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ARTICLE IN PRESS

Journal of Biomechanics 36 (2003) 1309–1316

Stretch-induced, steady-state force enhancement in single skeletal
muscle fibers exceeds the isometric force at optimum fiber length
Dilson E. Rassier, Walter Herzog*, Jennifer Wakeling, Douglas A. Syme
Faculty of Kinesiology, Human Performance Laboratory, University of Calgary, 2500, University Dr. N.W Calgary, Calgary, Canada AB T2N 1N4
Accepted 31 March 2003

Abstract

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 ¼ 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.
r 2003 Elsevier Science Ltd. All rights reserved.

Keywords: Striated muscle; Single fibers; Force enhancement; Muscle mechanics; Force production; Cross-bridge theory; Sarcomere length non-
uniformity theory

1. Introduction than any other theory (Edman et al., 1982; Edman and
Tsuchiya, 1996; Julian and Morgan, 1979b; Julian and
The steady-state isometric force following active Morgan, 1979a; Morgan, 1990; Morgan, 1994; Morgan
muscle stretch is greater than the purely isometric force et al., 2000). The sarcomere length non-uniformity
at the corresponding length. This property of skeletal theory is based on the idea that during stretch, on the
muscle has been observed at structural levels ranging descending limb of the force–length relationship, some
from single fibers (e.g. Edman et al., 1978) to in vivo sarcomeres elongate less than average (and so, can
human skeletal muscle (Lee and Herzog, 2002), and it produce more active force at steady-state than if they
has been termed ‘‘force enhancement following stretch’’ were at the average sarcomere length), while others
(Herzog, 1998). There is no generally accepted explana- elongate more than average and produce most of their
tion for this force enhancement, although the sarcomere force passively (Fig. 1).
length non-uniformity theory has received more support If sarcomere length non-uniformity was the only
mechanism for force enhancement, the steady-state
*Corresponding author. Tel.: +1-403-220-8525; fax: +1-403-284-
force enhancement following stretch should not exceed
3553. the purely isometric force at optimum muscle length.
E-mail address: walter@kin.ucalgary.ca (W. Herzog). However, recently we observed force enhancements of

0021-9290/03/$ - see front matter r 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0021-9290(03)00155-6
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approved by the University of Calgary Committee for
the ethical use of animals in research.
After dissection, the tendons of the dissected fibers
were gripped with small pieces of T-shaped aluminum
foil close to the end of the fibers to eliminate series
elastic compliance as much as possible. The fibers were
mounted in an experimental chamber between a
servomotor length controller (Aurora Scientific) and a
force transducer (sensonor). The chamber was filled with
Ringer’s solution (NaCl 115 mmol, KCl 2 mmol, CaCl2
2 mmol, NaH2PO4 2 mmol, NaHCO3 20 mmol,
pH ¼ 7:5), and the temperature was regulated at
B8 C (range: 7.2–9.5 C) during all experiments.
Stimulation (Grass S88, Grass Instruments) was given
Fig. 1. Schematic illustration of force enhancement following stretch
through two platinum wire electrodes placed in the
according to the sarcomere-length non-uniformity theory. A muscle is
stretched on the descending limb of the force–length relationship from chamber parallel to the muscle fibers, with square pulses
an initial average sarcomere length (open circle) to a final average (0.3–0.5 ms duration) delivered with an amplitude 25%
sarcomere length (filled square). During stretching of the muscle, it is above the voltage that gave maximal force production
assumed that some sarcomeres are stretched less than average (filled (range: 30–70 V). The frequency of stimulation was
circle, left) while others are stretched more than average (filled circle,
chosen for each fiber individually to induce a completely
right). The sarcomeres that are stretched less than average are stronger
than an average sarcomere would be, because of the slope of the force fused tetanic contraction; it ranged between 15 and
length relationship. The sarcomeres that are stretched more than 23 Hz in the lumbricals and 35 and 55 Hz in TA.
average become weaker initially, but then are ‘‘caught’’ by the passive
force of the muscle, and they elongate until a force equilibrium is 2.1. Muscle length and force measurements
established between the short and long sarcomeres. This force at
equilibrium (dashed line) is greater than the expected force at the
average sarcomere length, and therefore, this mechanism can At the beginning of the experiment, the optimum
potentially account for the observed force enhancement following voltage and frequency of stimulation were defined with
muscle stretch. 1 s tetanic contractions, after which the fibers were
paced during 30 min with intermittent twitch contrac-
up to 10% greater than the isometric force at optimum tions induced every 90 s. Following this procedure, fibers
length in pilot studies of single fibers from frog tibialis were inspected visually to check for any apparent
anterior (Wakeling et al., 2001), and whole soleus of cat damage. Fibers were evaluated for decrease in isometric
(Herzog and Leonard, 2002). Furthermore, in these force during 1 s tetanic reference contractions before and
experiments, there was an enhancement of passive force throughout testing. If the reference force decreased,
once the preparation was deactivated. We termed this fibers were discarded. Close to 200 fibers were tested in
novel observation ‘‘passive force enhancement’’. this way to provide the 34 fibers for which consistent
Motivated by these observations, the purposes of this reference contractions were obtained throughout the
study were: (a) to determine if force enhancement experimental protocol.
following active stretch exceeds the purely isometric After the initial procedures, fibers were subjected to
force at optimum length in single fibers given the two different series of contractions. During the first
appropriate stretch protocol; (b) to quantify the possible series, an active (total force–passive force) force–length
‘‘passive force enhancement’’ in single fibers; and (c) to (FL) relationship was derived from isometric tetanic
test if the passive force enhancement might explain the contractions (2 s duration). During these contractions, it
amount of force enhancement above the isometric force was possible to define the plateau of the FL relation,
at optimum length. All experiments were performed referred to as 0 mm hereafter, and the descending limb
using single fibers from frog (rana pipiens) tibialis of the FL relation. An interval of 5–8 min was given
anterior and lumbricals. between contractions and at the end of this series, a
tetanic reference contraction was made at 0 mm to check
if the isometric reference force was constant.
2. Methods A second series of contractions was performed to
evaluate the stretch-induced force enhancement. These
Muscle preparation: The experiments were performed contractions were of 3–4 s for TA and 6 s for the
with 22 single muscle fibers (E2 mm length) dissected lumbrical fibers. These times were sufficient to reach
from the lumbricals and with 12 fibers from the tibialis steady-state forces following active stretch. Steady-state
anterior (TA) (E 10 mm length) of frog, rana pipiens. was achieved, according to our definition, once the
Treatment of the animals and all procedures were force–time trace following active stretch was parallel to
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the corresponding isometric reference contractions. Par- decay following isometric and stretch contractions was
allelism was evaluated by fitting a least-squares straight evaluated by calculating the time from the last activa-
line through the data points for the last 0.5 s of tetanus tion pulse to the instant when force had decreased by
and testing for differences in these slopes (a ¼ 0:05). 50% (T50), and the time from 80% to 20% of the force
For stretching of the muscle fibers, the fibers were just after deactivation (T80–20); and (ii) linear regression
placed at an initial length (Li ), activated to reach at least analyses (a ¼ 0:05) were performed for passive force
95% of the maximal isometric force at that length enhancement as a function of stretch amplitude, passive
(E0.85 s), stretched to the final length (Lf ), and held at force enhancement as a function of total force enhance-
the final length until steady-state force was obtained (as ment, force decay times as a function of stretch
determined in pilot experiments). The initial fiber amplitude, and force enhancement as a function of
lengths were chosen at approximately 5%, 10%, and stretch amplitudes.
15% of fiber lengths beyond the plateau of the force–
length relationship (i.e. on the descending limb).
Stretch amplitudes ranged from 2.5% to 15% of fiber 3. Results
lengths, and the speed of stretch was 10%, 20%, 40%,
50%, 100% or 150% of fiber length/s. One full stretch For fibers from both muscles, and for all stretch
experiment consisted of the following eight tests: amplitudes and stretch speeds considered in this study,
isometric contractions at optimum length, Li ; and Lf ; the steady-state forces following active stretch were
the experimental stretch contraction; the experimental always greater than the purely isometric reference
stretch contraction without muscle activation (passive contractions at the corresponding length (Lf ) (Fig. 2).
stretch), and a repeat of the three initial isometric Similarly, the steady-state forces following active stretch
contractions. Following such a test, and assuming that were always equal or greater than the purely isometric
the isometric reference contractions were steady, the reference contractions at the length from which the
next stretch experiment (new Li ; new amplitude, or new stretch was initiated (Li ) (Figs. 2 and 3). Both these
stretch speed) was performed. results were statistically significant.
In many (but not all) cases, the steady-state forces
2.2. Data analysis and statistics following active stretch were greater than the isometric
reference forces at the plateau of the force–length
All calculations of force enhancement were made for relationship (i.e. at optimum length (Figs. 3a and b
active forces. In order to obtain the active forces for the and 4). Force enhancement above the plateau was likely
isometric contractions, the passive forces just before and to occur when the initial length was close to the plateau
just after activation were joined by a straight line, and (i.e. just slightly on the descending limb of the force–
the force values of this straight line were subtracted length relationship) and when stretch amplitudes were
from the total force. This was done to account for the great (Figs. 5 and 6). Often, force enhancement above
slow (but measurable) decrease in passive force as a
function of time. For the experimental stretch tests,
active and passive fiber stretching was performed for
identical stretch speeds and magnitudes, and the forces
of the passive stretch test were subtracted from the time-
synchronized total forces of the stretch test with the fiber
activated. The active forces recorded at 0.5 s before the
end of contraction, or at 2–3 s (TA) and at 5 s following
the end of the stretch lumbricals, and the residual
passive forces following the active stretch tests recorded
at 1.5 s after deactivation, were used for statistical
analysis. For each initial length investigated in these
experiments, the tetanic and passive force values
following active stretch (i.e. the enhanced forces) were
compared to the isometric reference forces recorded at
the plateau (L0 ), at Li and Lf by means of a one-way
ANOVA for repeated measures. When a significant Fig. 2. Exemplar raw data from a single fiber of TA. Shown are the
difference was observed, contrasts that were chosen a isometric force–time traces at the initial and at two final lengths (initial
plus 5% and initial plus 10% increase in fiber length). Also shown are
priori were used for subsequent mean comparisons. A
four force–time traces for stretches of 2.5%, 5%, 7.5%, and 10% from
significance level of po0:05 was set for all analyses. the initial length at a speed of 0.2 fiber lengths/s. Note that the steady-
Using this initial data analysis, the following post-hoc state force enhancement following all stretches is greater than the
analyses procedures were added: (i) the rate of force purely isometric forces at the final and initial lengths.
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Fig. 4. Exemplar raw data from a single fiber from the lumbricals.
Shown are the isometric force at optimum length (o, top isometric
trace) and the final length (f, bottom isometric trace). The active (s, top
trace) and passive (p, bottom trace) stretch tests are also shown. Note
that force enhancement following the active stretch greatly exceeds the
purely isometric force at optimum fiber length. Observe further that
the passive force in the active stretch experiments (after fiber
deactivation, arrow) is greater than the corresponding passive forces
of the isometric test at the final length and the passive force following
the passive stretch test. We called this additional passive force
following active fiber stretching ‘‘passive force enhancement’’ (see
arrow). Initial length was 5% greater than optimum length and the
stretch amplitude was 15% of optimum fiber length at a speed of 40%
fiber length/s.

Fig. 3. Exemplar raw data from one fiber from the lumbricals. Shown
are force–time traces of three isometric contractions at fiber optimum
length (o, top isometric trace), the initial length (i, mid-isometric trace),
and the final length (f, bottom isometric trace), as well as a stretch test
from the initial to the final fiber length (s). Note the sharp increase in
force at the onset of stretch (the short-range stiffness), followed by a
less steep slope in (a) and (b). Note further that the steady-state force
enhancement is greater than any of the isometric forces, particularly
the optimum isometric force (top isometric trace) in (a) and (b). In (c),
force enhancement does not exceed the optimum isometric force as the
stretch amplitude was not sufficient to achieve this result. Initial
lengths: 5%, 10%, and 15% fiber lengths greater than optimum Fig. 5. Mean force–length relationship and mean (71 S.E.) steady-
lengths for (a), (b), and (c), respectively. Final lengths: 20% greater state total and passive force enhancement following stretch tests in
than optimum length in all three cases, therefore the stretch amplitude lumbrical fibers (n=22). Forces were normalized with respect to the
was 15%, 10%, and 5% of fiber length for (a), (b), and (c). Stretch maximal isometric force for comparison across fibers. Fiber lengths
speed was 40% fiber lengths/s in all cases. were normalized relative to the optimum fiber length; i.e. the length at
which the active isometric force was greatest. Note that the mean force
enhancement for several conditions exceeded the maximal isometric
forces. Note further, that force enhancement was directly related to the
stretch magnitude for all initial lengths.
the plateau was associated with substantial passive
force enhancement following deactivation of the muscle
(Fig. 4). When the passive force enhancement values
were subtracted from the total force enhancement values
for the cases in which force enhancement exceeded the Passive force enhancement was positively correlated
plateau forces, force enhancement values were reduced with the stretch amplitude and the amount of total force
to the isometric plateau values, or below, at least in a enhancement (Figs. 10a and b).
statistical sense (Fig. 7). Finally, the force decay times, T50 and T80–20, were
Force enhancement was found to be positively related typically greater following the experimental stretch
to the magnitude of stretch, as had been shown in tests, compared to the decay times observed for the
previous studies (Figs. 5 and 6) (Edman et al., 1978; isometric contractions at the corresponding muscle
Edman et al., 1982). Interestingly, the amount of force lengths. Furthermore, force decay times tended to
enhancement had a small, but statistically significant, increase, i.e. the average rate of change in force
negative relationship with the stretch rate for TA fibers tended to decrease, with increasing stretch magnitudes
(Fig. 8), but not the lumbrical fibers (Fig. 9). (Fig. 11).
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4. Discussion

We found that the steady-state isometric forces
following active fiber stretching were greater than the
purely isometric forces at the corresponding fiber length
(Lf ) for all experimental conditions tested. New to the
literature is our observation that stretch-induced force
enhancement can also exceed peak isometric force and
that passive force enhancement can occur too. The first
observation confirms previous results performed on
single fibers (Edman et al., 1978; Edman et al., 1982;
Sugi and Tsuchiya, 1988), isolated muscles (Abbott and
Aubert, 1952; Mare! chal and Plaghki, 1979; Morgan
et al., 2000), and in vivo muscle preparations (Lee and
Fig. 6. Mean force–length relationship and mean (71 SD) steady-state Herzog, 2002). Although there is no accepted scientific
force enhancement following stretch tests in TA fibers (n=5). Forces
paradigm for force enhancement following stretch, the
were normalized with respect to the maximal isometric force for
comparison across fibers. Fiber lengths were normalized relative to the sarcomere length non-uniformity theory has received
optimum fiber length; i.e. the length at which the active isometric force more support than any other competing theory (Edman
was greatest. Note that the mean force enhancement for several and Tsuchiya, 1996; Julian and Morgan, 1979a;
conditions exceeded the maximal isometric forces. Note further, that Morgan, 1990; Morgan, 1994; Morgan et al., 2000).
force enhancement was directly related to the stretch magnitude.
One of the features of the sarcomere length non-
uniformity theory is that the steady-state isometric force
cannot exceed the isometric force at optimum fiber
(muscle) length. We are not aware of any published
results that show force enhancement values in single
fibers above the plateau force, except possibly those by
Edman et al. (1978, 1982) who found force enhancement
following stretch that exceeded plateau forces on some
occasions by 1–2%, but discarded these results as being
within the error of measurement rather than a true
steady-state force above the plateau (Edman et al., 1982;
Edman, personal communication, February 2001).
We obtained consistent force enhancement above the
Fig. 7. Mean force–length relationship and mean (71 S.E.) steady- isometric plateau forces in 22 fibers from the lumbricals
state active (i.e., total-passive) force enhancement following stretch (Fig. 5) and five fibers from TA (Fig. 6). Force
tests in lumbrical fibers (n=22). From a statistical point of view, active
enhancement exceeded the plateau forces by approxi-
force enhancement did not exceed the active isometric forces at
optimum length. mately 10% on some occasions, and was clearly above
the error of measurement (71%). These fibers were not
damaged, as isometric reference contractions following
the stretch tests gave the same values as the correspond-
ing contractions prior to the stretch test. It could be
argued that force enhancement above the plateau forces
might have occurred because incorrect passive values
were subtracted from the total force values. This is
somewhat a problem as the passive forces during tetanic
contraction cannot be determined, and the passive
forces during a passive stretch might not be exactly the
same as the passive forces during active muscle
stretching at corresponding fiber lengths. However,
force enhancement was determined during steady-state
isometric contractions several seconds following the
stretch tests, when passive force transients caused by
Fig. 8. Mean71 S.D. force enhancement of TA fibers as a function of
fiber stretching had subsided. Also, our approach of
stretch speed (n=12). The best fitting regression line was fit to the raw
data and showed a significant negative correlation between force calculating the active force enhancement was the same
enhancement and strain rate. This result was not found for lumbrical as that used by others (Edman et al., 1982; Morgan et al.,
fibers. 2000). Therefore, we are quite confident that the force
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Fig. 9. Exemplar raw data of stretch tests at different speeds for a single fiber from the lumbricals. Shown is an isometric contraction at the initial
length (i=5% greater than optimum length) and 5 stretch tests of 15% fiber length at speeds of approximately 20%, 30%, 40%, 100%, and 150%
fiber length/s (20, 30, 40, 100, and 150, respectively). Note that the steady-state forces following all stretches were similar. No significant relationship
between force enhancement and stretch speed was found in lumbrical fibers.

Fig. 10. Passive force enhancement in lumbrical fibers as a function of the stretch amplitude: (a), and the total force enhancement (b). The great
variation in the passive force enhancement for a given stretch amplitude is partly caused by the dependence of passive force enhancement on the
absolute fiber lengths. For example, a stretch of 5% starting at a fiber length of 5% greater than optimum length typically gave a smaller passive force
enhancement than a stretch of equal magnitude starting at a fiber length of 15% greater than optimum.

enhancement above the isometric forces at optimum the plateau forces requires a different or an additional,
length are a true reflection of the mechanisms underlying mechanism.
the force enhancement process, rather than an artefact There are conceptually two possibilities to explain the
associated with the calculation of active force. steady-state forces following active stretch above the
Based on our results, force enhancement following plateau forces: (a) cross-bridge based mechanisms; or (b)
stretch cannot be explained using the sarcomere length non-cross-bridge based mechanisms. If a cross-bridge
non-uniformity theory exclusively. At best, this theory based mechanism was responsible for the force enhance-
can explain force enhancements up to the isometric ment above plateau, then cross-bridges following active
plateau forces. Steady-state force enhancement above stretch should be stronger, or there should be a greater
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Simmons, 1971), the increased cross-bridge force and/
or the greater proportion of attached cross-bridges
cannot be maintained for several seconds following a
stretch. Therefore, cross-bridge-based explanations
must be dismissed, or the basic theoretical framework
of the cross-bridge theory (i.e. the idea that the
molecular events of contraction are independent of the
contractile history) would need conceptual changing.
Considering non-cross-bridge-based mechanisms, a
single explanation for force enhancement has been
mentioned much more frequently than any of the
remaining possibilities; the idea of a passive element
that (somehow) is engaged during active stretch of
muscles (fibers), and so produces additional force at the
stretched length compared to the corresponding iso-
metric force (DeRuiter et al., 2000; Edman et al., 1982;
Edman and Tsuchiya, 1996; Forcinito et al., 1998;
Noble, 1992). However, to date, there has been no direct
evidence for force enhancement through a passive elastic
element with the exception of our own work on whole
cat soleus (Herzog and Leonard, 2002) and in vivo
human adductor pollicis (Lee and Herzog, 2002). Here,
we found that, under some conditions, force enhance-
ment was associated with a passive force enhancement;
that is, a passive force following active stretch that was
Fig. 11. Mean decay times (7SE) from last stimulus to 50% force, substantially greater than the corresponding passive
T50, and 80% to 20% force, T80–20, as a function of the stretch force following passive stretch (Fig. 4). At present, we
amplitudes (a and b, respectively). 0% stretches are the isometric do not know the origin of this passive force enhance-
reference contractions. Note the increase in decay times with increasing
fiber stretch amplitudes. The three lines shown refer to stretches ending
ment. However, it appears that the passive force
at final lengths of 10% (10), 15% (15), and 20% (20) greater than enhancement was related to the stretch amplitude and
optimum length. When combining all stretch experiments, decay times the amount of total force enhancement (Figs. 10a and
were significantly greater for the stretch experiments than the isometric b), and therefore, the absolute fiber length. Further-
reference contractions. more, it appears that force enhancement above the
plateau forces was largely abolished once the passive
number of attached cross-bridges following stretch component of force enhancement was subtracted from
compared to the purely isometric conditions (Huxley, the total force enhancement (Fig. 7). These results
1957). Sugi and Tsuchiya (1988) reported that stiffness suggest that the passive component of force enhance-
following active stretch in single frog fibers was the same ment ‘‘engages’’ at the initial length at which the muscle
as that for purely isometric contractions at Lf ; suggest- is activated. When stretched from this initial length, the
ing that force enhancement was caused by an increase in passive component of force enhancement increases with
the average force per cross-bridge. In contrast, Linari increasing stretch magnitude, as does the total force
et al. (2000) found that stiffness of actively stretched enhancement. Finally, the results suggest that the
frog fibers was greater than that for purely isometric passive component of force enhancement gives rise to
contractions at Lf ; suggesting that force enhancement the steady-state force enhancement that exceeds the
was caused by an increase in the proportion of attached isometric plateau forces. Therefore, we believe that there
cross-bridges. However, Linari et al. (2000) made this might be two distinct components to the total force
stiffness measurement shortly (175 ms) following the enhancement: (i) an ‘‘active’’ component that permits
stretch when steady-state conditions had not been force enhancement up to the isometric plateau force;
reached. We observed in cat soleus that force enhance- and (ii) a passive component that gives rise to the force
ment at steady-state was associated with an increased enhancement in excess of the isometric plateau force.
muscles stiffness compared to the corresponding iso- The decay times, T50 and T8020, were greater for all
metric reference contractions (Herzog and Leonard, stretch tests combined, and typically increased with the
2000). Therefore, it appears that neither of the cross- magnitude of stretch, compared to the corresponding
bridge explanations can be dismissed at the moment. isometric reference contractions (Fig. 11). This result
However, according to the mathematical formulation of was only discovered in a post-hoc analysis, and no
the cross-bridge theory (Huxley, 1957; Huxley and systematic experiments were performed to elucidate the
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possible mechanisms for this decreased rate of force Edman, K.A.P., Elzinga, G., Noble, M.I.M., 1978. Enhancement of
decrease following active fiber stretching compared to mechanical performance by stretch during tetanic contractions
the isometric reference contractions. However, several of vertebrate skeletal muscle fibres. Journal of Physiology 281, 139–
155.
possibilities exist. These include a change in rate of Edman, K.A.P., Elzinga, G., Noble, M.I.M., 1982. Residual force
cross-bridge attachment/detachment, a decreased rate of enhancement after stretch of contracting frog single muscle fibers.
Ca2+ uptake into the sarcoplasmic reticulum, or an Journal of General Physiology 80, 769–784.
increase in a passive viscoelastic response (Brown and Forcinito, M., Epstein, M., Herzog, W., 1998. Can a rheological
Loeb, 2000). Future experiments should be conducted to muscle model predict force depression/enhancement? Journal of
Biomechanics 31, 1093–1099.
investigate this finding in detail. Herzog, W., 1998. History dependence of force production in skeletal
muscle: a proposal for mechanisms. Journal of Electromyography
and Kinesiology 8, 111–117.
5. Summary and conclusion Herzog, W., Leonard, T.R., 2000. The history dependence of force
production in mammaliar skeletal muscle following stretch-short-
ening and shortening-stretch cycles. Journal of Biomechanics 33,
This is the first study to demonstrate that the steady- 531–542.
state force enhancement following active fiber stretching Herzog, W., Leonard, T.R., 2002. Force enhancement following
can give rise to forces that are substantially greater than stretching of skeletal muscle: a new mechanism. Journal of
the isometric forces at optimum (plateau) length. These Experimental Biology 205, 1275–1283.
results eliminate the sarcomere length non-uniformity Huxley, A.F., 1957. Muscle structure and theories of con-
traction. Progress in Biophysics and Biophysical Chemistry 7,
theory as the sole explanation for force enhancement. 255–318.
Furthermore, we observed a passive component of force Huxley, A.F., Simmons, R.M., 1971. Proposed mechanism of force
enhancement that might contribute to the total force generation in striated muscle. Nature 233, 533–538.
enhancement, and might account for the steady-state Julian, F.J., Morgan, D.L., 1979a. Intersarcomere dynamics during
forces following active fiber stretch in excess of the fixed-end tetanic contractions of frog muscle fibres. Journal of
Physiology 293, 365–378.
isometric plateau forces. The details of this passive force Julian, F.J., Morgan, D.L., 1979b. The effects of tension on non-
enhancement are not known. However, the passive force uniform distribution of length changes applied to frog muscle
enhancement increases with increasing stretch magni- fibres. Journal of Physiology 293, 379–392.
tude, but is not, or only slightly, associated with the Lee, H.D., Herzog, W., 2002. Force enhancement following muscle
speed of stretch, and it is correlated with the magnitude stretch of electrically and voluntarily activated human adductor
pollicis. Journal of Physiology 545, 321–330.
of the total force enhancement. Others (DeRuiter et al., Linari, M., Lucii, L., Reconditi, M., Vannicelli Casoni, M.E.,
2000; Edman and Tsuchiya, 1996; Noble, 1992) have Amenitsch, H., Bernstorff, S., Piazzesi, G., 2000. A combined
suggested that the proteins titin or nebulin might engage mechanical and X-ray diffraction study of stretch potentiation
upon active stretching of muscle or muscle fibers, and so in single frog muscle fibres. Journal of Physiology 526 (3),
might produce the passive force enhancement observed 589–596.
Mar!echal, G., Plaghki, L., 1979. The deficit of the isometric tetanic
here for the first time in single fibers. tension redeveloped after a release of frog muscle at a constant
velocity. Journal of General Physiology 73, 453–467.
Morgan, D.L., 1990. New insights into the behavior of muscle during
References active lengthening. Biophysical Journal 57, 209–221.
Morgan, D.L., 1994. An explanation for residual increased tension in
Abbott, B.C., Aubert, X.M., 1952. The force exerted by active striated striated muscle after stretch during contraction. Experimental
muscle during and after change of length. Journal of Physiology Physiology 79, 831–838.
Morgan, D.L., Whitehead, N.P., Wise, A.K., Gregory, J.E., Proske,
117, 77–86.
Brown, I.E., Loeb, G.E., 2000. Measured and modeled properties of U., 2000. Tension changes in the cat soleus muscle following slow
mammalian skeletal muscle: III-the effects of stimulus frequency on stretch or shortening of the contracting muscle. Journal of
stretch-induced force enhancement and shortening-induced force Physiology 522 (3), 503–513.
Noble, M.I.M., 1992. Enhancement of mechanical performance of
depression. Journal of Muscle Research and Cell Motility 21,
21–31. striated muscle by stretch during contraction. Experimental
DeRuiter, C.J., Didden, W.J.M., Jones, D.A., de Haan, A., 2000. The Physiology 77, 539–552.
force–velocity relationship of human adductor pollicis muscle Sugi, H., Tsuchiya, T., 1988. Stiffness changes during enhancement
and deficit of isometric force by slow length changes in frog skeletal
during stretch and the effects of fatigue. Journal of Physiology 526
(3), 671–681. muscle fibres. Journal of Physiology 407, 215–229.
Edman, K.A.P., Tsuchiya, T., 1996. Strain of passive elements during Wakeling, J., Syme, D., Herzog, W., 2001. Force stability on the
force enhancement by stretch in frog muscle fibres. Journal of descending limb of the force–length relationship. Biophysical
Journal Book of Abstracts 80 (1), 270a.
Physiology 490 (1), 191–205.