title: Disrupting actin-myosin-actin connectivity in airway smooth muscle as a treatment for asthma?
abstract: Breathing is known to functionally antagonize bronchoconstriction caused by airway muscle contraction. During breathing, tidal lung inflation generates force fluctuations that are transmitted to the contracted airway muscle. In vitro, experimental application of force fluctuations to contracted airway smooth muscle strips causes them to relengthen. Such force fluctuation-induced relengthening (FFIR) likely represents the mechanism by which breathing antagonizes bronchoconstriction. Thus, understanding the mechanisms that regulate FFIR of contracted airway muscle could suggest novel therapeutic interventions to increase FFIR, and so to enhance the beneficial effects of breathing in suppressing bronchoconstriction. Here we propose that the connectivity between actin filaments in contracting airway myocytes is a key determinant of FFIR, and suggest that disrupting actin-myosin-actin connectivity by interfering with actin polymerization or with myosin polymerization merits further evaluation as a potential novel approach for preventing prolonged bronchoconstriction in asthma.
authors.affiliation: Department of Medicine, University of Chicago, MC6026, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
authors.forename: Tera L
authors.initials: TL
authors.lastname: Lavoie
authors.forename: Maria L
authors.initials: ML
authors.lastname: Dowell
authors.forename: Oren J
authors.initials: OJ
authors.lastname: Lakser
authors.forename: William T
authors.initials: WT
authors.lastname: Gerthoffer
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.forename: Chun Y
authors.initials: CY
authors.lastname: Seow
authors.forename: Richard W
authors.initials: RW
authors.lastname: Mitchell
authors.forename: Julian
authors.initials: J
authors.lastname: Solway
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000502:physiology; D006801:Humans; D024745:Smooth Muscle Myosins / Q000502:physiology
chemical_list: D024745:Smooth Muscle Myosins