Regulatory mechanism of smooth muscle contraction studied with gelsolin-treated strips of taenia caeci in guinea pig

2009 ◽  
Vol 296 (5) ◽  
pp. C1024-C1033 ◽  
Author(s):  
Ying-Ming Liou ◽  
Masaru Watanabe ◽  
Masatoshi Yumoto ◽  
Shin'ichi Ishiwata
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Actin Filaments ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Irreversible Damage ◽  
Cross Sectional ◽  
Thin Filaments ◽  
Force Development ◽  
Skinned Smooth Muscle

The potential roles of the regulatory proteins actin, tropomyosin (Tm), and caldesmon (CaD), i.e., the components of the thin filament, in smooth muscle have been extensively studied in several types of smooth muscles. However, controversy remains on the putative physiological significance of these proteins. In this study, we intended to determine the functional roles of Tm and CaD in the regulation of smooth muscle contraction by using a reconstitution system of the thin filaments. At appropriate conditions, the thin (actin) filaments within skinned smooth muscle strips of taenia caeci in guinea pigs could be selectively removed by an actin-severing protein, gelsolin, without irreversible damage to the contractile apparatus, and then the thin filaments were reconstituted with purified components of thin filaments, i.e., actin, Tm, and CaD. We found that the structural remodeling of actin filaments or thin filaments was functionally linked to the Ca2+-induced force development and reduction in muscle cross-sectional area (CSA). That is, after the reconstitution of the gelsolin-treated skinned smooth muscle strips with pure actin, the Ca2+-dependent force development was partially restored, but the Ca2+-induced reduction in CSA occurred once. In contrast, the reconstitution with actin, followed by Tm and CaD, restored not only the force generation but also both its Ca2+sensitivity and the reversible Ca2+-dependent reduction in CSA. We confirmed that both removal of the thin filaments by gelsolin treatment and reconstitution of the actin (thin) filaments with Tm and CaD caused no significant changes in the level of myosin regulatory light chain phosphorylation. We thus conclude that Tm and CaD are necessary for the full regulation of smooth muscle contraction in addition to the other regulatory systems, including the myosin-linked one.

Smooth muscle: contraction hypothesis based on the arrangement of actin and myosin filaments in different states of contraction*

1973 ◽  
Vol 265 (867) ◽  
pp. 213-217 ◽  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Hexagonal Lattice ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Thin Filaments ◽  
Random Fashion ◽  
Filament Bundles ◽  
Small Contraction ◽  
Electron Microscopical

Electron microscopical studies were m ade of the changes occurring during contraction of mouse taenia coli. In relaxed fibres actin filaments were found clearly ordered into bundles. W ithin the bundles the filaments were often arranged in rows or in a hexagonal lattice. In the areas between the filament bundles thick filaments were detected. The shortened fibres showed a different appearance. Thick and thin filaments were interm ingled in a random fashion. By com paring these findings with observations m ade on invertebrate smooth muscles, a model for smooth muscle contraction is proposed. According to this hypothesis the contractile apparatus of smooth muscles is composed of small contraction units of interdigitating bundles of thick and thin filaments. They seem to be irregularly shaped and random ly arranged. During the contraction the sets of filaments slide into each other. The result is the intermingling of the thick and thin filaments found in contracted fibres.

scholarly journals Abl activation regulates the dissociation of CAS from cytoskeletal vimentin by modulating CAS phosphorylation in smooth muscle

2010 ◽  
Vol 299 (3) ◽  
pp. C630-C637 ◽  
Author(s):  
Li Jia ◽  
Dale D. Tang
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Actin Polymerization ◽  
Spatial Location ◽  
Smooth Muscle Contraction ◽  
Nonreceptor Tyrosine Kinase ◽  
Force Development ◽  
Muscle Inhibition ◽  
A Cell ◽  
Contractile Activation

Abl is a nonreceptor tyrosine kinase that is required for smooth muscle contraction. However, the mechanism by which Abl regulates smooth muscle contraction is not completely understood. In the present study, Abl underwent phosphorylation at Tyr412 (an index of Abl activation) in smooth muscle in response to contractile activation. Treatment with a cell-permeable decoy peptide, but not the control peptide, attenuated Abl phosphorylation during contractile stimulation. Treatment with the decoy peptide did not affect the association of Abl with the cytoskeletal protein vinculin and the spatial location of vinculin in smooth muscle. Inhibition of Abl phosphorylation by the decoy peptide attenuated the agonist-induced phosphorylation of Crk-associated substrate (CAS), an adapter protein participating in the signaling processes that regulate force development in smooth muscle. Additionally, previous studies have shown that contractile stimulation triggers the dissociation of CAS from the vimentin network, which is important for cytoskeletal signaling and contraction in smooth muscle. In this report, the decrease in the amount of CAS in cytoskeletal vimentin in response to contractile activation was reversed by the Abl inhibition with the decoy peptide. Moreover, force development and the enhancement of F-actin-to-G-actin ratios (an indication of actin polymerization) upon contractile activation were also attenuated by the Abl inhibition. However, myosin phosphorylation induced by contractile activation was not affected by the inhibition of Abl. These results suggest that Abl regulates the dissociation of CAS from the vimentin network, actin polymerization, and contraction by modulating CAS phosphorylation in smooth muscle.

Blebbistatin, a myosin II inhibitor, suppresses contraction and disrupts contractile filaments organization of skinned taenia cecum from guinea pig

2010 ◽  
Vol 298 (5) ◽  
pp. C1118-C1126 ◽  
Author(s):  
Masaru Watanabe ◽  
Masatoshi Yumoto ◽  
Hideyuki Tanaka ◽  
Hon Hui Wang ◽  
Takeshi Katayama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Ii ◽  
Smooth Muscle Contraction ◽  
Myosin Light Chain Phosphorylation ◽  
Thin Filaments ◽  
Tension Development

To explore the precise mechanisms of the inhibitory effects of blebbistatin, a potent inhibitor of myosin II, on smooth muscle contraction, we studied the blebbistatin effects on the mechanical properties and the structure of contractile filaments of skinned (cell membrane permeabilized) preparations from guinea pig taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca2+-induced tension development at any given Ca2+ concentration but had little effects on the Ca2+-induced myosin light chain phosphorylation. Blebbistatin also suppressed the 10 and 2.75 mM Mg2+-induced, “myosin light chain phosphorylation-independent” tension development at more than 10 μM. Furthermore, blebbistatin induced conformational change of smooth muscle myosin (SMM) and disrupted arrangement of SMM and thin filaments, resulting in inhibition of actin-SMM interaction irrespective of activation with Ca2+. In addition, blebbistatin partially inhibited Mg2+-ATPase activity of native actomyosin from guinea pig taenia cecum at around 10 μM. These results suggested that blebbistatin suppressed skinned smooth muscle contraction through disruption of structure of SMM by the agent.

scholarly journals Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

2016 ◽  
Vol 21 (2) ◽  
pp. 19-23
Author(s):  
P. Virych ◽  
O. Shelyuk ◽  
V. Martynyuk ◽  
V. Pavlovsky
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Competitive Inhibitor ◽  
Smooth Muscle Contraction ◽  
Gastric Smooth Muscle ◽  
Low Concentrations

The effect of compounds based on 3-substituted-1,4-benzodiazepine-2-ones on contractile activity of smooth muscles of the rat's stomach was analyzed. Action substances MX-1626, MX-1775 for the smooth muscle contraction of like competitive inhibitor of bradykinin – des-Arg9- [Leu8]-Bradykinin acetate, which is observed as increase normalized rate of contraction with increasing of bradykinin concentration and characterized by a slowdown in the first phase of contraction. The most effective 3-subtituted 1,4-benzodiazepin-2-ones was at low concentrations of bradykinin, increasing it concentration their effect is reduced.

Myosin phosphorylation/dephosphorylation and regulation of airway smooth muscle contractility

1991 ◽  
Vol 261 (2) ◽  
pp. L1-L14 ◽  
Author(s):  
P. de Lanerolle ◽  
R. J. Paul
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Protein Kinases ◽  
Airway Smooth Muscle ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Energy Transduction ◽  
Signal Integration ◽  
Myosin Phosphorylation

Airway smooth muscles contract due to the activation of a highly sophisticated signal transduction mechanism. Signal transduction in muscle must include 1) a mechanism for converting chemical energy (i.e., ATP) into mechanical work (energy transduction) and 2) a mechanism for integrating the response to multiple stimuli (signal integration). In smooth and striated muscles, ATP hydrolysis due to the cyclic interaction of actin and myosin is the final site for both energy transduction and signal integration. There is growing consensus that this interaction in smooth muscles is regulated by the phosphorylation/dephosphorylation of the 20-kDa light chain of smooth muscle myosin. By phosphorylation/dephosphorylation we mean the enzyme-catalyzed transfer of the terminal phosphate of ATP to a serine or threonine residue on a protein, by a class of enzymes known as protein kinases, with the formation of a covalent phosphoester linkage and the enzyme-catalyzed removal of the phosphate group by phosphoprotein phosphatases. Smooth muscles contain many protein kinases and phosphatases, and the research emphasis on the regulation of smooth muscle contraction has focused on how these enzymes act individually and in concert to regulate the actin-myosin interaction. This review will describe the biochemical and physiological experiments that have been performed to understand the role of myosin phosphorylation/dephosphorylation in regulating smooth muscle contraction. Although data from studies on vascular and other smooth muscles will be summarized, this review will focus on studies performed on airway smooth muscle. More detailed reviews of studies on nonairway smooth muscles can be found in Refs. 47 and 79.

Involvement of the Tyr Kinase/JNK Pathway in Carbachol-induced Bronchial Smooth Muscle Contraction in the Rat

2013 ◽  
Vol 118 (5) ◽  
pp. 1076-1085 ◽  
Author(s):  
Hiroyasu Sakai ◽  
Yu Watanabe ◽  
Mai Honda ◽  
Rika Tsuiki ◽  
Yusuke Ueda ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Kinase Inhibitors ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Organ Bath ◽  
Bronchial Smooth Muscle ◽  
Jnk Pathway ◽  
Circular Smooth Muscle ◽  
Mitogen Activated Protein

Abstract Background: Tyrosine (Tyr) kinases and mitogen-activated protein kinases have been thought to participate in the contractile response in various smooth muscles. The aim of the current study was to investigate the involvement of the Tyr kinase pathway in the contraction of bronchial smooth muscle. Methods: Ring preparations of bronchi isolated from rats were suspended in an organ bath. Isometric contraction of circular smooth muscle was measured. Immunoblotting was used to examine the phosphorylation of c-Jun N-terminal kinasess (JNKs) in bronchial smooth muscle. Results: To examine the role of mitogen-activated protein kinase(s) in bronchial smooth muscle contraction, the effects of MPAK inhibitors were investigated in this study. The contraction induced by carbachol (CCh) was significantly inhibited by pretreatment with selective Tyr kinase inhibitors (genistein and ST638, n = 6, respectively), and a JNK inhibitor (SP600125, n = 6). The contractions induced by high K+ depolarization (n = 4), orthovanadate (a potent Tyr phosphatase inhibitor) and sodium fluoride (a G protein activator; NaF) were also significantly inhibited by selective Tyr kinase inhibitors and a JNK inhibitor (n = 4, respectively). However, the contraction induced by calyculin-A was not affected by SP600125. On the other hand, JNKs were phosphorylated by CCh (2.2 ± 0,4 [mean±SEM] fold increase). The JNK phosphorylation induced by CCh was significantly inhibited by SP600125 (n = 4). Conclusion: These findings suggest that the Tyr kinase/JNK pathway may play a role in bronchial smooth muscle contraction. Strategies to inhibit JNK activation may represent a novel therapeutic approach for diseases involving airway obstruction, such as asthma and chronic obstructive pulmonary disease.

scholarly journals Characterization of Cecal Smooth Muscle Contraction in Laying Hens

2021 ◽  
Vol 8 (6) ◽  
pp. 91
Author(s):  
Katrin Röhm ◽  
Martin Diener ◽  
Korinna Huber ◽  
Jana Seifert
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Laying Hens ◽  
Ex Vivo ◽  
Isometric Force ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Force Transducer ◽  
Different Levels

The ceca play an important role in the physiology of the gastrointestinal tract in chickens. Nevertheless, there is a gap of knowledge regarding the functionality of the ceca in poultry, especially with respect to physiological cecal smooth muscle contraction. The aim of the current study is the ex vivo characterization of cecal smooth muscle contraction in laying hens. Muscle strips of circular cecal smooth muscle from eleven hens are prepared to investigate their contraction ex vivo. Contraction is detected using an isometric force transducer, determining its frequency, height and intensity. Spontaneous contraction of the chicken cecal smooth muscle and the influence of buffers (calcium-free buffer and potassium-enriched buffer) and drugs (carbachol, nitroprusside, isoprenaline and Verapamil) affecting smooth muscle contraction at different levels are characterized. A decrease in smooth muscle contraction is observed when a calcium-free buffer is used. Carbachol causes an increase in smooth muscle contraction, whereas atropine inhibits contraction. Nitroprusside, isoprenaline and Verapamil result in a depression of smooth muscle contraction. In conclusion, the present results confirm a similar contraction behavior of cecal smooth muscles in laying hens as shown previously in other species.

Tyrosine phosphorylation of the dense plaque protein paxillin is regulated during smooth muscle contraction

1996 ◽  
Vol 271 (5) ◽  
pp. C1594-C1602 ◽  
Author(s):  
Z. Wang ◽  
F. M. Pavalko ◽  
S. J. Gunst
Keyword(s):  
Smooth Muscle ◽  
Cell Membrane ◽  
Tyrosine Phosphorylation ◽  
Actin Filaments ◽  
Time Course ◽  
Smooth Muscle Contraction ◽  
External Stress ◽  
Force Development ◽  
Contraction And Relaxation

Regulation of the attachment of actin filaments to the cell membrane at membrane-associated dense plaque (MADP) sites could allow smooth muscle cells to modulate their cytostructure in response to changes in external stress. In this study, changes in the tyrosine phosphorylation of the MADP protein paxillin were measured by Western blot during the contraction and relaxation of tracheal smooth muscle strips. Tyrosine phosphorylation of paxillin increased by three- to fourfold with a time course similar to force development during contractile stimulation with acetylcholine (ACh), 5-hydroxytryptamine, and KCl and decreased during washout of contractile stimuli and during relaxation induced by forskolin. Immunoprecipitation of muscle extracts with multiple rounds of anti-phosphotyrosine antibody removed approximately 20% of the total paxillin in resting muscles and approximately 60% of paxillin in muscles maximally stimulated with ACh. These results provide the first evidence associating the tyrosine phosphorylation of paxillin with the active contraction of smooth muscle or with any functional response of a fully differentiated tissue in vivo. The results are consistent with a role for MADP proteins in the regulation of force development in smooth muscle.

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.

scholarly journals The optical registration system for isometric contraction of smooth muscle

2016 ◽  
Vol 20 (1) ◽  
pp. 11-14
Author(s):  
P. Virych ◽  
O. Shelyuk ◽  
V. Martynyuk ◽  
S. Chumakov
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Optical System ◽  
Isometric Contraction ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Isometric Contractions ◽  
Rat Stomach ◽  
Mechanical Method ◽  
Registration System

The optical system registration of smooth muscle contraction in isometric mode was developed. Testing of system on smooth muscle strips of rat stomach and caecum was performed. It was tested the possibility of recording optical system spontaneous activity of smooth muscle. The resulting muscle contractions parameters correspond to the literature. Thus designed optical-mechanical method for detecting force and speed can be used for recording isometric contractions of smooth muscles of the stomach and caecum of rats and, therefore, to study the effect of different effectors their mechanokinetic.

Sign in / Sign up

Export Citation Format

Share Document