The contractile apparatus and mechanical properties of airway smooth muscle

Abstract

The functional properties of airway smooth muscle are fundamental to the properties of the airways in vivo. However, many of the distinctive characteristics of smooth muscle are not easily accounted for on the basis of molecular 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 properties.The molecular organization and structure of the contractile apparatus in smooth muscle is consistent with a model of force generation based on the relative sliding of adjacent actin and myosin filaments. In airway smooth muscle, actomyosin activation is initiated by the phosphorylation of the 20 kDa light chain of myosin; but there is conflicting evidence regarding the role of myosin light chain phosphorylation in tension maintenance. Tension generated 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 anchorage sites may participate in regulating the shape of the smooth muscle cell and the organization of its contractile filament system. These proteins may also participate in signalling pathways that regulate the crossbridge activation and other functions of the actin cytoskeleton.The length-dependence of active force and the mechanical plasticity of airway smooth muscle may play an important role in determining airway responsiveness during lung volume changes in vivo. The molecular basis for the length-dependence of tension in smooth muscle differs from that in skeletal muscle, and may involve mechano-transduction mechanisms that modulate contractile filament activation and cytoskeletal organization in response to changes in muscle length. The reorganization of contractile filaments may also underlie the plasticity of the mechanical response of airway smooth muscle. Changes in the structural organization and signalling pathways of airway smooth muscle cells resulting form alterations in mechanical forces in the lung may be important factors in the development of pathophysiological conditions of chronic airway hyperresponsiveness. Eur Respir J 2000; 15: 600±616. The mechanical properties of airway smooth muscle are fundamental to the regulation of airway contractility and airway tone in vivo. These mechanical properties have traditionally been interpreted in terms of the "sliding filament model" of muscle contraction first proposed by HUXLEY and NIEDERGERKE [1] and HUXLEY and HANSON [2] to explain the contractile behaviour of skeletal muscle. Like other smooth muscles, airway smooth muscle exhibits the same hyperbolic force-velocity relationship that is characteristic of striated muscles, and the lengthtension relationship is also qualitatively similar to that of striated muscles [3]. The qualitative similarities be...

The Association of Cortactin with Profilin-1 Is Critical for Smooth Muscle Contraction

“…Actin polymerization may enhance the linkage of actin filaments to integrins, strengthening the transduction of mechanical force between contractile units and extracellular matrix (4,7,32,33,46,47). In addition, actin filament assembly may also increase the numbers of contractile units and the length of actin filaments, providing more and efficient contractile elements for force development (48).…”

Spatial and temporal traction response in human airway smooth muscle cells

“…10). Calcium concentration is spatially inhomogeneous throughout the cytoplasm: local Ca 2ϩ transients, named Ca 2ϩ sparks, occur spontaneously in smooth muscle cells (14,15,25).…”

Mechanotransduction, asthma and airway smooth muscle

“…In smooth muscle cells, the actin and myosin filaments still overlap, but they do not terminate at well-defined z-disks but instead are interconnected at multiple sites -the dense bodies or dense plaques -throughout the cell or the cell membrane, respectively [7,29]. Moreover, the actin and myosin filaments can lengthen, shorten, cross-link with each other, and -together with the dense plaques and dense bodies -they can completely disassemble or re-appear at a different location.…”

“…Adhesion receptors such as integrins are transmembranen proteins that mechanically connect the extracellular matrix with intracellular focal adhesion proteins such as talin, vinculin, paxillin, zyxin, α-actinin [30]. Upon integrin activation, usually through binding to specific recognition sites at the extracellular matrix, the focal adhesion proteins cluster into what in smooth muscle cells is called a dense plaque [7,31]. Several members of the dense plaque can directly connect to actin filaments (talin, vinculin, α-actinin) while others, such as focal adhesion kinase, are involved in downstream signaling via mitogenactivated protein (MAP) kinases and members of the Ras superfamily of small GTPases such as Rho, Rac, and Cdc42, [31].…”

“…Such a force balance need not be static in the sense that the degree of airway constriction reaches a steadystate, and indeed, over the past decade numerous experimental and theoretical studies have shown that airway caliber is equilibrated dynamically rather than statically [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Indeed, the force-length curve of activated smooth muscle is constantly changing as the muscle adapts to its mechanical surroundings, such as the length to which it is stretched or the load against which it must contract.…”