Effects of membrane depolarization and changes in extracellular [K+] on the Ca2+ transients of fast skeletal muscle fibers. Implications for muscle fatigue

Repetitive activation of skeletal muscle fibers leads to a reduced transmembrane K+ gradient. The resulting membrane depolarization has been proposed to play a major role in the onset of muscle fatigue. Nevertheless, raising the extracellular K+ (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{K}}_{\text{o}}^{ + }$$\end{document}) concentration (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$[ {\text{K}}^{ + } ]_{\text{o}}$$\end{document}) to 10 mM potentiates twitch force of rested amphibian and mammalian fibers. We used a double Vaseline gap method to simultaneously record action potentials (AP) and Ca2+ transients from rested frog fibers activated by single and tetanic stimulation (10 pulses, 100 Hz) at various \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$[ {\text{K}}^{ + } ]_{\text{o}}$$\end{document} and membrane potentials. Depolarization resulting from current injection or raised \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$[ {\text{K}}^{ + } ]_{\text{o}}$$\end{document} produced an increase in the resting [Ca2+]. Ca2+ transients elicited by single stimulation were potentiated by depolarization from −80 to −60 mV but markedly depressed by further depolarization. Potentiation was inversely correlated with a reduction in the amplitude, overshoot and duration of APs. Similar effects were found for the Ca2+ transients elicited by the first pulse of 100 Hz trains. Depression or block of Ca2+ transient in response to the 2nd to 10th pulses of 100 Hz trains was observed at smaller depolarizations as compared to that seen when using single stimulation. Changes in Ca2+ transients along the trains were associated with impaired or abortive APs. Raising \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$[ {\text{K}}^{ + } ]_{\text{o}}$$\end{document} to 10 mM potentiated Ca2+ transients elicited by single and tetanic stimulation, while raising \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$[ {\text{K}}^{ + } ]_{\text{o}}$$\end{document} to 15 mM markedly depressed both responses. The effects of 10 mM \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{K}}_{\text{o}}^{ + }$$\end{document} on Ca2+ transients, but not those of 15 mM \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{K}}_{\text{o}}^{ + }$$\end{document}, could be fully reversed by hyperpolarization. The results suggests that the force potentiating effects of 10 mM \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{K}}_{\text{o}}^{ + }$$\end{document} might be mediated by depolarization dependent changes in resting [Ca2+] and Ca2+ release, and that additional mechanisms might be involved in the effects of 15 mM \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{K}}_{\text{o}}^{ + }$$\end{document} on force generation

Joint-action coordination in transferring objects

Here we report a study of joint-action coordination in transferring objects. Fourteen dyads were asked to repeatedly reposition a cylinder in a shared workspace without using dialogue. Variations in task constraints concerned the size of the two target regions in which the cylinder had to be (re)positioned and the size and weight of the transferred cylinder. Movements of the wrist, index finger and thumb of both actors were recorded by means of a 3D motion-tracking system. Data analyses focused on the interpersonal transfer of lifting-height and movement-speed variations. Whereas the analyses of variance did not reveal any interpersonal transfer effects targeted data comparisons demonstrated that the actor who fetched the cylinder from where the other actor had put it was systematically less surprised by cylinder-weight changes than the actor who was first confronted with such changes. In addition, a moderate, accuracy-constraint independent adaptation to each other’s movement speed was found. The current findings suggest that motor resonance plays only a moderate role in collaborative motor control and confirm the independency between sensorimotor and cognitive processing of action-related information

Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle

The Effectiveness of RNAi in Caenorhabditis elegans Is Maintained during Spaceflight

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Overcoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; however the efficacy of RNAi in space is currently unknown. METHODS: Caenorhabditis elegans were prepared in liquid media on Earth using standard techniques and treated acutely with RNAi or a vector control upon arrival in Low Earth Orbit. After culturing during 4 and 8 d spaceflight, experiments were stopped by freezing at -80°C until analysis by mRNA and microRNA array chips, microscopy and Western blot on return to Earth. Ground controls (GC) on Earth were simultaneously grown under identical conditions. RESULTS: After 8 d spaceflight, mRNA expression levels of components of the RNAi machinery were not different from that in GC (e.g., Dicer, Argonaute, Piwi; P>0.05). The expression of 228 microRNAs, of the 232 analysed, were also unaffected during 4 and 8 d spaceflight (P>0.05). In spaceflight, RNAi against green fluorescent protein (gfp) reduced chromosomal gfp expression in gonad tissue, which was not different from GC. RNAi against rbx-1 also induced abnormal chromosome segregation in the gonad during spaceflight as on Earth. Finally, culture in RNAi against lysosomal cathepsins prevented degradation of the muscle-specific α-actin protein in both spaceflight and GC conditions. CONCLUSIONS: Treatment with RNAi works as effectively in the space environment as on Earth within multiple tissues, suggesting RNAi may provide an effective tool for combating spaceflight-induced pathologies aboard future long-duration space missions. Furthermore, this is the first demonstration that RNAi can be utilised to block muscle protein degradation, both on Earth and in space.This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Japan Society for the Promotion of Science, and “Ground-Based Research Announcement for Space Utilization” promoted by the Japan Space Forum. TE was supported by the Medical Research Council UK (G0801271). NJS was supported by the National Institutes of Health (NIH NIAMS ARO54342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Predicting the Effect of Surface Texture on the Qualitative Form of Prehension

Reach-to-grasp movements change quantitatively in a lawful (i.e. predictable) manner with changes in object properties. We explored whether altering object texture would produce qualitative changes in the form of the precontact movement patterns. Twelve participants reached to lift objects from a tabletop. Nine objects were produced, each with one of three grip surface textures (high-friction, medium-friction and low-friction) and one of three widths (50 mm, 70 mm and 90 mm). Each object was placed at three distances (100 mm, 300 mm and 500 mm), representing a total of 27 trial conditions. We observed two distinct movement patterns across all trials—participants either: (i) brought their arm to a stop, secured the object and lifted it from the tabletop; or (ii) grasped the object ‘on-the-fly’, so it was secured in the hand while the arm was moving. A majority of grasps were on-the-fly when the texture was high-friction and none when the object was low-friction, with medium-friction producing an intermediate proportion. Previous research has shown that the probability of on-the-fly behaviour is a function of grasp surface accuracy constraints. A finger friction rig was used to calculate the coefficients of friction for the objects and these calculations showed that the area available for a stable grasp (the ‘functional grasp surface size’) increased with surface friction coefficient. Thus, knowledge of functional grasp surface size is required to predict the probability of observing a given qualitative form of grasping in human prehensile behaviour

The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55–92 Years): a double-blind randomized study

<p>Abstract</p> <p>Background</p> <p>Ageing is associated with a significant reduction in skeletal muscle carnosine which has been linked with a reduction in the buffering capacity of muscle and in theory, may increase the rate of fatigue during exercise. Supplementing beta-alanine has been shown to significantly increase skeletal muscle carnosine. The purpose of this study, therefore, was to examine the effects of ninety days of beta-alanine supplementation on the physical working capacity at the fatigue threshold (PWC_FT) in elderly men and women.</p> <p>Methods</p> <p>Using a double-blind placebo controlled design, twenty-six men (n = 9) and women (n = 17) (age ± SD = 72.8 ± 11.1 yrs) were randomly assigned to either beta-alanine (BA: 800 mg × 3 per day; n = 12; CarnoSyn™) or Placebo (PL; n = 14) group. Before (pre) and after (post) the supplementation period, participants performed a discontinuous cycle ergometry test to determine the PWC_FT.</p> <p>Results</p> <p>Significant increases in PWC_FT(28.6%) from pre- to post-supplementation were found for the BA treatment group (p < 0.05), but no change was observed with PL treatment. These findings suggest that ninety days of BA supplementation may increase physical working capacity by delaying the onset of neuromuscular fatigue in elderly men and women.</p> <p>Conclusion</p> <p>We suggest that BA supplementation, by improving intracellular pH control, improves muscle endurance in the elderly. This, we believe, could have importance in the prevention of falls, and the maintenance of health and independent living in elderly men and women.</p

Shoulder muscle endurance: the development of a standardized and reliable protocol

<p>Abstract</p> <p>Background</p> <p>Shoulder muscle fatigue has been proposed as a possible link to explain the association between repetitive arm use and the development of rotator cuff disorders. To our knowledge, no standardized clinical endurance protocol has been developed to evaluate the effects of muscle fatigue on shoulder function. Such a test could improve clinical examination of individuals with shoulder disorders. Therefore, the purpose of this study was to establish a reliable protocol for objective assessment of shoulder muscle endurance.</p> <p>Methods</p> <p>An endurance protocol was developed on a stationary dynamometer (Biodex System 3). The endurance protocol was performed in isotonic mode with the resistance set at 50% of each subject's peak torque as measured for shoulder external (ER) and internal rotation (IR). Each subject performed 60 continuous repetitions of IR/ER rotation. The endurance protocol was performed by 36 healthy individuals on two separate occasions at least two days apart. Maximal isometric shoulder strength tests were performed before and after the fatigue protocol to evaluate the effects of the endurance protocol and its reliability. Paired <it>t</it>-tests were used to evaluate the reduction in shoulder strength due to the protocol, while intraclass correlation coefficients (ICC) and minimal detectable change (MDC) were used to evaluate its reliability.</p> <p>Results</p> <p>Maximal isometric strength was significantly decreased after the endurance protocol (<it>P </it>< 0.001). The total work performed during the last third of the protocol was significantly less than the first third of the protocol (P < 0.05). The test-retest reliability of the post-fatigue strength measures was excellent (ICC >0.84).</p> <p>Conclusions</p> <p>Changes in muscular performance observed during and after the muscular endurance protocol suggests that the protocol did result in muscular fatigue. Furthermore, this study established that the resultant effects of fatigue of the proposed isotonic protocol were reproducible over time. The protocol was performed without difficulty by all volunteers and took less than 10 minutes to perform, suggesting that it might be feasible for clinical practice. This protocol could be used to induce local muscular fatigue in order to evaluate the effects of fatigue on shoulder kinematics or to evaluate changes in shoulder muscle endurance following rehabilitation.</p