Mechanosensitive modulation of receptor-mediated crossbridge activation and cytoskeletal organization in airway smooth muscle

Recent findings indicate that mechanical strain (deformation) exerted by th e extracellular matrix modulates activation of airway smooth muscle cells. Furthermore, cytoskeletal organization in airway smooth muscle appears to b e dynamic, and subject to modulation by receptor activation and mechanical strain. Mechanosensitive modulation of crossbridge activation and cytoskele tal organization may represent intracellular feedback mechanisms that limit the shortening of airway smooth muscle during bronchoconstriction. Recent findings suggest that receptor-mediated signal transduction is the primary target of mechanosensitive modulation. Mechanical strain appears to regulat e the number of functional G-proteins and/or phospholipase C enzymes in the cell membrane possibly by membrane trafficking and/or protein translocatio n. Dense plaques, membrane structures analogous to focal adhesions, appear to be the primary target of cytoskeletal regulation. Mechanical strain and receptor-binding appear to regulate the assembly and phosphorylation of den se plaque proteins in airway smooth muscle cells. Understanding these mecha nisms may reveal new pharmacological targets for controlling airway resista nce in airway diseases.