Muscle Contraction
The motion of muscle shortening occurs as myosin heads bind to actin and pull the actin
inwards. This action requires energy, which is provided by ATP. Myosin binds to actin at a
binding site on the globular actin protein. Myosin has another binding site for ATP at which
enzymatic activity hydrolyzes ATP to ADP, releasing an inorganic phosphate molecule and
energy.
ATP binding causes myosin to release actin, allowing actin and myosin to detach from each
other. After this happens, the newly bound ATP is converted to ADP and inorganic phosphate, Pi.
The enzyme at the binding site on myosin is called ATPase. The energy released during ATP
hydrolysis changes the angle of the myosin head into a “cocked” position. The myosin head is
then in a position for further movement, possessing potential energy, but ADP and Pi are still
attached. If actin binding sites are covered and unavailable, the myosin will remain in the high
energy configuration with ATP hydrolyzed, but still attached.
If the actin binding sites are uncovered, a cross-bridge will form; that is, the myosin head spans
the distance between the actin and myosin molecules. Pi is then released, allowing myosin to
expend the stored energy as a conformational change. The myosin head moves toward the M
line, pulling the actin along with it. As the actin is pulled, the filaments move approximately 10
nm toward the M line. This movement is called the power stroke, as it is the step at which force
is produced. As the actin is pulled toward the M line, the sarcomere shortens and the muscle
contracts.
When the myosin head is “cocked,” it contains energy and is in a high-energy configuration. This
energy is expended as the myosin head moves through the power stroke; at the end of the
power stroke, the myosin head is in a low-energy position. After the power stroke, ADP is
released; however, the cross-bridge formed is still in place, and actin and myosin are bound
together. ATP can then attach to myosin, which allows the cross-bridge cycle to start again and
further muscle contraction can occur (Figure 1). The movement of the myosin head back to its
original position is called the recovery stroke. Resting muscles store energy from ATP in the
myosin heads while they wait for another contraction.
Regulatory Proteins
When a muscle is in a resting state, actin and myosin are separated. To keep actin from binding
to the active site on myosin, regulatory proteins block the molecular binding sites. Tropomyosin
blocks myosin binding sites on actin molecules, preventing cross-bridge formation and
preventing contraction in a muscle without nervous input. Troponin binds to tropomyosin and
helps to position it on the actin molecule; it also binds calcium ions.
To enable a muscle contraction, tropomyosin must change conformation, uncovering the
myosin-binding site on an actin molecule and allowing cross-bridge formation. This can only
happen in the presence of calcium, which is kept at extremely low concentrations in the
sarcoplasm. If present, calcium ions bind to troponin, causing conformational changes in
troponin that allow tropomyosin to move away from the myosin binding sites on actin. Once the
tropomyosin is removed, a cross-bridge can form between actin and myosin, triggering
contraction. Cross-bridge cycling continues until Ca2+ ions and ATP are no longer available and
tropomyosin again covers the binding sites on actin.
