384 Chapter 12
may help the myosin proteins assemble into the A bands, and
nebulin is needed for the globular actin proteins to assemble
into thin filaments of the appropriate length for the muscle.
Titin serves a scaffolding function in addition to its previously
described contribution to muscle elasticity, unfolding and
developing passive tension when a muscle is stretched.fibers in elderly people. Endurance training can increase the
density of blood capillaries in the muscles, improving the abil-
ity of the blood to deliver oxygen to the muscles. The muscle
glycogen of older people can also be increased by endurance
training, but it cannot be raised to the levels present in youth.
Muscle Damage and Repair
Destruction of striated muscle fibers is particularly damaging
because the remaining healthy fibers cannot divide to replace
the damaged ones. However, skeletal muscles have stem cells
known as satellite cells, located between the sarcolemma
(plasma membrane) and the endomysium (basement mem-
brane). The satellite cells are activated at the site of muscle
injury to differentiate into myoblasts that can fuse with the
damaged muscle fibers. If the damage is more extensive, a
number of satellite cells can form myoblasts that fuse to pro-
duce new muscle fibers, which can then grow thicker by the
fusion of additional myoblasts. This muscle regeneration can
occur in normal physiology when intense resistance training
injures muscle fibers. When muscles hypertrophy, or grow
larger as a result of increased fiber thickness, the number of
nuclei in each fiber must increase in proportion to the larger
volume of the fiber. These new nuclei are provided by the sat-
ellite cells.
Satellite cells are normally in a quiescent state until stimu-
lated to divide and differentiate into myoblasts. However, with
advanced age they enter a senescent state in which they are
unable to replenish themselves or repair muscles. This leads
to a decline in muscle mass and strength, a condition called
sarcopenia. Scientists believe that the reduction in satellite
cells with age is caused by cytokines that influence genetic
activity. Cytokines in youth may maintain the reversible qui-
escent state, and/or cytokines in aged muscles may induce the
senescent state.
Myostatin is a myokine in skeletal muscles that is able
to inhibit satellite cell function and muscle growth. Lowering
myostatin might thus be expected to increase muscle mass.
Indeed, mice and cattle with the gene for producing myostatin
“knocked out” have greatly increased muscle mass. The func-
tions of myostatin, and the mechanisms that regulate satel-
lite cell proliferation and formation of myotubes, have many
potential health applications and are currently active areas of
research.
The formation of new sarcomeres and the consequent
growth of myofibrils within the muscle fiber require three
gigantic muscle proteins. Titin (previously discussed) is an
extremely long protein that spans half the length of the sar-
comere, with its amino-terminal end anchored in one of the
Z-discs on each side of the sarcomere and its carboxyl-
terminal end in the M-band. Two other giant proteins associ-
ated with the myofibrils are nebulin (within the actin of the
I bands) and obscurin (surrounding the sarcomeres primarily
around the Z-discs and M-bands). These three giant proteins
serve as molecular scaffolding for the formation of new sarco-
meres during muscle growth and repair. For example, obscurin
FITNESS APPLICATION
Muscle atrophy (reduction in size), with its accompanying
declines in strength, is most severe when it results from
damage to the motor nerves innervating the muscles. This
neurogenic atrophy may be the result of diseases such
as ALS (discussed in the next Clinical Application box) or
trauma. Disuse atrophy, as the name implies, can result
when a person is bedridden for a period of time or is in
a cast, so that the muscles are not working as they nor-
mally do to move a load against the force of gravity. This is
the case for the muscles of an astronaut during prolonged
periods of microgravity (weightlessness). Experience in
extended spaceflights has shown that some muscle atro-
phy can be mitigated by exercise, but so far not all of the
atrophy can be prevented. Scientists have suggested that
hormones such as glucocorticoids, growth hormone, and
others might be altered and promote muscle atrophy during
prolonged exposure to microgravity.| CHECKPOINT
- Draw a figure illustrating the relationship between
ATP and creatine phosphate, and explain the
physiological significance of this relationship. - Describe the characteristics of slow- and fast-twitch
fibers (including intermediate fibers). Explain how the
fiber types are determined and list the functions of
different fiber types. - Explain the different causes of muscle fatigue with
reference to the various fiber types. - Describe the effects of endurance training and
resistance training on the fiber characteristics of
muscles.
12.5 Neural Control of Skeletal Muscles
Skeletal muscles contain stretch receptors called muscle
spindles that stimulate the production of impulses in sen-
sory neurons when a muscle is stretched. These sensory
neurons can synapse with alpha motoneurons, which stim-
ulate the muscle to contract in response to the stretch.