. ROK-induced cross-link formation stiffens passive muscle: reversible strain-induced stress softening in rabbit detrusor.

Until the 1990s, the passive and active length-tension (L-T) relationships of smooth muscle were believed to be static, with a single passive force value and a single maximum active force value for each muscle length. However, recent studies have demonstrated that the active L-T relationship in airway smooth muscle is dynamic and adapts to length changes over a period of time. Furthermore, our prior work showed that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that in addition to viscoelastic behavior, DSM displays strain-softening behavior characterized by a loss of passive stiffness at shorter lengths following a stretch to a new longer length. This loss of passive stiffness appears to be irreversible when the muscle is not producing active force and during submaximal activation but is reversible on full muscle activation, which indicates that the stiffness component of passive force lost to strain softening is adjustable in DSM. The present study demonstrates that the passive L-T curve for DSM is not static and can shift along the length axis as a function of strain history and activation history. This study also demonstrates that adjustable passive stiffness (APS) can modulate total force (35% increase) for a given muscle length, while active force remains relatively unchanged (4% increase). This finding suggests that the structures responsible for APS act in parallel with the contractile apparatus, and the results are used to further justify the configuration of modeling elements within our previously proposed mechanical model for APS.

Strips of rabbit detrusor smooth muscle (DSM) exhibit adjustable passive stiffness characterized by strain softening: a loss of stiffness on stretch to a new length distinct from viscoelastic behavior. At the molecular level, strain softening appears to be caused by cross-link breakage and is essentially irreversible when DSM is maintained under passive conditions (i.e., when cross bridges are not cycling to produce active force). However, on DSM activation, strain softening is reversible and likely due to cross-link reformation. Thus DSM displays adjustable passive stiffness that is dependent on the history of both muscle strain and activation. The present study provides empirical data showing that, in DSM, 1) passive isometric force relaxation includes a very slow component requiring hours to approach steady state, 2) the level of passive force maintained at steady state is less if the tissue has previously been strain softened, and 3) tissues subjected to a quick-release protocol exhibit a biphasic response consisting of passive force redevelopment followed by force relaxation. To explain these and previously identified characteristics, a mechanical model for adjustable passive stiffness is proposed based on the addition of a novel cross-linking element to a hybrid Kelvin/Voigt viscoelastic model.

No abstract