Muscular System
n an autoimmune disorder, the immune sys-
tem attacks part of the body. In myasthenia
gravis (MG), that part is the muscular system.
The body produces antibodies that target recep-
tors for the neurotransmitter acetylcholine on
muscle cells at neuromuscular junctions. People
with MG have one-third the normal number of
acetylcholine receptors here. On a whole-body
level, this causes weak and easily fatigued muscles.
ects hundreds of thousands of people
worldwide, mostly women beginning in their
twenties or thirties, and men in their sixties and
seventies. The speci±
c symptoms depend upon
the site of attack. ²or 85% of patients, the disease
causes generalized muscle weakness. Many peo-
ple develop a characteristic ³
at smile and nasal
voice and have di´
culty chewing and swallow-
ing due to aF
ected facial and neck muscles. Many
have limb weakness. About 15% of patients expe-
rience the illness only in the muscles surrounding
their eyes. The disease reaches crisis level when
respiratory muscles are aF
ected, requiring a ven-
tilator to support breathing. MG does not aF
sensation or re³
MG can usually be controlled, thanks to a
combination of the following treatments:
Drugs that inhibit acetylcholinesterase,
the enzyme that normally breaks down
acetylcholine, thus increasing levels of the
neurotransmitter increase.
Removing the thymus gland, which
oversees much of the immune response.
Immunosuppressant drugs that decrease
production of antibodies.
Intravenous antibodies that bind and
inactivate the ones causing the damage.
Plasma exchange, which rapidly removes
the damaging antibodies from the
circulation, helping people in crisis.
Myasthenia Gravis
the troponin, changing its shape (conformation) and altering
the position of the tropomyosin. The movement of the tro-
pomyosin molecules exposes the binding sites on the actin
F laments, allowing linkages to form between myosin cross-
bridges and actin (F
g. 9.10
To Chapter 2, Proteins, pages 64–66.
The Sliding Filament
Model of Muscle Contraction
The sarcomere is considered the functional unit of skeletal
muscles because contraction of an entire skeletal muscle can
be described in terms of the shortening of the sarcomeres of
its muscle F
bers. According to the
sliding ±
lament model,
when sarcomeres shorten, the thick and thin F
laments do
not change length. Rather, they slide past one another, with
the thin F
laments moving toward the center of the sarco-
mere from both ends. As this occurs, the H zones and the I
bands narrow; the regions of overlap widen; and the Z lines
move closer together, shortening the sarcomere
(f g. 9.11)
Cross-Bridge Cycling
The force that shortens the sarcomeres comes from cross-
bridges pulling on the thin F laments. A myosin cross-bridge
can attach to an actin binding site and bend slightly, pulling
on the actin F lament. Then the head can release, straighten,
combine with another binding site further down the actin
lament, and pull again (see F
g. 9.10
Myosin cross-bridges contain the enzyme
catalyzes the breakdown of ATP to ADP and phosphate. This
When the bacterium
Clostridium botulinum
grows in an anaerobic
(oxygen-poor) environment, such as in a can of unrefrigerated food,
it produces a toxin that prevents the release of acetylcholine from
nerve terminals if ingested by a person. Symptoms include nausea,
vomiting, and diarrhea; headache, dizziness, and blurred or double
vision; and ±
nally, weakness, hoarseness, and di´
culty swallowing
and, eventually, breathing. Physicians can administer an antitoxin
substance that binds to and inactivates botulinum toxin in the blood-
stream, stemming further symptoms, although not correcting dam-
age already done. Small amounts of botulinum toxin are used to treat
migraine headaches and to temporarily paralyze selected facial mus-
cles, smoothing wrinkles.
Excitation Contraction Coupling
The sarcoplasmic reticulum has a high concentration of
calcium ions compared to the cytosol. This is due to active
transport of calcium ions (calcium pump) in the membrane
of the sarcoplasmic reticulum. In response to a muscle
impulse, the membranes of the cisternae become more per-
meable to these ions, and the calcium ions diffuse out of the
cisternae into the cytosol of the muscle F
ber (see F
g. 9.7).
To Chapter 3, Active Transport, page 95.
When a muscle fiber is at rest, the troponin-tropomyosin
complexes block the binding sites on the actin molecules
and thus prevent the formation of linkages with myosin
g. 9.10
. As the concentration of calcium
ions in the cytosol rises, however, the calcium ions bind to
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