225 ADJUSTABLE PASSIVE STIFFNESS AND LENGTH ADAPTATION IN MOUSE DETRUSOR SMOOTH MUSCLE: A MECHANICAL MODEL FOR DISORDERS OF CONTRACTILITY AND OVERACTIVITY

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.

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Adjustable passive length-tension curve in rabbit detrusor smooth muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.00548.2006 ◽

2007 ◽

Vol 102 (5) ◽

pp. 1746-1755 ◽

Cited By ~ 32

Author(s):

John E. Speich ◽

Christopher Dosier ◽

Lindsey Borgsmiller ◽

Kevin Quintero ◽

Harry P. Koo ◽

...

Keyword(s):

Smooth Muscle ◽

Strain Softening ◽

Muscle Length ◽

Strain History ◽

Total Force ◽

Detrusor Smooth Muscle ◽

Passive Force ◽

Passive Stiffness ◽

Active Force ◽

Length Changes

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.

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Functional properties and connective tissue content of pediatric human detrusor muscle

AJP Renal Physiology ◽

10.1152/ajprenal.00380.2014 ◽

2014 ◽

Vol 307 (9) ◽

pp. F1072-F1079 ◽

Cited By ~ 5

Author(s):

Navroop Johal ◽

Dan N. Wood ◽

Adrian S. Wagg ◽

Peter Cuckow ◽

Christopher H. Fry

Keyword(s):

Smooth Muscle ◽

Connective Tissue ◽

Functional Properties ◽

Biomechanical Properties ◽

Detrusor Muscle ◽

Detrusor Smooth Muscle ◽

Passive Stiffness ◽

Adult Tissue ◽

Management Options ◽

Intracellular Ca

The functional properties of human pediatric detrusor smooth muscle are poorly described, in contrast to those of adult tissue. Characterization is necessary for more informed management options of bladder dysfunction in children. We therefore compared the histological, contractile, intracellular Ca2+ concentration responses and biomechanical properties of detrusor biopsy samples from pediatric (3–48 mo) and adults (40–60 yr) patients who had functionally normal bladders and were undergoing open surgery. The smooth muscle fraction of biopsies was isolated to measure proportions of smooth muscle and connective tissue (van Gieson stain); in muscle strips, isometric tension to contractile agonists or electrical field stimulation and their passive biomechanical properties; in isolated myocytes, intracellular Ca2+ concentration responses to agonists. Pediatric detrusor tissue compared with adult tissue showed several differences: a smaller smooth muscle-to-connective tissue ratio, similar contractures to carbachol or α,β-methylene ATP when corrected for smooth muscle content, and similar intracellular Ca2+ transients to carbachol, α,β-methylene ATP, raised K+ concentration or caffeine, but smaller nerve-mediated contractions and greater passive stiffness with slower stress relaxation. In particular, there were significant atropine-resistant nerve-mediated contractions in pediatric samples. Detrusor smooth muscle from functionally normal pediatric human bladders is less contractile than that from adult bladders and exhibits greater passive stiffness. Reduced bladder contractile function is not due to reduced smooth muscle contractility but to greater connective tissue deposition and to functional denervation. Significant atropine resistance in pediatric detrusor, unlike in adult tissue, demonstrates a different profile of functional neurotransmitter activation. These data have implications for the management of pediatric bladder function by therapeutic approaches.

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Adaptation of the length-active tension relationship in rabbit detrusor

AJP Renal Physiology ◽

10.1152/ajprenal.00298.2009 ◽

2009 ◽

Vol 297 (4) ◽

pp. F1119-F1128 ◽

Cited By ~ 25

Author(s):

John E. Speich ◽

Atheer M. Almasri ◽

Hersch Bhatia ◽

Adam P. Klausner ◽

Paul H. Ratz

Keyword(s):

Smooth Muscles ◽

Muscle Length ◽

Strain History ◽

Detrusor Smooth Muscle ◽

Active Tension ◽

Passive Stiffness ◽

Vascular Smooth Muscles ◽

Length Changes ◽

Adjustable Passive Stiffness ◽

First Time

Studies have shown that the length-tension ( L-T) relationships in airway and vascular smooth muscles are dynamic and can adapt to length changes over a period of time. Our prior studies have shown that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that can shift along the length axis as a function of strain history and activation history. The present study demonstrates that the active L-T curve for DSM is also dynamic and that the peak active tension produced at a particular muscle length is a function of both strain and activation history. More specifically, this study reveals that the active L-T relationship, or curve, does not have a unique peak tension value with a single ascending and descending limb, but instead reveals that multiple ascending and descending limbs can be exhibited in the same DSM strip. This study also demonstrates that for DSM strips not stretched far enough to reveal a descending limb, the peak active tension produced by a maximal KCl-induced contraction at a short, passively slack muscle length of 3 mm was reduced by 58.6 ± 4.1% ( n = 1 5) following stretches to and contractions at threefold the original muscle length, 9 mm. Moreover, five subsequent contractions at the short muscle length displayed increasingly greater tension; active tension produced by the sixth contraction was 91.5 ± 9.1% of that produced by the prestretch contraction at that length. Together, these findings indicate for the first time that DSM exhibits length adaptation, similar to vascular and airway smooth muscles. In addition, our findings demonstrate that preconditioning, APS and adaptation of the active L-T curve can each impact the maximum total tension observed at a particular DSM length.

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