An expanded latch-bridge model of protein kinase C-mediated smooth muscle contraction.
A thin-filament-regulated latch-bridge model of smooth muscle contraction is proposed to integrate thin-filament-based inhibition of actomyosin ATPase activity with myosin phosphorylation in the regulation of smooth muscle mechanics. The model included two latch-bridge cycles, one of which was identical to the four-state model as proposed by Hai and Murphy (Am J Physiol Cell Physiol 255: C86-C94, 1988), whereas the ultraslow cross-bridge cycle has lower cross-bridge cycling rates. The model-fitted phorbol ester induced slow contractions at constant myosin phosphorylation and predicted steeper dependence of force on myosin phosphorylation in phorbol ester-stimulated smooth muscle. By shifting cross bridges between the two latch-bridge cycles, the model predicts that a smooth muscle cell can either maintain force at extremely low-energy cost or change its contractile state rapidly, if necessary. Depending on the fraction of cross bridges engaged in the ultraslow latch-bridge cycle, the model predicted biphasic kinetics of smooth muscle mechanics and variable steady-state dependencies of force and shortening velocity on myosin phosphorylation. These results suggest that thin-filament-based regulatory proteins may function as tuners of actomyosin ATPase activity, thus allowing a smooth muscle cell to have two discrete cross-bridge cycles with different cross-bridge cycling rates.
Hai
Chi-Ming
CM
Brown University, Box G-B3, Providence, RI 02912, USA. Chi-Ming_Hai@brown.edu
Kim
Hak Rim
HR
D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000502:physiology*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D013314:Stress, Mechanical; D014132:Trachea / Q000502:physiology
D020409:Molecular Motor Proteins; D011493:Protein Kinase C; D009218:Myosins