Fast-twitch muscle fibers have the ability to convert into slow-twitch muscle fibers and vice versa, depending on the stimulation pattern. Chronic electrical stimulation of a fast-twitch muscle leads to the expression of slow-twitch myosin and a decrease in fast-twitch myosin expression. This change is accompanied by an increase in oxidative capacity. The mechanisms behind this change in gene expression are still unknown, but it seems to be a result of an increase in resting intracellular [Ca++] levels. The transition from fast-twitch to slow-twitch phenotype has been linked to the Ca++-dependent phosphatase calcineurin and the transcription factor NFAT. Additionally, the Ca++/calmodulin-dependent kinase and the transcription factor MEF2 may also play a role in this phenotype transition.

Denervation causes skeletal muscle fibers to undergo atrophy. The maintenance of the differentiated phenotype in muscle fibers relies on the activity of their motor nerves. However, these changes can be reversed through reinnervation, which occurs when axons regrow along the original nerve sheath. Skeletal muscle has a limited ability to replace cells lost due to trauma or disease. Disuse atrophy is characterized by a decreased rate of protein synthesis and an increased rate of protein degradation, which can be attributed to the inhibition of the PI3K/Akt signaling pathways and activation of the FoxO pathway. The increased protein degradation during atrophy is a result of elevated levels of ubiquitin ligases and increased protease activity, such as the activation of caspase 3.

Skeletal muscle displays significant phenotypic plasticity. During normal growth, cellular hypertrophy occurs as a response to skeletal growth. This hypertrophy is achieved by adding more myofibrils and sarcomeres at the ends of the muscle cells. Strength training induces cellular hypertrophy, while endurance training enhances the oxidative capacity of all motor units involved. However, training regimens cannot alter fiber type or the expression of myosin isoforms.

Muscle fatigue during exercise is not caused by ATP depletion. The specific mechanisms underlying exercise-induced fatigue are not fully understood, but the accumulation of metabolic byproducts such as lactate, Pi, and ADP has been implicated. To prevent depletion of myoplasmic ATP, which could jeopardize the cell's viability, multiple mechanisms are likely to have evolved to induce fatigue and reduce the rate of ATP hydrolysis, thus preventing injury or death of the skeletal muscle cell.

During exercise, if the energy demands of a muscle exceed its oxidative metabolism capacity, an oxygen debt is incurred. The increased breathing observed during the recovery period after exercise is a reflection of this oxygen debt. The extent of reliance on anaerobic metabolism to meet the energy requirements of muscle contraction determines the magnitude of the oxygen debt.
Fast-twitch muscle fibers can be converted to slow-twitch muscle fibers (and vice versa), depending on the stimulation pattern. Chronic electrical stimulation of a fast-twitch muscle results in the expression of slow-twitch myosin and decreased expression of fast-twitch myosin, along with an increase in oxidative capacity. The mechanism or mechanisms underlying this change in gene expression are unknown, but the change appears to be secondary to an elevation in resting intracellular [Ca++]. The Ca++-dependent phosphatase calcineurin and the transcription factor NFAT have been implicated in this transition from the fast-twitch to the slow-twitch phenotype. Ca++/calmodulin-dependent kinase and the transcription factor MEF2 may also participate in the phenotype transition.
8.
Skeletal muscle fibers atrophy after denervation. Muscle fibers depend on the activity of their motor nerves for maintenance of the differentiated phenotype. Reinnervation by axon growth along the original nerve sheath can reverse these changes. Skeletal muscle has a limited capacity to replace cells lost as a result of trauma or disease. Inhibition of the PI3K/Akt signaling pathways and activation of the FoxO pathway appears to contribute to the decreased rate of protein synthesis and the increased rate of protein degradation (respectively) observed during disuse atrophy. The increased protein degradation during atrophy is attributed to increases in both protease activity (e.g., activation of caspase 3) and ubiquitination (through elevated levels of ubiquitin ligases).
9.
Skeletal muscle exhibits considerable phenotypic plasticity. Normal growth is associated with cellular hypertrophy, caused by the addition of more myofibrils and more sarcomeres at the ends of the cell to match skeletal growth. Strength training induces cellular hypertrophy, whereas endurance training increases the
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oxidative capacity of all involved motor units. Training regimens cannot alter fiber type or the expression of myosin isoforms.
10.
Muscle fatigue during exercise is not due to depletion of ATP. The mechanism or mechanisms underlying exercise-induced fatigue are not known, although the accumulation of various metabolic products (lactate, Pi, ADP) has been implicated. In view of the importance of preventing depletion of myoplasmic ATP, which would affect the viability of the cell, it is likely that multiple mechanisms may have been developed to induce fatigue and hence lower the rate of ATP hydrolysis before the individual risks injury or death of the skeletal muscle cell.
11.
When the energy demands of an exercising muscle cannot be met by oxidative metabolism, an oxygen debt is incurred. Increased breathing during the recovery period after exercise reflects this oxygen debt. The greater the reliance on anaerobic metabolism to meet the energy requirements of muscle contraction, the greater the oxygen debt.