contraction
Dilson E. Rassier and Walter Herzog
Journal of Applied Physiology 96:419-427, 2004. doi:10.1152/japplphysiol.00653.2003
This article cites 74 articles, 38 of which you can access free at:
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Active force inhibition and stretch-induced force enhancement in frog muscle treated with
BDM
D. E. Rassier and W. Herzog
J Appl Physiol, October 1, 2004; 97 (4): 1395-1400.
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J Appl Physiol 96: 419–427, 2004;
10.1152/japplphysiol.00653.2003. Invited Review
Rassier, Dilson E., and Walter Herzog. Considerations on the history dependence
of muscle contraction. J Appl Physiol 96: 419–427, 2004; 10.1152/japplphysiol.00653.
2003.—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
THE CROSS-BRIDGE MODEL OF muscle contraction was proposed cannot be explained directly by the degree of myofilament
by Huxley (38) and was further characterized in experiments overlap in sarcomeres (27).
conducted in his laboratory (41). Together with the sliding In the past two decades, it has been suggested repeatedly
filament theory (39, 40, 42, 43), and strengthened by the that force depression after shortening and force enhance-
description of the sarcomere force-length relationship (27), ment after stretching are associated with nonuniformity and
the cross-bridge model has been accepted to the point that it dispersion of sarcomere lengths (e.g., Refs. 10, 19, 45,
may be considered a true scientific paradigm. According to 56–58, 73). By using sarcomere length nonuniformity and
Kuhn (48), a scientific paradigm is expected to explain most dispersion, many results could be interpreted without alter-
but not necessarily all experimental observations in a given ing the basis of the cross-bridge model of muscle contrac-
area of investigation. In the field of muscle mechanics and tion, thereby providing a convincing and simple explanation
physiology, most studies are interpreted and explained for experimental findings that had no ready explanation on
within the framework of the cross-bridge model. the molecular level. However, there is mounting evidence
Abbott and Aubert (1) observed that the steady-state that sarcomere length nonuniformities alone cannot explain
isometric force after active shortening and active stretching force depression after shortening and force enhancement
of muscles is lower and higher, respectively, than the purely after stretch (28, 32, 61, 63, 64). Furthermore, hypotheses
isometric force at the corresponding lengths. These results based on novel findings have been proposed to explain
have been observed consistently for over 50 years in a history-dependent properties of muscle contraction (5, 32,
variety of experimental preparations (e.g., Refs. 19, 21, 30, 34).
50). This history dependence of force production is typically The purpose of this review is to present key observations
not accounted for in the mathematical formulation of the associated with force depression after shortening and force
cross-bridge model of muscle contraction (38, 41) and enhancement after stretch, to describe the main hypotheses
that have been proposed to explain these history-dependent
phenomena (including the sarcomere length nonuniformity
Address for reprint requests and other correspondence: W. Herzog, Human
Performance Laboratory, Faculty of Kinesiology, Univ. of Calgary, 2500 Univer- hypothesis), and to critically interpret the experimental
sity Dr., Calgary, AB, Canada T2N 1N4 (E-mail: walter@kin.ucalgary.ca). evidence.
http://www.jap.org 8750-7587/04 $5.00 Copyright © 2004 the American Physiological Society 419
Invited Review
420 HISTORY DEPENDENCE OF MUSCLE CONTRACTION
steady-state value within a few seconds (19, 30, 33, 58). This
steady-state force is lower than the purely isometric force
obtained at the corresponding final length.
The amount of force depression has been found to increase
with increasing amplitudes of shortening (1, 30, 34, 55, 58),
decreasing speeds of shortening (1, 13, 30, 34, 58), and
increasing forces for constant speeds during the shortening
phase (30). Force depression after shortening appears largely
unaffected by previous muscle stretch (31). Absolute force
depression in human muscles increases with increasing activa-
tion (13).
Mechanisms of Force Depression After Shortening
There are a number of hypotheses that have been proposed
in the literature to explain force depression. The following
hypotheses are the most prominent in our view: 1) sarcomere
Fig. 1. Force depression (FD) after shortening of a single fiber from the
lumbrical muscle of frog. In the length traces, 1.0 corresponds to the optimal length nonuniformity (19, 45, 58), 2) accumulation of fatigue
length for force production (Lo). Starting from a length of 20% greater than Lo, products (28), and 3) stress-induced inhibition of cross-bridge
the fiber was shortened by 10% fiber length along the descending limb of the attachment (55).
force-length relationship, at a speed of 40% fiber length/s. An isometric Sarcomere length nonuniformity hypothesis. The sarcomere
Experimental Observations
Fig. 2. Schematic representation of the sarcomere length nonuniformity hy-
An example of force depression after active muscle short- pothesis and force depression. E, Average sarcomere (fiber) length; F, different
populations of sarcomeres. During shortening of a muscle fiber (from A to B),
ening from experiments on a single muscle fiber is shown in some sarcomeres shorten by a small amount (C), whereas other sarcomeres
Fig. 1. During shortening, force rapidly decreases, and once shorten more than average (D). At equilibrium, total force is smaller than the
shortening is completed, force recovers and attains a new isometric force at the corresponding final length, generating FD.
This mechanism of force depression provides the following Fig. 4. During active stretch, force rapidly increases (20, 21,
testable predictions: 1) force depression should be long lasting 23, 32, 35, 64). After the stretch is completed, force decreases
if myofilament stress is maintained but should be abolished and reaches a steady state until the end of activation (21, 23,
instantaneously on full stress release, 2) force depression 32, 35, 64). This steady-state force is higher than the purely
should be associated with a decreased stiffness, and 3) force isometric force observed at the corresponding final length.
depression should increase with increasing shortening dis- Most studies show that the amount of force enhancement
tances, and with increasing forces during shortening, and, increases with increasing amplitudes of stretch (1, 20, 21, 64)
therefore, force depression should be directly related to the and increasing fiber or sarcomere lengths (20, 21, 64) but is
mechanical work produced during shortening. independent (or nearly so) of the speed of stretch (1, 21, 64).
All these predictions have been supported by experimental Recently, it has been shown that, at long muscle lengths, force
results. Force depression is long lasting (1, 28, 30, 33, 34, 45, enhancement is accompanied by a long-lasting increase in the
58), but when the stress from muscle or fiber preparations is passive force after deactivation of the muscle or fiber (32, 35,
released for brief moments (by deactivation), such that force 50, 64, 66, 67).
will not go to zero, there is a loss of force depression that is
directly proportional to the decrease in force during stress Mechanisms of Force Enhancement After Stretch
release (34). If deactivation is long enough, so that force goes
to zero, all force depression is abolished on reactivation (1, 34). The following comprise the primary hypotheses that have
Force depression and stiffness are closely correlated; i.e., the been proposed to explain force enhancement after stretch: 1)
greater the force depression, the smaller the muscle or fiber sarcomere length nonuniformity and instability (45, 56–58), 2)
stiffness (49, 69). Finally, it has been shown that force depres- increase in the proportion of attached cross bridges (5), and 3)
engagement of a passive element (32, 35, 60).
Fig. 6. FE after stretch along the ascending limb of the force-length relation-
Fig. 5. Schematic representation of the sarcomere length nonuniformity and
ship of a single fiber from the lumbrical muscle of frog. In the length traces,
instability hypothesis for force enhancement. E, Average sarcomere (fiber)
1.0 corresponds to the Lo. Starting at a length of 20% below Lo, the fiber was
length; F, different populations of sarcomeres. During stretch of a muscle fiber
stretched by 10% of the fiber length, at a velocity of 40% fiber length/s. The
(from A to B), some sarcomeres are stretched by a small amount (C), whereas
isometric contraction performed at the corresponding Lf is also shown.
other sarcomeres are stretched more than average (D). The overstretched
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