Dissociation between myosin phosphorylation and shortening velocity in canine trachea

Merkel, Linda; Gerthoffer, William T.; Torphy, T. J.

doi:10.1152/ajpcell.1990.258.3.c524

Cited by 33 publications

(19 citation statements)

References 21 publications

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“…A transient increase in MLC phosphorylation is observed in association with a transient increase in shortening velocity during the maximal activation of rabbit trachealis muscle by muscarinic stimuli [115,125]; however, under many other conditions of stimulation, this correlation breaks down. Canine trachealis muscle activated by potassium (K + )-depolarization exhibits a decline in shortening velocity during the course of the contraction while high levels of active tension and myosin light chain phosphorylation are sustained [126,127]. A similar dissociation between shortening velocity and MLC phosphorylation is observed when trachealis muscles are activated with submaximal concentrations of muscarinic agonists or with agonists of lower efficacy, such as 5-hydroxytryptamine [126,128].…”

Section: Molecular Basis For the Mechanical Properties Of Tracheal Smmentioning

confidence: 98%

“…Canine trachealis muscle activated by potassium (K + )-depolarization exhibits a decline in shortening velocity during the course of the contraction while high levels of active tension and myosin light chain phosphorylation are sustained [126,127]. A similar dissociation between shortening velocity and MLC phosphorylation is observed when trachealis muscles are activated with submaximal concentrations of muscarinic agonists or with agonists of lower efficacy, such as 5-hydroxytryptamine [126,128]. It is therefore unclear whether the decline in shortening velocity that occurs in airway muscle during a sustained contraction can be attributed to the dephosphorylation of attached crossbridges (latchbridges).…”

Section: Molecular Basis For the Mechanical Properties Of Tracheal Smmentioning

confidence: 99%

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The contractile apparatus and mechanical properties of airway smooth muscle

Gunst¹,

Tang²

2000

Eur Respir J

146

122

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The functional properties of airway smooth muscle are fundamental to the properties of the airways in vivo. However, many of the distinctive characteristics of smooth muscle are not easily accounted for on the basis of molecular models developed to account for the properties of striated muscles. The specialized ultrastructural features and regulatory mechanisms present in smooth muscle are likely to form the basis for many of its characteristic properties.The molecular organization and structure of the contractile apparatus in smooth muscle is consistent with a model of force generation based on the relative sliding of adjacent actin and myosin filaments. In airway smooth muscle, actomyosin activation is initiated by the phosphorylation of the 20 kDa light chain of myosin; but there is conflicting evidence regarding the role of myosin light chain phosphorylation in tension maintenance. Tension generated by the contractile filaments is transmitted throughout the cell via a network of actin filaments anchored at dense plaques at the cell membrane, where force is transmitted to the extracellular matrix via transmembrane integrins. Proteins bound to actin and/or localized to actin filament anchorage sites may participate in regulating the shape of the smooth muscle cell and the organization of its contractile filament system. These proteins may also participate in signalling pathways that regulate the crossbridge activation and other functions of the actin cytoskeleton.The length-dependence of active force and the mechanical plasticity of airway smooth muscle may play an important role in determining airway responsiveness during lung volume changes in vivo. The molecular basis for the length-dependence of tension in smooth muscle differs from that in skeletal muscle, and may involve mechano-transduction mechanisms that modulate contractile filament activation and cytoskeletal organization in response to changes in muscle length. The reorganization of contractile filaments may also underlie the plasticity of the mechanical response of airway smooth muscle. Changes in the structural organization and signalling pathways of airway smooth muscle cells resulting form alterations in mechanical forces in the lung may be important factors in the development of pathophysiological conditions of chronic airway hyperresponsiveness. Eur Respir J 2000; 15: 600±616. The mechanical properties of airway smooth muscle are fundamental to the regulation of airway contractility and airway tone in vivo. These mechanical properties have traditionally been interpreted in terms of the "sliding filament model" of muscle contraction first proposed by HUXLEY and NIEDERGERKE [1] and HUXLEY and HANSON [2] to explain the contractile behaviour of skeletal muscle. Like other smooth muscles, airway smooth muscle exhibits the same hyperbolic force-velocity relationship that is characteristic of striated muscles, and the lengthtension relationship is also qualitatively similar to that of striated muscles [3]. The qualitative similarities be...

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Section: Molecular Basis For the Mechanical Properties Of Tracheal Smmentioning

confidence: 98%

Section: Molecular Basis For the Mechanical Properties Of Tracheal Smmentioning

confidence: 99%

The contractile apparatus and mechanical properties of airway smooth muscle

Gunst¹,

Tang²

2000

Eur Respir J

146

122

View full text Add to dashboard Cite

show abstract

“…Many studies have suggested that the cross-bridge cycling rate is proportional to the amount of MLCK and the resulting LC 20 phosphorylation levels (64,65). However, this direct link remains controversial (66)(67)(68). Nonetheless, several studies have reported significant increases of MLCK expression in asthma and in models of asthma.…”

Section: Total Smmhc In Asthmamentioning

confidence: 99%

Myosin, Transgelin, and Myosin Light Chain Kinase

Léguillette¹,

Laviolette²,

Bergeron³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Airway smooth muscle (SM) of patients with asthma exhibits a greater velocity of shortening (Vmax) than that of normal subjects, and this is thought to contribute to airway hyperresponsiveness. A greater Vmax can result from increased myosin activation. This has been reported in sensitized human airway SM and in models of asthma. A faster Vmax can also result from the expression of specific contractile proteins that promote faster cross-bridge cycling. This possibility has never been addressed in asthma. Objectives: We tested the hypothesis that the expression of genes coding for SM contractile proteins is altered in asthmatic airways and contributes to their increased Vmax. Methods: We quantified the expression of several genes that code for SM contractile proteins in mild allergic asthmatic and control human airway endobronchial biopsies. The function of these contractile proteins was tested using the in vitro motility assay. Measurements and Main Results:We observed an increased expression of the fast myosin heavy chain isoform, transgelin, and myosin light chain kinase in patients with asthma. Immunohistochemistry demonstrated the expression of these genes at the protein level. To address the functional significance of this overexpression, we purified tracheal myosin from the hyperresponsive Fisher rats, which also overexpress the fast myosin heavy chain isoform as compared with the normoresponsive Lewis rats, and found a faster rate of actin filament propulsion. Conversely, transgelin did not alter the rate of actin filament propulsion. Conclusions: Selective overexpression of airway smooth muscle genes in asthmatic airways leads to increased Vmax, thus contributing to the airway hyperresponsiveness observed in asthma.

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“…Our model of innate airway hyperresponsiveness behaved similarly in that increased contractility was also associated with a greater level of phosphorylation. However, the specific role of this increased phosphorylation to enhanced Fischer airway smooth muscle contractility remains unclear given that recent reports have disputed the association between LC 20 phosphorylation and rate of shortening (32,34).…”

Section: Physiological Significance Of Increased Lc 20 Phosphorylationmentioning

confidence: 99%

Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

Gil¹,

Zitouni²,

Maghni³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Four smooth muscle myosin heavy chain (SMMHC) isoforms are generated by alternative mRNA splicing of a single gene. Two of these isoforms differ by the presence [(ϩ)insert] or absence [(Ϫ)insert] of a 7-amino acid insert in the motor domain. The rate of actin filament propulsion of the (ϩ)insert SMMHC isoform, as measured in the in vitro motility assay, is twofold greater than that of the (Ϫ)insert isoform. We hypothesized that a greater expression of the (ϩ)insert SMMHC isoform and greater regulatory light chain (LC 20) phosphorylation contribute to airway hyperresponsiveness. We measured airway responsiveness to methacholine in Fischer hyperresponsive and Lewis normoresponsive rats and determined SMMHC isoform mRNA and protein expression, as well as essential light chain (LC 17) isoforms, h-caldesmon, and ␣-actin protein expression in their tracheae. We also measured tracheal muscle strip contractility in response to methacholine and corresponding LC 20 phosphorylation. We found Fischer rats have more (ϩ)insert mRNA (69.4 Ϯ 2.0%) (mean Ϯ SE) than Lewis rats (53.0 Ϯ 2.4%; P Ͻ 0.05) and a 44% greater content of (ϩ)insert isoform relative to total myosin protein. No difference was found for LC 17 isoform, h-caldesmon, and ␣-actin expression. The contractility experiments revealed a greater isometric force for Fischer trachealis segments (4.2 Ϯ 0.8 mN) than Lewis (1.9 Ϯ 0.4 mN; P Ͻ 0.05) and greater LC 20 phosphorylation level in Fischer (55.1 Ϯ 6.4) than in Lewis (41.4 Ϯ 6.1; P Ͻ 0.05) rats. These results further support the contention that innate airway hyperresponsiveness is a multifactorial disorder in which increased expression of the fast (ϩ)insert SMMHC isoform and greater activation of LC20 lead to smooth muscle hypercontractility. myosin heavy chain; 7-amino acid insert; phasic muscle; tonic muscle; myosin regulatory light chain; trachealis

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Dissociation between myosin phosphorylation and shortening velocity in canine trachea

Cited by 33 publications

References 21 publications

The contractile apparatus and mechanical properties of airway smooth muscle

The contractile apparatus and mechanical properties of airway smooth muscle

Myosin, Transgelin, and Myosin Light Chain Kinase

Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness

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Dissociation between myosin phosphorylation and shortening velocity in canine trachea

Cited by 33 publications

References 21 publications

The contractile apparatus and mechanical properties of airway smooth muscle

The contractile apparatus and mechanical properties of airway smooth muscle

Myosin, Transgelin, and Myosin Light Chain Kinase

Smooth muscle myosin isoform expression and LC20phosphorylation in innate rat airway hyperresponsiveness

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Smooth muscle myosin isoform expression and LC₂₀phosphorylation in innate rat airway hyperresponsiveness