force enhancement. Increasing stretch amplitudes and increasing concentrations of BDM caused relaxation after stretch to be slower, and because passive force enhancement is increased at the greatest stretch amplitudes and the highest BDM concentrations, it appears that passive force enhancement may be related to slow-detaching cross bridges.
Animals↗
Effects of shortening on stretch-induced force enhancement in single skeletal muscle fibers.
The main purpose of this study was to evaluate the effects of shortening on the stretch-induced force enhancement in single muscle fibers, and indirectly test the hypothesis that force enhancement may be associated with the engagement of a passive element upon activation. Fibers were placed on the descending limb of the force-length relationship, and stretch and shortening contractions were performed. Fibers underwent two sets of shortening-stretch cycles. First, fibers were shortened by a fixed amplitude and speed (10% fiber length, and at 40% fiber length/s), and then were stretched (10% fiber length, and at 40% fiber length/s) immediately following shortening, or 500 or 1000 ms following the shortening. Second, fibers were shortened by varying amounts (5%, 10% and 15% fiber length) and at a constant speed (40% fiber length/s) immediately preceding a given fiber stretch (10% fiber length, and at 40% fiber length/s). When stretching was immediately preceded by shortening, force enhancement was decreased proportionally with the shortening magnitude. When intervals were introduced between shortening and stretch, the effects of shortening on the stretch-induced force enhancement became less prominent. We concluded that, in contrast to published suggestions, shortening affects the stretch-induced force enhancement in an amplitude-dependent manner in single fibers, as it does in whole muscles, but this effect is diminished by increasing the time period between the shortening and stretch phases.
Adaptation, Physiological↗
Considerations on the history dependence of muscle contraction.
When a skeletal muscle that is actively producing force is shortened or stretched, the resulting steady-state isometric force after the dynamic phase is smaller or greater, respectively, than the purely isometric force obtained at the corresponding final length. The cross-bridge model of muscle contraction does not readily explain this history dependence of force production. The most accepted proposal to explain both, force depression after shortening and force enhancement after stretch, is a nonuniform behavior of sarcomeres that develops during and after length changes. This hypothesis is based on the idea of instability of sarcomere lengths on the descending limb of the force-length relationship. However, recent evidence suggests that skeletal muscles may be stable over the entire range of active force production, including the descending limb of the force-length relationship. The purpose of this review was to critically evaluate hypotheses aimed at explaining the history dependence of force production and to provide some novel insight into the possible mechanisms underlying these phenomena. It is concluded that the sarcomere nonuniformity hypothesis cannot always explain the total force enhancement observed after stretch and likely does not cause all of the force depression after shortening. There is evidence that force depression after shortening is associated with a reduction in the proportion of attached cross bridges, which, in turn, might be related to a stress-induced inhibition of cross-bridge attachment in the myofilament overlap zone. Furthermore, we suggest that force enhancement is not associated with instability of sarcomeres on the descending limb of the force-length relationship and that force enhancement has an active and a passive component. Force depression after shortening and force enhancement after stretch are likely to have different origins.
Animals↗
Force enhancement in single skeletal muscle fibres on the ascending limb of the force-length relationship.
It has been assumed that force enhancement in single fibres of skeletal muscles only occurs on the descending, and not the ascending or plateau region, of the force-length relationship. This assumption has been based, however, on theoretical considerations or isolated experiments, in which neither stretch conditions nor fibre lengths were optimized for force enhancement. Therefore, the purpose of this study was to investigate the residual, steady-state force enhancement following active stretch in single muscle fibres of frog on the ascending limb of the force-length relationship. Twenty-nine stretch experiments on ten single fibres from the lumbrical muscle of the frog Rana pipiens were carried out on the ascending limb of the force-length relationship. Force enhancement was observed in 28 out of the 29 tests. Moreover, the force produced for stretch experiments finishing at optimal fibre length always exceeded the force obtained for an isometric contraction at optimal length. We conclude from these results that steady-state force enhancement occurs systematically on the ascending limb of the force-length relationship, and that the steady-state force in the enhanced state can easily exceed the maximal isometric force of the fibre.
Analysis of Variance↗
Dynamics of individual sarcomeres during and after stretch in activated single myofibrils.
It is generally assumed that sarcomere lengths (SLs) change in isometric fibres following activation and following stretch on the descending limb of the force-length relationship, because of an inherent instability. Although this assumption has never been tested directly, instability and SL non-uniformity have been associated with several mechanical properties, such as 'creep' and force enhancement. The aim of this study was to test directly the hypothesis that sarcomeres are unstable on the descending limb of the force-length relationship. We used single myofibrils, isolated from rabbit psoas, that were attached to glass needles that allowed for controlled stretching of myofibrils. Images of the sarcomere striation pattern were projected onto a linear photodiode array, which was scanned at 20 Hz to produce dark-light patterns corresponding to the A- and I-bands, respectively. Starting from a mean SL of 2.55 +/- 0.07 microm, stretches of 11.2 +/- 1.6% of SL at a speed of 118.9 +/- 5.9 nm s(-1) were applied to the activated myofibrils (pCa(2+) = 4.75). SLs along the myofibril were non-uniform before, during and after the stretch, but with few exceptions, they remained constant during the isometric period before stretch, and during the extended isometric period after stretch. Sarcomeres never lengthened to a point beyond thick and thin filament overlap. We conclude that sarcomeres are non-uniform but generally stable on the descending limb of the force-length relationship.
Animals↗
Stretch-induced force enhancement and stability of skeletal muscle myofibrils.
The main purpose of the experiments presented in this chapter was to test the hypothesis that the stretch-induced force enhancement commonly observed in skeletal muscle is associated with sarcomere length instability. Single myofibrils isolated from the rabbit psoas muscle were attached to a nanolever pair for force measurement at the one end, and to a glass needle for controlled displacements at the other end. The image of the striation pattern was projected onto a linear 1024-element photodiode array, which was scanned (20 Hz) to produce a dark-light pattern corresponding to the A- and I-bands, respectively. Starting from a mean SL of approximately 2.55 microm, stretches of a nominal amplitude of 4 to 10% of SL, at a nominal speed of 100 nm x sec(-1) were applied to activated myofibrils (pCa2+ = 4.75). Following stretch, the isometric, steady-state force was greater by 10.9% to 45.9% than the force produced before stretch, and was greater than the force predicted at the corresponding final length. Passive force could not account for the force enhancement. Sarcomere lengths along the activated myofibrils were non-uniform, but remained constant before stretch or during the extended isometric period after stretch. Further, sarcomeres never stretched to a length beyond thick and thin filament overlap. It is concluded that sarcomeres are stable, and therefore the increased force observed after stretch must be a sarcomeric property, not associated with continuous length changes of unstable sarcomeres, as had been assumed in the past.
Animals↗
Stretch-induced, steady-state force enhancement in single skeletal muscle fibers exceeds the isometric force at optimum fiber length.
Stretch-induced force enhancement has been observed in a variety of muscle preparations and on structural levels ranging from single fibers to in vivo human muscles. It is a well-accepted property of skeletal muscle. However, the mechanism causing force enhancement has not been elucidated, although the sarcomere-length non-uniformity theory has received wide support. The purpose of this paper was to re-investigate stretch-induced force enhancement in frog single fibers by testing specific hypotheses arising from the sarcomere-length non-uniformity theory. Single fibers dissected from frog tibialis anterior (TA) and lumbricals (n=12 and 22, respectively) were mounted in an experimental chamber with physiological Ringer's solution (pH=7.5) between a force transducer and a servomotor length controller. The tetantic force-length relationship was determined. Isometric reference forces were determined at optimum length (corresponding to the maximal, active, isometric force), and at the initial and final lengths of the stretch experiments. Stretch experiments were performed on the descending limb of the force-length relationship after maximal tetanic force was reached. Stretches of 2.5-10% (TA) and 5-15% lumbricals of fiber length were performed at 0.1-1.5 fiber lengths/s. The stretch-induced, steady-state, active isometric force was always equal or greater than the purely isometric force at the muscle length from which the stretch was initiated. Moreover, for stretches of 5% fiber length or greater, and initiated near the optimum length of the fiber, the stretch-enhanced active force always exceeded the maximal active isometric force at optimum length. Finally, we observed a stretch-induced enhancement of passive force. We conclude from these results that the sarcomere length non-uniformity theory alone cannot explain the observed force enhancement, and that part of the force enhancement is associated with a passive force that is substantially greater after active compared to passive muscle stretch.
Animals↗
Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle.
BACKGROUND: It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. METHODS: Mouse extensor digitorum longus (EDL) muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL), by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22 degrees C and 35 degrees C at sarcomere lengths ranging from 2.35 microm to 3.85 microm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22 degrees C or during 10 s of 10 Hz stimulation at 22 degrees C or 35 degrees C. RESULTS: Staircase potentiation was greater at 35 degrees C than 22 degrees C, and the relative magnitude of the twitch contraction (Pt*/Pt) was proportional to sarcomere length with a negative slope, over the range 2.3 microm - 3.7 microm. Linear regression yielded the following: Pt*/Pt = -0.59 x SL+3.27 (r2 = 0.74); Pt*/Pt = -0.39 x SL+2.34 (r2 = 0.48); and Pt*/Pt = -0.50 x SL+2.45 (r2 = 0.80) for staircase at 35 degrees C, and 22 degrees C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. CONCLUSION: There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles.
Animals↗
Force enhancement following an active stretch in skeletal muscle.
When skeletal muscle is stretched during a tetanic contraction, the resulting force is greater than the purely isometric force obtained at the corresponding final length. Several mechanisms have been proposed to explain this phenomenon, but the most accepted mechanism is the sarcomere length non-uniformity theory. This theory is associated with the notion of instability of sarcomeres on the descending limb of the force-length relationship. However, recent evidence suggests that this theory cannot account solely for the stretch-induced force enhancement. Some of this evidence is presented in this paper, and a new mechanism for force enhancement is proposed: one that is associated with the engagement of a passive force during stretch. We speculate that this passive force enhancement may be caused by titin, a protein associated with passive force production at long sarcomere lengths.
Biomechanical Phenomena↗
What is fatigue?
Fatigue and potentiation are two forms of force modulation. A general definition of fatigue is "a circumstance where less than the anticipated contractile response is obtained." Fatigue is associated with depressed Ca2+ release and possibly decreased Ca2+ sensitivity. Potentiation results from increased Ca2+ sensitivity due to regulatory light chain phosphorylation. Muscle fatigue and potentiation can coexist, making it difficult to quantify these processes. With repetitive 10Hz stimulation, the developed tension first increases, then decreases. Is fatigue present when developed tension first begins to decrease or when it falls below the developed tension of the first response? Intermittent incompletely fused tetanic contractions for which peak developed tension first decreases, then increases, is another unusual example of fatigue. A third example is when twitch contractions following a tetanic contraction decrease to a level below the pretetanic twitch amplitude, indicating that fatigue may have been coexistent with posttetanic potentiation. These observations illustrate the complexity of detecting fatigue, based on the simple, but commonly accepted definition presented above. Care must be taken in interpreting "before vs. after" contractile responses. Even when the contraction amplitude is greater than the initial response, there is no guarantee that mechanisms associated with fatigue are not present.
Calcium↗
Length-dependent twitch contractile characteristics of skeletal muscle.
The length dependence of force development of mammalian skeletal muscles was evaluated during twitch, double-pulse, and tetanic contractions, and the relation between muscle length and the time-dependent characteristics of twitch and double-pulse contractions were determined. In situ isometric contractions of the rat gastrocnemius muscle were analyzed at seven different lengths, based on a reference length at which the maximal response to double-pulse contractions occurred (Lopt-2P). Twitch and double-pulse contractions were analyzed for developed tension (DT), contraction time (tC), average rate of force development (DT-tC(-1)), half-relaxation time (t50%R), peak rate of relaxation (DT x dtmin(-1)), and 90%-relaxation time (t90%R). Considering the length at which maximal tetanic DT occurred to be the optimal length (Lo-TET), the peak DT for twitch contractions and double-pulse contractions was observed at Lo-TET + 0.75 mm (p < 0.05) and Lo-TET + 0.1 mm (p > 0.05), respectively. When measured at the length for which maximal twitch and double-pulse contractions were obtained, tetanic DT was 95.2 +/- 3 and 99.0 +/- 2% of the maximal value, respectively. These observations suggest that double-pulse contractions are more suitable for setting length for experimental studies than twitch contractions. Twitch and double-pulse contraction tC were 15.53 +/- 1.14 and 25.0 +/- 0.6 ms, respectively, at Lopt-2P, and increased above Lopt-2P and decreased below Lopt-2P. Twitch t50%R was 12.18 +/- 0.90 ms at Lopt-2P, and increased above Lopt-2P and below Lopt-2P. Corresponding changes for double-pulse contractions were greater. Stretching the muscle leads to slower twitch contractions and double-pulse contractions, but the mechanisms of this change in time course remain unclear.
Animals↗
Effects of pH on the length-dependent twitch potentiation in skeletal muscle.
When muscle is elongated, there is a length dependence of twitch potentiation and an increased Ca(2+) sensitivity of the myofilaments. Changes in the charge potential of myofilaments, induced by a decrease in pH, are known to abolish the length dependence of Ca(2+) sensitivity. This study was aimed at testing the hypothesis that a decrease in pH, and the concomitant loss of length dependence of Ca(2+) sensitivity, depresses the length dependence of staircase potentiation. In vitro, isometric twitch contractions of fiber bundles dissected from the mouse extensor digitorum longus, performed before and after 10 s of 10-Hz stimulation (i.e., the staircase potentiation protocol) were analyzed at five different lengths, ranging from optimal length for maximal force production (L(o); = 12 +/- 0.7 mm) to L(o) + 1.2 mm (L(o) + 10%). These measurements were made at an extracellular pH of 6.6, 7.4, and 7.8 (pH changes induced by altering the CO(2) concentration of the bath solution). At pH 7.4 and 7.8, the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased fiber bundle length (r(2) = 0.95 and r(2) = 0.99, respectively). At pH 6.6, the length dependence of potentiation was abolished, and the slope of the length-potentiation relationship was not different from zero (r(2) = 0.05). The results of this study indicate that length dependence of potentiation in intact skeletal muscle is abolished by lowering the pH. Because decreasing the pH decreases Ca(2+) sensitivity and changes the charge potential of the filaments, the mechanism of length-dependent potentiation may be closely related to the length dependence of Ca(2+) sensitivity, and changes in the charge potential of the myofilaments may be important in regulating this relationship.
Animals↗