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Κυριακή 9 Ιουνίου 2019

Muscle Research and Cell Motility

Skeletal muscle fibre swelling contributes to force depression in rats and humans: a mechanically-skinned fibre study

Abstract

This study investigated the effects of fibre swelling on force production in rat and human skinned muscle fibres, using osmotic compression to reverse the fibre swelling. In mechanically-skinned fibres, the sarcolemma is removed but normal excitation–contraction coupling remains functional. Force responses in mechanically-skinned fibres were examined with and without osmotic compression by polyvinylpyrrolidone 40 kDa (PVP-40) or Dextran 500 kDa (dextran). Fibre diameter increased to 116 ± 2% (mean ± SEM) when rat skinned type II fibres were immersed in the standard intracellular solution, but remained close to the in situ size when 3% (mass/volume) PVP-40 or 4% Dextran were present. Myofibrillar Ca2+ sensitivity, as indicated by pCa50 (− log10[Ca2+] at half-maximal force), was increased in 4% Dextran (0.072 ± 0.007 pCa50 shift), but was not significantly changed in 3% PVP-40. Maximum Ca2+-activated force increased slightly to 103 ± 1% and 104 ± 1% in PVP-40 and Dextran, respectively. Both tetanic and depolarization-induced force responses in rat skinned type II fibres, elicited by electrical stimulation and ion substitution respectively, were increased by ~ 10 to 15% when the fibres were returned to their normal in situ diameter by addition of PVP-40 or Dextran. Interestingly, the potentiation of these force responses in PVP-40 was appreciably greater than could be explained by potentiation of myofibrillar function alone. These results indicate that muscle fibre swelling, as can occur with intense exercise, decreases evoked force responses by reducing both the Ca2+-sensitivity of the contractile apparatus properties and Ca2+ release from the sarcoplasmic reticulum.



The role of the microcirculation in muscle function and plasticity

Abstract

It is widely acknowledged that maintenance of muscle, size, strength and endurance is necessary for quality of life and the role that skeletal muscle microcirculation plays in muscle health is becoming increasingly clear. Here we discuss the role that skeletal muscle microcirculation plays in muscle function and plasticity. Besides the density of the capillary network, also the distribution of capillaries is crucial for adequate muscle oxygenation. While capillaries are important for oxygen delivery, the capillary supply to a fibre is related to fibre size rather than oxidative capacity. This link between fibre size and capillary supply is also reflected by the similar time course of hypertrophy and angiogenesis, and the cross-talk between capillaries and satellite cells. A dense vascular network may in fact be more important for a swift repair of muscle damage than the abundance of satellite cells and a lower capillary density may also attenuate the hypertrophic response. Capillary rarefaction does not only occur during ageing, but also during conditions as chronic heart failure, where endothelial apoptosis has been reported to precede muscle atrophy. It has been suggested that capillary rarefaction precedes sarcopenia. If so, stimulation of angiogenesis by for instance endurance training before a hypertrophic stimulus may enhance the hypertrophic response. The microcirculation may thus well be a little-explored target to improve muscle function and the success of rehabilitation programmes during ageing and chronic diseases.



The giant titin: how to evaluate its role in cardiomyopathies

Abstract

Titin, the largest protein known, has attracted a lot of interest in the cardiovascular field in recent years, since the discovery that truncating variants in titin are commonly found in patients with dilated cardiomyopathy. This review will discuss the contribution of variants in titin to inherited cardiac conditions (cardiomyopathies) and how model systems, such as animals and cellular systems, can help to provide insights into underlying disease mechanisms. It will also give an outlook onto exciting technological developments, such as in the field of CRISPR, which may facilitate future research on titin variants and their contributions to cardiomyopathies.



Insights into myosin regulatory and essential light chains: a focus on their roles in cardiac and skeletal muscle function, development and disease

Abstract

The activity of cardiac and skeletal muscles depends upon the ATP-coupled actin–myosin interactions to execute the power stroke and muscle contraction. The goal of this review article is to provide insight into the function of myosin II, the molecular motor of the heart and skeletal muscles, with a special focus on the role of myosin II light chain (MLC) components. Specifically, we focus on the involvement of myosin regulatory (RLC) and essential (ELC) light chains in striated muscle development, isoform appearance and their function in normal and diseased muscle. We review the consequences of isoform switching and knockout of specific MLC isoforms on cardiac and skeletal muscle function in various animal models. Finally, we discuss how dysregulation of specific RLC/ELC isoforms can lead to cardiac and skeletal muscle diseases and summarize the effects of most studied mutations leading to cardiac or skeletal myopathies.



The discovery of actin: "to see what everyone else has seen, and to think what nobody has thought"*

Abstract

Actin is among the most highly abundant and ubiquitous proteins in eukaryotic cells. The structure, dynamics and functional diversity of actin have continued to mesmerise cell and molecular biologists, biophysicists and physiologists for more than three quarters of a century. The discovery and initial characterization of actin, which took place in the laboratory of Albert Szent-Györgyi by Ilona Banga and Brúnó F. Straub during the second world war in Hungary, is a remarkable and inspiring moment in the history of science. Many of the early thoughts and ideas on the properties and functions of actin and particularly actomyosin, which are referred to in this short historical overview, resonate freshly even today.



Actin–tropomyosin distribution in non-muscle cells

Abstract

The interactions of cytoskeletal actin filaments with myosin family motors are essential for the integrity and function of eukaryotic cells. They support a wide range of force-dependent functions. These include mechano-transduction, directed transcellular transport processes, barrier functions, cytokinesis, and cell migration. Despite the indispensable role of tropomyosins in the generation and maintenance of discrete actomyosin-based structures, the contribution of individual cytoskeletal tropomyosin isoforms to the structural and functional diversification of the actin cytoskeleton remains a work in progress. Here, we review processes that contribute to the dynamic sorting and targeted distribution of tropomyosin isoforms in the formation of discrete actomyosin-based structures in animal cells and their effects on actin-based motility and contractility.



Troponin structure and function: a view of recent progress

Abstract

The molecular mechanism by which Ca2+ binding and phosphorylation regulate muscle contraction through Troponin is not yet fully understood. Revealing the differences between the relaxed and active structure of cTn, as well as the conformational changes that follow phosphorylation has remained a challenge for structural biologists over the years. Here we review the current understanding of how Ca2+, phosphorylation and disease-causing mutations affect the structure and dynamics of troponin to regulate the thin filament based on electron microscopy, X-ray diffraction, NMR and molecular dynamics methodologies.



The role of satellite and other functional cell types in muscle repair and regeneration

Abstract

Skeletal muscles play essential roles in physiological processes, including motor function, energy hemostasis, and respiration. Skeletal muscles also have the capacity to regenerate after injury. Regeneration of skeletal muscle is an extremely complex biological process, which involves multiple cell types. Skeletal muscle stem cells (also known as satellite cells; SCs) are crucial for the development, growth, maintenance and repair of the skeletal muscle. Cell fates and function have been extensively studied in the context of skeletal muscle regeneration. In addition to SCs, other cell types, such as fibro-adipogenic precursors (FAPs), endothelial cells, fibroblasts, pericytes and certain immune cells, play important regulatory roles during skeletal muscle regeneration. In this review, we summarize and discuss the current research progress on the different cell types and their respective functions in skeletal muscle regeneration and repair.



An acoustic myography functional assessment of cerebral palsy subjects compared to healthy controls during physical exercise

Abstract

Individuals with cerebral palsy (CP) participate in reduced levels of physical activity and spend an increased amount of time in a sedentary state compared with healthy control subjects. Whether this in part can be explained by impaired muscle function is still unclear. The aim of the present study was to elucidate differences in muscle fibre recruitment during treadmill exercise between CP subjects and healthy age-, sex- and BMI-matched controls. This is a case–control study. Acoustic myography (AMG), a method recording fibre use and efficiency from contracting muscles, was applied during a period of treadmill exercise. The recorded AMG parameters revealed that the CP subjects had a significantly lower initial S-score (spatial summation) than the controls (P < 0.01). However, the T-score (temporal summation) and the E-score (efficiency) showed no significant differences between individuals with CP and the healthy control subjects. The present findings indicate that CP subjects use a higher degree of spatial summation (more fibres recruited) to keep up the same speed during treadmill exercise when compared to healthy matched control subjects. Our results suggest that individuals with CP have a tendency to recruit far more muscle fibres during bouts of exercise than healthy individuals. This may partly explain why CP subjects experience premature fatigue.



Proteomic profiling of the mouse diaphragm and refined mass spectrometric analysis of the dystrophic phenotype

Abstract

The diaphragm is a crucial muscle involved in active inspiration and whole body homeostasis. Previous biochemical, immunochemical and cell biological investigations have established the distribution and fibre type-specific expression of key diaphragm proteins. Building on these findings, it was of interest to establish the entire experimentally assessable diaphragm proteome and verify the presence of specific protein isoforms within this specialized subtype of skeletal muscle. A highly sensitive Orbitrap Fusion Tribrid mass spectrometer was used for the systematic identification of the mouse diaphragm-associated protein population. Proteomics established 2925 proteins by high confidence peptide identification. Bioinformatics was used to determine the distribution of the main protein classes, biological processes and subcellular localization within the diaphragm proteome. Following the establishment of the respiratory muscle proteome with special emphasis on protein isoform expression in the contractile apparatus, the extra-sarcomeric cytoskeleton, the extracellular matrix and the excitation–contraction coupling apparatus, the mass spectrometric analysis of the diaphragm was extended to the refined identification of proteome-wide changes in X-linked muscular dystrophy. The comparative mass spectrometric profiling of the dystrophin-deficient diaphragm from the mdx-4cv mouse model of Duchenne muscular dystrophy identified 289 decreased and 468 increased protein species. Bioinformatics was employed to analyse the clustering of changes in protein classes and potential alterations in interaction patterns of proteins involved in metabolism, the contractile apparatus, proteostasis and the extracellular matrix. The detailed pathoproteomic profiling of the mdx-4cv diaphragm suggests highly complex alterations in a variety of crucial cellular processes due to deficiency in the membrane cytoskeletal protein dystrophin.



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

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