The contractile apparatus and mechanical properties of airway smooth muscle

The functional properties of airway smooth muscle are fundamental to the pr operties of the airways in vivo. However, many of the distinctive character istics of smooth muscle are not easily accounted for on the basis of molecu lar models developed to account for the properties of striated muscles. The specialized ultrastructural features and regulatory mechanisms present in smooth muscle are likely to form the basis for many of its characteristic p roperties. The molecular organization and structure of the contractile apparatus in sm ooth muscle is consistent with a model of force generation based on the rel ative sliding of adjacent actin and myosin filaments, In airway smooth musc le, actomyosin activation is initiated by the phosphorylation of the 20 kDa light chain of myosin; but there is conflicting evidence regarding the rol e of myosin light chain phosphorylation in tension maintenance. Tension gen erated by the contractile filaments is transmitted throughout the cell via a network of actin filaments anchored at dense plaques at the cell membrane , where force is transmitted to the extracellular matrix via transmembrane integrins. Proteins bound to actin and/or localized to actin filament ancho rage sites may participate in regulating the shape of the smooth muscle cel l and the organization of its contractile filament system. These proteins m ay also participate in signalling pathways that regulate the crossbridge ac tivation and other functions of the actin cytoskeleton. The length-dependence of active force and the mechanical plasticity of airw ay smooth muscle may play an important role in determining airway responsiv eness during lung volume changes in vivo. The molecular basis for the lengt h-dependence of tension in smooth muscle differs from that in skeletal musc le, and may involve mechano-transduction mechanisms that modulate contracti le filament activation and cytoskeletal organization in response to changes in muscle length. The reorganization of contractile filaments may also und erlie the plasticity of the mechanical response of airway smooth muscle, Ch anges in the structural organization and signalling pathways of airway smoo th muscle cells resulting form alterations in mechanical forces in the lung may be important factors in the development of pathophysiological conditio ns of chronic airway hyperresponsiveness.