The Sliding Filament Model of Contraction

The sliding filament model of contraction can be used to demonstrate the process of muscle contraction (Figure 10.10). When signaled by a motor neuron, a skeletal muscle fiber contracts as actin is pulled and then slides past the myosin within the fiber’s sarcomeres. The sliding can only occur when myosin-binding sites on the actin filaments are exposed by a series of steps as explained above.

When a sarcomere contracts, the Z lines, or the junction of actin filaments marking the boundaries of each sarcomere, move closer together.  The I bands, or areas of myosin only, becomes smaller. The A band, or areas of both actin and myosin, stays the same width. At full contraction, the actin and myosin filaments overlap completely.

LABEL RELAXED VS CONTRACTED MUSCLE & ACTIN VS MYOSIN & SARCOMERE IN IMAGE + Change fig #s if necessary:

Figure 10.10 The Sliding Filament Model of Muscle Contraction. Z lines anchor the ends of actin filaments marking the boundaries of each sarcomere. The M line is the attachment site for thick filaments and is in the center of the A band. The H band is a region which contains only myosin while I bands contain only actin. The A band is the site where filament movement starts and contains both actin and myosin and has a dense appearance. A myofibril is composed of many sarcomeres running along its length; thus, myofibrils and muscle cells contract as the sarcomeres contract.

ATP and Muscle Contraction

Tropomyosin (a protein that winds around actin and covers actin’s myosin-binding sites) binds to troponin to form a complex. This troponin-tropomyosin complex prevents the myosin “heads” from binding to the active sites on the actin microfilaments. To initiate muscle contraction, tropomyosin has to expose the myosin-binding site on an actin filament. The first step in the process of contraction is for Ca²⁺ to bind to Ca²⁺ binding sites on troponin so that tropomyosin can slide away from the binding sites on the actin strands. This allows the myosin heads to bind to these exposed binding sites and form cross-bridges. The actin filaments are then pulled by the myosin heads to slide past the myosin filaments toward the center of the sarcomere. But each head can only pull a very short distance before it has reached its limit and must be “re-cocked” (or reset) before it can pull again, a step that requires energy provided by ATP.

For actin filaments to continue to slide past myosin filaments during muscle contraction, myosin heads must:

1. Pull the actin at the binding sites
2. Detach
3. Re-cock (reset)
4. Repeat (attach to more binding sites)

This repeated movement is known as the cross-bridge cycle. This motion of the myosin heads is similar to the oars when an individual rows a boat: The paddle of the oars (the myosin heads) pull, are lifted from the water (detach), repositioned (re-cocked) and then immersed again to pull (Figure 10.11).

Figure 10.11 Skeletal Muscle Contraction. (a) The active site on actin is exposed as Ca²⁺ binds to troponin. (b) The myosin (thick filament) head is attracted to actin (thin filament), and myosin binds actin at its actin-binding site, forming the cross-bridge. (c) During the power stroke, the phosphate generated in the previous contraction cycle is released. This results in the myosin head pivoting toward the center of the sarcomere, after which the attached ADP and phosphate group are released. (d) A new molecule of ATP attaches to the myosin head, causing the cross-bridge to detach. (e) The myosin head hydrolyzes ATP to ADP and phosphate, which returns the myosin to the cocked position.

Cross-bridge formation occurs when the myosin head attaches to the actin while adenosine diphosphate (ADP) and inorganic phosphate (P_i) are still bound to myosin (Figure 10.11a,b). P_i is then released, causing myosin to form a stronger attachment to the actin, after which the myosin head moves toward the M-line, pulling the actin along with it. The filaments move approximately 10 nm toward the M-line. This movement is called the power stroke (Figure 10.11c). In the absence of ATP, the myosin head will not detach from actin.

One part of the myosin head attaches to the binding site on the actin, but has another binding site for ATP that allows the myosin head to detach from the actin (Figure 10.11d). After this occurs, ATP is converted to ADP and P_i by the intrinsic ATPase activity of myosin. The energy released during ATP hydrolysis changes the angle of the myosin head into a cocked position (Figure 10.11e). The myosin head is now in position for further movement.

When the myosin head is cocked, myosin 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 formed cross-bridge is still in place, and actin and myosin are bound together. As long as ATP is available, it readily attaches to myosin, the cross-bridge cycle can recur, and muscle contraction can continue.

Note that each thick filament of roughly 300 myosin molecules has multiple myosin heads, and many cross-bridges form and break continuously during muscle contraction. Multiply this by all of the sarcomeres in one myofibril, all the myofibrils in one muscle fiber, and all of the muscle fibers in one skeletal muscle, and you can understand why so much ATP is needed to keep skeletal muscles working. In fact, it is the loss of ATP that results in the rigor mortis observed soon after someone dies. With no further ATP production possible, there is no ATP available for myosin heads to detach from the myosin-binding sites on actin, so the cross-bridges stay in place, causing the rigidity in the skeletal muscles.

Relaxation of a Skeletal Muscle

Sources of ATP

In addition to its direct role in the cross-bridge cycle, ATP also provides the energy for the active-transport Ca²⁺ pumps in the SR. Muscle contraction does not occur without sufficient amounts of ATP. The amount of ATP stored in muscle is very low, only sufficient to power a few seconds worth of contractions. As it is broken down, ATP must therefore be regenerated and replaced quickly to allow for sustained contraction. There are three mechanisms by which ATP can be regenerated: creatine phosphate metabolism, anaerobic glycolysis, and fermentation and aerobic respiration.

Creatine Phosphate Metabolism

Creatine phosphate is a molecule that can store energy in its phosphate bonds. In a resting muscle, excess ATP transfers its energy to creatine, producing ADP and creatine phosphate. This acts as an energy reserve that can be used to quickly create more ATP. When the muscle starts to contract and needs energy, creatine phosphate transfers its phosphate back to ADP to form ATP and creatine. This reaction is catalyzed by the enzyme creatine kinase and occurs very quickly; thus, creatine phosphate-derived ATP powers the first few seconds of muscle contraction. However, creatine phosphate can only provide approximately 15 seconds worth of energy, at which point another energy source has to be used (Figure 10.12a).

Anaerobic Glycolysis

As the ATP produced by creatine phosphate is depleted, muscles turn to glycolysis as an ATP source. Glycolysis is an anaerobic process that breaks down glucose (sugar) to produce ATP; however, glycolysis cannot generate ATP as quickly as creatine phosphate. Thus, the switch to glycolysis results in a slower rate of ATP availability to the muscle. The sugar used in glycolysis can be provided by blood glucose or by metabolizing glycogen that is stored in the muscle. The breakdown of one glucose molecule produces two ATP and two molecules of pyruvic acid, which can be used in aerobic respiration or converted to lactic acid when oxygen levels are low (Figure 10.12b).

Lactic Acid Fermentation and Aerobic Respiration

If oxygen is available, pyruvic acid is used in aerobic respiration. However, if oxygen is not available, pyruvic acid is converted to lactic acid, which may contribute to muscle fatigue. This conversion allows the recycling of the enzyme NAD⁺ from NADH, which is needed for glycolysis to continue. This occurs during strenuous exercise when high amounts of energy are needed but oxygen cannot be sufficiently delivered to muscle. Glycolysis itself cannot be sustained for very long (approximately 1 minute of muscle activity), but it is useful in facilitating short bursts of high-intensity output. This is because glycolysis does not utilize glucose very efficiently, producing a net gain of two ATPs per molecule of glucose, and the end product of lactic acid, which may contribute to muscle fatigue as it accumulates.

Aerobic respiration is the breakdown of glucose or other nutrients in the presence of oxygen (O₂) to produce carbon dioxide, water, and ATP. Approximately 95 percent of the ATP required for resting or moderately active muscles is provided by aerobic respiration, which takes place in mitochondria. The inputs for aerobic respiration include glucose circulating in the bloodstream, pyruvic acid, and fatty acids. Aerobic respiration is much more efficient than anaerobic glycolysis, producing approximately 36 ATPs per molecule of glucose versus four from glycolysis. However, aerobic respiration cannot be sustained without a steady supply of O₂ to the skeletal muscle and is much slower (Figure 10.12c). To compensate, muscles store small amount of excess oxygen in proteins call myoglobin, allowing for more efficient muscle contractions and less fatigue. Aerobic training also increases the efficiency of the circulatory system so that O₂ can be supplied to the muscles for longer periods of time.

Figure 10.12Muscle Metabolism.(a) Creatine conversion (b) Glycolysis of one glucose produces two ATP and two molecules of pyruvic acid, which can be used in aerobic respiration or converted to lactic acid. (c) Aerobic respiration is the breakdown of glucose in the presence of oxygen (O₂) to produce carbon dioxide, water, and ATP. 

Muscle fatigue occurs when a muscle can no longer contract in response to signals from the nervous system. The exact causes of muscle fatigue are not fully known, but certain factors have been noted:

1. ATP is needed for normal muscle contraction, and as ATP reserves are reduced, muscle function may decline. Although, this may be more of a factor in brief, intense muscle output rather than sustained, lower intensity efforts.
2. Lactic acid buildup may lower intracellular pH, affecting enzyme and protein activity.
3. Imbalances in Na⁺ and K⁺ levels as a result of membrane depolarization may disrupt Ca²⁺ flow out of the SR.
4. Long periods of sustained exercise may damage the SR and the sarcolemma, resulting in impaired Ca²⁺ regulation.

Intense muscle activity results in an oxygen debt, which is the amount of oxygen needed to compensate for ATP produced without oxygen during muscle contraction. Oxygen is required to restore ATP and creatine phosphate levels, convert lactic acid to pyruvic acid, and, in the liver, to convert lactic acid into glucose or glycogen. Other systems used during exercise also require oxygen, and all of these combined processes result in the increased breathing rate that occurs after exercise. Until the oxygen debt has been met, oxygen intake is elevated, even after exercise has stopped.