Contraction of skeletal muscle

Learning objectives What evidence supports the sliding filament mechanism of muscle contraction? How does the sliding filament mechanism cause a muscle to contract and relax? Where does the energy for muscle contraction come from?

Muscle Contraction Knowing the structure of the sarcomere enables us to understand what happens when a muscle contracts. The mechanism of muscle contraction can be deduced by comparing electron micrographs of relaxed and contracted muscle:

The Sliding Filament Theory These show that each sarcomere gets shorter when the muscle contracts, so the whole muscle gets shorter. But the dark band, which represents the thick filament, does not change in length. This shows that the filaments don’t contract themselves, but instead they slide past each other.

The Sliding Filament Theory What makes the filaments slide past each other? Energy is provided by the splitting of ATP, and the ATPase that does this splitting is located in the myosin cross bridge head. These cross bridges can also attach to actin, so they are able to cause the filament sliding by "walking" along the thin filament. This cross bridge walking is called the cross bridge cycle, and it has 4 steps. One step actually causes the sliding, while the other 3 simply reset the cross bridge back to its starting state.

The Sliding Filament Theory 1. The cross bridge swings out from the thick filament and attaches to the thin filament. [Put oars in water.] 2. The cross bridge changes shape and rotates through 45°, causing the filaments to slide. The energy from ATP splitting is used for this "power stroke" step, and the products (ADP + Pi) are released. [Pull oars to drive boat through water.] 3. A new ATP molecule binds to myosin and the cross bridge detaches from the thin filament. [push oars out of water.] 4. The cross bridge changes back to its original shape, while detached (so as not to push the filaments back again). It is now ready to start a new cycle, but further along the thin filament. [push oars into starting position.] One ATP molecule is split by each cross bridge in each cycle, which takes a few milliseconds. During a contraction, thousands of cross bridges in each sarcomere go through this cycle thousands of times. Fortunately the cross bridges are all out of synch, so there are always many cross bridges attached at any time to maintain the force.

How is the cross bridge cycle switched off in a relaxed muscle? This is where the regulatory proteins on the thin filament, troponin and tropomyosin, are involved. Tropomyosin is a long thin molecule, and it can change its position on the thin filament. In a relaxed muscle it is on the outside of the filament, covering the actin molecules so that myosin cross bridges can’t attach. This is why relaxed muscle is compliant: there are no connections between the thick and thin filaments. In a contracting muscle the tropomyosin has moved into the groove of the double helix, revealing the actin molecules and allowing the cross bridges to attach.

Cross-section of actin filament Actin Myosin head binding site Tropomysin Troponin Here calcium has bound to the troponin to move tropomysin and allow the myosin heads to bind.

T-System Transverse system (T-tubules) – an infolding of the sarcolemma (membrane surrounding muscle fibre) that spread across the muscle fibre. Sarcoplasmic Reticulum – accumulates calcium ions in a resting muscle. The depolarisation of the muscle spread across the sarcolemma and into the T-tubules and the sarcoplasmic reticulum Calcium ions are released into the sarcoplasm (cytoplasm of muscle fibre)

The Neuromuscular Junction 1.A muscle is supplied with only one nerve fibre 2.There is no threshold for stimulation – if an impulse arrives at the motor end plate it will always stimulate the muscle fibre.

Controlling Contraction 1. An action potential arrives at the end of a motor neurone, at the neuromuscular junction. 2. This causes the release of the neurotransmitter acetylcholine. 3 This initiates an action potential in the muscle cell membrane. 4. This action potential is carried quickly throughout the large muscle cell by invaginations in the cell membrane called T- tubules. 5. The action potential causes the sarcoplasmic reticulum (large membrane vesicles) to release its store of calcium into the myofibrils. 6. The calcium binds to troponin on the thin filament, which changes shape, moving tropomyosin into the groove in the process. 7. Myosin cross bridges can now attach and the cross bridge cycle can take place.

Axon terminal - motor end plate Neurotransmitter = acetylcholine