Skeletal muscle. Skeletal muscle is the most massive tissue in the body, making up 40–50% of a human body’s mass (Ten Broek, Xxxxxx et al. 2010). Critical bodily functions including breathing, swallowing, and moving require skeletal muscle function. In addition to its role in contraction, skeletal muscle also plays a major role in the immune response and in metabolic homeostasis and thermal homeostasis in mammals. Skeletal muscle is the primary amino acid reserve, supplying the body with nutrients when protein or glucose intake is limited (Xxxxxx 1970, Biolo, Zhang et al. 1995). When the body is exposed to cold, skeletal muscle shivering is induced as a means of thermogenesis (Jubrias, Xxxxxxxxx et al. 2008, Nakamura and Xxxxxxxx 2011). Shivering is also induced in response to infection as a means of thermogenesis to combat the pathogen (Xxxxxx, Xxxxxxx et al. 1976). Survival depends on proper development and maintenance of skeletal muscle. Skeletal muscle tissue is made up of many different cell types (Figure 1.1). Crucial supporting cells in a muscle include afferent neurons, muscle spindles that sense the muscle length, endothelial cells that make up blood vessels, and fibroblasts that help deposit extracellular matrix. Some cells present in small numbers in uninjured muscle expand their populations dramatically to support tissue repair following injury; these cell populations include muscle resident stem cells called satellite cells (Mauro 1961), fibroadipogenic progenitor cells (FAPs) (Xxx, Yi et al. 2010), and macrophages (Xxxxxxx and Xxxxxxxx 2010). While all of these cell types play an important role in supporting and maintaining skeletal muscle, the primary cell type in muscle is large multinucleated myofibers. Myofibers can extend from a muscle’s origin to its insertion site. The ends of a myofiber are specialized to form a myotendinous junction that anchors the cell. A neuromuscular junction in the middle of the myofiber, where a motor neuron synapses onto the myofiber, conveys action potentials signaling the myofiber to contract. The body of a myofiber is densely packed with contractile units called sarcomeres. The principle components of a sarcomere are actin and myosin. Myosin motors move along actin filaments, shortening the sarcomere and contracting the myofiber. Four major isoforms of myosin heavy chain exist, and each has a different rate of contraction. Fast cycling myosin motors are found in myofibers relying predominantly on glycolytic phosphorylation ...
