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.

Influence of calcium on myosin thick filament formation in intact airway smooth muscle

2002 ◽  
Vol 282 (2) ◽  
pp. C310-C316 ◽  
Author(s):  
Ana M. Herrera ◽  
Kuo-Hsing Kuo ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Calcium Level ◽  
Muscle Activation ◽  
Isometric Force ◽  
Smooth Muscles ◽  
Thick Filament ◽  
Filament Formation ◽  
Cross Sectional ◽  
Thick Filaments

Myosin thick filaments have been shown to be structurally labile in intact smooth muscles. Although the mechanism of thick filament assembly/disassembly for purified myosins in solution has been well described, regulation of thick filament formation in intact muscle is still poorly understood. The present study investigates the effect of resting calcium level on thick filament maintenance in intact airway smooth muscle and on thick filament formation during activation. Cross-sectional density of the thick filaments measured electron microscopically showed that the density increased substantially (144%) when the muscle was activated. The abundance of filamentous myosins in relaxed muscle was calcium sensitive; in the absence of calcium (with EGTA), the filament density deceased by 35%. Length oscillation imposed on the muscle under zero-calcium conditions produced no further reduction in the density. Isometric force and filament density recovered fully after reincubation of the muscle in normal physiological saline. The results suggest that in airway smooth muscle, filamentous myosins exist in equilibrium with monomeric myosins; muscle activation favors filament formation, and the resting calcium level is crucial for preservation of the filaments in the relaxed state.

Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling

2005 ◽  
Vol 99 (2) ◽  
pp. 634-641 ◽  
Author(s):  
Linhong Deng ◽  
Nigel J. Fairbank ◽  
Darren J. Cole ◽  
Jeffrey J. Fredberg ◽  
Geoffrey N. Maksym
Keyword(s):  
Smooth Muscle ◽  
Mechanical Stress ◽  
Applied Stress ◽  
Airway Smooth Muscle ◽  
Cell Activation ◽  
Structural Changes ◽  
Muscle Tone ◽  
Residual Effects ◽  
Cell Stiffness ◽  
Functional Changes

The application of mechanical stresses to the airway smooth muscle (ASM) cell causes time-dependent cytoskeletal stiffening and remodeling (Deng L, Fairbank NJ, Fabry B, Smith PG, and Maksym GN. Am J Physiol Cell Physiol 287: C440–C448, 2004). We investigated here the extent to which these behaviors are modulated by the state of cell activation (tone). Localized mechanical stress was applied to the ASM cell in culture via oscillating beads (4.5 μm) that were tightly bound to the actin cytoskeleton (CSK). Tone was reduced from baseline level using a panel of relaxant agonists (10−3 M dibutyryl cAMP, 10−4 M forskolin, or 10−6 M formoterol). To assess functional changes, we measured cell stiffness (G′) using optical magnetic twisting cytometry, and to assess structural changes of the CSK we measured actin accumulation in the neighborhood of the bead. Applied mechanical stress caused a twofold increase in G′ at 120 min. After cessation of applied stress, G′ diminished only 24 ± 6% (mean ± SE) at 1 h, leaving substantial residual effects that were largely irreversible. However, applied stress-induced stiffening could be prevented by ablation of tone. Ablation of tone also inhibited the amount of actin accumulation induced by applied mechanical stress ( P < 0.05). Thus the greater the contractile tone, the greater was applied stress-induced CSK stiffening and remodeling. As regards pathobiology of asthma, this suggests a maladaptive positive feedback in which tone potentiates ASM remodeling and stiffening that further increases stress and possibly leads to worsening airway function.

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.

Filament lattice changes in smooth muscle assessed using birefringence

2005 ◽  
Vol 83 (10) ◽  
pp. 933-940 ◽  
Author(s):  
A V Smolensky ◽  
L E Ford
Keyword(s):  
Smooth Muscle ◽  
Time Course ◽  
Structural Changes ◽  
Thick Filament ◽  
Myosin Filament ◽  
Filament Formation ◽  
Tension Development ◽  
Thick Filaments ◽  
Contractile Parameters ◽  
In Series

The long functional range of some types of smooth muscle has been the subject of recent study. It has been proposed that the muscle filament lattice adapts to longer lengths by placing more filaments in series and that lattice plasticity is facilitated by myosin filament evanescence, with filaments dissociating during relaxation and reforming upon activation. Support for these dynamic changes in the filament lattice has been provided partly by changes in contractile parameters at different times in the contraction–relaxation cycle at different lengths. If the changes in contractile parameters result from filament formation and dissociation, these structural changes must occur on the time scale of tension development and relaxation. To assess whether thick-filament formation could account for the contractile changes, we measured birefringence continuously during activation and relaxation and compared these optical changes with the time course of force development and relaxation. Birefringence is a well-known property of muscle; striations in skeletal and cardiac muscle result from the A-bands being anisotropic, i.e., birefringent, and it is now known that this optical property is due to the presence of myosin thick filaments in the A-bands. Thus, the strength of birefringence is expected to represent the density of thick filaments. Here, we describe the principle of the method, the techniques for recording the optical signals, some initial results, and discuss the interpretation of results and some limitations of the method.Key words: airway smooth muscle, myosin filament, plasticity.

Cardiotrophin-1 alters airway smooth muscle structure and mechanical properties in airway explants

2004 ◽  
Vol 287 (6) ◽  
pp. L1165-L1171 ◽  
Author(s):  
Xueyan Zheng ◽  
Danyi Zhou ◽  
Chun Y. Seow ◽  
Tony R Bai
Keyword(s):  
Mechanical Properties ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Structural Changes ◽  
Treated Group ◽  
Structural Features ◽  
Passive Tension ◽  
Airway Wall ◽  
Optimal Length ◽  
Functional Changes

Induction of hypertrophy and inhibition of apoptosis may be important mechanisms contributing to increased airway smooth muscle (ASM) mass in asthma. Data from our laboratory indicate that cardiotrophin-1 (CT-1) induces hypertrophy and inhibits apoptosis in isolated human ASM cells. To determine whether these novel effects of CT-1 also occur in the airway tissue milieu and to determine whether structural changes are accompanied by functional changes, matched pairs of guinea pig airway explants were treated with or without CT-1 for 7 days, and structural features as well as isometric and isotonic contractile and relaxant mechanical properties were measured. CT-1 (0.2–5 ng/ml) increased both myocyte mass and extracellular matrix in a concentration-dependent fashion. CT-1 (10 ng/ml)-treated tissues exhibited a significant increase in passive tension at all lengths on day 7; at optimal length, passive tension generated by CT-1-treated tissues was 1.72 ± 0.12 vs. 1.0 ± 0.1 g for control. Maximal isometric stress was decreased in the CT-1-treated group on day 7 (0.39 ± 0.10 kg/cm2) vs. control (0.77 ± 0.15 kg/cm2, P < 0.05). Isoproterenol-induced relaxant potency was reduced in CT-1-treated tissues, log EC50 being −7.28 ± 0.34 vs. −8.12 ± 0.25 M in control, P < 0.05. These data indicate that CT-1 alters ASM structural and mechanical properties in the tissue environment and suggest that structural changes found in the airway wall in asthma are not necessarily associated with increased responsiveness.

Mechanical strain increases velocity and extent of shortening in cultured airway smooth muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. L343-L348 ◽  
Author(s):  
Paul G. Smith ◽  
Chaity Roy ◽  
Jamie Dreger ◽  
Frank Brozovich
Keyword(s):  
Smooth Muscle ◽  
Mechanical Stress ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Mechanical Strain ◽  
Airway Smooth Muscle Cells ◽  
Maximal Velocity ◽  
Cell Contractility ◽  
Cell Shortening

Abnormal mechanical stress on lung tissue is associated with increased mass and contractility of airway smooth muscle (ASM). We have reported that cultured ASM cells subjected to cyclic strain exhibit increased myosin light chain kinase (MLCK) and stress filaments. Increased MLCK may increase contractile velocity, whereas increased stress filaments could impede cell shortening by increasing the cell’s internal load. To study strain-induced changes in cell contractility, the time course of shortening of individual cells exposed to 90 mM KCl was recorded. Length vs. time plots revealed significantly greater maximal velocity of shortening in strain cells than control (no strain). This correlated with an increase in MLCK and myosin light chain phosphorylation measured in strain cells in separate experiments. The extent of cell shortening tended to be greater in the strain cells so that increased impedance to shortening was not detected. Mechanical stress may therefore increase the contractility of ASM by increasing the content of MLCK.

scholarly journals The Na,K-ATPase-Dependent Src Kinase Signaling Changes with Mesenteric Artery Diameter

2018 ◽  
Vol 19 (9) ◽  
pp. 2489 ◽  
Author(s):  
Lin Zhang ◽  
Christian Aalkjaer ◽  
Vladimir Matchkov
Keyword(s):  
Smooth Muscle ◽  
Binding Sites ◽  
Isometric Force ◽  
Src Kinase ◽  
Ouabain Binding ◽  
Arterial Diameter ◽  
Small Arteries ◽  
Functional Changes ◽  
High Affinity ◽  
Different Diameters

Inhibition of the Na,K-ATPase by ouabain potentiates vascular tone and agonist-induced contraction. These effects of ouabain varies between different reports. In this study, we assessed whether the pro-contractile effect of ouabain changes with arterial diameter and the molecular mechanism behind it. Rat mesenteric small arteries of different diameters (150–350 µm) were studied for noradrenaline-induced changes of isometric force and intracellular Ca2+ in smooth muscle cells. These functional changes were correlated to total Src kinase and Src phosphorylation assessed immunohistochemically. High-affinity ouabain-binding sites were semi-quantified with fluorescent ouabain. We found that potentiation of noradrenaline-sensitivity by ouabain correlates positively with an increase in arterial diameter. This was not due to differences in intracellular Ca2+ responses but due to sensitization of smooth muscle cell contractile machinery to Ca2+. This was associated with ouabain-induced Src activation, which increases with increasing arterial diameter. Total Src expression was similar in arteries of different diameters but the density of high-affinity ouabain binding sites increased with increasing arterial diameters. We suggested that ouabain binding induces more Src kinase activity in mesenteric small arteries with larger diameter leading to enhanced sensitization of the contractile machinery to Ca2+.

scholarly journals Logarithmic superposition of force response with rapid length changes in relaxed porcine airway smooth muscle

2010 ◽  
Vol 299 (6) ◽  
pp. L898-L904 ◽  
Author(s):  
G. Ijpma ◽  
A. M. Al-Jumaily ◽  
S. P. Cairns ◽  
G. C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Power Law ◽  
Logarithmic Scale ◽  
Force Response ◽  
Linear Superposition ◽  
Passive Dynamics ◽  
Cross Bridge ◽  
Force Relaxation ◽  
Length Changes

We present a systematic quantitative analysis of power-law force relaxation and investigate logarithmic superposition of force response in relaxed porcine airway smooth muscle (ASM) strips in vitro. The term logarithmic superposition describes linear superposition on a logarithmic scale, which is equivalent to multiplication on a linear scale. Additionally, we examine whether the dynamic response of contracted and relaxed muscles is dominated by cross-bridge cycling or passive dynamics. The study shows the following main findings. For relaxed ASM, the force response to length steps of varying amplitude (0.25–4% of reference length, both lengthening and shortening) are well-fitted with power-law functions over several decades of time (10−2 to 103 s), and the force response after consecutive length changes is more accurately fitted assuming logarithmic superposition rather than linear superposition. Furthermore, for sinusoidal length oscillations in contracted and relaxed muscles, increasing the oscillation amplitude induces greater hysteresivity and asymmetry of force-length relationships, whereas increasing the frequency dampens hysteresivity but increases asymmetry. We conclude that logarithmic superposition is an important feature of relaxed ASM, which may facilitate a more accurate prediction of force responses in the continuous dynamic environment of the respiratory system. In addition, the single power-function response to length changes shows that the dynamics of cross-bridge cycling can be ignored in relaxed muscle. The similarity in response between relaxed and contracted states implies that the investigated passive dynamics play an important role in both states and should be taken into account.

Natural Variability in the Length of Thin and Thick Filaments in Single Fibres From a Crab, Portunus Depurator

1970 ◽  
Vol 6 (2) ◽  
pp. 559-592
Author(s):  
CLARA FRANZINI-ARMSTRONG
Keyword(s):  
Thick Filament ◽  
Natural Variability ◽  
Thin Filaments ◽  
Thick Filaments ◽  
Striation Spacing ◽  
Free Region ◽  
Cross Striation ◽  
Single Fibres ◽  
Length Changes ◽  
Medium Type

The carpopodite flexor of the walking legs of the crab Portunus depurator contains fibres belonging to 3 groups. These are characterized by differences in the cross-striation spacing. Fibres having sarcomeres of approximately 4, 5 and 7 µm are here called short, medium and long sarcomere types, respectively. Within individual fibres belonging to any of the groups the length of the A band is not constant. Up to 25 % length differences have been measured in A bands belonging even to the same fibril. The bridge-free regions of the thick filaments are not always in the centre, so that the filaments are often asymmetric. Analogally, the L line, resulting from the alignment of the bridge-free regions of the thick filaments, may be asymmetrically placed in the Z band. The length of the bridge-free region in crab thick filaments is 60 nm, while the corresponding region in vertebrate thick filaments is 120 nm. This is discussed in terms of a possible model of the filament. The length of the thin filaments is proportional to that of the thick filaments in the corresponding portion of the sarcomere. When two A bands of different length occur in adjacent positions along the fibril, the Z line is not a centre of symmetry. The ratio of thin to thick filament number is variable in individual fibrils. In general, the ratio is higher in the medium sarcomere type fibres than in the short sarcomere type. Stretched and shorter portions of single fibres of the medium type have been examined and the A-band length populations compared. From such a study it can be deduced that passive length changes occur in crab fibres by sliding of thin and thick filaments.

Mechanical strain memory in airway smooth muscle

2000 ◽  
Vol 278 (5) ◽  
pp. C895-C904 ◽  
Author(s):  
Wah-Lun Chan ◽  
Jeanette Silberstein ◽  
Chi-Ming Hai
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Mechanical Strain ◽  
Control Level ◽  
High Stress ◽  
Peak Stress ◽  
Airway Smooth Muscle Cells ◽  
Initial Length ◽  
Myosin Phosphorylation ◽  
Contraction And Relaxation

We investigated the effect of a single rapid stretch on poststretch force and myosin phosphorylation in bovine tracheal smooth muscle. When unstimulated muscle strips were stretched from suboptimal length to optimal length ( L o), poststretch steady-state force was not significantly different from that of unstretched control at L o. However, when carbachol-activated muscle strips were stretched from suboptimal length to L o, poststretch force and myosin phosphorylation were lower than control and significantly correlated with initial length. When poststretch muscle strips were allowed to relax for 1 h and then activated by K+ depolarization, the developed force remained significantly correlated with initial length. When the same strain was applied in 23 increments to minimize peak stress, poststretch force and myosin phosphorylation increased significantly, approaching the levels expected at L o. Furthermore, poststretch force development increased after each cycle of contraction and relaxation, approaching the control level after four cycles. These results suggest that activated airway smooth muscle cells can retain relatively precise memory of past strain when they are stretched rapidly with high stress.

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