scholarly journals Is titin a ‘winding filament’? A new twist on muscle contraction

2011 ◽  
Vol 279 (1730) ◽  
pp. 981-990 ◽  
Author(s):  
Kiisa C. Nishikawa ◽  
Jenna A. Monroy ◽  
Theodore E. Uyeno ◽  
Sang Hoon Yeo ◽  
Dinesh K. Pai ◽  
...  
Keyword(s):  
Muscle Contraction ◽  
Muscle Activation ◽  
Active Muscle ◽  
Thin Filaments ◽  
Force Development ◽  
Force Depression ◽  
Elastic Potential Energy ◽  
The Difference ◽  
Elastic Protein ◽  
Cross Bridges

Recent studies have demonstrated a role for the elastic protein titin in active muscle, but the mechanisms by which titin plays this role remain to be elucidated. In active muscle, Ca 2+ -binding has been shown to increase titin stiffness, but the observed increase is too small to explain the increased stiffness of parallel elastic elements upon muscle activation. We propose a ‘winding filament’ mechanism for titin's role in active muscle. First, we hypothesize that Ca 2+ -dependent binding of titin's N2A region to thin filaments increases titin stiffness by preventing low-force straightening of proximal immunoglobulin domains that occurs during passive stretch. This mechanism explains the difference in length dependence of force between skeletal myofibrils and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as motors that pull thin filaments towards the M-line, but also as rotors that wind titin on the thin filaments, storing elastic potential energy in PEVK during force development and active stretch. Energy stored during force development can be recovered during active shortening. The winding filament hypothesis accounts for force enhancement during stretch and force depression during shortening, and provides testable predictions that will encourage new directions for research on mechanisms of muscle contraction.

scholarly journals Characterizing differential poststroke corticomotor drive to the dorsi- and plantarflexor muscles during resting and volitional muscle activation

2017 ◽  
Vol 117 (4) ◽  
pp. 1615-1624 ◽  
Author(s):  
Jacqueline A. Palmer ◽  
Ryan Zarzycki ◽  
Susanne M. Morton ◽  
Trisha M. Kesar ◽  
Stuart A. Binder-Macleod
Keyword(s):  
Muscle Contraction ◽  
Muscle Activation ◽  
Foot Drop ◽  
Stroke Survivors ◽  
Active Muscle ◽  
Corticomotor Excitability ◽  
Paretic Limb ◽  
Walking Recovery ◽  
Neurologically Intact ◽  
Plantarflexor Muscles

Imbalance of corticomotor excitability between the paretic and nonparetic limbs has been associated with the extent of upper extremity motor recovery poststroke, is greatly influenced by specific testing conditions such as the presence or absence of volitional muscle activation, and may vary across muscle groups. However, despite its clinical importance, poststroke corticomotor drive to lower extremity muscles has not been thoroughly investigated. Additionally, whereas conventional gait rehabilitation strategies for stroke survivors focus on paretic limb foot drop and dorsiflexion impairments, most contemporary literature has indicated that paretic limb propulsion and plantarflexion impairments are the most significant limiters to poststroke walking function. The purpose of this study was to compare corticomotor excitability of the dorsi- and plantarflexor muscles during resting and active conditions in individuals with good and poor poststroke walking recovery and in neurologically intact controls. We found that plantarflexor muscles showed reduced corticomotor symmetry between paretic and nonparetic limbs compared with dorsiflexor muscles in individuals with poor poststroke walking recovery during active muscle contraction but not during rest. Reduced plantarflexor corticomotor symmetry during active muscle contraction was a result of reduced corticomotor drive to the paretic muscles and enhanced corticomotor drive to the nonparetic muscles compared with the neurologically intact controls. These results demonstrate that atypical corticomotor drive exists in both the paretic and nonparetic lower limbs and implicate greater severity of corticomotor impairments to plantarflexor vs. dorsiflexor muscles during muscle activation in stroke survivors with poor walking recovery. NEW & NOTEWORTHY The present study observed that lower-limb corticomotor asymmetry resulted from both reduced paretic and enhanced nonparetic limb corticomotor excitability compared with neurologically intact controls. The most asymmetrical corticomotor drive was observed in the plantarflexor muscles of individuals with poor poststroke walking recovery. This suggests that neural function of dorsi- and plantarflexor muscles in both paretic and nonparetic limbs may play a role in poststroke walking function, which may have important implications when developing targeted poststroke rehabilitation programs to improve walking ability.

scholarly journals Hypothesis: Single Actomyosin Properties Account for Ensemble Behavior in Active Muscle Shortening and Isometric Contraction

2020 ◽  
Vol 21 (21) ◽  
pp. 8399
Author(s):  
Alf Månsson
Keyword(s):  
Muscle Contraction ◽  
Single Molecule ◽  
Isometric Contraction ◽  
Contractile Function ◽  
Experimental Studies ◽  
Experimental Tests ◽  
Thick Filament ◽  
Crystalline Lattice ◽  
Thin Filaments ◽  
Elastic Protein

Muscle contraction results from cyclic interactions between myosin II motors and actin with two sets of proteins organized in overlapping thick and thin filaments, respectively, in a nearly crystalline lattice in a muscle sarcomere. However, a sarcomere contains a huge number of other proteins, some with important roles in muscle contraction. In particular, these include thin filament proteins, troponin and tropomyosin; thick filament proteins, myosin binding protein C; and the elastic protein, titin, that connects the thin and thick filaments. Furthermore, the order and 3D organization of the myofilament lattice may be important per se for contractile function. It is possible to model muscle contraction based on actin and myosin alone with properties derived in studies using single molecules and biochemical solution kinetics. It is also possible to reproduce several features of muscle contraction in experiments using only isolated actin and myosin, arguing against the importance of order and accessory proteins. Therefore, in this paper, it is hypothesized that “single molecule actomyosin properties account for the contractile properties of a half sarcomere during shortening and isometric contraction at almost saturating Ca concentrations”. In this paper, existing evidence for and against this hypothesis is reviewed and new modeling results to support the arguments are presented. Finally, further experimental tests are proposed, which if they corroborate, at least approximately, the hypothesis, should significantly benefit future effective analysis of a range of experimental studies, as well as drug discovery efforts.

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.

Introductory Remarks

1980 ◽  
Vol 38 ◽  
pp. 598-599
Author(s):  
H. Mohri
Keyword(s):  
Muscle Contraction ◽  
Experimental Evidence ◽  
Sea Urchin ◽  
Constant Length ◽  
Thin Filaments ◽  
Bridge Formation ◽  
Thick Filaments ◽  
Sliding Mechanism ◽  
Radial Spokes ◽  
Cilia And Flagella

In 1959, Afzelius observed the presence of two rows of arms projecting from each outer doublet microtubule of the so-called 9 + 2 pattern of cilia and flagella, and suggested a possibility that the outer doublet microtubules slide with respect to each other with the aid of these arms during ciliary and flagellar movement. The identification of the arms as an ATPase, dynein, by Gibbons (1963)strengthened this hypothesis, since the ATPase-bearing heads of myosin molecules projecting from the thick filaments pull the thin filaments by cross-bridge formation during muscle contraction. The first experimental evidence for the sliding mechanism in cilia and flagella was obtained by examining the tip patterns of molluscan gill cilia by Satir (1965) who observed constant length of the microtubules during ciliary bending. Further evidence for the sliding-tubule mechanism was given by Summers and Gibbons (1971), using trypsin-treated axonemal fragments of sea urchin spermatozoa. Upon the addition of ATP, the outer doublets telescoped out from these fragments and the total length reached up to seven or more times that of the original fragment. Thus, the arms on a certain doublet microtubule can walk along the adjacent doublet when the doublet microtubules are disconnected by digestion of the interdoublet links which connect them with each other, or the radial spokes which connect them with the central pair-central sheath complex as illustrated in Fig. 1. On the basis of these pioneer works, the sliding-tubule mechanism has been established as one of the basic mechanisms for ciliary and flagellar movement.

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.

The Filament Lattice of Striated Muscle

1998 ◽  
Vol 78 (2) ◽  
pp. 359-391 ◽  
Author(s):  
BARRY M. MILLMAN
Keyword(s):  
Muscle Contraction ◽  
Structural Changes ◽  
Striated Muscle ◽  
Muscle Fibers ◽  
Lattice Stability ◽  
X Ray Diffraction ◽  
Thin Filaments ◽  
Intact Muscle ◽  
Radial Forces ◽  
Speed Of Shortening

Millman, Barry M. The Filament Lattice of Striated Muscle. Physiol. Rev. 78: 359–391, 1998. — The filament lattice of striated muscle is an overlapping hexagonal array of thick and thin filaments within which muscle contraction takes place. Its structure can be studied by electron microscopy or X-ray diffraction. With the latter technique, structural changes can be monitored during contraction and other physiological conditions. The lattice of intact muscle fibers can change size through osmotic swelling or shrinking or by changing the sarcomere length of the muscle. Similarly, muscle fibers that have been chemically or mechanically skinned can be compressed with bathing solutions containing very large inert polymeric molecules. The effects of lattice change on muscle contraction in vertebrate skeletal and cardiac muscle and in invertebrate striated muscle are reviewed. The force developed, the speed of shortening, and stiffness are compared with structural changes occurring within the lattice. Radial forces between the filaments in the lattice, which can include electrostatic, Van der Waals, entropic, structural, and cross bridge, are assessed for their contributions to lattice stability and to the contraction process.

scholarly journals Troponin C modulates the activation of thin filaments by rigor cross-bridges

1997 ◽  
Vol 72 (5) ◽  
pp. 2262-2267 ◽  
Author(s):  
P.W. Brandt ◽  
F.H. Schachat
Keyword(s):  
Troponin C ◽  
Thin Filaments ◽  
Cross Bridges

Muscle Contraction: Calcium in Muscle Activation.

Science ◽  
1987 ◽  
Vol 238 (4824) ◽  
pp. 223-223 ◽  
Author(s):  
A. G. SZENT-GYORGYI
Keyword(s):  
Muscle Contraction ◽  
Muscle Activation

Cooperative attachment of cross bridges predicts regulation of smooth muscle force by myosin phosphorylation

2004 ◽  
Vol 287 (3) ◽  
pp. C594-C602 ◽  
Author(s):  
Christopher M. Rembold ◽  
Robert L. Wardle ◽  
Christopher J. Wingard ◽  
Timothy W. Batts ◽  
Elaine F. Etter ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Time Course ◽  
Muscle Force ◽  
Regulatory System ◽  
Force Development ◽  
Cross Bridge ◽  
Cross Bridges ◽  
The Relationship ◽  
Cooperative Activation

Serine 19 phosphorylation of the myosin regulatory light chain (MRLC) appears to be the primary determinant of smooth muscle force development. The relationship between MRLC phosphorylation and force is nonlinear, showing that phosphorylation is not a simple switch regulating the number of cycling cross bridges. We reexamined the MRLC phosphorylation-force relationship in slow, tonic swine carotid media; fast, phasic rabbit urinary bladder detrusor; and very fast, tonic rat anococcygeus. We found a sigmoidal dependence of force on MRLC phosphorylation in all three tissues with a threshold for force development of ∼0.15 mol Pi/mol MRLC. This behavior suggests that force is regulated in a highly cooperative manner. We then determined whether a model that employs both the latch-bridge hypothesis and cooperative activation could reproduce the relationship between Ser19-MRLC phosphorylation and force without the need for a second regulatory system. We based this model on skeletal muscle in which attached cross bridges cooperatively activate thin filaments to facilitate cross-bridge attachment. We found that such a model describes both the steady-state and time-course relationship between Ser19-MRLC phosphorylation and force. The model required both cooperative activation and latch-bridge formation to predict force. The best fit of the model occurred when binding of a cross bridge cooperatively activated seven myosin binding sites on the thin filament. This result suggests cooperative mechanisms analogous to skeletal muscle that will require testing.

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