Summary tables are used to bring
together large amounts of information
that may be scattered throughout
the book or to summarize small or
moderate amounts of information.
The tables complement the
accompanying ﬁ gures to provide a
rapid means of reviewing the most
important material in the chapter.
Guided Tour Through a Chapter
Every chapter starts with an outline
giving the reader a brief view of what is
to be covered in that chapter.
Every chapter starts with a brief
A number of diseases can affect the contraction of skeletal
muscle. Many of them are caused by defects in the parts of
the nervous system that control contraction of the muscle
ﬁ bers rather than by defects in the muscle ﬁ bers themselves.
is a viral disease that destroys
motor neurons, leading to the paralysis of skeletal muscle, and
may result in death due to respiratory failure.
Involuntary tetanic contraction of skeletal muscles produces
During cramping, action potentials ﬁ re at
abnormally high rates, a much greater rate than occurs during
maximal voluntary contraction. The speciﬁ c cause of this high
activity is uncertain, but it is probably related to electrolyte
imbalances in the extracellular ﬂ uid surrounding both the
muscle and nerve ﬁ bers. These imbalances may arise from
overexercise or persistent dehydration, and they can directly
induce action potentials in motor neurons and muscle ﬁ bers.
Another theory is that chemical imbalances within the muscle
stimulate sensory receptors in the muscle, and the motor
neurons to the area are activated by reﬂ ex when those signals
reach the spinal cord.
is the involuntary tetanic contraction
of skeletal muscles that occurs when the extracellular calcium
concentration falls to about 40 percent of its normal value.
This may seem surprising, because we have seen that calcium
is required for excitation-contraction coupling. However,
recall that this calcium is sarcoplasmic reticulum calcium, not
extracellular calcium. The effect of changes in extracellular
calcium is exerted not on the sarcoplasmic reticulum calcium,
but directly on the plasma membrane. Low extracellular
) increases the opening of sodium
channels in excitable membranes, leading to membrane
depolarization and the spontaneous ﬁ ring of action potentials.
This causes the increased muscle contractions, which are
similar to muscular cramping. Chapter 11 discusses the
mechanisms controlling the extracellular concentration of
This disease is one of the most frequently encountered
genetic diseases, affecting one in every 3500 males (but
many fewer females) born in America.
is associated with the progressive degeneration of skeletal
and cardiac muscle ﬁ bers, weakening the muscles and
leading ultimately to death from respiratory or cardiac
). The symptoms become evident at
about 2 to 6 years of age, and most affected individuals do
not survive far beyond the age of 20.
The recessive gene responsible for a major form of
muscular dystrophy (
Duchenne muscular dystrophy
ADDITIONAL CLINICAL EXAMPLES
been identiﬁ ed on the X chromosome, and Duchenne
muscular dystrophy is thus a sex-linked recessive disease. (As
described in Chapter 17, girls have two X chromosomes and
boys only one. Consequently, a girl with one abnormal X
chromosome and one normal one will not generally develop
the disease. This is why the disease is so much more common
in boys.) This gene codes for a protein known as dystrophin,
which is either present in a nonfunctional form or absent
in patients with the disease. Dystrophin is a large protein
that links cytoskeletal proteins to membrane glycoproteins.
It resembles other known cytoskeletal proteins and may be
involved in maintaining the structural integrity of the plasma
membrane or of elements within the membrane, such as ion
channels. In its absence, ﬁ bers subjected to repeated structural
deformation during contraction are susceptible to membrane
rupture and cell death. Preliminary attempts are being
made to treat the disease by inserting the normal gene into
dystrophic muscle cells.
is a collection of neuromuscular
disorders characterized by muscle fatigue and weakness that
progressively worsens as the muscle is used. It affects about
one out of every 7500 Americans, occurring more often in
women than men. The most common cause is the destruction
of nicotinic ACh receptor proteins of the motor end plate,
mediated by antibodies of a person’s own immune system
(see Chapter 18 for a description of autoimmune diseases).
The release of ACh from the nerve terminals is normal, but
the magnitude of the end-plate potential is markedly reduced
because of the decreased availability of receptors. Even
in normal muscle, the amount of ACh released with each
action potential decreases with repetitive activity, and thus
the magnitude of the resulting EPP falls. In normal muscle,
however, the EPP remains well above the threshold necessary
to initiate a muscle action potential. In contrast, after a few
motor nerve impulses in a myasthenia gravis patient, the
magnitude of the EPP falls below the threshold for initiating
a muscle action potential.
A number of approaches are currently used to treat the
disease. One is to administer acetylcholinesterase inhibitors
). This can partially compensate for the
reduction in available ACh receptors by prolonging the time
that acetylcholine is available at the synapse. Other therapies
aim at blunting the immune response. Treatment with
glucocorticoids is one way that immune function is suppressed
(Chapter 11). Removal of the thymus gland (
reduces the production of antibodies and reverses symptoms
in about 50 percent of patients.
is a treatment
that involves removing the liquid fraction of blood (plasma),
which contains the offending antibodies. A combination of
these treatments has greatly reduced the mortality rate for
Additional Clinical Examples
The authors have drawn from their
teaching experiences to provide students
with real-life applications through