Residual force enhancement in myofibrils and sarcomeres

Abstract

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 (nZ18) that, owing to the strict in series arrangement, allowed for evaluation of this property in individual sarcomeres (nZ79). 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.

Is titin a ‘winding filament’? A new twist on muscle contraction

“…In addition, the passive force after deactivation of an actively stretched muscle fibre is higher than the force produced after passive stretch, or after deactivation from an isometric contraction at a corresponding length [18], further suggesting that 'passive force enhancement' is owing to recruitment of a passive element, namely titin [18]. Joumaa et al [34] measured passive force enhancement in myofibrils in which active force production was prevented by removal of troponin C. Like Labeit et al [20], they also observed a Ca 2þ -induced increase in titin-based stiffness, but the increase was too small to account for passive force enhancement. They proposed that passive force enhancement not only requires Ca 2þ influx, but also requires cross-bridge formation or active force production [34].…”

Force produced by isolated sarcomeres and half-sarcomeres after an imposed stretch

“…The force remains elevated after the stretch to reach a steady-state level that is higher than that produced during isometric contractions at corresponding lengths (8,24,38). The mechanisms responsible for this "residual force enhancement" remain elusive and there is substantial disagreement in the literature.Recent studies with isolated myofibrils, preparations in which individual sarcomeres (22,23,36,37,41,43) and half-sarcomeres in series (44, 45) can be evaluated, have shown intriguing results. Whereas a few studies suggest that force enhancement could be linked to sarcomeres and half-SL nonuniformity, as half-sarcomeres change their length continuously during activation and relaxation (36,44,45), some others show that sarcomeres may be stable (22,37), and that the increase in force after stretch are caused by contractile and/or passive structures.…”

“…Whereas a few studies suggest that force enhancement could be linked to sarcomeres and half-SL nonuniformity, as half-sarcomeres change their length continuously during activation and relaxation (36,44,45), some others show that sarcomeres may be stable (22,37), and that the increase in force after stretch are caused by contractile and/or passive structures. Furthermore, studies that attribute the residual force enhancement to sarcomeric structures present experimental data and interpretations that are highly variable.…”

Contractile Performance of Striated Muscle

“…10B) that remains at the end of a long (5-10 s) tetanus was originally observed on isolated whole muscles of the frog (Fenn, 1924;Abbott & Aubert, 1952;Hill & Howarth, 1959) and has later been subjected to detailed studies on isolated single muscle fibres (Edman et al, 1978Sugi, 1972;Edman & Tsuchiya, 1996, Sugi & Tsuchiya, 1988Julian & Morgan, 1979;Rassier & Herzog, 2004a, 2004b, Herzog & Rassier, 2006 and, recently, on isolated cardiac and skeletal muscle myofibrils (Telley et al, 2006;Joumaa et al, 2008;Rassier et al, 2003). The continued interest in this phenomenon is based on the fact that the longlasting force enhancement by stretch does not seem to be readily explainable on the basis of the slidingfilament hypothesis.…”