Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

BACKGROUNDLevels of MBCK can be increased in patients with skeletal muscle injury or renal failure in the absence of myocardial injury, causing diagnostic confusion. This study was designed to determine whether measurement of cardiac troponin I (cTnI), a myocardial regulatory protein with comparable sensitivity to MBCK, has sufficient specificity to clarify the etiology of MBCK elevations in patients with acute or chronic skeletal muscle disease or renal failure.METHODS AND RESULTSOf the patients (n = 215) studied, 37 had acute skeletal muscle injury, 10 had chronic muscle disease, nine were marathon runners, and 159 were chronic dialysis patients. Patients were evaluated clinically, by ECG, and by two-dimensional echocardiography. Total creatine kinase (normal, < 170 IU/L) was determined spectrophotometrically, and cTnI (normal, < 3.1 ng/mL) and MBCK (normal, < 6.7 ng/mL) were determined with specific monoclonal antibodies. Values above the upper reference limit were considered "elevated." Elevations of ...

Cardiac troponin I. A marker with high specificity for cardiac injury.

Skeletal muscle mass increases during postnatal development through a process of hypertrophy, i.e. enlargement of individual muscle fibers, and a similar process may be induced in adult skeletal muscle in response to contractile activity, such as strength exercise, and specific hormones, such as androgens and β-adrenergic agonists. Muscle hypertrophy occurs when the overall rates of protein synthesis exceed the rates of protein degradation. Two major signaling pathways control protein synthesis, the IGF1-Akt-mTOR pathway, acting as a positive regulator, and the myostatin-Smad2/3 pathway, acting as a negative regulator, and additional pathways have recently been identified. Proliferation and fusion of satellite cells, leading to an increase in the number of myonuclei, may also contribute to muscle growth during early but not late stages of postnatal development and in some forms of muscle hypertrophy in the adult. Muscle atrophy occurs when protein degradation rates exceed protein synthesis, and may be induced in adult skeletal muscle in a variety of conditions, including starvation, denervation, cancer cachexia, heart failure and aging. Two major protein degradation pathways, the proteasomal and the autophagic-lysosomal pathways, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These pathways involve a variety of atrophy-related genes or atrogenes, which are controlled by specific transcription factors, such as FoxO3, which is negatively regulated by Akt, and NF-κB, which is activated by inflammatory cytokines.

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.12253

Mechanisms regulating skeletal muscle growth and atrophy

High-resistance strength training (HRST) is one of the most widely practiced forms of physical activity, which is used to enhance athletic performance, augment musculo-skeletal health and alter body aesthetics. Chronic exposure to this type of activity produces marked increases in muscular strength, which are attributed to a range of neurological and morphological adaptations. This review assesses the evidence for these adaptations, their interplay and contribution to enhanced strength and the methodologies employed. The primary morphological adaptations involve an increase in the cross-sectional area of the whole muscle and individual muscle fibres, which is due to an increase in myofibrillar size and number. Satellite cells are activated in the very early stages of training; their proliferation and later fusion with existing fibres appears to be intimately involved in the hypertrophy response. Other possible morphological adaptations include hyperplasia, changes in fibre type, muscle architecture, myofilament density and the structure of connective tissue and tendons. Indirect evidence for neurological adaptations, which encompasses learning and coordination, comes from the specificity of the training adaptation, transfer of unilateral training to the contralateral limb and imagined contractions. The apparent rise in whole-muscle specific tension has been primarily used as evidence for neurological adaptations; however, morphological factors (e.g. preferential hypertrophy of type 2 fibres, increased angle of fibre pennation, increase in radiological density) are also likely to contribute to this phenomenon. Changes in inter-muscular coordination appear critical. Adaptations in agonist muscle activation, as assessed by electromyography, tetanic stimulation and the twitch interpolation technique, suggest small, but significant increases. Enhanced firing frequency and spinal reflexes most likely explain this improvement, although there is contrary evidence suggesting no change in cortical or corticospinal excitability. The gains in strength with HRST are undoubtedly due to a wide combination of neurological and morphological factors. Whilst the neurological factors may make their greatest contribution during the early stages of a training programme, hypertrophic processes also commence at the onset of training.

http://performancetrainingsystems.net/Resources/Adaptations_to_Strength_Training.pdf

The adaptations to strength training : morphological and neurological contributions to increased strength.

Mammalian skeletal muscles consist of three main fibre types, type 1, 2A and 2B fibres, with different myosin heavy chain (MHC) composition. We have now identified another fibre type, called type 2X fibre, characterized by a specific MHC isoform. Type 2X fibres, which are widely distributed in rat skeletal muscles, can be distinguished from 2A and 2B fibres by histochemical ATPase activity and by their unique staining pattern with seven anti-MHC monoclonal antibodies. The existence of the 2X-MHC isoform was confirmed by immunoblotting analysis using muscles containing 2X fibres as a major component, such as the normal and hyperthyroid diaphragm, and the soleus muscle after high frequency chronic stimulation. 2X-MHC contains one determinant common to 2B-MHC and another common to all type 2-MHCs, but lacks epitopes specific for 2A- and 2B-MHCs, as well as an epitope present on all other MHCs. By SDS-polyacrylamide gel electrophoresis 2X-MHC shows a lower mobility compared to 2B-MHC and appears to comigrate with 2A-MHC. Muscles containing predominantly 2X-MHC display a velocity of shortening intermediate between that of slow muscles and that of fast muscles composed predominantly of 2B fibres.

Three myosin heavy chain isoforms in type 2 skeletal muscle fibres.

Troponin I switching in the developing heart.

Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle

Fetal rat skeletal muscles express a troponin T (TnT) isoform similar to the TnT isoform expressed in the embryonic heart with respect to electrophoretic mobility and immunoreactivity with cardiac TnT-specific monoclonal antibodies. Immunoblotting analyses reveal that both the embryonic and the adult isoforms of cardiac TnT are transiently expressed during the neonatal stages. In addition, other TnT species, different from both cardiac TnTs and from the TnT isoforms expressed in adult muscles, are present in skeletal muscles during the first two postnatal weeks. By immunocytochemistry, cardiac TnT is detectable at the somitic stage and throughout embryonic and fetal development, and disappears during the first weeks after birth, persisting exclusively in the bag fibers of the muscle spindles. Cardiac TnT is re-expressed in regenerating muscle fibers following a cold injury and in mature muscle fibers after denervation. Developmental regulation of this TnT variant is not coordinated with that of the embryonic myosin heavy chain with respect to timing of disappearance and cellular distribution. No obligatory correlation between the two proteins is likewise found in regenerating and denervated muscles.

/pdf/cardiac-troponin-t-in-developing-regenerating-and-denervated-5cbqljbu9u.pdf

Leopoldo Saggin

Papers

Three myosin heavy chain isoforms in type 2 skeletal muscle fibres.

Troponin I switching in the developing heart.

Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle

Cardiac troponin T in developing, regenerating and denervated rat skeletal muscle

Myosin heavy chain isoforms and velocity of shortening of type 2 skeletal muscle fibres