scholarly journals The cross-bridge cycle and skeletal muscle fatigue

2008 ◽  
Vol 104 (2) ◽  
pp. 551-558 ◽  
Author(s):  
Robert H. Fitts
Keyword(s):  
Peak Power ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Low Ph ◽  
Forward Rate ◽  
Maximal Velocity ◽  
Functional Changes ◽  
Cross Bridge ◽  
The Cross

The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P0), maximal velocity, and peak power. Establishing the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle. With actin-myosin binding, the cross-bridge transitions from a weakly bound low-force state to a strongly bound high-force state. Low pH reduces the number of high-force cross bridges in fast fibers, and the force per cross bridge in both fast and slow fibers. The former is thought to involve a direct inhibition of the forward rate constant for transition to the strong cross-bridge state. In contrast, inorganic phosphate (Pi) is thought to reduce P0 by accelerating the reversal of this step. Both H+ and Pi decrease myofibrillar Ca2+ sensitivity. This effect is particularly important as the amplitude of the Ca2+ transient falls with fatigue. The inhibitory effects of low pH and high Pi on P0 are reduced as temperature increases from 10 to 30°C. However, the H+-induced depression of peak power in the slow fiber type, and Pi inhibition of myofibrillar Ca2+ sensitivity in slow and fast fibers, are greater at high compared with low temperature. Thus the depressive effects of H+ and Pi at in vivo temperatures cannot easily be predicted from data collected below 25° C. In vitro, reactive oxygen species reduce myofibrillar Ca2+ sensitivity; however, the importance of this mechanism during in vivo exercise is unknown.

Fiber type-specific determinants of V maxfor insulin-stimulated muscle glucose uptake in vivo

2003 ◽  
Vol 284 (3) ◽  
pp. E541-E548 ◽  
Author(s):  
Hilary Ann Petersen ◽  
Patrick T. Fueger ◽  
Deanna P. Bracy ◽  
David H. Wasserman ◽  
Amy E. Halseth
Keyword(s):  
Glucose Uptake ◽  
Fiber Type ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Glucose Flux ◽  
Steady State Levels ◽  
Type I Fibers ◽  
Relationship Of

The aim of this study was to determine barriers limiting muscle glucose uptake (MGU) during increased glucose flux created by raising blood glucose in the presence of fixed insulin. The determinants of the maximal velocity ( V max) of MGU in muscles of different fiber types were defined. Conscious rats were studied during a 4 mU · kg−1 · min−1insulin clamp with plasma glucose at 2.5, 5.5, and 8.5 mM. [U-14C]mannitol and 3- O-methyl-[3H]glucose ([3H]MG) were infused to steady-state levels ( t = −180 to 0 min). These isotope infusions were continued from 0 to 40 min with the addition of a 2-deoxy-[3H]glucose ([3H]DG) infusion. Muscles were excised at t = 40 min. Glucose metabolic index (Rg) was calculated from muscle-phosphorylated [3H]DG. [U-14C]mannitol was used to determine extracellular (EC) H2O. Glucose at the outer ([G]om) and inner ([G]im) sarcolemmal surfaces was determined by the ratio of [3H]MG in intracellular to EC H2O and muscle glucose. Rg was comparable at the two higher glucose concentrations, suggesting that rates of uptake near V max were reached. In summary, by defining the relationship of arterial glucose to [G]om and [G]im in the presence of fixed hyperinsulinemia, it is concluded that 1) V max for MGU is limited by extracellular and intracellular barriers in type I fibers, as the sarcolemma is freely permeable to glucose; 2) V max is limited in muscles with predominantly type IIb fibers by extracellular resistance and transport resistance; and 3) limits to Rg are determined by resistance at multiple steps and are better defined by distributed control rather than by a single rate-limiting step.

Psoralen photoactivation promotes morphological and functional changes in fibroblasts in vitro reminiscent of cellular senescence

1998 ◽  
Vol 111 (6) ◽  
pp. 759-767
Author(s):  
G. Herrmann ◽  
P. Brenneisen ◽  
M. Wlaschek ◽  
J. Wenk ◽  
K. Faisst ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Molecular Data ◽  
Cellular Aging ◽  
Premature Aging ◽  
Functional Changes ◽  
Uva Irradiation ◽  
High Level

Premature aging of the skin is a prominent side effect of psoralen photoactivation, a treatment used widely for various skin disorders. The molecular mechanisms underlying premature aging upon psoralen photoactivation are as yet unknown. Here we show that treatment of fibroblasts with 8-methoxypsoralen (8-MOP) and subsequent ultraviolet A (UVA) irradiation resulted in a permanent switch of mitotic to stably postmitotic fibroblasts which acquired a high level of de novo expression of SA-beta-galactosidase, a marker for fibroblast senescence in vitro and in vivo. A single exposure of fibroblasts to 8-MOP/UVA resulted in a 5.8-fold up-regulation of two matrix-degrading enzymes, interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3), over a period of >120 days, while TIMP-1, the major inhibitor of MMP-1 and MMP-3, was only slightly induced. This imbalance between matrix-degrading metalloproteases and their inhibitor may lead to connective tissue damage, a hallmark of premature aging. Superoxide anion and hydrogen peroxide, but not singlet oxygen, were identified as important intermediates in the downstream signaling pathway leading to these complex fibroblast responses upon psoralen photoactivation. Collectively, the end phenotype induced upon psoralen photoactivation shares several criteria of senescent cells. In the absence of detailed molecular data on what constitutes normal aging, it is difficult to decide whether the changes reported here reflect mechanisms underlying normal cellular aging/senescence or rather produce a mimic of cellular aging/senescence by quite different pathways.

scholarly journals Reassociation of microvillar core proteins: making a microvillar core in vitro.

1989 ◽  
Vol 108 (2) ◽  
pp. 495-502 ◽  
Author(s):  
L M Coluccio ◽  
A Bretscher
Keyword(s):  
Actin Filaments ◽  
Direct Proof ◽  
Intestinal Epithelia ◽  
The Core ◽  
Cross Bridge ◽  
Core Proteins ◽  
The Cross ◽  
Cross Bridges

Intestinal epithelia have a brush border membrane of numerous microvilli each comprised of a cross-linked core bundle of 15-20 actin filaments attached to the surrounding membrane by lateral cross-bridges; the cross-bridges are tilted with respect to the core bundle. Isolated microvillar cores contain actin (42 kD) and three other major proteins: fimbrin (68 kD), villin (95 kD), and the 110K-calmodulin complex. The addition of ATP to detergent-treated isolated microvillar cores has previously been shown to result in loss of the lateral cross-bridges and a corresponding decrease in the amount of the 110-kD polypeptide and calmodulin associated with the core bundle. This provided the first evidence to suggest that these lateral cross-bridges to the membrane are comprised at least in part by a 110-kD polypeptide complexed with calmodulin. We now demonstrate that purified 110K-calmodulin complex can be readded to ATP-treated, stripped microvillar cores. The resulting bundles display the same helical and periodic arrangement of lateral bridges as is found in vivo. In reconstitution experiments, actin filaments incubated in EGTA with purified fimbrin and villin form smooth-sided bundles containing an apparently random number of filaments. Upon addition of 110K-calmodulin complex, the bundles, as viewed by electron microscopy of negatively stained images, display along their entire length helically arranged projections with the same 33-nm repeat of the lateral cross-bridges found on microvilli in vivo; these bridges likewise tilt relative to the bundle. Thus, reconstitution of actin filaments with fimbrin, villin, and the 110K-calmodulin complex results in structures remarkably similar to native microvillar cores. These data provide direct proof that the 110K-calmodulin is the cross-bridge protein and indicate that actin filaments bundled by fimbrin and villin are of uniform polarity and lie in register. The arrangement of the cross-bridge arms on the bundle is determined by the structure of the core filaments as fixed by fimbrin and villin; a contribution from the membrane is not required.

scholarly journals Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e109066 ◽  
Author(s):  
Charlotte Gineste ◽  
Coen Ottenheijm ◽  
Yann Le Fur ◽  
Sébastien Banzet ◽  
Emilie Pecchi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Muscle Function ◽  
Nemaline Myopathy ◽  
Cross Bridge ◽  
The Cross

scholarly journals Immunosenescence of Polymorphonuclear Neutrophils

2010 ◽  
Vol 10 ◽  
pp. 145-160 ◽  
Author(s):  
Inga Wessels ◽  
Judith Jansen ◽  
Lothar Rink ◽  
Peter Uciechowski
Keyword(s):  
Molecular Mechanisms ◽  
Adaptive Immune System ◽  
The Elderly ◽  
Polymorphonuclear Neutrophils ◽  
Traditional Role ◽  
Functional Changes ◽  
The Public ◽  
Age Related

All immune cells are affected by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. The effect of aging on cells of the adaptive immune system is well documented. In contrast, knowledge concerning age-related defects of polymorphonuclear neutrophils (PMN) is limited. During the past decade, it has become evident that in addition to their traditional role as phagocytes, neutrophils are able to secrete a wide array of immunomodulating molecules. Their importance is underlined by the finding that genetic defects that lead to neutropenia increase susceptibility to infections. Whereas there is consistence about the constant circulating number of PMN throughout aging, the abilities of tissue infiltration, phagocytosis, and oxidative burst of PMN from aged donors are discussed controversially. Furthermore, there are numerous discrepancies betweenin vivoandin vitroresults, as well as between results for murine and human PMN. Most of the reported functional changes can be explained by defective signaling pathways, but further research is required to get a detailed insight into the underlying molecular mechanisms. This could form the basis for drug development in order to prevent or treat age-related diseases, and thus to unburden the public health systems.

In vivo maximal fascicle-shortening velocity during plantar flexion in humans

2015 ◽  
Vol 119 (11) ◽  
pp. 1262-1271 ◽  
Author(s):  
Hugo Hauraix ◽  
Antoine Nordez ◽  
Gaël Guilhem ◽  
Giuseppe Rabita ◽  
Sylvain Dorel
Keyword(s):  
Angular Velocity ◽  
Fiber Type ◽  
Plantar Flexion ◽  
Load Condition ◽  
Ultrasound Images ◽  
Maximal Velocity ◽  
Shortening Velocity ◽  
Hill Model ◽  
Angular Velocities

Interindividual variability in performance of fast movements is commonly explained by a difference in maximal muscle-shortening velocity due to differences in the proportion of fast-twitch fibers. To provide a better understanding of the capacity to generate fast motion, this study aimed to 1) measure for the first time in vivo the maximal fascicle-shortening velocity of human muscle; 2) evaluate the relationship between angular velocity and fascicle-shortening velocity from low to maximal angular velocities; and 3) investigate the influence of musculo-articular features (moment arm, tendinous tissues stiffness, and muscle architecture) on maximal angular velocity. Ultrafast ultrasound images of the gastrocnemius medialis were obtained from 31 participants during maximal isokinetic and light-loaded plantar flexions. A strong linear relationship between fascicle-shortening velocity and angular velocity was reported for all subjects (mean R2 = 0.97). The maximal shortening velocity (VFmax) obtained during the no-load condition (NLc) ranged between 18.8 and 43.3 cm/s. VFmax values were very close to those of the maximal shortening velocity (Vmax), which was extrapolated from the F-V curve (the Hill model). Angular velocity reached during the NLc was significantly correlated with this VFmax ( r = 0.57; P < 0.001). This finding was in agreement with assumptions about the role of muscle fiber type, whereas interindividual comparisons clearly support the fact that other parameters may also contribute to performance during fast movements. Nevertheless, none of the biomechanical features considered in the present study were found to be directly related to the highest angular velocity, highlighting the complexity of the upstream mechanics that lead to maximal-velocity muscle contraction.

Thermal dependence of muscle function

1984 ◽  
Vol 247 (2) ◽  
pp. R217-R229 ◽  
Author(s):  
A. F. Bennett
Keyword(s):  
Fiber Type ◽  
Force Generation ◽  
Maximal Velocity ◽  
Body Temperatures ◽  
Temperature Dependent ◽  
Thermal Dependence ◽  
Mammalian Muscle ◽  
Rate Processes ◽  
Q10 Values

Maximal isometric forces during both twitch and tetanus are largely temperature independent in muscles from both endothermic and ectothermic vertebrates. Anuran muscle can develop maximal force at lower temperatures than mammalian muscle. Tetanic tension is maximal at normally experienced body temperatures in a variety of animals, but twitch tension seldom is. Thermal dependence of twitch tension varies with muscle fiber type: tension decreases with increasing temperature in fast-twitch muscles and remains constant in slow-twitch muscles. In contrast to the low temperature dependence of force generation, rates of development of tension (time to peak twitch tension and tetanic rise time) and maximal velocity of shortening and power output are markedly temperature dependent, with average temperature coefficient (Q10) values of 2.0-2.5 Q10 values for rate processes of anuran muscle are only slightly lower than those of mammalian muscle. High body temperatures permit rapid rates of muscle contraction; animals active at low body temperatures do not achieve the maximal rate performance their muscles are capable of delivering. Thermal acclimation or hibernation does not appear to result in compensatory adjustments in either force generation or rate processes. In vivo, dynamic processes dependent on contractile rates are positively temperature dependent, although with markedly lower Q10 values than those of isolated muscle. Static force application in vivo is nearly temperature independent.

scholarly journals Vitamin D supplementation blocks pulmonary structural and functional changes in a rat model of perinatal vitamin D deficiency

2014 ◽  
Vol 307 (11) ◽  
pp. L859-L867 ◽  
Author(s):  
Methap Yurt ◽  
Jie Liu ◽  
Reiko Sakurai ◽  
Ming Gong ◽  
Sumair M. Husain ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pulmonary Function ◽  
Rat Model ◽  
Childhood Asthma ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Lung Maturation ◽  
Functional Changes ◽  
Alveolar Epithelial

Whereas epidemiological data strongly link vitamin D (VD) deficiency to childhood asthma, the underlying molecular mechanisms remain unknown. Although VD is known to stimulate alveolar epithelial-mesenchymal interactions, promoting perinatal lung maturation, whether VD supplementation during this period protects against childhood asthma has not been demonstrated experimentally. Using an in vivo rat model, we determined the effects of perinatal VD deficiency on overall pulmonary function and the tracheal contraction as a functional marker of airway contractility. One month before pregnancy, rat dams were put on either a no cholecalciferol-added or a 250, 500, or 1,000 IU/kg cholecalciferol-added diet, which was continued throughout pregnancy and lactation. At postnatal day 21, offspring plasma 25(OH)D levels and pulmonary function (whole body plethysmography and tracheal contraction response to acetylcholine) were determined. 25(OH)D levels were lowest in the no cholecalciferol-supplemented group, increasing incrementally in response to cholecalciferol supplementation. Compared with the 250 and 500 IU/kg VD-supplemented groups, the no cholecalciferol-supplemented group demonstrated a significant increase in airway resistance following methacholine challenge. However, the cholecalciferol deficiency-mediated increase in tracheal contractility in the cholecalciferol-depleted group was only blocked by supplementation with 500 IU/kg cholecalciferol. Therefore, in addition to altering alveolar epithelial-mesenchymal signaling, perinatal VD deficiency also alters airway contractility, providing novel insights to asthma pathogenesis in perinatally VD-deficient offspring. Perinatal VD supplementation at 500 IU/kg appears to effectively block these effects of perinatal VD deficiency in the rat model used, providing a strong clinical rationale for effective perinatal VD supplementation for preventing childhood asthma.

scholarly journals Phosphate and acidosis act synergistically to depress peak power in rat muscle fibers

2014 ◽  
Vol 307 (10) ◽  
pp. C939-C950 ◽  
Author(s):  
Cassandra R. Nelson ◽  
Edward P. Debold ◽  
Robert H. Fitts
Keyword(s):  
Peak Power ◽  
Isometric Force ◽  
Muscle Fibers ◽  
Low Ph ◽  
Collective Effects ◽  
Fiber Types ◽  
Shortening Velocity ◽  
The Individual ◽  
Maximal Isometric Force

Skeletal muscle fatigue is characterized by the buildup of H+ and inorganic phosphate (Pi), metabolites that are thought to cause fatigue by inhibiting muscle force, velocity, and power. While the individual effects of elevated H+ or Pi have been well characterized, the effects of simultaneously elevating the ions, as occurs during fatigue in vivo, are still poorly understood. To address this, we exposed slow and fast rat skinned muscle fibers to fatiguing levels of H+ (pH 6.2) and Pi (30 mM) and determined the effects on contractile properties. At 30°C, elevated Pi and low pH depressed maximal shortening velocity ( Vmax) by 15% (4.23 to 3.58 fl/s) in slow and 31% (6.24 vs. 4.55 fl/s) in fast fibers, values similar to depressions from low pH alone. Maximal isometric force dropped by 36% in slow (148 to 94 kN/m2) and 46% in fast fibers (148 to 80 kN/m2), declines substantially larger than what either ion exerted individually. The strong effect on force combined with the significant effect on velocity caused peak power to decline by over 60% in both fiber types. Force-stiffness ratios significantly decreased with pH 6.2 + 30 mM Pi in both fiber types, suggesting these ions reduced force by decreasing the force per bridge and/or increasing the number of low-force bridges. The data indicate the collective effects of elevating H+ and Pi on maximal isometric force and peak power are stronger than what either ion exerts individually and suggest the ions act synergistically to reduce muscle function during fatigue.

Changes in force-velocity properties of trachealis due to oscillatory strains

2002 ◽  
Vol 92 (5) ◽  
pp. 1865-1872 ◽  
Author(s):  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Isometric Force ◽  
Dynamic Environment ◽  
Maximal Velocity ◽  
In Vitro Experiments ◽  
Functional Changes ◽  
Cross Bridge ◽  
Velocity Relationship ◽  
Before And After ◽  
Force Velocity

The physically dynamic environment of the lung constantly modulates the mechanical properties of airway smooth muscle. In vitro experiments have shown that contractility of the muscle is compromised by oscillatory strains, perhaps through disruption of cross-bridge interaction and organization of the contractile filaments. To understand the mechanism by which oscillation affects contractility, functional changes of the muscle in terms of force-velocity relationship were assessed before and after imposition of length oscillation in both relaxed and activated states. The oscillation protocol was designed to reduce isometric force by 15–20%, followed by measurement of force-velocity properties. Maximal velocity and power changed by +8 and −14%, respectively, after oscillation applied in the relaxed state and changed by −15 and −25%, respectively, after oscillation applied during contraction. A simple model of reduced activation could not account for the results; neither could the results be explained satisfactorily by the current cross-bridge theory of contraction. The results, however, could be explained if the possibility of reorganization of the contractile filaments due to oscillatory strains was considered.

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