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First published online September 5, 2008
Journal of Experimental Biology 211, 3001-3008 (2008)
Published by The Company of Biologists 2008
doi: 10.1242/jeb.021204
Is a parallel elastic element responsible for the enhancement of steady-state muscle force following active stretch?
Human Performance Lab, Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4
Author for correspondence (e-mail:
walter{at}kin.ucalgary.ca)
Accepted 17 July 2008
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Summary |
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 TOP Summary INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Key words: muscle mechanics, fibre, cell, slack test, eccentric contraction, lengthening
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INTRODUCTION |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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).
Stretch has also been shown to increase force during subsequent shortening
(Edman et al., 1978). This
`residual force enhancement' (rFE) after stretch has been observed in muscles
from fish and amphibians (Abbott and
Aubert, 1952), as well as in muscles from mammals
(Herzog and Leonard, 2002)
including humans (Lee and Herzog,
2002). This effect is of particular interest because it is not
predicted by the widely accepted `cross-bridge' model of muscle contraction
(Huxley, 1957). Therefore, it
is important to understand the mechanism underlying rFE in order to determine
whether it can be explained by making minor modifications to our understanding
of muscle contraction or whether current models need to be completely revised.
Despite extensive study, the mechanism of rFE is still the subject of intense
debate (e.g. Herzog et al.,
2006; Morgan and Proske,
2007).
One mechanism that has been proposed is that the extra force is provided by
an elastic element, which acts in parallel to the cross-bridges. It is
proposed that this element stiffens, or is engaged, when the muscle is
activated so that it exerts more force when the muscle is stretched while
activated than it would if the muscle were stretched while inactive and then
activated isometrically (Fig.
1). This mechanism was first proposed in 1978 by Edman et al. and
has found recent support as a partial
(Herzog and Leonard, 2002) or
complete (Pinniger et al.,
2006; Telley and Denoth,
2007) explanation for rFE. It has been suggested that the elastic
element involved could be titin (Bagni et
al., 2002; Herzog and Leonard,
2002), a protein that is an important contributor to passive force
in many muscles (Tskhovrebova and Trinick,
2003). There is evidence that the stiffness of titin increases
upon muscle activation in response to the rise in intracellular calcium
concentration (Joumaa et al.,
2008; Labeit et al.,
2003).
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;
Edman et al., 1982;
Schachar et al., 2004).
Previously, we have shown that when stretch distance is increased, by starting
the stretch at progressively shorter initial lengths, the amount of rFE
increases with stretch magnitude only up to a certain point and then levels
off (Bullimore et al., 2007).
This is consistent with an elastic element that has very low stiffness at
short lengths, which is typical of biological soft tissues
(Fung, 1967). The absolute
amount of rFE generated by a given stretch shows only small changes in
response to the application of drugs that have a substantial influence on the
force produced by the cross-bridges (Bagni
et al., 2002; Pinniger et al.,
2006; Rassier and Herzog,
2004a) and is maximum at a much longer muscle length than that at
which the cross-bridges produce maximum force
(Edman et al., 1982;
Schachar et al., 2004). This
suggests that rFE is generated by structures other than the cross-bridges. rFE
has also been shown to be associated with an increase in the passive force
remaining after the muscle has been deactivated (`passive force enhancement'),
suggesting that it may be associated with modification of a passive element
(Herzog and Leonard,
2002).
One way of testing this proposed mechanism is to activate a muscle, allow
it to shorten and then to stretch it again by the same amount or, conversely,
to stretch it and then allow it to shorten by the same amount. In either case,
no rFE should result from the stretch because an elastic element that is
shortened or stretched and then returned to its original length generates the
same force as it did initially. Several experiments of this type have been
performed with conflicting results. Edman et al. found that rapid shortening
performed either 
1 s before or immediately before, a stretch had no
effect on rFE compared with the stretch alone
(Edman et al., 1982;
Edman et al., 1984). Herzog
and Leonard and Lee et al. found that when stretch was followed by shortening
the effects of the stretch were eliminated, leaving a depression of isometric
force as would have occurred with shortening alone
(Herzog and Leonard, 2000;
Lee et al., 2001). When
shortening was followed by stretch, the rFE after stretch was either
eliminated (Herzog and Leonard,
2000) or substantially reduced
(Lee et al., 2001). However,
interpretation of these two studies is complicated by the fact that, because
they were designed to address a different question, they used low velocities
of shortening at which a substantial amount of force was produced. Shortening
under these conditions is known to depress the subsequent isometric muscle
force, whereas shortening at high or maximal velocities has been found not to
cause force depression (Edman et al.,
1993; Herzog and Leonard,
1997; Herzog and Leonard,
2007; Marechal and Plaghki,
1979). This factor makes it difficult to determine whether the
measured reduction in rFE was due to the superimposed effects of this force
depression or to a direct reduction in the rFE itself. Rassier and Herzog also
found that prior shortening reduced the rFE induced by stretch but again used
sub-maximal shortening velocities (Rassier
and Herzog, 2004b). In general, a difficulty with interpreting all
studies where shortening is performed before stretch is that, as we do not
know the identity of the elastic element or the mechanism of stiffening, we do
not know whether the resting length of the element would be re-established
after shortening, allowing it to still generate rFE during a subsequent
stretch. For example, titin is known to form bonds with actin
(Bianco et al., 2007) and it is
possible that such bonds could reform during and after shortening so that
titin would still be loaded during a subsequent stretch.
The present study was designed to overcome these limitations. Shortening was performed after stretch, to avoid the possibility of the elastic element being re-established at the shorter length, and was at maximal shortening velocity to avoid inducing force depression. It was hypothesised that rFE would be eliminated by shortening a distance equal to or greater than the initial stretch.
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MATERIALS AND METHODS |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The experiments were performed using a mechanical testing apparatus (model 801A; Aurora Scientific, Ontario, Canada). The fibre was suspended between a force transducer (model 400A; step response time, 0.3 ms) and a length controller (model 322C-I; step response time, 0.7 ms) in a bath containing Ringer's solution (composition: NaCl, 115 mmol l–1; KCl, 2.5 mmol l–1; CaCl2, 1.8 mmol l–1; Na2HPO4, 2.15 mmol l–1; NaH2PO4, 0.85 mmol l–1; pH 7.0). The solution was stored in a 500 ml reservoir adjacent to the apparatus and was circulated through the bath at a rate greater than 0.45 ml min–1 during the experiment. Bath temperature was measured using a thermocouple probe placed within a few millimetres of the fibre and was controlled using Peltier modules and a feedback control loop. The mean temperature of individual experiments was varied between 7.7 and 13°C depending on the temperature at which the fibre produced a good force response; however, temperature did not vary by more than 0.6°C during any individual experiment or by more than 0.3°C (usually less than 0.1°C) between contractions that were compared in order to calculate rFE. Electrical stimulation was delivered using two platinum plate electrodes situated alongside the fibre. Stimulus pulses were 0.5 ms square waves, and current was adjusted to the lowest value that gave maximal twitch force at room temperature (55–90 mA).
The fibres were attached to the force transducer and length controller
via thin wire hooks. They were attached to these hooks using
aluminium foil clips, which were folded around the tendons at the ends of the
fibres. The clips were modified from those described by Ford et al. so that
they had pieces that could be wrapped around the shaft of the hook to prevent
movement of the clip with respect to the hook
(Ford et al., 1977).
Experimental protocol
During the initial stages of the experiment, 1 s contractions with 2 or 3
min rest periods were used. Stimulation frequency was gradually increased in
sequential contractions until a fused contraction was obtained. Ten
`conditioning' contractions were performed at this frequency to bring the
fibre into a state where peak force was approximately constant in successive
tetani. Stimulation frequency was then adjusted to give maximal isometric
force, and a force–length relationship was obtained at this frequency by
performing seven isometric contractions at intervals of 5% fibre length. The
relationship between peak force and fibre length was fitted with a
second-order polynomial and the length at which force was maximal (optimal
length, Lopt) was identified to the nearest 2.5% fibre
length. Passive forces were typically low over the range used (1.2–3.2%
of maximal isometric force at 1.2 Lopt) and subtracting
passive force did not affect the choice of Lopt. The
maximum isometric stress generated by the fibres was 270 kPa to 360 kPa, which
is consistent with previous measurements on Xenopus laevis twitch
fibres over a similar temperature range
(Lannergren et al., 1982).
For the remainder of the experiment, 3 s contractions with 6 min rest
periods were used. The stimulation frequency was adjusted to give contractions
that were fused, or almost fused, and could be sustained for 3 s (23 Hz to 46
Hz). The fact that the stimulation frequency was slightly less than maximal
was not a concern because it has been shown that halving the stimulation rate
relative to that required for a fused contraction does not significantly
affect the rFE expressed as a percentage of isometric force
(Rassier and Herzog,
2005).
rFE was elicited by applying stretches of 5% fibre length, with a final length of 1.2 Lopt and a speed of 0.1 fibre lengths s–1. The stretch was followed by a rapid shortening with a distance equal to 0, 25, 50, 75, 100, 150, 200, 300 or 400% of stretch distance. In some fibres, shortening distances of 500, 600 and 700% stretch distance were also applied. To allow the fibres to shorten at their maximum velocity, the lever arm of the length controller was repositioned as quickly as possible. The speed of the lever arm was always at least 2.9 times the maximal velocity of the fibre (as measured using the `slack test', see below).
Three contractions were performed for each shortening distance in the
following order: (1) `isometric-shortening' – the fibre was activated at
1.2 Lopt, held isometric for 1.5 s, then rapidly shortened
by the specified distance and held isometric for the remainder of the
activation period; (2) `purely isometric' – the fibre was activated and
held isometric at the final length of the corresponding isometric-shortening
contraction; and (3) `stretch-shortening' the fibre was activated at 1.15
Lopt, stretched to 1.2 Lopt, held
isometric for 600 ms, and then rapidly shortened by the specified distance and
held isometric for the remainder of the activation period. The
isometric-shortening and purely isometric contractions provided control
conditions relative to which rFE in the stretch-shortening contractions was
calculated. The isometric-shortening contraction was compared with the purely
isometric contraction to determine whether shortening caused any force
depression. Contractions were performed in the above order so that a higher
force in the stretch-shortening compared with the other two contractions or a
lower force in the isometric-shortening contraction compared with the purely
isometric contraction could not be attributed to fatigue. Shortening was
performed 600 ms after stretch as a compromise between allowing some of the
stretch-induced transients to subside and avoiding fatigue due to excessively
long periods of activation. We did not expect these transients to influence
the final force however because they are eliminated by rapid shortening
(Edman et al., 1984). To
determine the longitudinal stiffness of the fibre, a short rapid stretch
(0.25% fibre length in 1 ms) was performed immediately before the end of
activation. An example of raw data from one set of three contractions with a
shortening distance of 100% of stretch distance is shown in
Fig. 2.
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As force depression was unexpectedly observed after rapid shortening, several tests were performed on two fibres to investigate this further. In all cases, the fibres were allowed to shorten at their maximum velocity, as in the rest of the experiment. Fibre 1 was always shortened from 1.2 Lopt to 1.1 Lopt and fibre 2 was always shortened from 1.1 Lopt to 1.05 Lopt but the stimulation rate and number of periods of force redevelopment were varied. The reasoning behind the investigations performed is explained in the Discussion. Force depression was calculated as described below by comparing force in the shortening contractions with force in a purely isometric contraction at the final length (which was performed immediately after the shortening contraction in question). In the control condition, the shortening was performed at the same time as in the isometric-shortening contractions used in the rest of the study (1.5 s into activation). To investigate the effect of increasing stimulation frequency, the control condition was repeated but with a 10 Hz increase in stimulation frequency in both the shortening and purely isometric contractions. The number of periods of force development occurring during a contraction was varied by: (1) performing the shortening 20 ms into activation so that there was only one period of force development (as opposed to two periods in the isometric-shortening contractions: initial force development and force redevelopment after shortening); and (2) breaking the shortening into two or (in one fibre) three equal steps at intervals of 1 s or 0.5 s, respectively, to give three or four periods of force development. When shortening was broken into multiple steps, the final step was always performed at the same time as the shortening in the control contraction.
Data recording and analysis
Force and length data were recorded at 10 kHz. To reduce file size and
processing time, the data points were then averaged in groups of 10 to produce
smoothed data at 1 kHz, except in the regions of the rapid force changes
during shortening and the stiffness test, which were left at 10 kHz. These
smaller files were analysed in order to obtain the data and figures presented
here.
The force at the end of each contraction was calculated by taking the mean force over a 100 ms–1 period immediately before the stiffness test, i.e. beginning 1.39 s after shortening (and at the equivalent time during the purely isometric contraction). rFE was calculated in two ways: (1) by subtracting force in the isometric-shortening contraction from force in the stretch-shortening contraction and expressing the result as a percentage of force in the isometric-shortening contraction; and (2) by subtracting force in the purely isometric contraction from force in the stretch-shortening contraction and expressing the result as a percentage of force in the purely isometric contraction. Force depression was calculated by subtracting force in the isometric-shortening contraction from force in the purely isometric contraction and expressing the result as a percentage of force in the purely isometric contraction.
The slopes of the force–time records were determined by linear regression over a 500 ms period immediately before the stiffness test. They were compared between the three different types of contraction and used to determine whether the force traces were converging or diverging at the time when rFE and force depression were calculated. Stiffness was calculated by dividing the change in force during the stiffness test by the change in length.
The protocol used in the present study, with a series of rapid shortening
steps of different distances, is similar to the `slack test' used to measure
maximal shortening velocity (Edman,
1979). We took advantage of this to determine whether maximal
shortening velocity was influenced by prior stretch. Shortening steps that
ended at lengths shorter than 0.95 Lopt (i.e. those
greater than 500%) were excluded because maximal shortening velocity is known
to decrease at short muscle lengths (Edman,
1979), probably due to internal resistance within the fibre.
Shorter steps, where there was not an appreciable duration of unloaded
shortening (those less than 200 or 300% depending on the fibre), were also
excluded. In two fibres, shortening steps of 250 and 350% were included in the
slack test, although they were excluded from the rest of the analysis because
they were not performed by the other fibres. This gave three to five data
points for each slack test. The 10 kHz force data were smoothed by applying a
21 point moving average. Visual examination confirmed that the smoothed curve
remained centred within the range of the variation caused by noise in the raw
data. For each contraction, the time after the start of shortening at which
force began to redevelop was calculated. This was determined by finding the
time at which force crossed a threshold of 5 µN above baseline
(approximately 0.25% maximal isometric force). This was typically about 10 ms
after the force first began to rise but was used instead of the initial rise
because it was easier to detect accurately and objectively. This overestimate
of the time for force development will not influence the calculated velocity
as long as the initial rate of force rise is independent of the size of the
shortening step. This seems a reasonable assumption because the initial rate
of force rise is expected to depend primarily upon the properties of the
series elasticity (which should be independent of step size) and the
force–velocity relationship (which should vary little with step size
because all final lengths were close to the plateau of the force–length
relationship). The relationship between time of force redevelopment and step
size was analysed separately for the isometric-shortening and
stretch-shortening contractions using linear regression, and maximal
shortening velocity was determined by taking the inverse of the calculated
slope. Time for force redevelopment was treated as the dependent variable
because it was expected to include more error than step size.
Statistical analysis
Significant differences of rFE and force depression from zero were detected
by calculating 95% confidence intervals for each shortening distance using the
t-distribution for N–1 degrees of freedom, where
N is the number of fibres. For example, for shortening steps that
were performed by all fibres (N=6), the confidence interval was
calculated as 2.571 (± s.e.m.). If the confidence interval did not
include zero, the data point was taken to be significantly different from
zero. The data for stiffness and for force–time slope were analysed
using analysis of variance (anovan.m, Matlab release 13, The Mathworks Inc.,
Natick, MA, USA) with fibre, shortening distance and contraction type
(isometric-shortening, stretch-shortening or purely isometric) as factors and
two-factor interactions included. This analysis indicated, however, that there
were significant interactions between shortening distance and contraction
type, so the data were reanalysed for each shortening distance separately with
fibre and contraction type as factors. Because there were significant
differences between fibres, only shortening distances that were performed by
all fibres were included. Post hoc comparisons for the effect of
contraction type were made using a Bonferroni adjustment for multiple
comparisons (multcompare.m, Matlab). Maximal shortening velocities in the
isometric-shortening and stretch-shortening contractions were compared using a
paired t-test (Microsoft Excel). Throughout, P<0.05 was
considered significant.
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RESULTS |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The observed force depression was further investigated in two fibres by varying the stimulation frequency and number of periods of force development during a contraction. In both fibres, force depression increased when stimulation frequency was increased by 10 Hz and increased as the number of periods of force development increased (Fig. 5).
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For all shortening distances, the force–time slopes for the stretch-shortening and purely isometric contractions were significantly different such that they were diverging, i.e. rFE calculated relative to the purely isometric contractions was increasing with time.
For all shortening distances, the force–time slopes for the isometric-shortening and purely isometric contractions were significantly different such that they were converging, i.e. force depression was decreasing with time. For a shortening distance of 100%, the rate of convergence was 0.024±0.006 mN s–1 (mean ± s.d.). If this rate of convergence had been maintained, the force depression would have been eliminated after a further 3.3±0.6 s (mean ± s.d.).
When the stiffness data were analysed using an ANOVA that combined all shortening distances and all fibres, there was a significant interaction between contraction type and shortening distance. When the data were analysed for each shortening distance separately, stiffness in the isometric-shortening contractions was significantly lower than in the purely isometric contractions for shortening distances of 25, 75, 150 and 300% and significantly lower than in the stretch-shortening contractions for shortening distances of 25, 50, 75 and 300%.
Maximal shortening velocity was not significantly affected by whether shortening was preceded by active stretch or by a purely isometric contraction (isometric-shortening, 3.76±0.96 fibre lengths s–1; stretch-shortening, 3.75±0.60 fibre lengths s–1 (mean ± s.d.); P=0.97).
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DISCUSSION |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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;
Herzog and Leonard, 1997;
Herzog and Leonard, 2007;
Marechal and Plaghki, 1979).
This observation has potentially important implications for understanding the
mechanism underlying force depression. Possible reasons for the difference
between the results of the present study and those of previous studies are
discussed below.
The occurrence of shortening-induced force depression meant that the
shortening could have had a dual effect on the force after stretch, i.e. a
direct depression of force, as well as a reduction in rFE. Calculating the rFE
relative to the isometric-shortening contraction implicitly assumed that the
direct force depression was the same regardless of whether shortening was
preceded by stretch. This is supported by studies that have found that prior
stretch did not influence the amount of force depression induced by subsequent
shortening (Herzog and Leonard,
2000; Lee et al.,
2001). However, these studies used slower shortening than the
present study and a different preparation so the findings may not be directly
applicable. It is possible that, under the conditions used in the present
study, prior stretch protected the fibres from the effects of shortening to
some extent, so that less force depression occurred after stretch. In this
case, rFE calculated relative to the isometric-shortening contraction would be
an overestimate.
The opposite extreme is to assume that prior stretch completely protects
the fibres from shortening-induced force depression. If this is true then rFE
should be calculated relative to the purely isometric contraction. However,
rFE calculated in this way was significantly below zero for shortening
distances of between 200 and 400% of stretch distance
(Fig. 4), i.e. force in the
stretch-shortening contractions was consistently lower than in the purely
isometric contractions over this range. It is unlikely that this depression of
force was due to the stretch because stretch is consistently found to enhance
subsequent force production (Herzog et
al., 2006). Therefore, this decrease in force can be attributed to
the effects of shortening and implies that the stretch did not completely
protect the fibres from force depression. This indicates that rFE calculated
by this method is probably an underestimate.
The true rFE is therefore expected to lie between the two curves shown in Fig. 4. For both curves the rFE for a shortening distance equal to 100% of stretch distance was significantly above zero. Therefore, we can reject the hypothesis that rapid shortening by a distance equal to the initial stretch eliminates rFE. We conclude that, although stiffening of a parallel elastic element may play a role in rFE, it is unlikely to provide a complete explanation.
Our findings also do not support the idea that rFE is generated solely by
cross-bridges that become `stuck' or detach very slowly after stretch because
a period of rapid shortening would force these cross-bridges to detach. An
alternative idea is that the forced detachment of cross-bridges during stretch
puts them into an alternative biochemical state, which enables them to
generate more force than usual (Herzog,
1998) and, which persists despite rapid shortening. In this case,
the results of the present study suggest that the number of cross-bridges
remaining in this state decreases as the period of shortening increases. We
found no difference in maximal shortening velocity following a stretch or an
isometric contraction, which concurs with previous findings based on the slack
test (Edman and Tsuchiya, 1996)
and extrapolation of the hyperbolic force-velocity relationship
(Edman et al., 1978;
Sugi and Tsuchiya, 1981).
Therefore, any change in the cross-bridges that is induced by stretch does not
produce a detectable change in maximal shortening velocity.
The finding that stiffness was significantly lower in the isometric-shortening contractions compared with the other two conditions suggests that stretch may have caused an increase in stiffness whereas shortening caused a decrease. In this case, the lack of a difference in stiffness in the stretch-shortening and purely isometric contractions could be explained by the effects of stretch and shortening cancelling out whereas the lower stiffness in the isometric-shortening conditions could be explained by the effect of stretch alone. This explanation is also compatible with the observation that significant differences in stiffness tended to occur at smaller shortening distances where force depression was high (Fig. 3), although the difference in stiffness was not always significant over this range.
Titin is known to bind to actin (Jin,
1995; Soteriou et al.,
1993) and to modify in vitro motility of actin moving on
myosin (Li et al., 1995;
Niederländer et al.,
2004). However it is not known whether these properties have an
influence on active muscle mechanics in vivo. Bianco et al. used
optical tweezers to measure the rupture forces of titin–actin bonds and
concluded that these bonds could act to stabilise resting muscle structure and
to modulate the viscous properties of active muscle
(Bianco et al., 2007). If these
interactions are also able to influence steady-state active muscle forces then
this raises the possibility that differences in titin–actin bonding
might play a role in the higher forces observed at the end of the
stretch-shortening contractions in the present study.
Possible explanations for the force depression induced by rapid shortening
In contrast to the present findings, previous studies have not found any
force depression after rapid shortening
(Edman et al., 1993;
Herzog and Leonard, 1997;
Herzog and Leonard, 2007;
Marechal and Plaghki, 1979).
This difference may be due to differences in methodology. Edman et al.,
shortened muscle fibres at the beginning of activation before significant
force had been developed [see figs 2 and 3 in Edman et al.
(Edman et al., 1993)] whereas
we shortened muscle fibres from the isometric plateau. When we shortened early
in activation in two fibres we found a small force depression in one fibre and
a small increase in force in the other fibre
(Fig. 5). Herzog and Leonard
measured force depression using a final muscle length on the ascending limb of
the force–length relationship
(Herzog and Leonard, 2007)
whereas, for shortening distances up to 400% stretch distance, we used final
lengths on the descending limb. Herzog and Leonard did not determine the
force–length relationship but may also have used final lengths on the
ascending limb (Herzog and Leonard,
1997). However, Maréchal and Plaghki used a very similar
protocol to that used in the present study (shortening by 7% fibre length from
the tension plateau on the descending limb of the force–length
relationship) but did not find any force depression after shortening at the
highest velocity that they used
(Maréchal and Plaghki,
1979).
In addition to the methodological differences discussed above, two other
possible explanations for the observed force depression were considered. The
first explanation was that we observed the shortening induced force depression
or `movement effect' described by Edman
(Edman, 1975;
Edman, 1980). This is different
from the permanent depression of isometric force described by Maréchal
and Plaghki (Maréchal and Plaghki,
1979) and Herzog and Leonard
(Herzog and Leonard, 1997) in
that it is transient, is not influenced by the velocity of shortening and
decreases as activation level increases. Edman reported that the movement
effect lasts up to 800–900ms after shortening
(Edman, 1975;
Edman, 1980). By contrast, we
found a depression of force almost 1.5s after shortening and calculated that
this would have remained for at least another 3.3s if stimulation had
continued. When we increased stimulation frequency by 10Hz in two fibres,
percentage force depression also increased
(Fig. 5) whereas the movement
effect would be expected to decrease. Therefore, the force depression that we
observed does not appear to be the same phenomenon as described by Edman.
The second explanation for the observed force depression that was
considered was that it was the same phenomenon as described by Maréchal
and Plaghki (Maréchal and Plaghki,
1979), and that it did not occur during the period of rapid
unloaded shortening but during the time when force was redeveloping and the
sarcomeres were shortening and doing work against the tendons at the end of
the fibre. The muscle fibres that we used were relatively short so that a
given extension of the tendons would allow more shortening per sarcomere than
in a longer fibre. The purely isometric contraction with which the
isometric-shortening contraction was compared also included a period of force
development when the muscle was initially activated. Therefore, this
explanation only makes sense if some of the effects of the initial period of
force development in the isometric-shortening contraction persisted despite
the rapid shortening and the fact that force remained at zero for an
appreciable time for the longer shortening distances. This is consistent with
the findings that rapid shortening, during which force dropped to zero, did
not completely eliminate the force depression induced by a previous period of
slow shortening (Herzog and Leonard,
2007).
To investigate this idea further, we performed a series of tests in two
fibres in which the distance of shortening was kept constant but the number of
periods of force development was varied
(Fig. 5). In both fibres we
found that the amount of force depression increased with the number of periods
of force development, as would be expected if the force depression arose
during force development. Lee et al. also determined the effect of using
multiple shortening steps (Lee et al.,
2001). They found that the number of steps did not affect the
amount of force depression. However, because they used slow speeds of
shortening, which would be expected to induce a large amount of force
depression, it is likely that the force depression during force redevelopment
was insignificant relative to that during shortening, explaining the
difference from the results observed in the present study.
The preliminary investigations that we performed support the possibility
that the force depression arose during force development rather than during
the period of unloaded shortening but further experiments with a greater
number of fibres are needed to confirm this. It is important to establish
whether force depression does occur after unloaded shortening because this has
implications for the mechanism of force depression. For example,
Maréchal and Plaghki proposed that force depression arises from a
stress-induced inhibition of cross-bridge attachment in the region of new
overlap that forms between actin and myosin filaments during shortening
(Maréchal and Plaghki,
1979). This implies that unloaded shortening, when stress is zero,
should not induce force depression.
Consideration of possible interactions between force enhancement and force
depression raises the question of whether they have the same underlying
mechanism. These two effects exhibit a number of differences in their
characteristics suggesting that they may have different mechanisms. For
example, force depression is very sensitive to shortening velocity
(Edman et al., 1993;
Herzog and Leonard, 1997;
Marechal and Plaghki, 1979)
whereas force enhancement is insensitive to stretch velocity
(Edman et al., 1978); force
depression continues to increase as shortening distance increases but force
enhancement increases with stretch distance only up to a point and then levels
out (Bullimore et al., 2007),
and force depression and force enhancement have different relationships to
muscle length (Schachar et al.,
2004). These differences suggest that the underlying mechanisms
are not the same but this does not address how force depression and
enhancement might be connected in stretch-shortening or shortening-stretch
experiments.
Role of rFE in vivo
In life, muscles rarely perform ramp stretches followed by prolonged
isometric contractions. Common tasks, such as locomotion, typically involve
short periods of activation during which muscle length and velocity vary
continuously; however, this does not mean that rFE cannot play a role in such
tasks. It has been shown that rFE is present almost immediately after the end
of stretch (Edman et al.,
1984), that isotonic as well as isometric force is enhanced
(Edman et al., 1978), and that
rFE occurs in muscles that are voluntarily activated to submaximal levels
(Oskouei and Herzog, 2005).
Therefore, it seems likely that rFE influences muscle force during everyday
activities. This effect is expected to be beneficial. Muscle stretch will
occur whenever the load on a muscle exceeds the isometric force at the current
level of activation. While such stretch is a desirable component of many
normal activities, it will also occur when the force on a muscle is
unexpectedly high, e.g. when an animal stumbles or slips, steps in a hole or
is carrying a load. By enhancing the force-producing capacity of a muscle
after stretch, rFE would help the muscle to support loads that are higher than
expected until activation level can be increased.
Conclusions
We have shown that rFE is unlikely to arise solely from a parallel elastic
element that increases in stiffness when the muscle is activated. Other
mechanisms that have been proposed include non-uniformity of half-sarcomere
properties and behaviour (Edman and
Tsuchiya, 1996; Morgan,
1990; Telley et al.,
2003) and an increase in the force generated by the cross-bridges
(Herzog, 1998;
Linari et al., 2000). It is
also quite possible that rFE is generated by more than one mechanism, e.g. the
combined effect of a passive and an active component
(Herzog and Leonard, 2002).
This would not be surprising because, as discussed above, rFE is expected to
play a beneficial role during everyday activities. From an evolutionary
viewpoint, this implies that any feature that results in rFE would be favoured
by natural selection. Therefore, it is quite possible that muscle has
developed several features that cause rFE. If this is the case, then it
presents a significant challenge to experimenters who must develop techniques
for partitioning the observed rFE between different causes.
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Acknowledgments |
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Footnotes |
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References |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Abbott, B. C. and Aubert, X. M. (1952). The
force exerted by active striated muscle during and after change of length.
J. Physiol. 117,77
-86.
Bagni, M. A., Cecchi, G., Colombini, B. and Colomo, F. (2002). A non-cross-bridge stiffness in activated frog muscle fibres. Biophys. J. 82,3118 -3127.[Medline]
Bianco, P., Nagy, A., Kengyel, A., Szatmári, D., Mártonfalvi, Z., Huber, T. and Kellermayer, M. S. Z. (2007). Interaction forces between F-actin and titin PEVK domain measured with optical tweezers. Biophys. J. 93,2102 -2109.[CrossRef][Medline]
Bullimore, S. R., Leonard, T. R., Rassier, D. E. and Herzog, W. (2007). History-dependence of isometric muscle force: effect of prior stretch or shortening amplitude. J. Biomech. 40,1518 -1524.[CrossRef][Medline]
Edman, K. A. P. (1975). Mechanical deactivation
induced by active shortening in isolated muscle fibers of frog. J.
Physiol. 246,255
-275.
Edman, K. A. P. (1979). Velocity of unloaded
shortening and its relation to sarcomere length and isometric force in
vertebrate muscle fibers. J. Physiol.
291,143
-159.
Edman, K. A. P. (1980). Depression of mechanical performance by active shortening during twitch and tetanus of vertebrate muscle fibres. Acta Physiol. Scand. 109, 15-26.[Medline]
Edman, K. A. P. and Tsuchiya, T. (1996). Strain
of passive elements during force enhancement by stretch in frog muscle fibres.
J. Physiol. 490,191
-205.
Edman, K. A. P., Elzinga, G. and Noble, M. I. M.
(1978). Enhancement of mechanical performance by stretch during
tetanic contractions of vertebrate skeletal muscle fibers. J.
Physiol. 281,139
-155.
Edman, K. A. P., Elzinga, G. and Noble, M. I. M.
(1982). Residual force enhancement after stretch of contracting
frog single muscle fibers. J. Gen. Physiol.
80,769
-784.
Edman, K. A. P., Elzinga, G. and Noble, M. I. M. (1984). Stretch of contracting muscle fibres: evidence for regularly spaced active sites along the filaments and enhanced mechanical performance. Adv. Exp. Med. Biol. 170,739 -751.[Medline]
Edman, K. A. P., Caputo, C. and Lou, F. (1993).
Depression of tetanic force induced by loaded shortening of frog muscle
fibers. J. Physiol. 466,535
-552.
Ford, L. E., Huxley, A. F. and Simmons, R. M.
(1977). Tension responses to sudden length change in stimulated
frog muscle fibres near slack length. J. Physiol.
269,441
-515.
Fung, Y. C. B. (1967). Elasticity of soft
tissues in simple elongation. Am. J. Physiol.
213,1532
-1544.
Herzog, W. (1998). History dependence of force production in skeletal muscle: a proposal for mechanisms. J. Electromyogr. Kinesiol. 8,111 -117.[CrossRef][Medline]
Herzog, W. and Leonard, T. R. (1997). Depression of cat soleus forces following isokinetic shortening. J. Biomech. 30,865 -872.[CrossRef][Medline]
Herzog, W. and Leonard, T. R. (2000). The history dependence of force production in mammalian skeletal muscle following stretch-shortening and shortening-stretch cycles. J. Biomech. 33,531 -542.[CrossRef][Medline]
Herzog, W. and Leonard, T. R. (2002). Force
enhancement following stretching of skeletal muscle: a new mechanism.
J. Exp. Biol. 205,1275
-1283.
Herzog, W. and Leonard, T. (2007). Residual force depression is not abolished following a quick shortening step. J. Biomech. 40,2806 -2810.[CrossRef][Medline]
Herzog, W., Lee, E. J. and Rassier, D. E.
(2006). Residual force enhancement in skeletal muscle.
J. Physiol. 574,635
-642.
Huxley, A. F. (1957). Muscle structure and theories of contraction. Prog. Biophys. Biophys. Chem. 7, 255-318.[Medline]
Jin, J. P. (1995). Cloned rat cardiac titin
class-I and class-Ii motifs-Expression, purification, characterization, and
interaction with F-actin. J. Biol. Chem.
270,6908
-6916.
Joumaa, V., Rassier, D. E., Leonard, T. R. and Herzog, W. (2008). The origin of passive force enhancement in skeletal muscle. Am. J. Physiol. 294,C74 -C78.[CrossRef]
Labeit, D., Watanabe, K., Witt, C., Fujita, H., Wu, Y., Lahmers,
S., Funck, T., Labeit, S. and Granzier, H. (2003).
Calcium-dependent molecular spring elements in the giant protein titin.
Proc. Natl. Acad. Sci. USA
100,13716
-13721.
Lannergren, J., Lindblom, P. and Johansson, B. (1982). Contractile properties of two varieties of twitch muscle fibres in Xenopus laevis. Acta Physiol. Scand. 114,523 -535.[Medline]
Lee, H. D. and Herzog, W. (2002). Force
enhancement following muscle stretch of electrically stimulated and
voluntarily activated human adductor pollicis. J.
Physiol. 545,321
-331.
Lee, H.-D., Herzog, W. and Leonard, T. (2001). Effects of cyclic changes in muscle length on force production in in situ cat soleus. J. Biomech. 34,979 -987.[CrossRef][Medline]
Li, Q. N., Jin, J. P. and Granzier, H. L. (1995). The effect of genetically expressed cardiac titin fragments on in vitro actin motility. Biophys. J. 69,1508 -1518.[Medline]
Linari, M., Lucii, L., Reconditi, M., Vannicelli Casoni, M. E.,
Amenitsch, H., Bernstorff, S., Piazzesi, G. and Lombardi, V.
(2000). A combined mechanical and X-ray diffraction study of
stretch potentiation in single frog muscle fibres. J.
Physiol. 526,589
-596.
Marechal, G. and Plaghki, L. (1979). The
deficit of the isometric tetanic tension redeveloped after a release of frog
muscle at a constant velocity. J. Gen. Physiol.
73,453
-467.
Morgan, D. L. (1990). New insights into the behavior of muscle during active lengthening. Biophys. J. 47,209 -221.
Morgan, D. L. and Proske, U. (2007). Can all
residual force enhancement be explained by sarcomere non-uniformities?
J. Physiol. 578,613
-615.
Niederländer, N., Raynaud, F., Astier, C. and Chaussepied, P. (2004). Regulation of the actin-myosin interaction by titin. Eur. J. Biochem. 271,4572 -4581.[Medline]
Oskouei, A. E. and Herzog, W. (2005).
Observations on force enhancement in submaximal voluntary contractions of
human adductor pollicis muscle. J. Appl. Physiol.
98,2087
-2095.
Pinniger, G. J., Ranatunga, K. W. and Offer, G. W.
(2006). Crossbridge and non-crossbridge contributions to tension
in lengthening rat muscle: force-induced reversal of the power stroke.
J. Physiol. 573,627
-643.
Rassier, D. E. and Herzog, W. (2004a). Active
force inhibition and stretch-induced force enhancement in frog muscle treated
with BDM. J. Appl. Physiol.
97,1395
-1400.
Rassier, D. E. and Herzog, W. (2004b). Effects of shortening on stretch-induced force enhancement in single skeletal muscle fibers. J. Biomech. 37,1305 -1312.[CrossRef][Medline]
Rassier, D. E. and Herzog, W. (2005).
Relationship between force and stiffness in muscle fibers after stretch.
J. Appl. Physiol. 99,1769
-1775.
Schachar, R., Herzog, W. and Leonard, T. R. (2004). The effects of muscle stretching and shortening on isometric forces on the descending limb of the force-length relationship. J. Biomech. 37,917 -926.[CrossRef][Medline]
Soteriou, A., Gamage, M. and Trinick, J. (1993). A survey of interactions made by the giant protein titin. J. Cell Sci. 104,119 -123.[Abstract]
Sugi, H. and Tsuchiya, T. (1981). Enhancement
of mechanical performance in frog muscle fibres after quick increases in load.
J. Physiol. 319,239
-252.
Telley, I. A. and Denoth, J. (2007). Sarcomere dynamics during muscular contraction and their implications to muscle function. J. Muscle Res. Cell. Motil. 28, 89-104.[CrossRef][Medline]
Telley, I. A., Denoth, J. and Ranatunga, K. W. (2003). Inter-sarcomere dynamics in muscle fibres: a neglected subject? Adv. Exp. Med. Biol. 538,481 -500.[Medline]
Tskhovrebova, L. and Trinick, J. (2003). Titin: properties and family relationships. Nat. Rev. Mol. Cell. Biol. 4,679 -689.[CrossRef][Medline]
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