Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis

2000 ◽  
Vol 88 (4) ◽  
pp. 1338-1345 ◽  
Author(s):  
Pasquale Chitano ◽  
Jizhong Wang ◽  
Carrie M. Cox ◽  
Newman L. Stephens ◽  
Thomas M. Murphy
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Force Production ◽  
Internal Resistance ◽  
Force Generation ◽  
Stress Generation ◽  
Shortening Velocity ◽  
Smooth Muscle Function ◽  
Old Adult ◽  
Force Velocity

Juveniles of many species, including humans, display greater airway responsiveness than do adults. This may involve changes in airway smooth muscle function. In the present work we studied force production and shortening velocity in trachealis from 1-wk-old (1 wk), 3-wk-old (3 wk), and 3-mo-old (adult) guinea pigs. Strips were electrically stimulated (60 Hz, 18 V) at their optimal length ( l o) to obtain maximum active stress (Po) and rate of stress generation. Then, force-velocity curves were elicited at 2.5 s from the onset of the stimulus. By applying a recently developed modification of Hill's equation for airway smooth muscle, the maximum shortening velocity at zero load ( V o) and the value α ⋅ γ/β, an index of internal resistance to shortening (Rsi), were calculated (α, β, and γ are the constants of the equation). Poincreased little with maturation, whereas the rate of stress generation increased significantly (0.40 ± 0.03, 0.45 ± 0.03, 0.51 ± 0.03 P o/s for 1 wk, 3 wk, and adult animals). V o slightly increased early with maturation to decrease significantly later (1.79 ± 0.67, 2.45 ± 0.92, and 0.55 ± 0.09 l o/s for 1 wk, 3 wk, and adult animals), whereas the Rsi showed an opposite trend (14.98 ± 5.19, 8.99 ± 3.01, and 32.07 ± 5.54 mN ⋅ mm−2 ⋅ l o −1 ⋅ s for 1 wk, 3 wk, and adult animals). This early increase of force generation in combination with late increase of Rsi may explain the changes of V o with age. An elevated V o may contribute to the incidence of airway hyperresponsiveness in healthy juveniles.

Calcium-independent contraction and sensitization of airway smooth muscle by p21-activated protein kinase

2003 ◽  
Vol 284 (5) ◽  
pp. L863-L870 ◽  
Author(s):  
P. K. McFawn ◽  
L. Shen ◽  
S. G. Vincent ◽  
A. Mak ◽  
J. E. Van Eyk ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Airway Smooth Muscle ◽  
Force Production ◽  
Force Generation ◽  
Glutathione S Transferase ◽  
Tonic Smooth Muscle ◽  
P21 Activated Kinase ◽  
Incremental Increase ◽  
Constitutively Active

In Triton-skinned phasic ileal smooth muscle, constitutively active recombinant p21-activated kinase (PAK3) has been shown to induce Ca2+-independent contraction, which is accompanied by phosphorylation of caldesmon and desmin (Van Eyk JE, Arrell DK, Foster DB, Strauss JD, Heinonen TY, Furmaniak-Kazmierczak E, Cote GP, and Mak AS. J Biol Chem 273: 23433–23439, 1998). In the present study, we investigated whether PAK has a broad impact on smooth muscle in general by testing the hypothesis that PAK induces Ca2+-independent contractions and/or Ca2+ sensitization in tonic airway smooth muscle and that the process is mediated via phosphorylation of caldesmon. In the absence of Ca2+ (pCa > 9), constitutively active glutathione- S-transferase-murine PAK3 (GST-mPAK3) caused force generation of Triton-skinned canine tracheal smooth muscle (TSM) fibers to ∼40% of the maximal force generated by Ca2+ at pCa 4.4. In addition, GST-mPAK3 enhanced Ca2+ sensitivity of contraction by increasing force generation by 80% at intermediate Ca2+ concentrations (pCa 6.2), whereas it had no effect at pCa 4.4. Catalytically inactive GST-mPAK3K297R had no effect on force production. Using antibody against one of the PAK-phosphorylated sites (Ser657) on caldesmon, we showed that a basal level of phosphorylation of caldesmon occurs at this site in skinned TSM and that PAK-induced contraction was accompanied by a significant increase in the level of phosphorylation. Western blot analyses show that PAK1 is the predominant PAK isoform expressed in murine, rat, canine, and porcine TSM. We conclude that PAK causes Ca2+-independent contractions and produces Ca2+ sensitization of skinned phasic and tonic smooth muscle, which involves an incremental increase in caldesmon phosphorylation.

Transient length-related mechanical states in smooth muscle

1994 ◽  
Vol 72 (11) ◽  
pp. 1325-1333 ◽  
Author(s):  
Richard A. Meiss
Keyword(s):  
Mechanical Properties ◽  
Mathematical Model ◽  
Smooth Muscle ◽  
Internal Resistance ◽  
Steady Increase ◽  
Kinetic Properties ◽  
Shortening Velocity ◽  
Force Velocity ◽  
Isotonic Contractions ◽  
Isotonic Shortening

The isotonic shortening of electrically stimulated ovarian ligament smooth muscle strips from rabbits was studied by briefly applying sudden increases in afterload (force steps, 0.6 to 3.0 s long) just sufficient to halt the shortening. Upon removal of the extra afterload, the isotonic shortening velocity significantly increased compared with prestep velocities measured at the same muscle lengths. The degree of potentiation depended upon the duration of the force step. Muscles yielded initially when the step was applied, and their stiffness decreased. During the zero-velocity portion of the force step there was a steady increase in stiffness back to levels appropriate to that force. Complete force–velocity curves were made following short (0.6 s) and long (3.0 s) force steps. The values for Vmax (and all intermediate velocities) were significantly greater following a long force step. In a final experimental series, muscles were held isometric immediately after removal of the force step. Force rose monotonically, with a more rapid redevelopment following a long force step. A mathematical model is presented, according to which the effect of the duration of the force step on the poststep mechanical properties may be due to either the alteration of an internal resistance to shortening or a change in the kinetic properties of the cross-bridge array. A hypothesis is proposed relating the steady decline in isotonic shortening velocity to a partial local depletion of energy-yielding substrates.Key words: smooth muscle, isotonic contractions, mechanics, models.

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.

Airway smooth muscle function in asthma

2000 ◽  
Vol 30 (5) ◽  
pp. 606-614 ◽  
Author(s):  
Knox ◽  
Pang ◽  
Johnson ◽  
Hamad
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Function ◽  
Smooth Muscle Function

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.

Effects of microtubule disruption on force, velocity, stiffness and [Ca2+]i in porcine coronary arteries

2000 ◽  
Vol 279 (5) ◽  
pp. H2493-H2501 ◽  
Author(s):  
Richard J. Paul ◽  
Peggy Sue Bowman ◽  
Michael S. Kolodney
Keyword(s):  
Smooth Muscle ◽  
Coronary Arteries ◽  
Isometric Force ◽  
Shortening Velocity ◽  
Cultured Fibroblasts ◽  
Microtubule Disruption ◽  
Highly Sensitive ◽  
Artery Stiffness ◽  
Force Velocity ◽  
Microtubule Stabilizer

Force generated by smooth muscle cells is believed to result from the interaction of actin and myosin filaments and is regulated through phosphorylation of the myosin regulatory light chain (LC20). The role of other cytoskeleton filaments, such as microtubules and intermediate filaments, in determining the mechanical output of smooth muscle is unclear. In cultured fibroblasts, microtubule disruption results in large increases in force similar to contractions associated with LC20 phosphorylation (15). One hypothesis, the “tensegrity” or “push-pull” model, attributes this increase in force to the disruption of microtubules functioning as rigid struts to resist force generated by actin-myosin interaction (9). In porcine coronary arteries, the disruption of microtubules by nocodazole (11 μM) also elicited moderate but significant increases in isometric force (10–40% of a KCl contracture), which could be blocked or reversed by taxol (a microtubule stabilizer). We tested whether this nocodazole-induced force was accompanied by changes in coronary artery stiffness or unloaded shortening velocity, parameters likely to be highly sensitive to microtubule resistance elements. Few changes were seen, ruling out push-pull mechanisms for the increase in force by nocodazole. In contrast, the intracellular calcium concentration, measured by fura 2 in the intact artery, was increased by nocodazole in parallel with force, and this was inhibited and/or reversed by taxol. Our results indicate that microtubules do not significantly contribute to vascular smooth muscle mechanical characteristics but, importantly, may play a role in modulation of Ca2+ signal transduction.

Effect of airway inflammation on smooth muscle shortening and contractility in guinea pig trachealis

1993 ◽  
Vol 265 (6) ◽  
pp. L549-L554 ◽  
Author(s):  
R. W. Mitchell ◽  
I. M. Ndukwu ◽  
K. Arbetter ◽  
J. Solway ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Neurogenic Inflammation ◽  
Isometric Force ◽  
Electrical Field Stimulation ◽  
Shortening Velocity ◽  
Lever System ◽  
Force Velocity

We studied the effect of either 1) immunogenic inflammation caused by aerosolized ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity relationships were determined for nine epithelium-intact TSM strips from ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls. Muscle strips were tethered to an electromagnetic lever system, which allowed isotonic shortening when load clamps [from 0 to maximal isometric force (Po)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18 V). Optimal length for each muscle was determined during equilibration. Maximal shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s) compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/- 0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/- 0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We demonstrate Vmax and delta max are augmented in TSM after ovalbumin sensitization; in contrast, neurogenic inflammation caused by capsaicin has no effect on isolated TSM contractility in vitro. These data suggest that airway hyperresponsiveness in vivo that occurs in association with immunogenic or neurogenic inflammation may result from different effects of these types of inflammation on airway smooth muscle.

scholarly journals CD4+T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression

2014 ◽  
Vol 592 (14) ◽  
pp. 2999-3012 ◽  
Author(s):  
Oleg S. Matusovsky ◽  
Emily M. Nakada ◽  
Linda Kachmar ◽  
Elizabeth D. Fixman ◽  
Anne-Marie Lauzon
Keyword(s):  
T Cells ◽  
Smooth Muscle ◽  
Protein Expression ◽  
Airway Smooth Muscle ◽  
Cd4 T Cells ◽  
Contractile Protein ◽  
Shortening Velocity

Mechanics and energetics of lengthening of active airway smooth muscle

1981 ◽  
Vol 241 (1) ◽  
pp. C42-C46 ◽  
Author(s):  
B. S. Hanks ◽  
N. L. Stephens
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Creatine Phosphate ◽  
Energy Liberation ◽  
Mechanical Instability ◽  
Active Muscle ◽  
Force Velocity ◽  
The Relationship ◽  
Tetanic Tension

For smooth muscle in general there appears only one report dealing with force-velocity (FV) relationships of active muscle subjected to forcible elongation by application of loads (P) greater than its maximum isometric tetanic tension (Po); for airway smooth muscle (ASM) there is none. Since ASM may be subjected to increasing stretch during inspiration, the relationship is important and was therefore studied with canine tracheal smooth muscle (TSM) as a model. FV data for P less than Po could be fitted by Hill's hyperbolic equation. For P greater than Po, lengthening velocity was greater than predicted by the equation. However at equivalent velocities, the muscle during elongation could support a load three times greater than during shortening; in this it resembled skeletal muscle. From this it may be speculated that distension of the airway during inspiration would not be associated with mechanical instability. With reference to energy requirements of the elongating TSM it was shown, as has been for skeletal muscle, that the net rate of energy liberation (assessed by measuring tissue levels of adenosine triphosphate and creatine phosphate) in an elongating active muscle is less than that of a muscle contracting isometrically.

Selected Contribution: Mechanical strain increases force production and calcium sensitivity in cultured airway smooth muscle cells

2000 ◽  
Vol 89 (5) ◽  
pp. 2092-2098 ◽  
Author(s):  
Paul G. Smith ◽  
Chaity Roy ◽  
Steven Fisher ◽  
Qi-Quan Huang ◽  
Frank Brozovich
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Force Production ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
Airway Smooth Muscle Cells ◽  
Maximal Force

Cultured airway smooth muscle cells subjected to cyclic deformational strain have increased cell content of myosin light chain kinase (MLCK) and myosin and increased formation of actin filaments. To determine how these changes may increase cell contractility, we measured isometric force production with changes in cytosolic calcium in individual permeabilized cells. The pCa for 50% maximal force production was 6.6 ± 0.4 in the strain cells compared with 5.9 ± 0.3 in control cells, signifying increased calcium sensitivity in strain cells. Maximal force production was also greater in strain cells (8.6 ± 2.9 vs. 5.7 ± 3.1 μN). The increased maximal force production in strain cells persisted after irreversible thiophosphorylation of myosin light chain, signifying that increased force could not be explained by differences in myosin light chain phosphorylation. Cells strained for brief periods sufficient to increase cytoskeletal organization but insufficient to increase contractile protein content also produced more force, suggesting that strain-induced cytoskeletal reorganization also increases force production.

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