2 How skeletal muscle works

The strength of skeletal muscle is directly proportional to its cross-sectional area. The strength of a body, however, is determined by a number of biomechanicalBiomechanics is the study of the mechanics and other physical aspects of living organisms and their parts. Some simple examples of biomechanics include the investigation of the forces that act on limbs, the aerodynamics of bird and insect flight, the hydr principles (the distance between muscle insertions and joints, muscle size, and so on). Muscles are normally arranged in opposition so that as one group of muscles contract, another group relaxes or expands.

Skeletal muscle cells are stimulated by acetylcholine, which is released at neuromuscular junctions by motor neurons. Once the cells are "excited", their sarcoplasmic reticulums will release ionic calcium (Ca²⁺), this interacts with the myofibrils and, thus, induces muscular contraction (via the sliding filament mechanism). Besides calcium, this process requires adenosine triphosphate (ATP). The ATP is produced by metabolizing creatine phosphate and glycogen, which are stored within the muscle cells; as well by metabolizing glucose and fatty acids, obtained from blood.

Each motor neuron "controls" a group of muscle cells, known as " motor units". When more strength is required, than what can be obtained from a single motor unit, more units will be stimulated; this is known as " motor unit recruitment ". If more strength is required than what can be obtained from the current degree of unit contraction, the motor neurons will send additional stimuli; this causes a process of contractile summation , which increases the degree of contraction. If a muscle is maximally contracted, it is said to be in a state of tetanic contraction.

3 Red and white fibers

Skeletal muscles contain two types of fibers, used to produce ATP; the amount of each varies from muscle to muscle, and from person to person.

• Red ("slow-twitch") fibers have more mitochondria, store oxygen in myoglobin, rely on aerobic metabolism, and are associated with endurance; these produce ATP more slowly. Marathoners tend to have more red fibers.
• White ("fast-twitch") fibers have fewer mitochondria, are capable of more powerful (but shorter) contractions, metabolize ATP more quickly, and are more likely to accumulate lactic acid. Weightlifters and Sprinters tend to have more white fibers.

4 Genes that define skeletal muscle phenotype

Skeletal muscle fiber-type phenotype is regulated by several independent signaling pathways. These include pathways involved with the Ras/mitogen-activated protein kinase (MAPK), calcineurin, calcium/calmodulin-dependent protein kinase IV, and the peroxisome proliferator γ coactivator 1 (PGC-1). The Ras/MAPK signaling pathway links the motor neurons and signaling systems, coupling excitation and transcription regulation to promote the nerve-dependent induction of the slow program in regenerating muscle. Calcineurin, a Ca2+/calmodulin-activated phosphatase implicated in nerve activity-dependent fiber-type specification in skeletal muscle, directly controls the phosphorylation state of the transcription factor NFAT, allowing for its translocation to the nucleus and leading to the activation of slow-type muscle proteins in cooperation with myocyte enhancer factor 2 (MEF2) proteins and other regulatory proteins. Calcium-dependent Ca2+/calmodulin kinase activity is also upregulated by slow motor neuron activity, possibly because it amplifies the slow-type calcineurin-generated responses by promoting MEF2 transactivator functions and enhancing oxidative capacity through stimulation of mitochondrial biogenesis.

Contraction-induced changes in intracellular calcium or reactive oxygen species provide signals to diverse pathways that include the MAPKs, calcineurin and calcium/calmodulin-dependent protein kinase IV to activate transcription factors that regulate gene expression and enzyme activity in skeletal muscle.

PGC1-α, a transcriptional coactivator of nuclear receptors important to the regulation of a number of mitochondrial genes involved in oxidative metabolism, directly interacts with MEF2 to synergistically activate selective ST muscle genes and also serves as a target for calcineurin signaling. A peroxisome proliferator-activated receptor δ (PPARδ)-mediated transcriptional pathway is involved in the regulation of the skeletal musclefiber phenotype. Mice that harbor an activated form of PPARd display an “endurance” phenotype, with a coordinated increase in oxidative enzymes and mitochondrial biogenesis and an increased proportion of ST fibers. Thus—through functional genomics—calcineurin, calmodulin-dependent kinase, PGC-1α, and activated PPARδ form the basis of a signaling network that controls skeletal muscle fiber-type transformation and metabolic profiles that protect against insulin resistance and obesity.

The transition from aerobic to anaerobic metabolism during intense work requires that several systems are rapidly activated to ensure a constant supply of ATP for the working muscles. These include a switch from fat-based to carbohydrate-based fuels, a redistribution of blood flow from nonworking to exercising muscles, and the removal of several of the byproducts of anaerobic metabolism, such as carbon dioxide and lactic acid. Some of these responses are governed by transcriptional control of the FT glycolytic phenotype. For example, skeletal muscle reprogramming from a ST glycolytic phenotype to a FT glycolytic phenotype involves the Six1/Eya1 complex, composed of members of the Six protein family. Moreover, the Hypoxia Inducible Factor-1α (HIF-1α) has been identified as a master regulator for the expression of genes involved in essential hypoxic responses that maintain ATP levels in cells. Ablation of HIF-1α in skeletal muscle was associated with an increase in the activity of rate-limiting enzymes of the mitochondria, indicating that the citric acid cycle and increased fatty acid oxidation may be compensating for decreased flow through the glycolytic pathway in these animals. However, hypoxia-mediated HIF-1α responses are also linked to the regulation of mitochondrial dysfunction through the formation of excessive reactive oxygen species in mitochondria.

Muscular system

Cardiac muscle - Skeletal muscle - Smooth muscle - List of muscles of the human body

Muscular system

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