title: Force maintenance and myosin filament assembly regulated by Rho-kinase in airway smooth muscle.
abstract: Smooth muscle contraction can be divided into two phases: the initial contraction determines the amount of developed force and the second phase determines how well the force is maintained. The initial phase is primarily due to activation of actomyosin interaction and is relatively well understood, whereas the second phase remains poorly understood. Force maintenance in the sustained phase can be disrupted by strains applied to the muscle; the strain causes actomyosin cross-bridges to detach and also the cytoskeletal structure to disassemble in a process known as fluidization, for which the underlying mechanism is largely unknown. In the present study we investigated the ability of airway smooth muscle to maintain force after the initial phase of contraction. Specifically, we examined the roles of Rho-kinase and protein kinase C (PKC) in force maintenance. We found that for the same degree of initial force inhibition, Rho-kinase substantially reduced the muscle's ability to sustain force under static conditions, whereas inhibition of PKC had a minimal effect on sustaining force. Under oscillatory strain, Rho-kinase inhibition caused further decline in force, but again, PKC inhibition had a minimal effect. We also found that Rho-kinase inhibition led to a decrease in the myosin filament mass in the muscle cells, suggesting that one of the functions of Rho-kinase is to stabilize myosin filaments. The results also suggest that dissolution of myosin filaments may be one of the mechanisms underlying the phenomenon of fluidization. These findings can shed light on the mechanism underlying deep inspiration induced bronchodilation.
authors.affiliation: Bioengineering College, Chongqing University, Chongqing, China; Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, China; and Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Lan
authors.affiliation: Bioengineering College, Chongqing University, Chongqing, China; Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, China; and.
authors.forename: Linhong
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Mathematics, University of Auckland, Auckland, New Zealand;
authors.forename: Graham M
authors.initials: GM
authors.lastname: Donovan
authors.affiliation: Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Leslie Y M
authors.initials: LY
authors.lastname: Chin
authors.affiliation: Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Harley T
authors.initials: HT
authors.lastname: Syyong
authors.affiliation: Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada; Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pascoe
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada; Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Norris
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada; Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Jeffrey C-Y
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Swyngedouw
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Saleha M
authors.initials: SM
authors.lastname: Banaem
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, Canada; Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada chun.seow@hli.ubc.ca.
authors.forename: Chun Y
authors.initials: CY
authors.lastname: Seow
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D001239:Inhalation / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012756:Sheep; D014132:Trachea / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000205:Actomyosin; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D009218:Myosins
keywords: asthma; bronchoprotection; muscle mechanics; ultrastructure