Variation in myoplasmic Ca2+ concentration during contraction and relaxation studied by the indicator fluo‐3 in frog muscle fibres.

Caputo, Carlo; Edman, K. A. P.; Lou, Fang; Sun, Yin-Biao

doi:10.1113/jphysiol.1994.sp020237

Cited by 91 publications

(125 citation statements)

References 38 publications

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“…However, the most important function of such a reverse signaling pathway may be in normal relaxation. Mechanical relaxation in isometric conditions is much slower than the fall of the Ca 2+ transient (38)(39)(40), but can be accelerated by stretching the muscle (41,42), such as might occur by the action of an antagonist muscle in vivo. Thus, the present results lead to a model of muscle regulation in which the rates of both activation and relaxation are not determined solely by the calcium transient and structural changes in the thin filament, but by coordinated changes in the structures of both thick and thin filaments in response to mechanical conditions.…”

Section: Discussionmentioning

confidence: 99%

Structural dynamics of troponin during activation of skeletal muscle

Fusi

Brunello

Sevrieva

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Time-resolved changes in the conformation of troponin in the thin filaments of skeletal muscle were followed during activation in situ by photolysis of caged calcium using bifunctional fluorescent probes in the regulatory and the coiled-coil (IT arm) domains of troponin. Three sequential steps in the activation mechanism were identified. The fastest step (1,100 s −1 ) matches the rate of Ca 2+ binding to the regulatory domain but also dominates the motion of the IT arm. The second step (120 s −1 ) coincides with the azimuthal motion of tropomyosin around the thin filament. The third step (15 s −1 ) was shown by three independent approaches to track myosin head binding to the thin filament, but is absent in the regulatory head. The results lead to a four-state structural kinetic model that describes the molecular mechanism of muscle activation in the thin filament-myosin head complex under physiological conditions. muscle regulation | excitation-contraction coupling | muscle signaling C ontraction of skeletal and cardiac muscle is initiated by a transient increase in the concentration of intracellular Ca 2+ ions, which bind to troponin in the thin filaments of the muscle sarcomere. This leads to azimuthal movement of tropomyosin around the thin filament, which uncovers the myosin binding sites on actin and allows the head domain of myosin from the thick filaments to bind to actin and generate force (1, 2). In vitro studies using isolated protein components showed that myosin head binding can produce a further motion of tropomyosin, at least in low [ATP] or rigor-like conditions (2-4), but the functional significance of this effect in physiological conditions and intact sarcomeres is not clear.To elucidate the molecular structural basis of muscle regulation and the role of myosin binding in situ, we introduced bifunctional fluorescent probes into the calcium-binding subunit of troponin, troponin C (TnC) (Fig. 1, yellow), in demembranated fibers from skeletal muscle (5-7). One probe cross-linked a pair of cysteines introduced into the C helix of TnC (Fig. 1, green), close to the regulatory Ca 2+ binding sites (Fig. 1, black spheres) in its N-terminal lobe, and reports the rotation and opening of this lobe on binding Ca 2+ (5). The N-lobe opening is associated with binding of the switch peptide of troponin I (TnI) (Fig. 1, blue) to a hydrophobic pocket on its surface, and this is a key step in the signaling pathway of calcium regulation (8, 9).A second probe was attached to the E helix of TnC (Fig. 1, magenta) in its C-terminal lobe, which contains a pair of divalent cation binding sites (Fig. 1, gray spheres) that can bind Mg 2+ as well as Ca 2+ . The C lobe of TnC is clasped between two long helices of TnI, one of which forms a coiled coil with part of the tropomyosin-binding component of troponin, troponin T (TnT) (Fig. 1, orange). The C lobe of TnC and these long TnI and TnT helices form a well-defined structural domain called the "IT arm" (9, 10). Although the C-lobe E helix of TnC is continuous with the N-lob...

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Section: Discussionmentioning

confidence: 99%

Structural dynamics of troponin during activation of skeletal muscle

Fusi

Brunello

Sevrieva

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been argued that as sarcomere length nonuniformities arise at the onset of contractile apparatus deactivation (Edman and Flitney, 1982), the capacity for strongly attached crossbridges to avoid further slippage or 'give' rapidly declines (Caputo et al, 1994). Length perturbations imposed during the early phase of force relaxation have been demonstrated to accelerate the transition between slow and fast relaxation phases and abbreviate the decay of active tension (Caputo et al, 1994;Tesi et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Additional in-series compliance reduces muscle force summation and alters the time course of force relaxation during fixed-end contractions

Mayfield

Launikonis

Cresswell

et al. 2016

Journal of Experimental Biology

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There are high mechanical demands placed on skeletal muscles in movements requiring rapid acceleration of the body or its limbs. Tendons are responsible for transmitting muscle forces, but, because of their elasticity, can manipulate the mechanics of the internal contractile apparatus. Shortening of the contractile apparatus against the stretch of tendon affects force generation according to known mechanical properties; however, the extent to which differences in tendon compliance alter force development in response to a burst of electrical impulses is unclear. To establish the influence of series compliance on force summation, we studied electrically evoked doublet contractions in the cane toad peroneus muscle in the presence and absence of a compliant artificial tendon. Additional series compliance reduced tetanic force by two-thirds, a finding predicted based on the force-length property of skeletal muscle. Doublet force and force-time integral expressed relative to the twitch were also reduced by additional series compliance. Active shortening over a larger range of the ascending limb of the force-length curve and at a higher velocity, leading to a progressive reduction in forcegenerating potential, could be responsible. Muscle-tendon interaction may also explain the accelerated time course of force relaxation in the presence of additional compliance. Our findings suggest that a compliant tendon limits force summation under constant-length conditions. However, high series compliance can be mechanically advantageous when a muscle-tendon unit is actively stretched, permitting muscle fibres to generate force almost isometrically, as shown during stretch-shorten cycles in locomotor activities. Restricting active shortening would likely favour rapid force development.

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“…This is probably due to a greater stretch velocity when both parts of the muscle relax together. Stretch during relaxation has been shown to cause muscle force to fall more rapidly (6).…”

Section: Isometric Contractions With Equal-duration Tetanimentioning

confidence: 99%

Nonlinear summation of force in cat soleus muscle results primarily from stretch of the common-elastic elements

Sandercock

2000

Journal of Applied Physiology

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The complex connective tissue structure of muscle and tendon suggests that forces from two parts of a muscle may not summate linearly. This study measured the nonlinear summation of force (Fnl) in whole cat soleus during isometric and ramp movements. In six anesthetized cats, the soleus was attached to a servomechanism to control muscle length and record force. The ventral roots were divided into two bundles, each innervating about half the soleus; thus the two parts could be stimulated alone or together. In all experiments, Fnl was small (<6% of maximum tetanic tension). Peak Fnl occurred during changes in muscle force, either as a result of imposed muscle movement or the onset or offset of a stimulus train. The data were fit to a model in which both parts of the muscle were assumed to stretch to a common elasticity. The servomechanism was programmed to compensate for reduced stretch of the common elasticity during partial compared with whole muscle activation. These compensatory movements showed how the model could account for most, but not all, of Fnl.

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Variation in myoplasmic Ca2+ concentration during contraction and relaxation studied by the indicator fluo‐3 in frog muscle fibres.

Cited by 91 publications

References 38 publications

Structural dynamics of troponin during activation of skeletal muscle

Structural dynamics of troponin during activation of skeletal muscle

Additional in-series compliance reduces muscle force summation and alters the time course of force relaxation during fixed-end contractions

Nonlinear summation of force in cat soleus muscle results primarily from stretch of the common-elastic elements

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