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Neuromuscular Physiology
Published in Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan, Strength and Conditioning in Sports, 2023
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan
Additional protein filaments primarily composed of titin (connectin) stabilize myosin myofilaments along the longitudinal axis. Titin is a large protein (3000 kD) that runs half the length of a sarcomere, essentially the length of the myosin myofilaments, and also attaches them to the Z-discs (91, 185). Titin also appears to stabilize and maintain myosin positioning within the middle of the sarcomere as well as stabilizing the entire sarcomere during both contraction and relaxation. Nebulin likely stabilizes actin in a similar manner. Titin is a molecular equivalent of a steel spring; both titin and nebulin likely contribute to the elastic properties of muscle (91, 127, 185). Differences in protein isoforms, particularly titin, may contribute to differences in strength, power (71, 126), and running economy (115) and may be related to training status. Skeletal muscle myosin-binding protein C (MyBP-C) is a myosin myofilament-associated protein (Figure 1.11c). It is localized in distinct regions (C-zones) of the sarcomere. MyBP-C activated by Ca++-sensitizes the actin myofilament and modulates actin myofilament velocity. At least two isoforms of MyBP-C (fast- and slow-type) are expressed in a fiber type specific manner (118).
Inherited Myopathic Diseases
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
Nemaline rod structure is a pathological spectrum associated with several neuromuscular diseases. Not every nemaline rod means nemaline rod myopathic disease. Pathologists should be well-oriented about patients' clinical history. Nemaline rod myopathy (NRM) is characterized histologically by the presence of multiple small rods in the muscle fibers, which are best visualized by Gomori trichrome stain (GT). Rods are seen green-blue by GT, dark-blue by NADH, and ultrastructurally seen as small elongated electron-dense structures (Figure 17.2b–d). The common childhood type of NRM is in the nebulin (NEB) gene mutation on exon 55. Late adult-onset type is observed in cases with ACTA1 gene mutation.
Physical Activity in Prevention of Glucocorticoid Myopathy and Sarcopenia in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Muscle weakness in corticosteroid myopathy is mainly the result of destruction and atrophy of the myofibrillar compartment of skeletal muscle [4]. In agreement with Kelly et al. [38], who about three decades ago stated that the terms catabolic and myopathic should be used carefully as they can be misleading descriptions of the action of glucocorticoids on the level of the organism as well as on the level of skeletal muscle. Disappearance of about 20% of myosin filaments from myofibrils of muscle fibers with low oxidative capacity and decrease of myosin heavy chain (MyHC) IIb isoform relative content [4] are the explanation for decreased muscle strength and motor activity in the case of corticosteroid myopathy. This is qualitative remodeling of the myofibrillar compartment of myopathic type II B/X fibers but not whole skeletal muscle. The higher the degree of atrophy, the lower the muscle elasticity and the higher the tone. Muscle tone is dependent on changes in innervation. It has been shown that the neuromuscular synapses of glucocorticoid myopathic FT muscles are destroyed [39]. A decrease of titin and myosin [40] and of the ratio of nebulin and MyHC in myopathic muscle [3], shows that these changes in contractile and elastic proteins are the result of elevated catabolism of the above-mentioned proteins in skeletal muscle. This is the reason for reduced elasticity and generation of tension in glucocorticoid-caused myopathic muscle.
Early clinical and pre-clinical therapy development in Nemaline myopathy
Published in Expert Opinion on Therapeutic Targets, 2022
Gemma Fisher, Laurane Mackels, Theodora Markati, Anna Sarkozy, Julien Ochala, Heinz Jungbluth, Sithara Ramdas, Laurent Servais
Another consideration is the protein levels needed to maintain a healthy neuromuscular phenotype: A nebulin knockout mouse model demonstrated that nebulin levels declined rapidly in the first weeks of life. Compared to controls, the average knockout nebulin levels at 3 weeks of age were reduced to 48%, to 4.8% at 5 weeks and to 2.2% at 6 months[137]. In the nebulin mouse model described earlier, muscle weight assessments during growth revealed that all muscles were of lower mass than that of control muscle initially. However, from 15 to 25 weeks of age most had increased from baseline, and some muscles such as diaphragm were of equivalent mass to that of controls and soleus was even slightly heavier, implying hypertrophy [138]. Although there was no data to indicate how the hypertrophied soleus muscle performed in terms of force generation and contractility, the observations on muscle hypertrophy may still be useful in the context of therapies aimed at increasing muscle growth such as anti-myostatin agents, IGF-1 or upregulation of IGF-1 in muscle.