scholarly journals Myosin filament polymerization and depolymerization in a model of partial length adaptation in airway smooth muscle

2011 ◽  
Vol 111 (3) ◽  
pp. 735-742 ◽  
Author(s):  
Gijs Ijpma ◽  
Ahmed M. Al-Jumaily ◽  
Simeon P. Cairns ◽  
Gary C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Actin Filaments ◽  
Isometric Force ◽  
Myosin Filament ◽  
Shortening Velocity ◽  
Partial Length ◽  
Myosin Filaments ◽  
Generating Capacity ◽  
Length Changes

Length adaptation in airway smooth muscle (ASM) is attributed to reorganization of the cytoskeleton, and in particular the contractile elements. However, a constantly changing lung volume with tidal breathing (hence changing ASM length) is likely to restrict full adaptation of ASM for force generation. There is likely to be continuous length adaptation of ASM between states of incomplete or partial length adaption. We propose a new model that assimilates findings on myosin filament polymerization/depolymerization, partial length adaptation, isometric force, and shortening velocity to describe this continuous length adaptation process. In this model, the ASM adapts to an optimal force-generating capacity in a repeating cycle of events. Initially the myosin filament, shortened by prior length changes, associates with two longer actin filaments. The actin filaments are located adjacent to the myosin filaments, such that all myosin heads overlap with actin to permit maximal cross-bridge cycling. Since in this model the actin filaments are usually longer than myosin filaments, the excess length of the actin filament is located randomly with respect to the myosin filament. Once activated, the myosin filament elongates by polymerization along the actin filaments, with the growth limited by the overlap of the actin filaments. During relaxation, the myosin filaments dissociate from the actin filaments, and then the cycle repeats. This process causes a gradual adaptation of force and instantaneous adaptation of shortening velocity. Good agreement is found between model simulations and the experimental data depicting the relationship between force development, myosin filament density, or shortening velocity and length.

Mechanism of partial adaptation in airway smooth muscle after a step change in length

2007 ◽  
Vol 103 (2) ◽  
pp. 569-577 ◽  
Author(s):  
Farah Ali ◽  
Leslie Chin ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Intermediate State ◽  
Ultrastructural Changes ◽  
Myosin Filament ◽  
Shortening Velocity ◽  
Myosin Filaments ◽  
Partial Adaptation ◽  
Static Conditions

The phenomenon of length adaptation in airway smooth muscle (ASM) is well documented; however, the underlying mechanism is less clear. Evidence to date suggests that the adaptation involves reassembly of contractile filaments, leading to reconfiguration of the actin filament lattice and polymerization or depolymerization of the myosin filaments within the lattice. The time courses for these events are unknown. To gain insights into the adaptation process, we examined ASM mechanical properties and ultrastructural changes during adaptation. Step changes in length were applied to isolated bundles of ASM cells; changes in force, shortening velocity, and myosin filament mass were then quantified. A greater decrease in force was found following an acute decrease in length, compared with that of an acute increase in length. A decrease in myosin filament mass was also found with an acute decrease in length. The shortening velocity measured immediately after the length change was the same as that measured after the muscle had fully adapted to the new length. These observations can be explained by a model in which partial adaptation of the muscle leads to an intermediate state in which reconfiguration of the myofilament lattice occurred rapidly, followed by a relatively slow process of polymerization of myosin filaments within the lattice. The partially adapted intermediate state is perhaps more physiologically relevant than the fully adapted state seen under static conditions, and it simulates a more realistic behavior for ASM in vivo.

scholarly journals Could an increase in airway smooth muscle shortening velocity cause airway hyperresponsiveness?

2011 ◽  
Vol 300 (1) ◽  
pp. L121-L131 ◽  
Author(s):  
Sharon R. Bullimore ◽  
Sana Siddiqui ◽  
Graham M. Donovan ◽  
James G. Martin ◽  
James Sneyd ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Isometric Force ◽  
Muscle Length ◽  
Shortening Velocity ◽  
Bridge Model ◽  
Generating Capacity ◽  
Cross Bridges

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma. It has been proposed that an increase in the shortening velocity of airway smooth muscle (ASM) could contribute to AHR. To address this possibility, we tested whether an increase in the isotonic shortening velocity of ASM is associated with an increase in the rate and total amount of shortening when ASM is subjected to an oscillating load, as occurs during breathing. Experiments were performed in vitro using 27 rat tracheal ASM strips supramaximally stimulated with methacholine. Isotonic velocity at 20% isometric force (Fiso) was measured, and then the load on the muscle was varied sinusoidally (0.33 ± 0.25 Fiso, 1.2 Hz) for 20 min, while muscle length was measured. A large amplitude oscillation was applied every 4 min to simulate a deep breath. We found that: 1) ASM strips with a higher isotonic velocity shortened more quickly during the force oscillations, both initially ( P < 0.001) and after the simulated deep breaths ( P = 0.002); 2) ASM strips with a higher isotonic velocity exhibited a greater total shortening during the force oscillation protocol ( P < 0.005); and 3) the effect of an increase in isotonic velocity was at least comparable in magnitude to the effect of a proportional increase in ASM force-generating capacity. A cross-bridge model showed that an increase in the total amount of shortening with increased isotonic velocity could be explained by a change in either the cycling rate of phosphorylated cross bridges or the rate of myosin light chain phosphorylation. We conclude that, if asthma involves an increase in ASM velocity, this could be an important factor in the associated AHR.

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

2003 ◽  
Vol 285 (2) ◽  
pp. C384-C390 ◽  
Author(s):  
Kuo-Hsing Kuo ◽  
Ana M. Herrera ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Lincoln E. Ford ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Power ◽  
Isometric Force ◽  
Muscle Length ◽  
Length Change ◽  
Cell Length ◽  
Myosin Filament ◽  
Shortening Velocity ◽  
Cross Sectional

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% ± 5.7 (SE) and 76.0% ± 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% ± 6.7, 34.6% ± 3.4, and 35.6% ± 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.

scholarly journals Force maintenance and myosin filament assembly regulated by Rho-kinase in airway smooth muscle

2015 ◽  
Vol 308 (1) ◽  
pp. L1-L10 ◽  
Author(s):  
Bo Lan ◽  
Linhong Deng ◽  
Graham M. Donovan ◽  
Leslie Y. M. Chin ◽  
Harley T. Syyong ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Initial Phase ◽  
Rho Kinase ◽  
Myosin Filament ◽  
Second Phase ◽  
Minimal Effect ◽  
Kinase Inhibition ◽  
Myosin Filaments ◽  
Force Maintenance

Smooth muscle contraction can be divided into two phases: the initial contraction determines the amount of developed force and the second phase determines how well the force is maintained. The initial phase is primarily due to activation of actomyosin interaction and is relatively well understood, whereas the second phase remains poorly understood. Force maintenance in the sustained phase can be disrupted by strains applied to the muscle; the strain causes actomyosin cross-bridges to detach and also the cytoskeletal structure to disassemble in a process known as fluidization, for which the underlying mechanism is largely unknown. In the present study we investigated the ability of airway smooth muscle to maintain force after the initial phase of contraction. Specifically, we examined the roles of Rho-kinase and protein kinase C (PKC) in force maintenance. We found that for the same degree of initial force inhibition, Rho-kinase substantially reduced the muscle's ability to sustain force under static conditions, whereas inhibition of PKC had a minimal effect on sustaining force. Under oscillatory strain, Rho-kinase inhibition caused further decline in force, but again, PKC inhibition had a minimal effect. We also found that Rho-kinase inhibition led to a decrease in the myosin filament mass in the muscle cells, suggesting that one of the functions of Rho-kinase is to stabilize myosin filaments. The results also suggest that dissolution of myosin filaments may be one of the mechanisms underlying the phenomenon of fluidization. These findings can shed light on the mechanism underlying deep inspiration induced bronchodilation.

Myosin thick filament lability induced by mechanical strain in airway smooth muscle

2001 ◽  
Vol 90 (5) ◽  
pp. 1811-1816 ◽  
Author(s):  
Kuo-Hsing Kuo ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Lincoln E. Ford ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cross Sections ◽  
Structural Changes ◽  
Isometric Force ◽  
Mechanical Strain ◽  
Thick Filament ◽  
Functional Changes ◽  
Thick Filaments ◽  
Length Changes

Airway smooth muscle adapts to different lengths with functional changes that suggest plastic alterations in the filament lattice. To look for structural changes that might be associated with this plasticity, we studied the relationship between isometric force generation and myosin thick filament density in cell cross sections, measured by electron microscope, after length oscillations applied to the relaxed porcine trachealis muscle. Muscles were stimulated regularly for 12 s every 5 min. Between two stimulations, the muscles were submitted to repeated passive ±30% length changes. This caused tetanic force and thick-filament density to fall by 21 and 27%, respectively. However, in subsequent tetani, both force and filament density recovered to preoscillation levels. These findings indicate that thick filaments in airway smooth muscle are labile, depolymerization of the myosin filaments can be induced by mechanical strain, and repolymerization of the thick filaments underlies force recovery after the oscillation. This thick-filament lability would greatly facilitate plastic changes of lattice length and explain why airway smooth muscle is able to function over a large length range.

scholarly journals Supercontracted state of vertebrate smooth muscle cell fragments reveals myofilament lengths.

1990 ◽  
Vol 111 (6) ◽  
pp. 2451-2461 ◽  
Author(s):  
J V Small ◽  
M Herzog ◽  
M Barth ◽  
A Draeger
Keyword(s):  
Smooth Muscle ◽  
Actin Filaments ◽  
Cytoskeletal Proteins ◽  
Terminal Phase ◽  
Myosin Filament ◽  
Protein Loss ◽  
Whole Cells ◽  
Myosin Filaments ◽  
Central Bundle ◽  
Cell Fragments

Isolated cell preparations from chicken gizzard smooth muscle typically contain a mixture of cell fragments and whole cells. Both species are spontaneously permeable and may be preloaded with externally applied phalloidin and antibodies and then induced to contract with Mg ATP. Labeling with antibodies revealed that the cell fragments specifically lacked certain cytoskeletal proteins (vinculin, filamin) and were depleted to various degrees in others (desmin, alpha-actinin). The cell fragments showed a unique mode of supercontraction that involved the protrusion of actin filaments through the cell surface during the terminal phase of shortening. In the presence of dextran, to minimize protein loss, the supercontracted products were star-like in form, comprising long actin bundles radiating in all directions from a central core containing myosin, desmin, and alpha-actinin. It is concluded that supercontraction is facilitated by an effective uncoupling of the contractile apparatus from the cytoskeleton, due to partial degradation of the latter, which allows unhindered sliding of actin over myosin. Homogenization of the cell fragments before or after supercontraction produced linear bipolar dimer structures composed of two oppositely polarized bundles of actin flanking a central bundle of myosin filaments. Actin filaments were shown to extend the whole length of the bundles and their length averaged integral to 4.5 microns. Myosin filaments in the supercontracted dimers averaged 1.6 microns in length. The results, showing for the first time the high actin to myosin filament length ratio in smooth muscle are readily consistent with the slow speed of shortening of this tissue. Other implications of the results are also discussed.

Maturation of guinea pig tracheal strip stiffness

2005 ◽  
Vol 289 (6) ◽  
pp. L902-L908 ◽  
Author(s):  
Lu Wang ◽  
Pasquale Chitano ◽  
Thomas M. Murphy
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Phase Angle ◽  
Dynamic Stiffness ◽  
Age Groups ◽  
Oscillation Mode ◽  
Tissue Response ◽  
Shortening Velocity ◽  
Length Changes

Previously, we showed the shortening velocity of guinea pig tracheal strips was the greatest in juvenile (3-wk-old) compared with infant (1-wk-old) and adult animals (3-mo-old). The greatest shortening velocity was associated with the least resistance to shortening calculated from force-velocity curves among the three age groups. It remained to be verified if the stiffness of tracheal tissue, a measure of tissue response to geometrical deformations, is different among the three age groups. We hypothesized that stiffness of intact tracheal strips is lowest in the juvenile group and that this can explain the ontogeny of airway smooth muscle resistance to shortening and shortening velocity. Static stiffness measured through stepwise deformations showed no age-related differences. Evaluation of tissue response to oscillatory deformations showed that the dynamic stiffness of unstimulated tracheal strips was 8.35 ± 0.88, 4.15 ± 1.09, and 8.21 ± 1.57 kPa, and the phase angle was 10.3 ± 2.93, 2.46 ± 0.67, and 7.87 ± 1.77° in infant, juvenile, and adult, respectively. Unstimulated juvenile strips were significantly lower in dynamic stiffness and phase angle compared with unstimulated infant or adult strips. This maturational profile was independent of muscle strip preset length or oscillation mode/amplitude but was abolished at peak of contraction to either carbachol or electric field stimulation. These results suggest that the noncontractile components of tracheal strips are less stiff and contain fewer viscous/frictional elements in juvenile than in other age groups. This may provide a functional basis for reduced resistance to length changes in juvenile airway smooth muscle.

scholarly journals The Huxley crossbridge model as the basic mechanism for airway smooth muscle contraction

2019 ◽  
Vol 317 (2) ◽  
pp. L235-L246 ◽  
Author(s):  
Ling Luo ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow ◽  
Pasquale Chitano
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Time Course ◽  
Striated Muscle ◽  
Isometric Force ◽  
Smooth Muscle Contraction ◽  
Time Dependent ◽  
Shortening Velocity ◽  
Mlc20 Phosphorylation

The cyclic interaction between myosin crossbridges and actin filaments underlies smooth muscle contraction. Phosphorylation of the 20-kDa myosin light chain (MLC20) is a crucial step in activating the crossbridge cycle. Our current understanding of smooth muscle contraction is based on observed correlations among MLC20 phosphorylation, maximal shortening velocity ( Vmax), and isometric force over the time course of contraction. However, during contraction there are changes in the extent of phosphorylation of many additional proteins as well as changes in activation of enzymes associated with the signaling pathways. As a consequence, the mechanical manifestation of muscle contraction is likely to change with time. To simplify the study of these relationships, we measured the mechanical properties of airway smooth muscle at different levels of MLC20 phosphorylation at a fixed time during contraction. A simple correlation emerged when time-dependent variables were fixed. MLC20 phosphorylation was found to be directly and linearly correlated with the active stress, stiffness, and power of the muscle; the observed weak dependence of Vmax on MLC20 phosphorylation could be explained by the presence of an internal load in the muscle preparation. These results can be entirely explained by the Huxley crossbridge model. We conclude that when the influence of time-dependent events during contraction is held constant, the basic crossbridge mechanism in smooth muscle is the same as that in striated muscle.

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation

1997 ◽  
Vol 83 (3) ◽  
pp. 739-745 ◽  
Author(s):  
X. Shen ◽  
M. F. Wu ◽  
R. S. Tepper ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Mechanical Response ◽  
Isometric Force ◽  
Shortening Velocity ◽  
Airway Reactivity ◽  
Pharmacological Modulation ◽  
Activation Mechanisms ◽  
Cross Bridges

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation. J. Appl. Physiol. 83(3): 739–745, 1997.—Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studied the effects of different pharmacological stimuli on airway smooth muscle to determine whether the muscle behavior during length oscillation can be modulated pharmacologically and to evaluate the role of different activation mechanisms in determining its behavior during the oscillation. Active force decreased below the static isometric force during the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic shortening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length oscillation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.

scholarly journals Myosin Crossbridge, Contractile Unit, and the Mechanism of Contraction in Airway Smooth Muscle: A Mechanical Engineer's Perspective

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Actin Filaments ◽  
Striated Muscle ◽  
Structural Data ◽  
Smooth Muscle Contraction ◽  
Shortening Velocity ◽  
Mathematical Analyses ◽  
Myosin Motors

Muscle contraction is caused by the action of myosin motors within the structural confines of contractile unit arrays. When the force generated by cyclic interactions between myosin crossbridges and actin filaments is greater than the average load shared by the crossbridges, sliding of the actin filaments occurs and the muscle shortens. The shortening velocity as a function of muscle load can be described mathematically by a hyperbola; this characteristic force–velocity relationship stems from stochastic interactions between the crossbridges and the actin filaments. Beyond the actomyosin interaction, there is not yet a unified theory explaining smooth muscle contraction, mainly because the structure of the contractile unit in smooth muscle (akin to the sarcomere in striated muscle) is still undefined. In this review, functional and structural data from airway smooth muscle are analyzed in an engineering approach of quantification and correlation to support a model of the contractile unit with characteristics revealed by mathematical analyses and behavior matched by experimental observation.

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