Effects of Force Enhancement and Force Depression on Postactivation Potentiation in the Human Adductor Pollicis

Force enhancement and force depression following active stretch and shortening are commonly observed muscle properties. However the mechanisms underlying these properties are not fully understood. Increased or decreased muscle potentiation (that is, the amount of phosphorylation of the myosin light chains) might contribute to force enhancement and force depression but has never been examined. In this study, we examined the effect of active stretch and shortening on potentiation of the in vivo human adductor pollicis muscle to determine whether the phosphorylation that causes muscle potentiation is a viable contributor to force enhancement and depression. Potentiation was assessed with twitch contractions and the contribution of potentiation to force enhancement/depression was assessed by comparing the force of isometric contractions prior to and following muscle potentiation. Subjects were given twitches before and after maximum voluntary isometric contractions at a thumb adduction angle of 30° and 0°, and these twitches were compared to twitches given before and after an active stretch from 0° to 30° (n=15) and an active shortening (n=12) from 30° to 0°. Stretch and shortening contractions were then followed 10s later by an isometric contraction at the finishing position to observe any effects of changed potentiation on maximal voluntary isometric contractions. Potentiation was increased significantly (17%) after active muscle stretching but remained unchanged following active muscle shortening. The increased potentiation following active muscle stretching did not affect isometric forces. We conclude from these results that active muscle stretching increases the amount of muscle potentiation, but does not contribute to the force enhancement observed following active muscle stretch. We speculate that the stretch-induced increase in muscle potentiation is a mechanism for saving energy during sub- maximal and maximal muscular contractions

A Mathematical Model of Muscle Containing Heterogeneous Half-Sarcomeres Exhibits Residual Force Enhancement

A skeletal muscle fiber that is stimulated to contract and then stretched from L1 to L2 produces more force after the initial transient decays than if it is stimulated at L2. This behavior has been well studied experimentally, and is known as residual force enhancement. The underlying mechanism remains controversial. We hypothesized that residual force enhancement could reflect mechanical interactions between heterogeneous half-sarcomeres. To test this hypothesis, we subjected a computational model of interacting heterogeneous half-sarcomeres to the same activation and stretch protocols that produce residual force enhancement in real preparations. Following a transient period of elevated force associated with active stretching, the model predicted a slowly decaying force enhancement lasting >30 seconds after stretch. Enhancement was on the order of 13% above isometric tension at the post-stretch muscle length, which agrees well with experimental measurements. Force enhancement in the model was proportional to stretch magnitude but did not depend strongly on the velocity of stretch, also in agreement with experiments. Even small variability in the strength of half-sarcomeres (2.1% standard deviation, normally distributed) was sufficient to produce a 5% force enhancement over isometric tension. Analysis of the model suggests that heterogeneity in half-sarcomeres leads to residual force enhancement by storing strain energy introduced during active stretch in distributions of bound cross-bridges. Complex interactions between the heterogeneous half-sarcomeres then dissipate this stored energy at a rate much slower than isolated cross-bridges would cycle. Given the variations in half-sarcomere length that have been observed in real muscle preparations and the stochastic variability inherent in all biological systems, half-sarcomere heterogeneity cannot be excluded as a contributing source of residual force enhancement

Residual force enhancement in myofibrils and sarcomeres

Residual force enhancement has been observed following active stretch of skeletal muscles and single fibres. However, there has been intense debate whether force enhancement is a sarcomeric property, or is associated with sarcomere length instability and the associated development of non-uniformities. Here, we studied force enhancement for the first time in isolated myofibrils (n=18) that, owing to the strict in series arrangement, allowed for evaluation of this property in individual sarcomeres (n=79). We found consistent force enhancement following stretch in all myofibrils and each sarcomere, and forces in the enhanced state typically exceeded the isometric forces on the plateau of the force–length relationship. Measurements were made on the plateau and the descending limb of the force–length relationship and revealed gross sarcomere length non-uniformities prior to and following active myofibril stretching, but in contrast to previous accounts, revealed that sarcomere lengths were perfectly stable under these experimental conditions. We conclude that force enhancement is a sarcomeric property that does not depend on sarcomere length instability, that force enhancement varies greatly for different sarcomeres within the same myofibril and that sarcomeres with vastly different amounts of actin–myosin overlap produce the same isometric steady-state forces. This last finding was not explained by differences in the amount of contractile proteins within sarcomeres, vastly different passive properties of individual sarcomeres or (half-) sarcomere length instabilities, suggesting that the basic mechanical properties of muscles, such as force enhancement, force depression and creep, which have traditionally been associated with sarcomere instabilities and the corresponding dynamic redistribution of sarcomere lengths, are not caused by such instabilities, but rather seem to be inherent properties of the mechanisms of contraction

Calcium sensitivity of residual force enhancement in rabbit skinned fibers

Isometric force after active stretch of muscles is higher than the purely isometric force at the corresponding length. This property is termed residual force enhancement. Active force in skeletal muscle depends on calcium attachment characteristics to the regulatory proteins. Passive force has been shown to influence calcium attachment characteristics, specifically the sarcomere length dependence of calcium sensitivity. Since one of the mechanisms proposed to explain residual force enhancement is the increase in passive force that results from engagement of titin upon activation and stretch, our aim was to test if calcium sensitivity of residual force enhancement was different from that of its corresponding purely isometric contraction and if such a difference was related to the molecular spring titin. Force-pCa curves were established in rabbit psoas skinned fibers for reference and residual force-enhanced states at a sarcomere length of 3.0 μm 1) in a titin-intact condition, 2) after treatment with trypsin to partially eliminate titin, and 3) after treatment with trypsin and osmotic compression with dextran T-500 to decrease the lattice spacing in the absence of titin. The force-pCa curves of residual force enhancement were shifted to the left compared with their corresponding controls in titin-intact fibers, indicating increased calcium sensitivity. No difference in calcium sensitivity was observed between reference and residual force-enhanced contractions in trypsin-treated and osmotically compressed trypsin-treated fibers. Furthermore, calcium sensitivity after osmotic compression was lower than that observed for residual force enhancement in titin-intact skinned fibers. These results suggest that titin-based passive force regulates the increase in calcium sensitivity of residual force enhancement by a mechanism other than reduction of the myofilament lattice spacing

Loss of KLF10 expression does not affect the passive properties of single myofibrils

International audienceThe purpose of this study was to gain insight into the origin of the passive behavior observed in KLF10 KO soleus and EDL muscles, at the fiber scale and at the myofibril (titin) scale. The conclusion from the results of this study is that the observed fibre-type specific changes in passive force in KLF10 KO mice muscles are not caused by sarcomere intrinsic structures but must originate outside the sarcomeres, likely in the collagen-based extracellular matrix