No abstract

. 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.

Ratz PH, Speich JE. Evidence that actomyosin cross bridges contribute to "passive" tension in detrusor smooth muscle. Am J Physiol Renal Physiol 298: F1424 -F1435, 2010. First published April 7, 2010 doi:10.1152/ajprenal.00635.2009.-Contraction of detrusor smooth muscle (DSM) at short muscle lengths generates a stiffness component we termed adjustable passive stiffness (APS) that is retained in tissues incubated in a Ca 2ϩ -free solution, shifts the DSM length-passive tension curve up and to the left, and is softened by muscle strain and release (strain softened). In the present study, we tested the hypothesis that APS is due to slowly cycling actomyosin cross bridges. APS and active tension produced by the stimulus, KCl, displayed similar length dependencies with identical optimum length values. The myosin II inhibitor blebbistatin relaxed active tension maintained during a KCl-induced contraction and the passive tension maintained during stress-relaxation induced by muscle stretch in a Ca 2ϩ -free solution. Passive tension was attributed to tension maintaining rather than tension developing cross bridges because tension did not recover after a rapid 10% stretch and release as it did during a KCl-induced contraction. APS generated by a KCl-induced contraction in intact tissues was preserved in tissues permeabilized with Triton X-100. Blebbistatin and the actin polymerization inhibitor latrunculin-B reduced the degree of APS generated by a KCl-induced contraction. The degree of APS generated by KCl was inhibited to a greater degree than was the peak KCl-induced tension by rhoA kinase and cyclooxygenase inhibitors. These data support the hypothesis that APS is due to slowly cycling actomyosin cross bridges and suggest that cross bridges may play a novel role in DSM that uniquely serves to ensure proper contractile function over an extreme working length range. urinary bladder; muscle mechanics; Triton X-100 permeabilization; Rho-kinase

AIMS The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0–100% scale) and standardized verbal sensory thresholds using a novel, touch-screen “sensation meter.” 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity–sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way.