Cross-bridge mechanisms underlying the history-dependent properties of muscle spindles and stretch reflexes

2004 ◽  
Vol 82 (8-9) ◽  
pp. 569-576 ◽  
Author(s):  
T Richard Nichols ◽  
Timothy C Cope

The effects of prior movement on the force responses of skeletal muscle are compared with the effects of movement history on the changes in firing rate of muscle spindle receptors. Prior release results in the linearization of the mechanical properties of skeletal muscles, which can be provisionally explained by cross-bridge models of muscular contraction. The history-dependence of responses of muscle spindle receptors in unanesthetized decerebrate preparations appears to result from the kinetics of cycling and noncycling cross-bridges. The results of this comparison indicate that the integration of mechanical properties of muscle and spindle receptor promotes stiffness regulation.Key words: predictive control, muscular stiffness, muscle receptors, reflex compensation, cross-bridge cycling, nonlinear mechanical properties, feline motor control.

2020 ◽  
Author(s):  
R Stehle

ABSTRACTThe release of inorganic phosphate (Pi) from the cross-bridge is a pivotal step in the cross-bridge ATPase cycle leading to force generation. It is well known that Pi release and the force-generating step are reversible, thus increase of [Pi] decreases isometric force by product inhibition and increases the rate constant kTR of mechanically-induced force redevelopment due to the reversible redistribution of cross-bridges among non-force-generating and force-generating states. The experiments on cardiac myofibrils from guinea pig presented here show that increasing [Pi] increases kTR almost reciprocally to force, i.e., kTR ≈ 1/force. To elucidate which cross-bridge models can explain the reciprocal kTR-force relation, simulations were performed for models varying in sequence and kinetics of 1) the Pi release-rebinding equilibrium, 2) the force-generating step and its reversal, and 3) the transitions limiting forward and backward cycling of cross-bridges between non-force-generating and force-generating states. Models consisting of fast reversible force generation before/after rapid Pi release-rebinding fail to describe the kTR–force relation observed in experiments. Models consistent with the experimental kTR-force relation have in common that Pi binding and/or force-reversal are/is intrinsically slow, i.e., either Pi binding or force-reversal or both limit backward cycling of cross-bridges from force-generating to non-force-generating states.STATEMENT OF SIGNIFICANCEPrevious mechanical studies on muscle fibers, myofibrils and myosin interacting with actin revealed that force production associated to phosphate release from myosin’s active site presents a reversible process in the cross-bridge cycle. The correlation of this reversible process to the process(es) limiting kinetics of backward cycling from force-generating to non-force-generating states remained unclear.Experimental data of cardiac myofibrils and model simulations show that the combined effects of [Pi] on force and the rate constant of force redevelopment (kTR) are inconsistent with fast reversible force generation before/after rapid Pi release-rebinding. The minimum requirement in sequential models for successfully describing the experimentally observed nearly reciprocal change of force and kTR is that either the Pi binding or the force-reversal step limit backward cycling.


2002 ◽  
Vol 282 (4) ◽  
pp. C647-C653 ◽  
Author(s):  
Jeffrey J. Widrick

Chemically skinned muscle fibers, prepared from the rat medial gastrocnemius and soleus, were subjected to four sequential slack tests in Ca2+-activating solutions containing 0, 15, 30, and 0 mM added Pi. Pi (15 and 30 mM) had no effect on the unloaded shortening velocity ( V o) of fibers expressing type IIb myosin heavy chain (MHC). For fibers expressing type I MHC, 15 mM Pi did not alter V o, whereas 30 mM Pireduced V o to 81 ± 1% of the original 0 mM Pi value. This effect was readily reversible when Pi was lowered back to 0 mM. These results are not compatible with current cross-bridge models, developed exclusively from data obtained from fast fibers, in which V o is independent of Pi. The response of the type I fibers at 30 mM Pi is most likely the result of increased internal drag opposing fiber shortening resulting from fiber type-specific effects of Pi on cross bridges, the thin filament, or the rate-limiting step of the cross-bridge cycle.


2001 ◽  
Vol 117 (2) ◽  
pp. 133-148 ◽  
Author(s):  
Daniel P. Fitzsimons ◽  
Jitandrakumar R. Patel ◽  
Kenneth S. Campbell ◽  
Richard L. Moss

Regulation of contraction in skeletal muscle is a highly cooperative process involving Ca2+ binding to troponin C (TnC) and strong binding of myosin cross-bridges to actin. To further investigate the role(s) of cooperation in activating the kinetics of cross-bridge cycling, we measured the Ca2+ dependence of the rate constant of force redevelopment (ktr) in skinned single fibers in which cross-bridge and Ca2+ binding were also perturbed. Ca2+ sensitivity of tension, the steepness of the force-pCa relationship, and Ca2+ dependence of ktr were measured in skinned fibers that were (1) treated with NEM-S1, a strong-binding, non–force-generating derivative of myosin subfragment 1, to promote cooperative strong binding of endogenous cross-bridges to actin; (2) subjected to partial extraction of TnC to disrupt the spread of activation along the thin filament; or (3) both, partial extraction of TnC and treatment with NEM-S1. The steepness of the force-pCa relationship was consistently reduced by treatment with NEM-S1, by partial extraction of TnC, or by a combination of TnC extraction and NEM-S1, indicating a decrease in the apparent cooperativity of activation. Partial extraction of TnC or NEM-S1 treatment accelerated the rate of force redevelopment at each submaximal force, but had no effect on kinetics of force development in maximally activated preparations. At low levels of Ca2+, 3 μM NEM-S1 increased ktr to maximal values, and higher concentrations of NEM-S1 (6 or 10 μM) increased ktr to greater than maximal values. NEM-S1 also accelerated ktr at intermediate levels of activation, but to values that were submaximal. However, the combination of partial TnC extraction and 6 μM NEM-S1 increased ktr to virtually identical supramaximal values at all levels of activation, thus, completely eliminating the activation dependence of ktr. These results show that ktr is not maximal in control fibers, even at saturating [Ca2+], and suggest that activation dependence of ktr is due to the combined activating effects of Ca2+ binding to TnC and cross-bridge binding to actin.


1972 ◽  
Vol 60 (3) ◽  
pp. 307-336 ◽  
Author(s):  
D. G. S. White ◽  
John Thorson

The nonlinear mechanical dynamics of glycerinated insect fibrillar flight muscle are investigated. The most striking nonlinearity reported previously, which often resulted in oscillatory work being limited to frequencies below those of natural flight, disappears if 5 mM or more orthophosphate is added to the experimental solutions. We show that two further asymmetric nonlinearities, which remain even though phosphate is present, are predicted by cross-bridge theory if one takes account of the expected distortion of attached cross-bridges as filament sliding becomes appreciable. Adenosine triphosphate and adenosine diphosphate have opponent effects upon the mechanical rate constants, suggesting a scheme for the sequential ordering of the events comprising the cross-bridge cycle.


1991 ◽  
Vol 65 (6) ◽  
pp. 1297-1312 ◽  
Author(s):  
A. Schaafsma ◽  
E. Otten ◽  
J. D. Van Willigen

1. A muscle spindle model for primary afferent firing is presented that contains two components representing a gamma d-dependent (bag1) and gamma s-dependent (bag2/nuclear chain) intrafusal fiber. Each of the intrafusal fibers is composed of a linear elastic element representing the sensory part and a muscle fiber representing the muscular part. 2. The muscular part of the bag1 was modeled as a slow twitch, that of the bag2 as a fast twitch muscle fiber. 3. The sensory regions were linear length transducers, generating a rising depolarization on increasing stretch. The input of both bags was fused by taking the largest depolarization to determine a generator potential. The rate of primary afferent firing depended on this generator potential as well as on its rate of change. 4. To simulate the high sensitivity of muscle spindles to small amplitudes of stretching, a model analogue of cross-bridge fixation (or stiction) has been included in the muscular part of the bag1 fiber. This makes use of one hundred cross-bridge regions that release one after the other, provided a certain breaking force is exceeded. 5. The values of the mechanical parameters that defined the model were selected by a computerized search procedure. 6. The values found by means of this procedure allowed the model to provide an accurate simulation of experimental data on ramp-and-hold stretches (for 6 different stretch velocities under variable conditions of fusimotor activity). 7. On sinusoidal stretches at a frequency of 1 Hz the spindle model responded with about one-half the discharge modulation reported in experimental studies. Its phase advance tended to be slightly lower than that observed for real spindles. 8. Frequency response curves showed the same high sensitivities at high frequencies as those observed in real spindles. 9. Close evaluation of the model compared with experimental results in literature reveal its merits as well as its limitations. Because the model is structural rather than phenomenologic, it provides insight into how intrafusal events may contribute to observed firing properties of real muscle spindles.


1988 ◽  
Vol 91 (6) ◽  
pp. 761-779 ◽  
Author(s):  
D M Warshaw ◽  
D D Rees ◽  
F S Fay

Force development in smooth muscle, as in skeletal muscle, is believed to reflect recruitment of force-generating myosin cross-bridges. However, little is known about the events underlying cross-bridge recruitment as the muscle cell approaches peak isometric force and then enters a period of tension maintenance. In the present studies on single smooth muscle cells isolated from the toad (Bufo marinus) stomach muscularis, active muscle stiffness, calculated from the force response to small sinusoidal length changes (0.5% cell length, 250 Hz), was utilized to estimate the relative number of attached cross-bridges. By comparing stiffness during initial force development to stiffness during force redevelopment immediately after a quick release imposed at peak force, we propose that the instantaneous active stiffness of the cell reflects both a linearly elastic cross-bridge element having 1.5 times the compliance of the cross-bridge in frog skeletal muscle and a series elastic component having an exponential length-force relationship. At the onset of force development, the ratio of stiffness to force was 2.5 times greater than at peak isometric force. These data suggest that, upon activation, cross-bridges attach in at least two states (i.e., low-force-producing and high-force-producing) and redistribute to a steady state distribution at peak isometric force. The possibility that the cross-bridge cycling rate was modulated with time was also investigated by analyzing the time course of tension recovery to small, rapid step length changes (0.5% cell length in 2.5 ms) imposed during initial force development, at peak force, and after 15 s of tension maintenance. The rate of tension recovery slowed continuously throughout force development following activation and slowed further as force was maintained. Our results suggest that the kinetics of force production in smooth muscle may involve a redistribution of cross-bridge populations between two attached states and that the average cycling rate of these cross-bridges becomes slower with time during contraction.


2010 ◽  
Vol 72 ◽  
pp. 46-52 ◽  
Author(s):  
Laurent Royer ◽  
Stéphane Mathieu ◽  
Christophe Liebaut ◽  
Pierre Steinmetz

For energy production and also for the glass industry, finding new refractory alloys which could permit to increase the process temperatures to 1200°C or more is a permanent challenge. Chromium base alloys can be good candidates, considering the melting point of Cr itself, and also its low corrosion rate in molten glass. Two families of alloys have been studied for this purpose, Cr-Mo-W and Cr-Ta-X alloys (X= Mo, Si..). A finer selection of compositions has been done, to optimize their chemical and mechanical properties. Kinetics of HT oxidation by air, of corrosion by molten glass and also creep properties of several alloys have been measured up to 1250°C. The results obtained with the best alloys (Cr-Ta base) give positive indications as regards the possibility of their industrial use.


Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 120
Author(s):  
Qing Peng

Although meta-generalized-gradient approximations (meta-GGAs) are believed potentially the most accurate among the efficient first-principles calculations, the performance has not been accessed on the nonlinear mechanical properties of two-dimensional nanomaterials. Graphene, like two-dimensional silicon carbide g-SiC, has a wide direct band-gap with applications in high-power electronics and solar energy. Taken g-SiC as a paradigm, we have investigated the performance of meta-GGA functionals on the nonlinear mechanical properties under large strains, both compressive and tensile, along three deformation modes using Strongly Constrained and Appropriately Normed Semilocal Density Functional (SCAN) as an example. A close comparison suggests that the nonlinear mechanics predicted from SCAN are very similar to that of Perdew-Burke-Ernzerhof (PBE) formulated functional, a standard Density Functional Theory (DFT) functional. The improvement from SCAN calculation over PBE calculation is minor, despite the considerable increase of computing demand. This study could be helpful in selection of density functionals in simulations and modeling of mechanics of materials.


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