Download LOOKING AT MUSCLE CONTRACTION

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Classic Experiment
19.1
LOOKING AT MUSCLE CONTRACTION
he contraction and relaxation of striated muscles allow us to perform all of
T
our daily tasks. How does this happen? Scientist have long looked to see how
fused muscles cells, called myofibrils, differ from other cells that cannot perform
powerful movement. In 1954, Jean Hanson and Hugh Huxley published their
microscopy studies on muscle contraction, which demonstrated the mechanism by
which it occurs.
Background
The Experiment
The ability of muscles to perform work has long been a
fascinating process. Voluntary muscle contraction is performed by striated muscles, which are named for their appearance when viewed under the microscope. By the
1950s, biologists studying myofibrils, the cells that make
up muscles, had named many of the structures they had
observed under the microscope. One contracting unit,
called a sarcomere, is made up of two main regions called
the A band, and the I band. The A band contains two
darkly colored thick striations and one thin striation. The
I band is made up primarily of light-colored striations,
which are divided by a darkly colored line known as the
Z disk. Although these structures had been characterized,
their role in muscle contraction remained unclear. At the
same time, biochemists also tried to tackle this problem
by looking for proteins that are more abundant in myofibrils than in other non-muscle cells. They found muscles to contain large amounts of the structural proteins
actin and myosin in a complex with each other. Actin and
myosin form polymers that can shorten when treated with
adenosine triphosphate (ATP).
With these observations in mind, Hanson and Huxley
began their study of cross striations in muscle. In a few
short years, they united the biochemical data with the microscopy observations and developed a model for muscle
contraction that holds true today.
Hanson and Huxley primarily used phase-contrast microscopy in their studies of striated muscles that they isolated from rabbits. The technique allowed them to obtain
clear pictures of the sarcomere, and to take careful measurements of the A and the I bands. By treating the muscles with a variety of chemicals, then studying them under
the phase-contrast microscope, they were able to successfully combine biochemistry with microscopy to describe
muscle structure as well as the mechanism of contraction.
In their first set of studies, Hanson and Huxley employed chemicals that are known to specifically extract either myosin or actin from myofibrils. First, they treated
myofibrils with a chemical that specifically removes
myosin from muscle. They used phase-contrast microscopy to compare untreated myofibrils to myosinextracted myofibrils. In the untreated muscle, they observed
the previously identified sarcometic structure, including
the darkly colored A band. When they looked at the
myosin-extracted cells, however, the darkly colored A
band was not observed. Next, they extracted actin from
the myosin-extracted muscle cells. When they extracted
both myosin and actin from the myofibril, they could see
no identifiable structure to the cell under phase-contrast
microscopy. From these experiments, they concluded that
myosin was located primarily in the A band, whereas actin
is found throughout the myofibril.
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With a better understanding of the biochemical nature
of muscle structures, Huxley and Hanson went on to study
the mechanism of muscle contraction. They isolated individual myofibrils from muscle tissue and treated them with
ATP, causing them to contract at a slow rate. Using this
technique, they could take pictures of various stages of
muscle contraction by using phase-contrast microscopy.
They could also mechanically induce stretching by manipulating the coverslip, which allowed them to also observe the relaxation process. With these techniques in
hand, they examined how the structure of the myofibril
changes during contraction and stretch.
First, Huxley and Hanson treated myofibrils with ATP,
then photographed the images they observed under phasecontrast microscopy. These pictures allowed them to measure the lengths of both the A band and the I band at various stages of contraction. When they looked at myofibrils
freely contracting, they noticed a consistent shortening of
the lightly colored I band, whereas the length of the A
band remained constant (see Figure 18.1). Within the A
Z disk
band, they observed the formation of an increasingly dense
area throughout the contraction.
Next, the two scientists examined how the myofibril
structure changes during a simulated muscle stretch. They
stretched isolated myofibrils mounted on glass slides by
manipulating the coverslip. They again photographed
phase-contrast microscopy images and measured the
lengths of the A and the I bands. During stretch the length
of the I band increased, rather than shortened, as it had
in contraction. Once again, the length of the A band remained unchanged. The dense zone that formed in the A
band during contraction, became less dense during stretch.
From their observations, Hanson and Huxley developed a model for muscle contraction and stretch (see Figure 18.1). In their model, the actin filaments in the I band
are drawn up into the A during contraction, and thus the
I band becomes shorter. This allows for increased interaction between the myosin located in the A band and the
actin filaments. As the muscle stretches, the actin filaments
withdraw from the A band. From these data, they proposed that muscle contraction is driven by actin moving
in and out of a mass of stationary myosin molecules.
I bands
S 2.8 µ
A 1.5 µ
I 1.3 µ
Stretched
120%
A band
Relaxed
100%
S 2.3 µ
A 1.5 µ
I 0.8 µ
Contracted
90%
S 2.0 µ
A 1.5 µ
I 0.5 µ
Contracted
80%
S 1.8 µ
A 1.5 µ
I 0.3 µ
Contracted
60%
S 1.5 µ
▲ FIGURE 19.1 Schematic diagram of muscle contraction
and stretch observed by Hanson and Huxley. The lengths of
the sarcomere (S), the A band (A), and the I band (I) were measured from 60 percent contraction (bottom) to 120 percent
stretch (top). The lengths of the sacromere, the I band, and A
band are noted on the left. Notice that from 120 percent stretch
to 70 percent contraction the A band does not change in the
length, whereas the length of the I band can stretch to 1.3 microns, then contract to 0.3 microns. At 60 percent contraction,
the I band disappears, and the A band shortens to the overall
length of the sarcomere. [Adapted from J. Hanson and H. E.
Huxley, 1955, Symp. Soc. Exp. Biol. Fibrous Proteins and their
Biological Significance 9:249.]
Discussion
By combining microscopic observations with known biochemical treatments of muscle fibers, Hanson and Huxley
were able to describe the biochemical nature of muscle
structures and outline a mechanism for muscle contraction. A large body of research continues to focus on understanding the process of muscle contraction. Scientists
now know that muscles contract by ATP hydrolysis driving a conformational change in myosin that allows it to
push actin along. Researchers are continuing to uncover
the molecular details of this process, while the mechanism
contraction proposed by Hanson and Huxley remains in
place.