Signal transduction in smooth muscle - 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 pa thogenesis of asthma. Recent investigations have turned to the ways in whic h the muscle is influenced by its dynamic microenvironment. Ordinarily, air way smooth muscle presents little problem, even when maximally activated, b ecause unending mechanical perturbations provided by spontaneous tidal brea thing put airway smooth muscle in a perpetual state of "limbo," keeping its contractile machinery off balance and unable to achieve its force-generati ng potential. The dynamic microenvironment affects airway smooth muscle in at least two ways: by acute changes associated with disruption of myosin bi nding and by chronic changes associated with plastic restructuring of contr actile and cytoskeletal filament organization. Plastic restructuring can oc cur 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 ai rway hyperresponsiveness in asthma.