Slowly cycling rho kinase-dependent actomyosin crossbridge "slippage" explains intrinsic high compliance of detrusor smooth muscle
Published online on March 29, 2017
Abstract
Biological soft tissues are viscoelastic because they display time-independent pseudo-elasticity and time-dependent viscosity. Upon an imposed ramp increase then decrease in strain, the resultant stress changes, termed loading and unloading respectively, produce nonlinear stress-strain curves and a reversible reduction in the stress-strain work area that identifies viscosity. However, there is evidence that bladder may also display plasticity; an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic-plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared to the large increase produced when the viscosity was absent and only pseudo-elasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, and plasticity is by motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" crossbridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin crossbridge activity, and identifies a novel molecular target for compliance regulation both physiologically and therapeutically.