Foci of segmentally contracted sarcomeres in trapezius muscle biopsy specimens in myalgic and nonmyalgic human subjects : preliminary results

Objective The myofascial trigger point hypothesis postulates that there are small foci of contracted sarcomeres in resting skeletal muscle. Only one example, in canine muscle, has been published previously. This study evaluated human muscle biopsies for foci of contracted sarcomeres. Setting The Departments of Rehabilitation Sciences and Physiotherapy at Ghent University, Ghent, Belgium. Subjects Biopsies from 28 women with or without trapezius myalgia were evaluated, 14 in each group. Methods Muscle biopsies were obtained from regions of taut bands in the trapezius muscle and processed for light and electron microscopy and for histochemical analysis. Examination of the biopsies was blinded as to group. Results A small number of foci of segmentally contracted sarcomeres were identified. One fusiform segmental locus involved the entire muscle fiber in tissue from a myalgic subject. Several transition zones from normal to contracted sarcomeres were found in both myalgic and nonmyalgic subjects. The distance between Z-lines in contracted sarcomeres was about 25–45% of the same distance in normal sarcomeres. Z-lines were disrupted and smeared in the contracted sarcomeres. Conclusions A small number of foci of segmentally contracted sarcomeres were found in relaxed trapezius muscle in human subjects, a confirmation of the only other example of spontaneous segmental contraction of sarcomeres (in a canine muscle specimen), consistent with the hypothesis of trigger point formation and with the presence of trigger point end plate noise

Instabilities in the transient response of muscle

We investigate the isometric transient response of muscle using a quantitative stochastic model of the actomyosin cycle based on the swinging lever-arm hypothesis. We first consider a single pair of filaments, and show that when values of parameters such as the lever-arm displacement and the crossbridge elasticity are chosen to provide effective energy transduction, the T2 curve (the tension recovered immediately after a step displacement) displays a region of negative slope. If filament compliance and the discrete nature of the binding sites are taken into account, the negative slope is diminished, but not eliminated. This implies that there is an instability in the dynamics of individual half-sarcomeres. However, when the symmetric nature of whole sarcomeres is taken into account, filament rearrangement becomes important during the transient: as tension is recovered, some half-sarcomeres lengthen while others shorten. This leads to a flat T2 curve, as observed experimentally. In addition, we investigate the isotonic transient response and show that for a range of parameter values the model displays damped oscillations, as recently observed in experiments on single muscle fibers. We conclude that it is essential to consider the collective dynamics of many sarcomeres, rather than the dynamics of a single pair of filaments, when interpreting the transient response of muscle.Comment: 11 pages, 11 figures, Submitted to Biophysical Journa

Surface plasmon resonance study of the actin-myosin sarcomeric complex and tubulin dimers

Biosensors based on the principle of surface plasmon resonance (SPR) detection were used to measure biomolecular interactions in sarcomeres and changes of the dielectric constant of tubulin samples with varying concentration. At SPR, photons of laser light efficiently excite surface plasmons propagating along a metal (gold) film. This resonance manifests itself as a sharp minimum in the reflection of the incident laser light and occurs at a characteristic angle. The dependence of the SPR angle on the dielectric permittivity of the sample medium adjacent to the gold film allows the monitoring of molecular interactions at the surface. We present results of measurements of cross-bridge attachment/detachment within intact mouse heart muscle sarcomeres and measurements on bovine tubulin molecules pertinent to cytoskeletal signal transduction models.Comment: Submitted to Journal of Modern Optics *Corresponding author: Andreas Mershin ([email protected]

The Calcineurin-FoxO-MuRF1 signaling pathway regulates myofibril integrity in cardiomyocytes.

Altered Ca2+ handling is often present in diseased hearts undergoing structural remodeling and functional deterioration. However, whether Ca2+ directly regulates sarcomere structure has remained elusive. Using a zebrafish ncx1 mutant, we explored the impacts of impaired Ca2+ homeostasis on myofibril integrity. We found that the E3 ubiquitin ligase murf1 is upregulated in ncx1-deficient hearts. Intriguingly, knocking down murf1 activity or inhibiting proteasome activity preserved myofibril integrity, revealing a MuRF1-mediated proteasome degradation mechanism that is activated in response to abnormal Ca2+ homeostasis. Furthermore, we detected an accumulation of the murf1 regulator FoxO in the nuclei of ncx1-deficient cardiomyocytes. Overexpression of FoxO in wild type cardiomyocytes induced murf1 expression and caused myofibril disarray, whereas inhibiting Calcineurin activity attenuated FoxO-mediated murf1 expression and protected sarcomeres from degradation in ncx1-deficient hearts. Together, our findings reveal a novel mechanism by which Ca2+ overload disrupts myofibril integrity by activating a Calcineurin-FoxO-MuRF1-proteosome signaling pathway

Synchronization of active mechanical oscillators by an inertial load

Motivated by the operation of myogenic (self-oscillatory) insect flight muscle, we study a model consisting of a large number of identical oscillatory contractile elements joined in a chain, whose end is attached to a damped mass-spring oscillator. When the inertial load is small, the serial coupling favors an antisynchronous state in which the extension of one oscillator is compensated by the contraction of another, in order to preserve the total length. However, a sufficiently massive load can sychronize the oscillators and can even induce oscillation in situations where isolated elements would be stable. The system has a complex phase diagram displaying quiescent, synchronous and antisynchrononous phases, as well as an unsual asynchronous phase in which the total length of the chain oscillates at a different frequency from the individual active elements.Comment: 5 pages, 4 figures, To appear in Phys. Rev. Let

Requirements for contractility in disordered cytoskeletal bundles

Actomyosin contractility is essential for biological force generation, and is well understood in highly organized structures such as striated muscle. Additionally, actomyosin bundles devoid of this organization are known to contract both in vivo and in vitro, which cannot be described by standard muscle models. To narrow down the search for possible contraction mechanisms in these systems, we investigate their microscopic symmetries. We show that contractile behavior requires non-identical motors that generate large enough forces to probe the nonlinear elastic behavior of F-actin. This suggests a role for filament buckling in the contraction of these bundles, consistent with recent experimental results on reconstituted actomyosin bundles.Comment: 10 pages, 6 figures; text shortene

Parameter interdependence and success of skeletal muscle modelling

In muscle and movement modelling it is almost invariably assumed that force actually exerted is determined by several independent factors. This review considers the fact that length force characteristics are not a relatively fixed property of muscle but should be considered the product of a substantial number of interacting factors. Level of activation and recruitment are influential factors in relation to aspects of muscle architecture. For the level of activation effects of its short term history (potentiation, fatigue in sustained contractions) have to be taken into account and are reviewed on the basis of recent experimental results as well as available literature. History is also an important determinant for the effect of length changes. This concept is introduced on the basis of recent experimental evidence as well as available literature. Regarding effects of muscle architecture, the concepts of primary and secondary distribution of fibre mean sarcomere length are introduced as well as effects of muscle geometry for mono- and bi-articular muscles on those distributions. Implications for motor control are discussed and the need for intramuscular coordination indicated

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities

The effect of complex training on horizontal power production in rugby union players : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science at Massey University

The use of strength and power training regimes is common place among elite and recreational athletes. However, the application of such methods as direct determinants of improvement in sporting performance is a controversial and much debated topic because the degree of transfer from the training exercise to the sporting application is unknown. In recent years combining strength and sport specific training methods into one training session (complex training) has been promoted as a method to enhance training transfer. The purpose of this project was to examine the effect of complex training on horizontal power production in rugby players. 9 participants completed two four week phases of training (complex and standard) in a randomized order. Participant performance in 5RM squat, horizontal force and horizontal power was tested prior to and at the end of each training phase. A number of significant improvements were observed following complex training: maximum slope of the horizontal force curve increased by 12.29 ±33.59%, maximum power increased by 15.13 ±7.49%, width of the power curve increased by 28.30 ±18.16%, and maximum velocity during the horizontal power test improved by 20.63 ±14.21%. The improvements were significantly different from the respective standard training measures (p ≤.05). It is concluded that power gains were a product of an enhanced ability to produce force at higher velocities. No significant weight gain or significant improvement in 5RM force production was associated with the improvement in maximum power. Therefore it is inferred that neural mechanisms accounted for the difference following complex training. The results presented here suggest that complex training not only improves horizontal power production but also transfers performance improvements to an untrained task by improving the rate of force development in the horizontal force condition. It appears that the complex training regime has in some way created a persistent change in the control mechanisms regulating the performance of both the horizontal strength and power conditions