|
|
 |
| |
Back to MAAUA Scientific Program
Actomyosin “Catch-bridges” Are Responsible For Adjustable Passive Stiffness (aps) In Detrusor Smooth Muscle (dsm)
Vernon A Orton, II1, Adam P Klausner1, John E Speich2, Lindsey Borgsmiller1, Harry P Koo1, Paul H Ratz3
1Virginia Commonwealth University - Medical College of Virginia, Richmond, VA;2Virginia Commonwealth University - Department of Mechanical Engineering, Richmond, VA;3Virginia Commonwealth University - Departments of Biochemistry and Pediatrics, Richmond, VA
Introduction:
Uniquely among hollow organs, DSM may undergo a 7-fold length change during bladder voiding. How DSM can contract effectively over this wide length-range is not known. We recently identified an adjustable stiffness component during passive bladder filling (APS) caused by crosslinks that could be broken by strain. We tested the hypothesis that the molecular structure responsible for APS is the actomyosin cross-bridge.
Methods:
Longitudinal strips of DSM isolated from adult New Zealand White rabbits were incubated in aerated physiological salt solution and suspended by tissue clips between a micrometer and force transducer or electronic lever. KCl was used to cause contraction and induce APS.
Results:
Tissues incubated with blebbistatin, a selective myosin II inhibitor, and latrunculin, an actin depolarizing agent, blocked induction of APS by KCl, indicating that crosslinks involving myosin II participate in the “passive” force of APS. APS cross-bridges did not cycle, because force did not redevelop following a quick-stretch to break cross-bridges and reduce force. APS was retained in Triton X-100 permeabilized DSM.
Conclusions:
Inhibition by blebbistatin of APS provides strong support for the hypothesis that APS is caused by actomyosin cross-bridges. Because APS cross-bridges did not actively develop force, APS represents a “catch” mechanism similar to that of molluscan muscle designed to retain stiffness while conserving energy. APS during filling may permit proper actomyosin alignment over a wide length-range permitting voiding at any bladder volume. Detachment of APS catch-bridges during muscle cell lengthening may be responsible for high compliance during bladder filling.
Back to MAAUA Scientific Program
|
|
| |
|
|
| |
|
|
|
|
