ROK-induced cross-link formation stiffens passive muscle: reversible strain-induced stress softening in rabbit detrusor.
Passive mechanical properties of strips of rabbit detrusor smooth muscle were examined and found by cyclic loading in a calcium-free solution to display viscoelastic softening and strain-induced stress softening (strain softening). Strain softening, or the Mullins effect, is a loss of stiffness attributed to the breakage of cross-links, and appeared irreversible in detrusor even after the return of spontaneous rhythmic tone during 120 min of incubation in a calcium-containing solution. However, 3 min of KCl or carbachol (CCh)-induced contraction permitted rapid regeneration of the passive stiffness lost to strain softening, and 3 microM of the RhoA kinase (ROK) inhibitor Y-27632 prevented this regeneration. The degree of ROK-induced passive stiffness was inversely dependent on muscle length over a length range where peak CCh-induced force was length independent. Thus rabbit detrusor displayed variable passive stiffness both strain- and activation-history dependent. In conclusion, activation of ROK by KCl or CCh increased passive stiffness softened by muscle strain and thereby attributed to cross-links that remained stable during tissue incubation in a calcium-free solution. Degradation of this signaling system could potentially contribute to urinary incontinence.
Speich
John E
JE
Department of Mechanical Engineering, Virginia Commonwealth University, School of Medicine, 1101 E. Marshall St., PO Box 980614, Richmond, Virginia 23298-0614, USA.
Borgsmiller
Lindsey
L
Call
Chris
C
Mohr
Ryan
R
Ratz
Paul H
PH
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004548:Elasticity; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D012996:Solutions / Q000737:chemistry / Q000494:pharmacology; D013314:Stress, Mechanical; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014783:Viscosity; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018721:Muscarinic Agonists; D011725:Pyridines; D012996:Solutions; C108830:Y 27632; D011189:Potassium Chloride; D002217:Carbachol; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D002118:Calcium