10.3-10.4

• As long as Ca++ ions remain in the sarcoplasm to bind to troponin, which keeps the actin-binding sites “unshielded,” and as long as ATP is available to drive the cross-bridge cycling and the pulling of actin strands by myosin, the muscle fiber will continue to shorten to an anatomical limit.
• A cross-bridge forms between actin and the myosin heads triggering contraction. As
• contraction. As long as Ca++ ions remain in the sarcoplasm to bind to troponin, and as long as ATP is available, the muscle fiber will continue to shorten.
• Muscle contraction usually stops when signaling from the motor neuron ends, which repolarizes the sarcolemma and T-tubules, and closes the voltage-gated calcium channels in the SR. Ca++ions are then pumped back into the SR, which causes the tropomyosin to reshield (or re-cover) the binding sites on the actin strands.
• A muscle also can stop contracting when it runs out of ATP and becomes fatigued
• Thin filaments, anchored at their ends by the Z-discs, do not extend completely into the central region that only contains thick filaments, anchored at their bases at a spot called the M-line.
• When a sarcomere contracts, the Z lines move closer together, and the I band becomes smaller. The A band stays the same width. At full contraction, the thin and thick filaments overlap completely.
• The first step in the process of contraction is for Ca++ to bind to troponin so that tropomyosin can slide away from the binding sites on the actin strands.
• Each myosin head can only pull a very short distance before it has reached its limit and must be “re-cocked” before it can pull again, a step that requires ATP.
• cross-bridge cycle: myosin heads pull the actin at the binding sites, detach, re-cock, attach to more binding sites, pull, detach, re-cock, etc.
• 1. The active site on actin is exposed as calcium binds to troponin.
  2. Forming of the cross-bridge.
  3. 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.
  4. A new molecule of ATP attaches to the myosin head, causing the cross-bridge to detach.
  5. 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 (Pi) are still bound to myosin
• When Pi is released, myosin forms a stronger attachment to the actin, after which the myosin head moves toward the M-line, pulling the actin along with it.
• ATP is converted to ADP and Pi by the intrinsic ATPase activity of myosin.
• The energy released during ATP hydrolysis changes the angle of the myosin head into a cocked position
• 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, and at the end of the power stroke, the myosin head is in a low-energy position.
• each thick filament of roughly 300 myosin molecules has multiple myosin heads,
• The amount of ATP stored in muscle is very low, only sufficient to power a few seconds worth of contractions.
• There are three mechanisms by which ATP can be regenerated in muscle cells: creatine phosphate metabolism, anaerobic glycolysis, and aerobic respiration.
• 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
• Each glucose molecule produces two ATP and two molecules of pyruvic acid, which can be used in aerobic respiration or converted to lactic acid. If oxygen is not available, pyruvic acid is converted to lactic acid, which may contribute to muscle fatigue.
• Aerobic respiration is the breakdown of glucose 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.
• 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;
• 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.
• This conversion (pyruvic acid to lactic acid) allows the recycling of the enzyme NAD+ from NADH, which is needed for glycolysis to continue.
• 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.
• Aerobic respiration is the breakdown of glucose or other nutrients in the presence of oxygen (O2) to produce carbon dioxide, water, and ATP. Approximately
• 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.
• To compensate, muscles store a small amount of excess oxygen in proteins called 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.
• Muscle fatigue occurs when a muscle can no longer contract in response to signals from the nervous system.
• Muscle Fatigue Possible Factors:

  1. as ATP reserves are reduced, muscle function may decline. 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 Ca++ flow out of the SR.
  4. Long periods of sustained exercise may damage the SR and the sarcolemma, resulting in impaired Ca++ regulation.
• 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.
• oxygen debt: the amount of oxygen needed to compensate for ATP produced without oxygen during muscle contraction.