Decrease In Force Production Research Articles

Age-related changes affect rat rotator cuff muscle function

The influence of age on rotator cuff function and muscle structure remains poorly understood. We hypothesize that normal aging influences rotator cuff function, muscle structure, and regulatory protein expression in an established rat model of aging. Seventeen rats were obtained from the National Institute on Aging. The supraspinatus muscles in 11 middle-aged (12 months old) and 6 old (28 months old) rats were studied for age-related changes in rotator cuff neuromuscular function by in vivo muscle force testing and electromyography (EMG). Changes in muscle structure and molecular changes were assessed with quantitative immunohistochemistry for myogenic determination factor 1 (MyoD) and myogenic factor 5 (Myf5) expression. Old animals revealed significantly decreased peak tetanic muscle force at 0.5 N and 0.7 N preload tension (P < .05). The age of the animal accounted for 20.9% of variance and significantly influenced muscle force (P = .026). Preload tension significantly influenced muscle force production (P < .001) and accounted for 12.7% of total variance. There was regional heterogeneity in maximal compound motor action potential (CMAP) amplitude in the supraspinatus muscle; the proximal portion had a significantly higher CMAP than the middle and distal portions (P < .05). The expression of muscle regulatory factors MyoD and Myf5 was significantly decreased in old animals compared with middle-aged animals (P < .05). The normal aging process in this rat model significantly influenced contractile strength of the supraspinatus muscle and led to decreased expression of muscle regulatory factors. High preload tensions led to a significant decrease in force production in both middle-aged and old animals.

Targeted inhibition of TGF-β results in an initial improvement but long-term deficit in force production after contraction-induced skeletal muscle injury

Transforming growth factor-β (TGF-β) is a proinflammatory cytokine that regulates the response of many tissues following injury. Previous studies in our lab have shown that treating muscles with TGF-β results in a dramatic accumulation of type I collagen, substantial fiber atrophy, and a marked decrease in force production. Because TGF-β promotes atrophy and fibrosis, our objective was to investigate whether the inhibition of TGF-β after injury would enhance the recovery of muscle following injury. We hypothesized that inhibiting TGF-β after contraction-induced injury would improve the functional recovery of muscles by preventing muscle fiber atrophy and weakness, and by limiting the accumulation of fibrotic scar tissue. To test this hypothesis, we induced an injury using a series of in situ lengthening contractions to extensor digitorum longus muscles of mice treated with either a bioneutralizing antibody against TGF-β or a sham antibody. Compared with controls, muscles from mice receiving TGF-β inhibitor showed a greater recovery in force 3 days and 7 days after injury but had a decrease in force compared with controls at the 21-day time point. The early enhancement in force in the TGF-β inhibitor group was associated with an initial improvement in tissue morphology, but, at 21 days, while the control group was fully recovered, the TGF-β inhibitor group displayed an irregular extracellular matrix and an increase in atrogin-1 gene expression. These results indicate that the inhibition of TGF-β promotes the early recovery of muscle function but is detrimental overall to full muscle recovery following moderate to severe muscle injuries.

Selective inhibition of ATPase activity during contraction alters the activation of p38 MAP kinase isoforms in skeletal muscle

Muscle contractions strongly activate p38 MAP kinases, but the precise contraction-associated sarcoplasmic event(s) (e.g., force production, energetic demands, and/or calcium cycling) that activate these kinases are still unclear. We tested the hypothesis that during contraction the phosphorylation of p38 isoforms is sensitive to the increase in ATP demand relative to ATP supply. Energetic demands were inhibited using N-benzyl-p-toluene sulphonamide (BTS, type II actomyosin) and cyclopiazonic acid (CPA, SERCA). Extensor digitorum longus muscles from Swiss Webster mice were incubated in Ringer's solution (37°C) with or without inhibitors and then stimulated at 10 Hz for 15 min. Muscles were immediately freeze-clamped for metabolite and Western blot analysis. BTS and BTS + CPA treatment decreased force production by 85%, as measured by the tension time integral, while CPA alone potentiated force by 310%. In control muscles, contractions resulted in a 73% loss of ATP content and a concomitant sevenfold increase in IMP content, a measure of sustained energetic imbalance. BTS or CPA treatment lessened the loss of ATP, but BTS + CPA treatment completely eliminated the energetic imbalance since ATP and IMP levels were nearly equal to those of non-stimulated muscles. The independent inhibition of cytosolic ATPase activities had no effect on contraction-induced p38 MAPK phosphorylation, but combined treatment prevented the increase in phosphorylation of the γ isoform while the α/β isoforms unaffected. These observations suggest that an energetic signal may trigger phosphorylation of the p38γ isoform and also may explain how contractions differentially activate signaling pathways.

Surface Potential and Electric Field Measurements in Plasma Actuators at Low Pressure

A plasma actuator was operated at pressures from 760 to 88 torr to determine the mechanisms leading to decreased force production at low pressures. The actuator was driven with a 5 kHz sine wave and a peak to peak voltage of 13.4 kV. A passive measurement technique called the capacitive V-dot probe was adapted to the actuator to resolve the spatiotemporal evolution of the surface potential and electric field on the dielectric surface. At low pressures up to 20 times more plasma by visual inspection is present than at atmospheric conditions. Average force production is calculated and shown to decrease at lower pressures due to the fact that up to 88% of the plasma is created in regions where the electric field is relatively weak. The calculated average body force shows a slight increase up to a pressure of 429 torr before trending to 0 at lower pressures in good qualitative agreement with experimental force measurements. Performing a power analysis shows that as pressure is decreased more power is used creating plasma rather than accelerating it, leading to a decrease in efficiency.

AGAT knockout mice provide an opportunity to titrate tissue creatine content

Creatine (Cr) plays an important role in muscle energy homeostasis via the Cr phosphokinase reaction (ATP + Cr ↔ ADP + CrP). Previous experimental models designed to investigate the importance of Cr and CrP content in skeletal muscle have used competitive inhibitors of Cr transport such as β-guanidinoproprionic acid (β-GPA) (Shoubridge et al. 1985) or have utilized whole body gene knockout of guanidine acetate methyltransferase (GAMT) (Schmidt et al. 2004), the second of two enzymes required for endogenous Cr biosynthesis. In both these models skeletal muscle Cr and CrP content is essentially absent, but both models are imperfect examples of blocking energy supply from the Cr phosphokinase reaction. For instance, β-GPA can be phosphorylated and utilised for energy partly compensating for a lack of PCr. Similarly, in the GAMT knockout model, guanidinoacetate (GAA) accumulates and this molecule can also be phosphorylated and utilised for energy by skeletal muscle. Recently, Skelton et al. (2011) generated a whole body Cr transporter knockout mouse model which resulted in depletion of skeletal muscle and brain Cr content. The utility of this model for precise regulation of skeletal muscle Cr content is currently questionable given that muscle may be able to synthesise its own Cr in situations where Cr content is compromised (McClure et al. 2007). In an article in this issue of The Journal of Physiology, the problem of the unwanted side reactions from β-GPA and GAMT knockout models was ingeniously resolved by Nabuurs et al. (2013) by generating a whole body arginine-glycine amidinotransferase (AGAT) gene knock out mouse model. AGAT catalyses the first reaction involved in Cr synthesis and when eliminated no endogenous Cr biosynthesis is possible. The only available source of Cr for these knockout animals is from the diet. Furthermore, no accumulation of GAA and its subsequent effects occur because GAA is produced by AGAT. With this model the researchers were able to manipulate the Cr and CrP content of skeletal muscle and the brain by simply altering the period in which the mice were fed a Cr free diet. The findings reported by Nabuurs et al. (2013) clearly demonstrate that skeletal muscle devoid of Cr and CrP is severely affected. In summary, they found that Cr deficient muscle was characterised by atrophy and decreased force production, and exhibited major metabolic disturbances including decreased resting ATP content, elevated inorganic phosphate levels, increased intramyocellular lipid droplets and mitochondrial dysfunction. Importantly, all these muscle disturbances could be reversed reasonably rapidly when the AGAT knockout mice were fed a diet supplemented with Cr. Another interesting part of the work reported by Nabuurs et al. (2013) was the research into the rates of Cr accumulation and loss from skeletal muscle and brain in the AGAT knockout mice. Their results clearly showed that Cr accumulation into Cr deficient skeletal muscle was surprisingly rapid occurring within 24 h, whilst brain Cr stores took up to 20 days to fully recover. On the flip side, the rate of Cr loss from skeletal muscle and brain in AGAT knockout mice pre-loaded with Cr and then starved of dietary Cr appeared to be similar taking several months to be completely lost from these tissues. The work by Nabuurs et al. (2013) has important implications for future research into the effects of Cr content on the function of various organs. For the first time there is an animal model in which tissue Cr content can be easily manipulated from depleted to fully loaded without the interference of side reactions. For example, the AGAT knockout mouse model could be used to titrate Cr and CrP content in brain to establish dose–function relationships for this organ. In addition, the AGAT knockout model could be employed to investigate the effect of manipulating Cr content on other Cr containing tissues such as the heart and testes. In summary, the AGAT knockout mouse model will provide an important tool to advance our current knowledge of the effects of Cr content on the in vivo regulation and function of Cr containing tissues.

Effects of static stretching following a dynamic warm-up on speed, agility and power

Static Stretching prior to sport has been shown to decrease force production in comparison to the increasing popularity of dynamic warm-up methods. However some athletes continue to use a bout of static stretching following dynamic methods. The purpose of this study was to investigate the effects on speed, agility and power following a period of additional static stretching following a dynamic warm-up routine. Twenty-five male University students who participated in team sports performed two warm-up protocols concentrating on the lower body one week apart through a randomised cross over design. The Dynamic Warm-up (DW) protocol used a series of specific progressive exercises lasting 10 minutes over a distance of 20m. The Dynamic Warm-up plus Static Stretching (DWS) protocol used the same DW protocol followed by a 5 minute period during which 7 muscle groups were stretched. Following each warm-up the subjects performed a countermovement vertical jump, 20m sprint and Illinois agility test, 1 minute apart. The results demonstrated no significant differences in speed, agility and jump performance following the two protocols DW and DWS. The study concludes that performing static stretching following a dynamic warm-up prior to performance does not affect speed, agility and vertical jump performance.

Structural limits on force production and shortening of smooth muscle

This study determined the factors that limit force production and shortening in two smooth muscles having very different relationships between active and passive force as a function of muscle length. The rat anococcygeus muscle develops active force over the range of lengths 0.2-2.0× the optimum length for force production (Lo). Passive tension due to extension of the resting muscle occurs only at lengths exceeding Lo. In contrast, the rabbit taenia coli develops force in the range of lengths 0.4-1.1 Lo, and passive force which is detectable at 0.56 Lo, increases to ~0.45 maximum active force at Lo, and increases sharply with further extension. The anococcygeus muscle can shorten to 0.2 Lo and the taenia coli to 0.4 Lo. Dynamic stiffness and energy usage at short muscle lengths suggest that the limit of shortening in the taenia coli, in contrast to the anococcygeus muscle, is not due to a failure of cross bridge interaction. Phosphorylation of the regulatory myosin light chains in intact muscles decreased to a small extent at short lengths compared to the decrease in force production. The differences in force production and the extent of shortening in the two muscles was maintained even when, following permeabilization, the myosin light chains were irreversibly phosphorylated with ATPγS, indicating that differences in activation played little, if any role. Ultrastructural studies on resting and activated muscles show that the taenia coli, which is rich in connective tissue (unlike the anococcygeus muscle) undergoes marked cellular twisting and contractile filament misalignment at short lengths with compression of the extracellular matrix. As a result, force is not transmitted in the longitudinal axis of the muscle, but is dissipated against an internal load provided by the compressed extracellular matrix. These observations on two very different normal smooth muscles reveal how differences in the relative contribution of active and passive structural elements determine their mechanical behavior, and how this is potentially modified by remodeling that occurs in disease and in response to changes in functional demand.

Neuromuscular fatigue in young and older men using constant or variable resistance

The purpose of the present study was to determine: (1) if different acute neuromuscular responses occur between constant versus variable external resistance machines, two commonly used resistance machines and (2) whether the potential differences in fatigability between young and older men influence the magnitude of acute response between these resistance machines. Twelve young men (28 ± 5 year) and 13 older men (65.4 ± 4 year) performed 15 × 1 repetition maximum and 5 × 10 repetitions isotonic knee extension resistance loadings with both constant and variable resistance (four loadings in total). Maximum isometric knee extension torque, superimposed twitch, resting twitch torque, maximal M wave properties, electromyograph, and blood lactate concentration measured the effects of loading. Concentric torque reduced to a greater extent during variable 15 × 1 versus constant loading in young men only (P < 0.05). While three out of the four loadings caused decreased voluntary activation in young men, only 15 × 1 using variable resistance caused reductions in older men (P < 0.05). 5 × 10 variable resistance loading significantly increased M wave duration and decreased EMG median frequency, which was not observed following constant resistance loading in both age groups. Acute decreases in force production were significantly greater in young men following all loading protocols (P < 0.05). Both young and older men showed indications of greater fatigue from variable resistance loadings. Differing muscle properties may have led to different magnitudes of fatigue between groups, and older subjects may benefit from specifically tailored training programs.

Fatiguing handgrip exercise alters maximal force-generating capacity of plantar-flexors

Exercise-induced fatigue causes changes within the central nervous system that decrease force production capacity in fatigued muscles. The impact on unrelated, non-exercised muscle performance is still unclear. The primary aim of this study was to examine the impact of a bilateral forearm muscle contraction on the motor function of the distal and unrelated ankle plantar-flexor muscles. The secondary aim was to compare the impact of maximal and submaximal forearm contractions on the non-fatigued ankle plantar-flexor muscles. Maximal voluntary contractions (MVC) of the forearm and ankle plantar-flexor muscles as well as voluntary activation (VA) and twitch torque of the ankle plantar-flexor muscles were assessed pre-fatigue and throughout a 10-min recovery period. Maximal (100 % MVC) and submaximal (30 % MVC) sustained isometric handgrip contractions caused a decreased handgrip MVC (to 49.3 ± 15.4 and 45.4 ± 11.4 % of the initial MVC for maximal and submaximal contraction, respectively) that remained throughout the 10-min recovery period. The fatigue protocols also caused a decreased ankle plantar-flexor MVC (to 77 ± 8.3 and 92.4 ± 6.2 % of pre-fatigue MVC for maximal and submaximal contraction, respectively) and VA (to 84.3 ± 15.7 and 97.7 ± 16.1 % of pre-fatigue VA for maximal and submaximal contraction, respectively). These results suggest central fatigue created by the fatiguing handgrip contraction translated to the performance of the non-exercised ankle muscles. Our results also show that the maximal fatigue protocol affected ankle plantar-flexor MVC and VA more severely than the submaximal protocol, highlighting the task-specificity of neuromuscular fatigue.

Myosin Kinetics Influence Force Depression in Drosophila Jump Muscle

Force Depression (FD), a history-dependent phenomenon observed in skeletal muscle, is characterized by a decrease in force production after active shortening compared to an isometric contraction at the corresponding final length. FD measured at steady-state (FDss) increases with larger shortening amplitudes, and decreases with increasing shortening rates. Furthermore, an increase in FDss is associated with a slower rate of force redevelopment following active shortening. Despite these experimental characterizations, the underlying mechanism(s) of FD remain unknown.

Changes in Running Kinematics, Kinetics, and Spring-Mass Behavior over a 24-h Run

This study investigated the changes in running mechanics and spring-mass behavior over a 24-h treadmill run (24TR). Kinematics, kinetics, and spring-mass characteristics of the running step were assessed in 10 experienced ultralong-distance runners before, every 2 h, and after a 24TR using an instrumented treadmill dynamometer. These measurements were performed at 10 km·h, and mechanical parameters were sampled at 1000 Hz for 10 consecutive steps. Contact and aerial times were determined from ground reaction force (GRF) signals and used to compute step frequency. Maximal GRF, loading rate, downward displacement of the center of mass, and leg length change during the support phase were determined and used to compute both vertical and leg stiffness. Subjects' running pattern and spring-mass behavior significantly changed over the 24TR with a 4.9% higher step frequency on average (because of a significantly 4.5% shorter contact time), a lower maximal GRF (by 4.4% on average), a 13.0% lower leg length change during contact, and an increase in both leg and vertical stiffness (+9.9% and +8.6% on average, respectively). Most of these changes were significant from the early phase of the 24TR (fourth to sixth hour of running) and could be speculated as contributing to an overall limitation of the potentially harmful consequences of such a long-duration run on subjects' musculoskeletal system. During a 24TR, the changes in running mechanics and spring-mass behavior show a clear shift toward a higher oscillating frequency and stiffness, along with lower GRF and leg length change (hence a reduced overall eccentric load) during the support phase of running.

Neuromuscular fatigue in healthy muscle: Underlying factors and adaptation mechanisms

Objectives This review aims to define the concept of neuromuscular fatigue and to present the current knowledge of the central and peripheral factors at the origin of this phenomenon. This review also addresses the literature that focuses on the mechanisms responsible for the adaption to neuromuscular fatigue. Method One hundred and eighty-two articles indexed in PubMed (1954–2010) have been considered. Results Neuromuscular fatigue has central and peripheral origins. Central fatigue, preponderant during long-duration, low-intensity exercises, may involve a drop in the central command (motor, cortex, motoneurons) elicited by the activity of cerebral neurotransmitters and muscular afferent fibers. Peripheral fatigue, associated with an impairment of the mechanisms from excitation to muscle contraction, may be induced by a perturbation of the calcium ion movements, an accumulation of phosphate, and/or a decrease of the adenosine triphosphate stores. To compensate for the consequent drop in force production, the organism develops several adaptation mechanisms notably implicating motor units. Conclusion Fatigue onset is associated with an alteration of the mechanisms involved in force production. Then, the interaction between central and peripheral mechanisms leads to a series of events that ultimately contribute to the observed decrease in force production.

Deletion of 1- 43 Amino Acids from the N-terminus of Myosin Essential Light Chain in Transgenic Mice Decreases Force Production by Reducing the Number of Myosin Cross-Bridges

The N-terminus of the myosin essential light chain (ELC) has been shown to regulate myosin motor function by binding to actin and thus influencing the cross-bridge cycling kinetics. However, the role of the N-terminus of ELC in the Ca2+-regulation and the muscle length-dependent aspects of cardiac contractile function are still to be determined. In this study, we used transgenic (Tg) mouse hearts expressing the human ventricular ELC wild-type (Tg-WT) or a 43 amino acid deletion mutant of the human ventricular ELC (Tg-Δ43) (Kazmierczak et al., JMB 387, 706-725, 2009). We simultaneously measured force and ATPase activity at various levels of Ca2+ -activation under isometric conditions and the length-dependent force responses during constant activation in detergent-skinned papillary muscle fibers from the Tg-Δ43 and Tg-WT mice. As was shown by Kazmierczak et al., force was significantly lower in fibers from Tg-Δ43 mice, which was comparable to the decrease in ATPase activity, resulting in a tension cost that was not significantly different from Tg-WT fibers. However, our current study on fibers from 5-month old female Tg-Δ43 mice shows a small but significantly higher Ca2+ sensitivity when compared to Tg-WT mice. In addition, the relationship between the maximal tension and stiffness demonstrates that the average force production per cross-bridge is not altered in Tg-Δ43 fibers. Our findings demonstrate that the reduction in the Ca2+ -activated force in Tg-Δ43 fibers is most likely due to a decreased number of force-bearing myosin cross-bridges. Further studies are focused on gaining a better understanding of the functional significance of the N-terminus of cardiac ELC in mediating mechanisms of contractile activation.Supported by NIH-(MC) and NIH-HL071778 (DSC).

Reversal of the late phase of spike frequency adaptation in cat spinal motoneurons during fictive locomotion.

In spinal motoneurons, late spike frequency adaptation (SFA) is defined as the slowing of the firing rate over tens of seconds and can be seen during sustained or intermittent current injection. Although the function of late SFA is not known, it may result in a decrease in force production over time, or muscle fatigue. Because locomotion can persist for long periods of time without fatigue, late SFA was studied using intracellular recordings from adult cat motoneurons during fictive locomotion. Of eight lumbar motoneurons studied, all showed late adaptation during control conditions, but none demonstrated late adaptation during locomotor activity. The most consistent properties that correlated with the presence or absence of late SFA were those related to availability of fast, inactivating sodium channels, particularly action potential rate of rise. Evidence of the reversal of late SFA during locomotion was present for several minutes following locomotor trials, consistent with the suggestion that SFA is modulated through slow metabotropic pathways. The abolition of late adaptation in spinal motoneurons during fictive locomotion is an example of a state-dependent change in the "intrinsic" properties of mammalian motoneurons. This change contributes to increased excitability of motoneurons during locomotion and results in robust firing during sustained locomotion.

Clenbuterol and formoterol decrease force production in isolated intact mouse skeletal muscle fiber bundles through a β2-adrenoceptor-independent mechanism

Although the acute actions of short-acting β(2)-adrenoceptor agonists on force production in isolated mammalian skeletal muscle fibers have been the subject of a number of previous studies, those of long-acting β(2)-adrenoceptor agonists have never been investigated. Also, little is known about the cellular signal transduction events mediating their actions. Therefore, the primary aim of this study was to investigate the acute effects of treatment of mouse fast- and slow-twitch muscle fiber bundles with clenbuterol, formoterol, and salbutamol. Both clenbuterol and salbutamol increased the levels of cAMP in both fiber types, and this effect was reversed by ICI-118551. On the other hand, clenbuterol and formoterol decreased force production in both fiber types. They also increased the phosphorylation of phospholamban and β(2)-adrenoceptors in slow-twitch fiber bundles, and their effects were insensitive to propranolol, ICI-118551, and 14-22 amide. In contrast, salbutamol increased force production in both fiber types. It also increased the phosphorylation of β(2)-adrenoceptors in slow-twitch fibers only, but it had no effect on the phosphorylation of phospholamban in either fiber type. These effects were reversed by propranolol and ICI-118551 but not by 14-22 amide. Instead, 14-22 amide further potentiated the effects of salbutamol on force. In summary, long- and short-acting β(2)-adrenoceptor agonists have opposite effects on force production in isolated intact mouse skeletal muscle fiber bundles. From these results, we suggest that the acute actions of short-acting β(2)-adrenoceptor agonists on force production in mammalian skeletal muscles are mediated through the β(2)-adrenoceptor, whereas those of long-acting β(2)-adrenoceptor agonists are not.

Efficacy of tart cherry juice in reducing muscle pain during running: a randomized controlled trial

BackgroundLong distance running causes acute muscle damage resulting in inflammation and decreased force production. Endurance athletes use NSAIDs during competition to prevent or reduce pain, which carries the risk of adverse effects. Tart cherries, rich in antioxidant and anti-inflammatory properties, may have a protective effect to reduce muscle damage and pain during strenuous exercise. This study aimed to assess the effects of tart cherry juice as compared to a placebo cherry drink on pain among runners in a long distance relay race.MethodsThe design was a randomized, double blind, placebo controlled trial. Fifty-four healthy runners (36 male, 18 female; 35.8 ± 9.6 yrs) ran an average of 26.3 ± 2.5 km over a 24 hour period. Participants ingested 355 mL bottles of tart cherry juice or placebo cherry drink twice daily for 7 days prior to the event and on the day of the race. Participants assessed level of pain on a standard 100 mm Visual Analog Scale (VAS) at baseline, before the race, and after the race.ResultsWhile both groups reported increased pain after the race, the cherry juice group reported a significantly smaller increase in pain (12 ± 18 mm) compared to the placebo group (37 ± 20 mm) (p < .001). Participants in the cherry juice group were more willing to use the drink in the future (p < 0.001) and reported higher satisfaction with the pain reduction they attributed to the drink (p < 0.001).ConclusionsIngesting tart cherry juice for 7 days prior to and during a strenuous running event can minimize post-run muscle pain.

H2-Helical Region of Cardiac Troponin T Contributes to Length-Dependent Regulation of Cardiac Contractile Activation

An alpha-helical region of cardiac troponin T, cH2(T), is centrally positioned in the core domain of the troponin complex (Takeda et al., Nature 2003 vol.424(6944):p35-41). cH2(T)-troponin I and cH2(T)-troponin C interactions have been illustrated through biochemical studies and visualized in the crystal structure of the core domain of human cardiac troponin, suggesting an important regulatory role for cH2(T). However, little is known about how the cardiac-specific structure of cH2(T) relates to cardiac-specific contractile function. To better understand the functional significance of cH2(T), we created a chimeric rat cardiac troponin T (TnT) in which cH2(T) was replaced by the corresponding helical region of rat slow skeletal TnT and studied how replacement of native TnT with chimeric TnT affected contractile function of rat cardiac muscle. We measured isometric force, ATPase activity, and length-dependent contractile dynamics in detergent skinned papillary muscle bundles reconstituted with either wild-type or chimeric TnT, held at either sarcomere length (SL) 2.0 μm or 2.2 μm. Preliminary studies suggest that the SL dependence of Ca2+-activated maximal force production and tension cost was depressed in bundles containing chimeric TnT. For example, bundles containing the chimeric TnT showed an 8.4% decrease in force production when SL was decreased from 2.2 μm to 2.0 μm, whereas bundles containing the wild-type TnT showed a 43.9% decrease in force production. In addition, length-dependent contractile dynamics were significantly altered in bundles containing the chimeric TnT. For example, the length-dependent rate constant of crossbridge recruitment was slower, and the rate constant of crossbridge detachment was faster in bundles containing the chimeric TnT. Thus, our data suggest that cH2(T) plays a role in cardiac-specific length-mediated myofilament activation, an important mechanism underlying the Frank-Starling relationship.

Mechanisms of excitation-contraction uncoupling relevant to activity-induced muscle fatigueThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

If the free [Ca2+] in the cytoplasm of a skeletal muscle fiber is raised substantially for a period of seconds to minutes or to high levels just briefly, it leads to disruption of the normal excitation-contraction (E-C) coupling process and a consequent long-lasting decrease in force production. It appears that the disruption to the coupling occurs at the triad junction, where the voltage-sensor molecules (dihydropyridine receptors) normally interact with and open the Ca2+ release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum (SR). This disruption results in inadequate release of SR Ca2+ upon stimulation. Such E-C uncoupling may underlie the long-duration low-frequency fatigue that can occur after various types of exercise, as well as possibly being a contributing factor to the muscle weakness in certain muscle diseases. The process or processes causing the disruption of the coupling between the voltage sensors and the release channels is not known with certainty, but might be associated with structural changes at the triad junction, possibly caused by activation of the Ca2+-dependent protease, micro-calpain.

Go rinse your mouth: a novel way to improve endurance performance?

Go rinse your mouth: a novel way to improve endurance performance?

Is a progressive recruitment of muscle fibers required for the development of the slow component of V̇o2 kinetics?

to the editor: Zoladz et al. ([6][1]) present a reanalysis of data taken from their previous study ([3][2]) and they evaluated the oxygen uptake (Vo2) response in isolated dog gastrocnemius in situ during 4-min of contractions at ∼60–70% of peak Vo2. In their preparation, all muscle fibers