Time course of isotonic shortening and the underlying contraction mechanism in airway smooth muscle

Abstract

Syyong HT, Raqeeb A, Paré PD, Seow CY. Time course of isotonic shortening and the underlying contraction mechanism in airway smooth muscle. J Appl Physiol 111: 642-656, 2011. First published June 2, 2011; doi:10.1152/japplphysiol.00085.2011.-Although the structure of the contractile unit in smooth muscle is poorly understood, some of the mechanical properties of the muscle suggest that a sliding-filament mechanism, similar to that in striated muscle, is also operative in smooth muscle. To test the applicability of this mechanism to smooth muscle function, we have constructed a mathematical model based on a hypothetical structure of the smooth muscle contractile unit: a side-polar myosin filament sandwiched by actin filaments, each attached to the equivalent of a Z disk. Model prediction of isotonic shortening as a function of time was compared with data from experiments using ovine tracheal smooth muscle. After equilibration and establishment of in situ length, the muscle was stimulated with ACh (100 M) until force reached a plateau. The muscle was then allowed to shorten isotonically against various loads. From the experimental records, length-force and force-velocity relationships were obtained. Integration of the hyperbolic force-velocity relationship and the linear length-force relationship yielded an exponential function that approximated the time course of isotonic shortening generated by the modeled sliding-filament mechanism. However, to obtain an accurate fit, it was necessary to incorporate a viscoelastic element in series with the sliding-filament mechanism. The results suggest that a large portion of the shortening is due to filament sliding associated with muscle activation and that a small portion is due to continued deformation associated with an element that shows viscoelastic or power-law creep after a step change in force. mathematical model; contractile unit; sliding-filament mechanism THE STRUCTURE OF THE CONTRACTILE unit in smooth muscle is unknown, despite the common belief that the cycling-crossbridge/sliding-filament mechanism of contraction, which operates in striated muscle, is also responsible for smooth muscle contraction. The predominant model for the sarcomere-equivalent contractile unit in smooth muscle is a side-polar myosin (thick) filament sandwiched by two oppositely oriented actin (thin) filaments, each attached to a dense body that is believed to function like a Z disk in striated muscle (18,21,27), as shown in Fig. 1. An important assumption associated with the model is that the sliding of the thick and thin filaments relative to each other is caused by repetitive interaction of the myosin heads (cross bridges) of the thick filament with the thin filaments, in the same manner described for striated muscle (22,23). Such a cross-bridge mechanism for smooth muscle myosin has been observed in experiments where the interaction of isolated individual myosin heads with thin filaments was visualized and quantified directly (14, 15, 28). As predicted by Huxley's 1957 model (22), the ...

Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips

“…The first order kinetics imposed on this adaptation process, while convenient mathematically, are also in good agreement with the available experimental data (Wang et al 2001). Many more complex phenomena of ASM, for example power law stress relaxation (Lenormand et al 2004, Syyong et al 2011 or fluidization (Krishnan et al 2008) are neglected on this scale.…”

Modelling airway smooth muscle passive length adaptation via thick filament length distributions

“…Recently, the hypothesis that the force exerted by ASM is controlled by the ASM length-dependent overlap between adjacent thin filaments has gained traction (Seow, 2005; Ali et al, 2007; Seow and Fredberg, 2011; Syyong et al, 2011; Brook and Jensen, in press), and thus that changes in muscle length lead to changes in filament overlap and thus altered ASM force. Combined with the quantitative measurement of the distribution of thick filament lengths found in ASM, this allows the construction of a crossbridge-type model in which crossbridge binding sites are preferentially available within and near the thin filament overlap region, and dependent on the thick filament length distribution.…”

A structural constitutive model for smooth muscle contraction in biological tissues

“…_ λ p ðtÞ ¼ ÀVe À μt . This exponential decaying function for the axial stretch of PCFs is assumed based on experimental data and previous models[22,23].…”