scholarly journals Cytoskeletal remodeling slows cross‐bridge cycling and ATP hydrolysis rates in airway smooth muscle

2020 ◽  
Vol 8 (16) ◽  
Author(s):  
Philippe Delmotte ◽  
Young‐soo Han ◽  
Gary C. Sieck
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Atp Hydrolysis ◽  
Cytoskeletal Remodeling ◽  
Cross Bridge ◽  
Hydrolysis Rates

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.

Effects of substrate and inhibition of oxidative metabolism on contraction and myosin phosphorylation in ASM

1993 ◽  
Vol 264 (6) ◽  
pp. L553-L559 ◽  
Author(s):  
C. M. Hai ◽  
C. Watson ◽  
S. J. Wallach ◽  
V. Reyes ◽  
E. Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Airway Smooth Muscle ◽  
Oxidative Metabolism ◽  
Energy Utilization ◽  
Atp Content ◽  
Active Stress ◽  
Myosin Phosphorylation ◽  
Intracellular Calcium Store ◽  
Cross Bridge

Steady-state active stress in smooth muscle is maintained by cross bridges which undergo continuous cycling and myosin phosphorylation, and the two processes both consume ATP. In this study, we investigated whether energy utilization by cross-bridge cycling and myosin phosphorylation is compartmentalized and examined their relative affinities for ATP in airway smooth muscle. We measured active stress, myosin phosphorylation, O2 consumption, and tissue ATP content in bovine tracheal smooth muscle activated by K+ depolarization when glucose was replaced by pyruvate and when oxidative metabolism was inhibited by hypoxia or uncoupled by 2,4-dinitrophenol. The results indicate that ATP produced from both glycolysis and oxidative metabolism is available to both cross-bridge cycling and myosin phosphorylation. However, steady-state myosin phosphorylation was insensitive to the inhibition of oxidative metabolism by hypoxia and mitochondrial uncoupling when steady-state isometric stress and tissue ATP content were significantly reduced. These results suggest that, relative to actomyosin adenosine 5'-triphosphatase, myosin light chain kinase has a higher affinity for ATP in intact airway smooth muscle. However, peak myosin phosphorylation associated with the initial rapid stress development was sensitive to inhibition of oxidative metabolism, probably reflecting a lower content of intracellular calcium store as a result of metabolic inhibition.

scholarly journals Friction in airway smooth muscle: mechanism, latch, and implications in asthma

1996 ◽  
Vol 81 (6) ◽  
pp. 2703-2703 ◽  
Author(s):  
J. J. Fredberg ◽  
K. A. Jones ◽  
M. Nathan ◽  
S. Raboudi ◽  
Y. S. Prakash ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Mechanical Energy ◽  
Frictional Stress ◽  
Turnover Rates ◽  
Shortening Velocity ◽  
Biphasic Pattern ◽  
Cross Bridge

Fredberg, J. J., K. A. Jones, M. Nathan, S. Raboudi, Y. S. Prakash, S. A. Shore, J. P. Butler, and G. C. Sieck. Friction in airway smooth muscle: mechanism, latch, and implications in asthma. J. Appl. Physiol. 81(6): 2703–2712, 1996.—In muscle, active force and stiffness reflect numbers of actin-myosin interactions and shortening velocity reflects their turnover rates, but the molecular basis of mechanical friction is somewhat less clear. To better characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and the rate of actomyosin ATP utilization simultaneously in activated canine airway smooth muscle subjected to small periodic stretches as occur in breathing. The amplitude of the frictional stress is proportional to ηE, where E is the tissue stiffness defined by the slope of the resulting force vs. displacement loop and η is the hysteresivity defined by the fatness of that loop. From contractile stimulus onset, the time course of frictional stress amplitude followed a biphasic pattern that tracked that of the rate of actomyosin ATP consumption. The time course of hysteresivity, however, followed a different biphasic pattern that tracked that of shortening velocity. Taken together with an analysis of mechanical energy storage and dissipation in the cross-bridge cycle, these results indicate, first, that like shortening velocity and the rate of actomyosin ATP utilization, mechanical friction in airway smooth muscle is also governed by the rate of cross-bridge cycling; second, that changes in cycling rate associated with conversion of rapidly cycling cross bridges to slowly cycling latch bridges can be assessed from changes of hysteresivity of the force vs. displacement loop; and third, that steady-state force maintenance (latch) is a low-friction contractile state. This last finding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration.

scholarly journals Series-to-parallel transition in the filament lattice of airway smooth muscle

2000 ◽  
Vol 89 (3) ◽  
pp. 869-876 ◽  
Author(s):  
Chun Y. Seow ◽  
Victor R. Pratusevich ◽  
Lincoln E. Ford
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Thick Filament ◽  
Cycling Rate ◽  
Cross Bridge ◽  
Parallel Change ◽  
Force Velocity ◽  
Cross Bridges ◽  
Trachealis Muscle

Force-velocity curves measured at different times during tetani of sheep trachealis muscle were analyzed to assess whether velocity slowing could be explained by thick-filament lengthening. Such lengthening increases force by placing more cross bridges in parallel on longer filaments and decreases velocity by reducing the number of filaments spanning muscle length. From 2 s after the onset of stimulation, when force had achieved 42% of it final value, to 28 s, when force had been at its tetanic plateau for ∼15 s, velocity decreases were exactly matched by force increases when force was adjusted for changes in activation, as assessed from the maximum power value in the force-velocity curves. A twofold change in velocity could be quantitatively explained by a series-to-parallel change in the filament lattice without any need to postulate a change in cross-bridge cycling rate.

scholarly journals Modeling the impairment of airway smooth muscle force by stretch

2015 ◽  
Vol 118 (6) ◽  
pp. 684-691 ◽  
Author(s):  
Jason H. T. Bates
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Coarse Grained ◽  
Active Force ◽  
Cross Bridge ◽  
Bulk Force ◽  
Length Changes ◽  
Cross Bridges ◽  
Large Stretch ◽  
Two State Model

Imposed length changes of only a small percent produce transient reductions in active force in strips of airway smooth muscle (ASM) due to the temporary detachment of bound cross-bridges caused by the relative motion of the actin and myosin fibers. More dramatic and sustained reductions in active force occur following large changes in length. The Huxley two-state model of skeletal muscle originally proposed in 1957 and later adapted to include a four-state description of cross-bridge kinetics has been widely used to model the former phenomenon, but is unable to account for the latter unless modified to include mechanisms by which the contractile machinery in the ASM cell becomes appropriately rearranged. Even so, the Huxley model itself is based on the assumption that the contractile proteins are all aligned precisely in the direction of bulk force generation, which is not true for ASM. The present study derives a coarse-grained version of the Huxley model that is free of inherent assumptions about cross-bridge orientation. This simplified model recapitulates the key features observed in the force-length behavior of activated strips of ASM and, in addition, provides a mechanistically based way of accounting for the sustained force reductions that occur following large stretch.

Relaxant effect of superimposed length oscillation on sensitized airway smooth muscle

2015 ◽  
Vol 308 (5) ◽  
pp. L479-L484 ◽  
Author(s):  
Miguel Jo-Avila ◽  
Ahmed M. Al-Jumaily ◽  
Jun Lu
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Smooth Muscles ◽  
Airway Hyperreactivity ◽  
Frequency Range ◽  
Relaxant Effect ◽  
Airway Lumen ◽  
Cross Bridge ◽  
The Cross

Asthma is associated with reductions in the airway lumen and breathing difficulties that are attributed to airway smooth muscles (ASM) hyperconstriction. Pharmaceutical bronchodilators such as salbutamol and isoproterenol are normally used to alleviate this constriction. Deep inspirations and tidal oscillations (TO) have also been reported to relax ASM in healthy airways with less response in asthmatics. Little information is available on the effect of other forms of oscillation on asthmatic airways. This study investigates the effect of length oscillations (LO), with amplitude 1 and 1.5% in the frequency range 5–20 Hz superimposed on breathing equivalent LO, on contracted ASM dissected from sensitized mice. These mice are believed to show some symptoms such as airway hyperreactivity similar to those associated with asthma in humans. In the frequency range used in this work, this study shows an increase in ASM relaxation of an average of 10% for 1.5% amplitude when compared with TO, ISO, or the combination of both. No similar finding is observed with 1% amplitude. This suggests that superimposed length oscillation acting over the interaction of myosin and actin during contraction may lead to temporal rearrangement and disturbance of the cross-bridge process in asthmatic airways.

Temporal aspects of excitation-contraction coupling in airway smooth muscle

2001 ◽  
Vol 91 (5) ◽  
pp. 2266-2274 ◽  
Author(s):  
Gary C. Sieck ◽  
Young-Soo Han ◽  
Christina M. Pabelick ◽  
Y. S. Prakash
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Force Generation ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Caged Atp ◽  
Cross Bridge

In airway smooth muscle (ASM), ACh induces propagating intracellular Ca2+ concentration ([Ca2+]i) oscillations (5–30 Hz). We hypothesized that, in ASM, coupling of elevations and reductions in [Ca2+]i to force generation and relaxation (excitation-contraction coupling) is slower than ACh-induced [Ca2+]i oscillations, leading to stable force generation. When we used real-time confocal imaging, the delay between elevated [Ca2+]i and contraction in intact porcine ASM cells was found to be ∼450 ms. In β-escin-permeabilized ASM strips, photolytic release of caged Ca2+ resulted in force generation after ∼800 ms. When calmodulin (CaM) was added, this delay was shortened to ∼500 ms. In the presence of exogenous CaM and 100 μM Ca2+, photolytic release of caged ATP led to force generation after ∼80 ms. These results indicated significant delays due to CaM mobilization and Ca2+-CaM activation of myosin light chain kinase but much shorter delays introduced by myosin light chain kinase-induced phosphorylation of the regulatory myosin light chain MLC20 and cross-bridge recruitment. This was confirmed by prior thiophosphorylation of MLC20, in which force generation occurred ∼50 ms after photolytic release of caged ATP, approximating the delay introduced by cross-bridge recruitment alone. The time required to reach maximum steady-state force was >15 s. Rapid chelation of [Ca2+]i after photolytic release of caged diazo-2 resulted in relaxation after a delay of ∼1.2 s and 50% reduction in force after ∼57 s. We conclude that in ASM cells agonist-induced [Ca2+]i oscillations are temporally and spatially integrated during excitation-contraction coupling, resulting in stable force production.

Myosin cross-bridge kinetics in airway smooth muscle: a comparative study of humans, rats, and rabbits

2002 ◽  
Vol 282 (1) ◽  
pp. L83-L90 ◽  
Author(s):  
Y. Lecarpentier ◽  
F.-X. Blanc ◽  
S. Salmeron ◽  
J.-C. Pourny ◽  
D. Chemla ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Comparative Study ◽  
Mechanical Behavior ◽  
Airway Smooth Muscle ◽  
Rate Constants ◽  
Species Differences ◽  
Isometric Tension ◽  
New Formalism ◽  
Cross Bridge ◽  
Cross Bridges

To analyze the kinetics and unitary force of cross bridges (CBs) in airway smooth muscle (ASM), we proposed a new formalism of Huxley's equations adapted to nonsarcomeric muscles (Huxley AF. Prog Biophys Biophys Chem7: 255–318, 1957). These equations were applied to ASM from rabbits, rats, and humans ( n = 12/group). We tested the hypothesis that species differences in whole ASM mechanics were related to differences in CB mechanics. We calculated the total CB number per square millimeter at peak isometric tension (Ψ ×109), CB unitary force (Π), and the rate constants for CB attachment ( f 1) and detachment ( g 1 and g 2). Total tension, Ψ, and Π were significantly higher in rabbits than in humans and rats. Values of Π were 8.6 ± 0.1 pN in rabbits, 7.6 ± 0.3 pN in humans, and 7.7 ± 0.2 pN in rats. Values of Ψ were 4.0 ± 0.5 in rabbits, 1.2 ± 0.1 in humans, and 1.9 ± 0.2 in rats; f 1 was lower in humans than in rabbits and rats; g 2 was higher in rabbits than in rats and in rats than in humans. In conclusion, ASM mechanical behavior of different species was characterized by specific CB kinetics and CB unitary force.

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