MOLECULAR MECHANISMOF MUSCLE CONTRACTION

Myosin Thick Filaments Slide along Actin Thin Filaments

The interaction between actin and myosin, like that betweenall proteins and ligands, involves weak bonds.When ATP is not bound to myosin, a face on the myosinhead group binds tightly to actin. When ATPbinds to myosin and is hydrolyzed to ADP and phosphate, a coordinated and cyclic series of conformational changes occurs in which myosin releases the F-actin subunit and binds another subunit farther along the thin filament.

The cycle has four major steps. In step 1, ATP binds to myosin and a cleft in the myosin molecule opens, disrupting the actin-myosin interaction so that the bound actin is released. ATP is then hydrolyzed in step 2, causing a conformational change in the protein to a “high-energy” state that moves the myosin head and changes its orientation in relation to the actin thin filament. Myosin then binds weakly to an F-actin subunit closer to the Z disk than the one just released. As the phosphate product of ATP hydrolysis is released from myosin in step 3, another conformational change occurs in which the myosin cleft closes, strengthening the myosin-actin binding. This is followed quickly by step 4, a “power stroke” during which the conformation of the myosin head returns to the original resting state, its orientation relative to the bound actin changing so as to pull the tail of the myosin toward the Z disk. ADP is then released to complete the cycle. Each cycle generates about 3 to 4 pN (piconewtons) of force and moves the thick filament 5 to 10 nm relative to the thin filament. Because there are many myosin heads in a thick filament,at any given moment some (probably 1% to 3%)are bound to the thin filaments. This prevents the thickfilaments from slipping backward when an individualmyosin head releases the actin subunit to which it wasbound. The thick filament thus actively slides forwardpast the adjacent thin filaments. This process, coordinatedamong the many sarcomeres in a muscle fiber,

brings about muscle contraction.

Types of muscle contraction

1. Isotonic contraction

-        tension produced exceeds the resistance (load), and the muscle fibers shorten, resulting in movement

-        Two types of isotonic contractions:

a)      Concentric- the muscle tension exceeds the resistance and the muscle shortens

b)      Eccentric- the peak tension developed is less than the resistance, and the muscle elongates owing to the contraction of another muscle or the pull of gravity.

2.      Isometric contraction

-        length of the muscle does not change because the tension produced never exceeds the resistance (load) tension is generated, but not enough to move the load

Terminologies

1.      Muscle Tone

-        In any skeletal muscle, some motor units are always active, even when the entire muscle is not contracting. Their contractions do not produce enough tension to cause movement, but they do tense and firm the muscle. This resting tension in a skeletal muscle is called muscle tone. A muscle with little muscle tone appears limp and flaccid, whereas one with moderate muscle tone is firm and solid.

2.      Hypotonia- decreased muscle tone, flaccid

3.      Flaccid paralysis- loss of muscle tone, loss of tendon reflexes, atrophy

4.      Hypertonia- increased muscle tone, spasticity or rigidity.

5.      Spasticity- increased muscle tone, increased tendon reflexes (e.g. Babinski).

6.      Rigidity- increased muscle tone where reflexes are not affected (e.g. tetanus)