Structure-function correlation in airway smooth muscle adapted to different lengths

Abstract

Airway smooth muscle is able to adapt and maintain a nearly constant maximal force generation over a large length range. This implies that a fixed filament lattice such as that found in striated muscle may not exist in this tissue and that plastic remodeling of its contractile and cytoskeletal filaments may be involved in the process of length adaptation that optimizes contractile filament overlap. Here, we show that isometric force produced by airway smooth muscle is independent of muscle length over a twofold length change; cell cross-sectional area was inversely proportional to cell length, implying that the cell volume was conserved at different lengths; shortening velocity and myosin filament density varied similarly to length change: increased by 69.4% Ϯ 5.7 (SE) and 76.0% Ϯ 9.8, respectively, for a 100% increase in cell length. Muscle power output, ATPase rate, and myosin filament density also have the same dependence on muscle cell length: increased by 35.4% Ϯ 6.7, 34.6% Ϯ 3.4, and 35.6% Ϯ 10.6, respectively, for a 50% increase in cell length. The data can be explained by a model in which additional contractile units containing myosin filaments are formed and placed in series with existing contractile units when the muscle is adapted at a longer length. muscle contraction; myosin filaments; ATPase activity; electron microscopy RECENT STUDIES HAVE DEMONSTRATED that the cycle of contraction and relaxation in airway smooth muscle involves polymerization and depolymerization of the actin (9, 13) and myosin (6) filaments. This lability of contractile filaments during muscle activation resembles that of nonmuscle motile cells that rely on impromptu assembly of contractile apparatus for motility. Oscillatory strains applied to single airway smooth muscle cells have revealed plastic deformation similar to that observed in soft glassy materials (3). Functional studies of airway smooth muscle indicate that the cells maintain maximal isometric force production (optimal contractile filament overlap) over a threefold length change by varying the number of contractile units in series (15). This newly emerged "plasticity" model of smooth muscle contraction is incompatible with the current concept of contraction based on the relatively restrictive model of striated muscle that possesses filament arrays in fixed lattice, which cannot accommodate large changes in cell length without compromising force production (4).The feasibility of the plasticity model can be tested experimentally based on the model predictions: the recruitment of additional contractile units in muscles adapted to longer lengths should result in an increase in thick filament content (or mass) in individual muscle cells, and as a consequence, the metabolic rate should increase with muscle length. In the present study, we tested the plasticity hypothesis through quantitative analysis of mechanical properties and ultrastructure, and measurement of the rate of ATP consumption in airway smooth muscles adapted to different lengths. MATERIALS AND METHODSMuscl...

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…Other structures include myosin filaments, actin filaments, cytoskeletal cross-linker molecules, cytosolic dense bodies, membrane adhesion plaques and cell-cell connections [55,185]. There is ample evidence for each of these candidates to be somehow involved in the response to external perturbation [168,174,[186][187][188][189][190][191].…”

“…By examining the details of length-dependent properties of ASM, including adapted and nonadapted isometric force, shortening velocity, power output, rate of adenosine tiphosphate utilisation and change in myosin filament density (or filament mass), KUO et al [188], QI et al [192] and HERRERA and co-workers [192][193][194][195] have provided evidence that length adaptation in ASM involves changes in the number of contractile units in series and in parallel. They also showed that externally applied strain on ASM in the relaxed state led directly to partial disassembly of the myosin filaments [168], thus providing an explanation for the strain-induced inhibition of muscle force, which could underlie the phenomenon of deepinspiration-induced bronchoprotection, as discussed in the previous section.…”

Length adaptation of smooth muscle contractile filaments in response to sustained activation

“…One of the most obvious differences is that smooth muscle lacks the highly regular organisation of contractile filaments which give rise to the banded structure in striated muscle. In addition, various types of smooth muscles are able to generate the same maximum isometric force over a wide range of lengths given time to adapt (Pratusevich et al, 1995;Kuo et al, 2003;Herrera et al, 2005;Martinez-Lemus et al, 2008;Tuna et al, 2011). This is in sharp contrast to striated muscle where the maximum isometric force is associated with a particular length (Gordon et al, 1966).…”

“…Evidence suggests that smooth muscle length adaptation is connected to a structurally and 'plastic-like' mechanism of contractile and other cytoskeletal filaments (Kuo et al, 2003;Herrera et al, 2005;Seow, 2005;van den Akker et al, 2010). Both actin and myosin polymerise and depolymerise rapidly in response to activation (Mehta & Gunst, 1999;Herrera et al, 2002).…”

“…This theory is also supported by experimental observations. First, the maximal isometric force remains invariant of the adapted length (Kuo et al, 2003;Herrera et al, 2005;Bossé et al, 2008). Second, the contraction velocity and power output are proportional to the adapted length (Kuo et al, 2003;Herrera et al, 2005).…”