Historical perspective on airway smooth muscle: the saga of a frustrated cell

Despite the lack of a clearly defined physiological function, airway smooth muscle receives substantial attention because of its involvement in the pathogenesis of asthma. Recent investigations have turned to the ways in which the muscle is influenced by its dynamic microenvironment. Ordinarily, airway smooth muscle presents little problem, even when maximally activated, because unending mechanical perturbations provided by spontaneous tidal breathing put airway smooth muscle in a perpetual state of "limbo," keeping its contractile machinery off balance and unable to achieve its force-generating potential. The dynamic microenvironment affects airway smooth muscle in at least two ways: by acute changes associated with disruption of myosin binding and by chronic changes associated with plastic restructuring of contractile and cytoskeletal filament organization. Plastic restructuring can occur when dynamic length changes occur between sequential contractile events or within a single contractile event. Impairment of these normal responses of airway smooth muscle to its dynamic environment may be implicated in airway hyperresponsiveness in asthma.