scholarly journals Cross-Bridges and Sarcomeric Non-cross-bridge Structures Contribute to Increased Work in Stretch-Shortening Cycles

2020 ◽  
Vol 11 ◽  
Author(s):  
André Tomalka ◽  
Sven Weidner ◽  
Daniel Hahn ◽  
Wolfgang Seiberl ◽  
Tobias Siebert
Keyword(s):  
Cross Bridge ◽  
Bridge Structures ◽  
Cross Bridges

scholarly journals Two distinct functions of the carboxyl-terminal tail domain of NF-M upon neurofilament assembly: cross-bridge formation and longitudinal elongation of filaments.

1995 ◽  
Vol 129 (2) ◽  
pp. 411-429 ◽  
Author(s):  
T Nakagawa ◽  
J Chen ◽  
Z Zhang ◽  
Y Kanai ◽  
N Hirokawa
Keyword(s):  
Neuronal Cell ◽  
Molecular Architecture ◽  
Tail Domain ◽  
Bridge Formation ◽  
Cross Bridge ◽  
Filament Assembly ◽  
Bridge Structures ◽  
Carboxyl Terminal ◽  
Cross Bridges ◽  
10 Nm Filaments

Neurofilaments are the major cytoskeletal elements in the axon that take highly ordered structures composed of parallel arrays of 10-nm filaments linked to each other with frequent cross-bridges, and they are believed to maintain a highly polarized neuronal cell shape. Here we report the function of rat NF-M in this characteristic neurofilament assembly. Transfection experiments were done in an insect Sf9 cell line lacking endogenous intermediate filaments. NF-L and NF-M coassemble to form bundles of 10-nm filaments packed in a parallel manner with frequent cross-bridges resembling the neurofilament domains in the axon when expressed together in Sf9 cells. Considering the fact that the expression of either NF-L or NF-M alone in these cells results in neither formation of any ordered network of 10-nm filaments nor cross-bridge structures, NF-M plays a crucial role in this parallel filament assembly. In the case of NF-H the carboxyl-tail domain has been shown to constitute the cross-bridge structures. The similarity in molecular architecture between NF-M and NF-H suggests that the carboxyl-terminal tail domain of NF-M also constitutes cross-bridges. To examine this and to further investigate the function of the carboxyl-terminal tail domain of NF-M, we made various deletion mutants that lacked part of their tail domains, and we expressed these with NF-L. From this deletion mutant analysis, we conclude that the carboxyl-terminal tail domain of NF-M has two distinct functions. First, it is the structural component of cross-bridges, and these cross-bridges serve to control the spacing between core filaments. Second, the portion of the carboxyl-terminal tail domain of NF-M that is directly involved in cross-bridge formation affects the core filament assembly by helping them to elongate longitudinally so that they become straight.

Oxytocin-mediated recruitment of slowly cycling cross bridges and isometric force in rat myometrium

1996 ◽  
Vol 270 (2) ◽  
pp. E203-E208
Author(s):  
A. L. Ruzycky ◽  
B. T. Ameredes
Keyword(s):  
Isometric Force ◽  
Additional Stress ◽  
Shortening Velocity ◽  
Cycling Rate ◽  
Quick Release ◽  
Cross Bridge ◽  
Cross Bridges ◽  
Unit Stress ◽  
Release Method ◽  
The Relationship

The relationship between cross-bridge cycling rate and isometric stress was investigated in rat myometrium. Stress production by myometrial strips was measured under resting, K+ depolarization, and oxytocin-stimulated conditions. Cross-bridge cycling rates were determined from measurements of maximal unloaded shortening velocity, using the quick-release method. Force redevelopment after the quick release was used as an index of cross-bridge attachment. With maximal K+ stimulation, stress increased with increased cross-bridge cycling (+76%; P < 0.05) and attached cross bridges (+112%; P < 0.05). Addition of oxytocin during K+ stimulation further increased stress (+30%; P < 0.05). With this force component, the cross-bridge cycling rate decreased (-60%; P < 0.05) similar to that under resting conditions. Attached cross-bridges did not increase with this additional stress. The results suggest two distinct mechanisms mediating myometrial contractions. One requires elevated intracellular calcium and rapidly cycling cross bridges. The other mechanism may be independent of calcium and appears to be mediated by slowly cycling cross bridges, supporting greater unit stress.

Cross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers

2003 ◽  
Vol 285 (4) ◽  
pp. C781-C787 ◽  
Author(s):  
Iain S. Young ◽  
Claire L. Harwood ◽  
Lawrence C. Rome
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Direct Measurement ◽  
Motor Behavior ◽  
Force Generation ◽  
Skinned Fibers ◽  
Control Value ◽  
Cross Bridge ◽  
Direct Measurements ◽  
Hill Coefficients ◽  
Cross Bridges

Because the major processes involved in muscle contraction require rapid utilization of ATP, measurement of ATP utilization can provide important insights into the mechanisms of contraction. It is necessary, however, to differentiate between the contribution made by cross-bridges and that of the sarcoplasmic reticulum (SR) Ca2+ pumps. Specific and potent SR Ca2+ pump blockers have been used in skinned fibers to permit direct measurement of cross-bridge ATP utilization. Up to now, there was no analogous cross-bridge blocker. Recently, N-benzyl- p-toluene sulfonamide (BTS) was found to suppress force generation at micromolar concentrations. We tested whether BTS could be used to block cross-bridge ATP utilization, thereby permitting direct measurement of SR Ca2+ pump ATP utilization in saponin-skinned fibers. At 25 μM, BTS virtually eliminates force and cross-bridge ATP utilization (both <4% of control value). By taking advantage of the toadfish swimbladder muscle's unique right shift in its force-Ca2+ concentration ([Ca2+]) relationship, we measured SR Ca2+ pump ATP utilization in the presence and absence of BTS. At 25 μM, BTS had no effect on SR pump ATP utilization. Hence, we used BTS to make some of the first direct measurements of ATP utilization of intact SR over a physiological range of [Ca2+]at 15°C. Curve fits to SR Ca2+ pump ATP utilization vs. pCa indicate that they have much lower Hill coefficients (1.49) than that describing cross-bridge force generation vs. pCa (∼5). Furthermore, we found that BTS also effectively eliminates force generation in bundles of intact swimbladder muscle, suggesting that it will be an important tool for studying integrated SR function during normal motor behavior.

Heat production of rat anococcygeus muscle during isometric contraction

1988 ◽  
Vol 255 (4) ◽  
pp. C536-C542 ◽  
Author(s):  
J. S. Walker ◽  
I. R. Wendt ◽  
C. L. Gibbs
Keyword(s):  
Energy Expenditure ◽  
Heat Production ◽  
Progressive Increase ◽  
Isometric Contractions ◽  
Shortening Velocity ◽  
Anococcygeus Muscle ◽  
Cross Bridge ◽  
Time Integral ◽  
Rat Anococcygeus Muscle ◽  
Cross Bridges

Heat production, unloaded shortening velocity (Vus), and load-bearing capacity (LBC) were studied in the isolated rat anococcygeus muscle during isometric contractions at 27 degrees C. The relation between the total suprabasal heat produced and the stress-time integral for isometric contractions of various durations was curvilinear, demonstrating a decreasing slope as contractile duration increased. The rate of heat production at 600 s was approximately 68% of the peak value of 6.55 mW/g that occurred at 10 s. At the same time, force rose from a mean of 92 mN/mm2 at 10 s to a value of 140 mN/mm2 at 600 s. This produced a nearly threefold increase in the economy of force maintenance. The decline in the rate of heat production was accompanied by a decline in Vus from 0.56 Lo/s at 10 s to 0.28 Lo/s at 600 s, where Lo is the length for optimal force development. This suggests the fall in the rate of heat production was caused, at least in part, by a slowing of cross-bridge kinetics. The ratio of LBC to developed tension at 10 s was not significantly different from the ratio at 600 s, suggesting that the increase in tension was due to an increased number of attached cross bridges. The decline in heat production, therefore, appears contradictory, since an increased number of attached cross bridges would predict an increased rate of energy expenditure. The observations can be reconciled if either 1) the increase in force is caused by a progressive increase in the attachment time of a constant number of cross bridges that cycle at a lower frequency or 2) the decline in energy expenditure caused by the slowing of cross-bridge cycling is sufficient to mask the increase caused by the recruitment of additional cross bridges.

Structural cross-bridges between microtubules and mitochondria in central axons of an insect (Periplaneta americana)

1977 ◽  
Vol 27 (1) ◽  
pp. 255-272
Author(s):  
D.S. Smith ◽  
U. Jarlfors ◽  
M.L. Cayer
Keyword(s):  
Electron Micrographs ◽  
Mitochondrial Membrane ◽  
Periplaneta Americana ◽  
Freeze Fracture ◽  
Outer Mitochondrial Membrane ◽  
Thin Sections ◽  
Cross Bridge ◽  
Multiple Association ◽  
Random Models ◽  
Cross Bridges

The distribution of microtubules and mitochondria in central axons of an insect (Periplaneta americana) is assessed by comparison between counts on micrographs and computed axon random ‘models’. These studies show that the observed multiple association of microtubules with individual mitochondria is statistically highly significant. Electron micrographs of thin sections show that linkage is effected by physical cross-bridge, possibly comprising components from the microtubule and mitochondrion. Linear particle arrays are described on the outer mitochondrial membrane in freeze-fracture replicas, and tentatively related to the bridges seen in thin sections. The results are discussed in terms of proposed roles of microtubules in neurons and other cells.

The effects of pH on force and stiffness development in mouse muscles

1987 ◽  
Vol 65 (8) ◽  
pp. 1798-1801 ◽  
Author(s):  
J. M. Renaud ◽  
R. B. Stein ◽  
T. Gordon
Keyword(s):  
High Frequency ◽  
Small Amplitude ◽  
Force Production ◽  
Muscle Length ◽  
Low Ph ◽  
Muscle Stiffness ◽  
Average Force ◽  
Cross Bridge ◽  
Effects Of Ph ◽  
Cross Bridges

Changes in force and stiffness during contractions of mouse extensor digitorum longus and soleus muscles were measured over a range of extracellular pH from 6.4 to 7.4. Muscle stiffness was measured using small amplitude (<0.1% of muscle length), high frequency (1.5 kHz) oscillations in length. Twitch force was not significantly affected by changes in pH, but the peak force during repetitive stimulation (2, 3, and 20 pulses) was decreased significantly as the pH was reduced. Changes in muscle stiffness with pH were in the same direction, but smaller in extent. If the number of attached cross-bridges in the muscle can be determined from the measurement of small amplitude, high frequency muscle stiffness, then these findings suggest that (a) the number of cross-bridges between thick and thin filaments declines in low pH and (b) the average force per cross-bridge also declines in low pH. The decline in force per cross-bridge could arise from a reduction in the ability of cross-bridges to generate force during their state of active force production and (or) in an increased percentage of bonds in a low force, "rigor" state.

scholarly journals Slowly cycling Rho kinase-dependent actomyosin cross-bridge “slippage” explains intrinsic high compliance of detrusor smooth muscle

2017 ◽  
Vol 313 (1) ◽  
pp. F126-F134 ◽  
Author(s):  
Christopher J. Neal ◽  
Jia B. Lin ◽  
Tanner Hurley ◽  
Amy S. Miner ◽  
John E. Speich ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Soft Tissues ◽  
Plastic Material ◽  
Rho Kinase ◽  
Detrusor Smooth Muscle ◽  
Display Time ◽  
Protein Activation ◽  
Cross Bridge ◽  
Cross Bridges ◽  
Dependent Viscosity

Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as “slipping” cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.

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.

Abstract P338: Myopeptide Improves Contractile Mechanics In A Mouse Model Of Heart Failure Expressing Phosphoablated Cardiac Myosin Binding Protein-C

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Rohit Singh ◽  
Sakthivel Sadayappan
Keyword(s):  
Heart Failure ◽  
Mouse Model ◽  
Protein C ◽  
Cardiac Myosin ◽  
Bridge Formation ◽  
Cross Bridge ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding ◽  
Cross Bridges

Rationale: Normal heart function depends on cardiac myosin binding protein-C (cMyBP-C) phosphorylation. Its decrease is associated with heart failure (HF) by inhibiting actomyosin interactions. In absence of cMyBP-C phosphorylation, the protein is bound to myosin S2, but released when phosphorylated, allowing myosin to form cross-bridges with actin. Challenging cMyBP-C/myosin S2 interaction by myopeptide (the first 126 amino acids of myosin S2) could promote actomyosin interaction in vitro , but its ability to improve contractility in HF remains untested. Objective: To test contractile function in skinned papillary fibers of a cMyBP-C dephosphorylated mouse model using myopeptide. Methods and Results: To mimic constitutive phosphoablation, a knock-in mouse model was established to express cMyBP-C in which serines 273, 282 and 302 were mutated to alanine (cMyBP-C AAA ). Western blotting revealed 50% and 100% of cMyBP-C AAA in het and homo mouse hearts, respectively. Echocardiography showed a decreased percentage of ejection fraction (28%, p<0.01) and fractional shortening (30%, p< 0.05) in both het and homo cMyBP-C AAA mice at 3 months of age, compared to knock-in negative controls. These mice also developed diastolic dysfunction with elevated ratio of E/A and E/e’ waves. Next, pCa-force measurements using skinned papillary fibers determined that maximal force (F max ) and rate of cross-bridge formation ( k tr ) were decreased in the cMyBP-C AAA groups, compared to the control. However, administration of dose-dependent myopeptide increased F max and k tr in wild-type and cMyBP-C AAA permeabilized skinned papillary fibers without affecting myofilament Ca 2+ sensitivity. Conclusions: Myopeptide can increase contractile force and rate of cross-bridge formation by releasing cMyBP-C/myosin S2 and promoting actomyosin formation of cross-bridges, thus validating its therapeutic potential.

Regulation of shortening velocity by cross-bridge phosphorylation in smooth muscle

1988 ◽  
Vol 255 (1) ◽  
pp. C86-C94 ◽  
Author(s):  
C. M. Hai ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Shortening Velocity ◽  
Internal Load ◽  
Cross Bridge ◽  
Bridge Model ◽  
The Family ◽  
Cross Bridges ◽  
Latch State ◽  
The Relationship ◽  
State Stress

We have proposed a model that incorporates a dephosphorylated "latch bridge" to explain the mechanics and energetics of smooth muscle. Cross-bridge phosphorylation is proposed as a prerequisite for cross-bridge attachment and rapid cycling. Features of the model are 1) myosin light chain kinase and phosphatase can act on both free and attached cross bridges, 2) dephosphorylation of an attached phosphorylated cross bridge produces a noncycling "latch bridge," and 3) latch bridges have a slow detachment rate. This model quantitatively predicts the latch state: stress maintenance with reduced phosphorylation, cross-bridge cycling rates, and ATP consumption. In this study, we adapted A. F. Huxley's formulation of crossbridge cycling (A. F. Huxley, Progr. Biophys. Mol. Biol. 7: 255-318, 1957) to the latch-bridge model to predict the relationship between isotonic shortening velocity and phosphorylation. The model successfully predicted the linear dependence of maximum shortening velocity at zero external load (V0) on phosphorylation, as well as the family of stress-velocity curves determined at different times during a contraction when phosphorylation values varied. The model implies that it is unnecessary to invoke an internal load or multiple regulatory mechanisms to explain regulation of V0 in smooth muscle.

Sign in / Sign up

Export Citation Format

Share Document