scholarly journals Active force inhibition and stretch-induced force enhancement in frog muscle treated with BDM

2004 ◽  
Vol 97 (4) ◽  
pp. 1395-1400 ◽  
Author(s):  
Dilson E. Rassier ◽  
Walter Herzog
Keyword(s):  
Fiber Length ◽  
Isometric Force ◽  
Ringer Solution ◽  
Total Force ◽  
Passive Force ◽  
Force Enhancement ◽  
Cross Bridge ◽  
Length Relationship ◽  
Cross Bridges ◽  
Lumbrical Muscles

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.

scholarly journals Relationship between force and stiffness in muscle fibers after stretch

2005 ◽  
Vol 99 (5) ◽  
pp. 1769-1775 ◽  
Author(s):  
Dilson E. Rassier ◽  
Walter Herzog
Keyword(s):  
Fiber Length ◽  
Muscle Activation ◽  
Isometric Force ◽  
Ringer Solution ◽  
Isometric Contractions ◽  
Force Enhancement ◽  
Weakly Bound ◽  
Length Relationship ◽  
Cross Bridges ◽  
The Relationship

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.

scholarly journals Are Force Enhancement after Stretch and Muscle Fatigue Due to Effects of Elevated Inorganic Phosphate and Low Calcium on Cross Bridge Kinetics?

Medicina ◽  
2020 ◽  
Vol 56 (5) ◽  
pp. 249
Author(s):  
Hans Degens ◽  
David A. Jones
Keyword(s):  
Muscle Fatigue ◽  
Isometric Force ◽  
Force Enhancement ◽  
Shortening Velocity ◽  
Cross Bridge ◽  
Fatigued Muscle ◽  
Butanedione Monoxime ◽  
Combined Action ◽  
Cross Bridges ◽  
Muscle Contractile

Background and Objectives: Muscle fatigue is characterised by (1) loss of force, (2) decreased maximal shortening velocity and (3) a greater resistance to stretch that could be due to reduced intracellular Ca2+ and increased Pi, which alter cross bridge kinetics. Materials and Methods: To investigate this, we used (1) 2,3-butanedione monoxime (BDM), believed to increase the proportion of attached but non-force-generating cross bridges; (2) Pi that increases the proportion of attached cross bridges, but with Pi still attached; and (3) reduced activating Ca2+. We used permeabilised rat soleus fibres, activated with pCa 4.5 at 15 °C. Results: The addition of 1 mM BDM or 15 mM Pi, or the lowering of the Ca2+ to pCa 5.5, all reduced the isometric force by around 50%. Stiffness decreased in proportion to isometric force when the fibres were activated at pCa 5.5, but was well maintained in the presence of Pi and BDM. Force enhancement after a stretch increased with the length of stretch and Pi, suggesting a role for titin. Maximum shortening velocity was reduced by about 50% in the presence of BDM and pCa 5.5, but was slightly increased by Pi. Neither decreasing Ca2+ nor increasing Pi alone mimicked the effects of fatigue on muscle contractile characteristics entirely. Only BDM elicited a decrease of force and slowing with maintained stiffness, similar to the situation in fatigued muscle. Conclusions: This suggests that in fatigue, there is an accumulation of attached but low-force cross bridges that cannot be the result of the combined action of reduced Ca2+ or increased Pi alone, but is probably due to a combination of factors that change during fatigue.

Considerations on the history dependence of muscle contraction

2004 ◽  
Vol 96 (2) ◽  
pp. 419-427 ◽  
Author(s):  
Dilson E. Rassier ◽  
Walter Herzog
Keyword(s):  
Muscle Contraction ◽  
Isometric Force ◽  
Force Production ◽  
Passive Component ◽  
Force Enhancement ◽  
History Dependence ◽  
Cross Bridge ◽  
Force Depression ◽  
Length Relationship ◽  
Length Changes

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.

scholarly journals Passive force enhancement in striated muscle

2019 ◽  
Vol 126 (6) ◽  
pp. 1782-1789 ◽  
Author(s):  
Walter Herzog
Keyword(s):  
Molecular Mechanisms ◽  
Striated Muscle ◽  
Isometric Force ◽  
Muscle Length ◽  
Passive Force ◽  
Force Enhancement ◽  
Sarcomeric Protein ◽  
Residual Force ◽  
Residual Force Enhancement ◽  
Cross Bridges

Passive force enhancement is defined as the increase in passive, steady-state, isometric force of an actively stretched muscle compared with the same muscle stretched passively to that same length. Passive force enhancement is long lasting, increases with increasing muscle length and increasing stretch magnitudes, contributes to the residual force enhancement in skeletal and cardiac muscle, and is typically only observed at muscle lengths at which passive forces occur naturally. Passive force enhancement is typically equal to or smaller than the total residual force enhancement, it persists when a muscle is deactivated and reactivated, but can be abolished instantaneously when a muscle is shortened quickly from its stretched length. There is strong evidence that the passive force enhancement is caused by the filamentous sarcomeric protein titin, although the detailed molecular mechanisms underlying passive force enhancement remain unknown. Here I propose a tentative mechanism based on experimental evidence that associates passive force enhancement with the shortening of titin’s free spring length in the I-band region of sarcomeres. I suggest that this shortening is accomplished by titin binding to actin and that the trigger for titin-actin interactions is associated with the formation of strongly bound cross bridges between actin and myosin that exposes actin attachment sites for titin through movement of the regulatory proteins troponin and tropomyosin.

scholarly journals The active force–length relationship is invisible during extensive eccentric contractions in skinned skeletal muscle fibres

2017 ◽  
Vol 284 (1854) ◽  
pp. 20162497 ◽  
Author(s):  
André Tomalka ◽  
Christian Rode ◽  
Jens Schumacher ◽  
Tobias Siebert
Keyword(s):  
Muscle Force ◽  
Isometric Force ◽  
Eccentric Contractions ◽  
Muscle Fibres ◽  
Active Force ◽  
Optimal Length ◽  
Cross Bridge ◽  
Length Relationship ◽  
Maximum Isometric Force ◽  
Cross Bridges

In contrast to experimentally observed progressive forces in eccentric contractions, cross-bridge and sliding-filament theories of muscle contraction predict that varying myofilament overlap will lead to increases and decreases in active force during eccentric contractions. Non-cross-bridge contributions potentially explain the progressive total forces. However, it is not clear whether underlying abrupt changes in the slope of the nonlinear force–length relationship are visible in long isokinetic stretches, and in which proportion cross-bridges and non-cross-bridges contribute to muscle force. Here, we show that maximally activated single skinned rat muscle fibres behave (almost across the entire working range) like linear springs. The force slope is about three times the maximum isometric force per optimal length. Cross-bridge and non-cross-bridge contributions to the muscle force were investigated using an actomyosin inhibitor. The experiments revealed a nonlinear progressive contribution of non-cross-bridge forces and suggest a nonlinear cross-bridge contribution similar to the active force–length relationship (though with increased optimal length and maximum isometric force). The linear muscle behaviour might significantly reduce the control effort. Moreover, the observed slight increase in slope with initial length is in accordance with current models attributing the non-cross-bridge force to titin.

Force enhancement following stretching of skeletal muscle

2002 ◽  
Vol 205 (9) ◽  
pp. 1275-1283 ◽  
Author(s):  
W. Herzog ◽  
T. R. Leonard
Keyword(s):  
Structural Damage ◽  
Great Part ◽  
Force Production ◽  
Isometric Contractions ◽  
Total Force ◽  
Passive Force ◽  
Force Enhancement ◽  
Structural Element ◽  
Length Relationship ◽  
Relationship Of

SUMMARY We investigated force enhancement following stretching in the in situ cat soleus muscle on the ascending and descending limb of the force-length relationship by varying the amount and speed of stretching and the frequency of activation (5 Hz, 30 Hz). There was a small but consistent(P<0.05) amount of force enhancement following muscle stretching on the ascending limb of the force—length relationship for both stimulation frequencies. The steady-state active isometric forces following stretches of 9 mm on the descending limb of the force—length relationship were always equal to or greater than the corresponding forces from the purely isometric contractions at the length at which the stretch was started. Therefore, force production for these trials showed positive stiffness and was associated with stable behavior. Following active stretching of cat soleus on the descending limb of the force—length relationship,the passive forces at the end of the test were significantly greater than the corresponding passive forces for purely isometric contractions, or the passive forces following stretching of the passive muscle. This passive force enhancement following active stretching increased with increasing magnitude of stretch, was not associated with structural damage, and only disappeared once the muscle was shortened. For stretches of 6 mm and 9 mm, the passive force enhancement accounted for more than 50 % of the total force enhancement,reaching a peak contribution of 83.7 % for the stretches of 9 mm at a speed of 3 mm s-1. The results of this study suggest that a passive structural element provides a great part of the force enhancement on the descending limb of the force—length relationship of the cat soleus. Furthermore, the results indicate that mechanisms other than sarcomere length non-uniformity alone are operative.

Oxytocin-mediated recruitment of slowly cycling cross bridges and isometric force in rat myometrium

1996 ◽  
Vol 270 (2) ◽  
pp. E203-E208
Author(s):  
A. L. Ruzycky ◽  
B. T. Ameredes
Keyword(s):  
Isometric Force ◽  
Additional Stress ◽  
Shortening Velocity ◽  
Cycling Rate ◽  
Quick Release ◽  
Cross Bridge ◽  
Cross Bridges ◽  
Unit Stress ◽  
Release Method ◽  
The Relationship

The relationship between cross-bridge cycling rate and isometric stress was investigated in rat myometrium. Stress production by myometrial strips was measured under resting, K+ depolarization, and oxytocin-stimulated conditions. Cross-bridge cycling rates were determined from measurements of maximal unloaded shortening velocity, using the quick-release method. Force redevelopment after the quick release was used as an index of cross-bridge attachment. With maximal K+ stimulation, stress increased with increased cross-bridge cycling (+76%; P < 0.05) and attached cross bridges (+112%; P < 0.05). Addition of oxytocin during K+ stimulation further increased stress (+30%; P < 0.05). With this force component, the cross-bridge cycling rate decreased (-60%; P < 0.05) similar to that under resting conditions. Attached cross-bridges did not increase with this additional stress. The results suggest two distinct mechanisms mediating myometrial contractions. One requires elevated intracellular calcium and rapidly cycling cross bridges. The other mechanism may be independent of calcium and appears to be mediated by slowly cycling cross bridges, supporting greater unit stress.

The origin of passive force enhancement in skeletal muscle

2008 ◽  
Vol 294 (1) ◽  
pp. C74-C78 ◽  
Author(s):  
V. Joumaa ◽  
D. E. Rassier ◽  
T. R. Leonard ◽  
W. Herzog
Keyword(s):  
Calcium Concentration ◽  
Force Production ◽  
Primary Source ◽  
Passive Force ◽  
Active Force ◽  
Force Enhancement ◽  
Bridge Formation ◽  
Calcium Dependent ◽  
Cross Bridge ◽  
High Calcium

The aim of the present study was to test whether titin is a calcium-dependent spring and whether it is the source of the passive force enhancement observed in muscle and single fiber preparations. We measured passive force enhancement in troponin C (TnC)-depleted myofibrils in which active force production was completely eliminated. The TnC-depleted construct allowed for the investigation of the effect of calcium concentration on passive force, without the confounding effects of actin-myosin cross-bridge formation and active force production. Passive forces in TnC-depleted myofibrils ( n = 6) were 35.0 ± 2.9 nN/ μm2 when stretched to an average sarcomere length of 3.4 μm in a solution with low calcium concentration (pCa 8.0). Passive forces in the same myofibrils increased by 25% to 30% when stretches were performed in a solution with high calcium concentration (pCa 3.5). Since it is well accepted that titin is the primary source for passive force in rabbit psoas myofibrils and since the increase in passive force in TnC-depleted myofibrils was abolished after trypsin treatment, our results suggest that increasing calcium concentration is associated with increased titin stiffness. However, this calcium-induced titin stiffness accounted for only ∼25% of the passive force enhancement observed in intact myofibrils. Therefore, ∼75% of the normally occurring passive force enhancement remains unexplained. The findings of the present study suggest that passive force enhancement is partly caused by a calcium-induced increase in titin stiffness but also requires cross-bridge formation and/or active force production for full manifestation.

Regulation of energy consumption in cardiac muscle: analysis of isometric contractions

1999 ◽  
Vol 276 (3) ◽  
pp. H998-H1011 ◽  
Author(s):  
Amir Landesberg ◽  
Samuel Sideman
Keyword(s):  
Energy Consumption ◽  
Cardiac Muscle ◽  
Feedback Mechanism ◽  
Isometric Contractions ◽  
Cross Bridge ◽  
Time Integral ◽  
Length Relationship ◽  
Cross Bridges ◽  
Force Time ◽  
Force Time Integral

The well-known linear relationship between oxygen consumption and force-length area or the force-time integral is analyzed here for isometric contractions. The analysis, which is based on a biochemical model that couples calcium kinetics with cross-bridge cycling, indicates that the change in the number of force-generating cross bridges with the change in the sarcomere length depends on the force generated by the cross bridges. This positive-feedback phenomenon is consistent with our reported cooperativity mechanism, whereby the affinity of the troponin for calcium and, hence, cross-bridge recruitment depends on the number of force-generating cross bridges. Moreover, it is demonstrated that a model that does not include a feedback mechanism cannot describe the dependence of energy consumption on the loading conditions. The cooperativity mechanism, which has been shown to determine the force-length relationship and the related Frank-Starling law, is shown here to provide the basis for the regulation of energy consumption in the cardiac muscle.

scholarly journals Activation Dependence of Stretch Activation in Mouse Skinned Myocardium: Implications for Ventricular Function

2006 ◽  
Vol 127 (2) ◽  
pp. 95-107 ◽  
Author(s):  
Julian E. Stelzer ◽  
Lars Larsson ◽  
Daniel P. Fitzsimons ◽  
Richard L. Moss
Keyword(s):  
Isometric Force ◽  
Force Characteristic ◽  
Stretch Activation ◽  
Thin Filaments ◽  
Cross Bridge ◽  
Steady Level ◽  
Myocardial Stretch ◽  
Myosin Subfragment 1 ◽  
Activation Response ◽  
Cross Bridges

Recent evidence suggests that ventricular ejection is partly powered by a delayed development of force, i.e., stretch activation, in regions of the ventricular wall due to stretch resulting from torsional twist of the ventricle around the apex-to-base axis. Given the potential importance of stretch activation in cardiac function, we characterized the stretch activation response and its Ca2+ dependence in murine skinned myocardium at 22°C in solutions of varying Ca2+ concentrations. Stretch activation was induced by suddenly imposing a stretch of 0.5–2.5% of initial length to the isometrically contracting muscle and then holding the muscle at the new length. The force response to stretch was multiphasic: force initially increased in proportion to the amount of stretch, reached a peak, and then declined to a minimum before redeveloping to a new steady level. This last phase of the response is the delayed force characteristic of myocardial stretch activation and is presumably due to increased attachment of cross-bridges as a consequence of stretch. The amplitude and rate of stretch activation varied with Ca2+ concentration and more specifically with the level of isometric force prior to the stretch. Since myocardial force is regulated both by Ca2+ binding to troponin-C and cross-bridge binding to thin filaments, we explored the role of cross-bridge binding in the stretch activation response using NEM-S1, a strong-binding, non-force–generating derivative of myosin subfragment 1. NEM-S1 treatment at submaximal Ca2+-activated isometric forces significantly accelerated the rate of the stretch activation response and reduced its amplitude. These data show that the rate and amplitude of myocardial stretch activation vary with the level of activation and that stretch activation involves cooperative binding of cross-bridges to the thin filament. Such a mechanism would contribute to increased systolic ejection in response to increased delivery of activator Ca2+ during excitation–contraction coupling.

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