SECTION A: SKELETAL MUSCLE

1. SKELETAL MUSCLE
   1. There are three types of muscleC skeletal, smooth, and cardiac. Skeletal muscle is attached to bones and moves and supports the skeleton. Smooth muscle surrounds hollow cavities and tubes. Cardiac muscle is the muscle of the heart.

2. STRUCTURE OF SKELETAL MUSCLE
   1. Skeletal muscles, composed of cylindrical muscle fibers (cells), are linked to bones by tendons at each end of the muscle.
   2. Skeletal-muscle fibers have a repeating, striated pattern of light and dark bands, due to the location of the thick and thin filaments within the myofibrils.
   3. Actin-containing thin filaments are anchored to the Z lines at each end of a sarcomere, while their free ends partially overlap the myosin-containing thick filaments in the A band.

3. MOLECULAR MECHANISMS OF CONTRACTION
   1. When a skeletal-muscle fiber actively shortens, the thin filaments are propelled toward the center of their sarcomere by movements of the myosin cross bridges that bind to actin.
      1. The globular head of each myosin molecule contains a binding site for actin and an enzymatic site that splits ATP.
      2. The four steps occurring during each cross-bridge cycle are summarized in Figure 11-12. The cross bridges undergo repeated cycles during a contraction, each producing only a small increment of movement.
      3. The three functions of ATP in muscle contraction are summarized in Table 11-1.

   2. In a resting muscle, attachment of cross bridges to actin is prevented by tropomyosin molecules that are in contact with the actin subunits of the thin filaments.
   3. Contraction is initiated by an increase in cytosolic calcium concentration. The calcium ions bind to troponin on the thin filaments, producing a change in its shape that is transmitted via tropomyosin to the binding sites on actin, allowing the cross bridges to bind to the thin filaments.
      1. The rise in cytosolic calcium concentration is triggered by an action potential in the plasma membrane. The action potential is propagated into the interior of the fiber along the transverse tubules to the region of the sarcoplasmic reticulum, where it produces a release of calcium ions from the reticulum.
      2. Relaxation of a contracting muscle fiber is achieved by actively transporting the cytosolic calcium ions back into the sarcoplasmic reticulum.

   4. Branches of a motor neuron axon form neuromuscular junctions with many muscle fibers in a muscle. Each muscle fiber is innervated by a branch from only one motor neuron. A motor unit consists of a single motor neuron and the muscle fibers it innervates.
      1. Acetylcholine released by an action potential in a motor neuron binds to receptors on the motor end plate of the muscle membrane, opening ion channels that allow the passage of sodium and potassium ions, which depolarize the end-plate membrane.
      2. A single action potential in a motor neuron is sufficient to produce an action potential in a skeletal-muscle fiber.

   5. Table 11-2 summarizes the events leading to the contraction of a skeletal-muscle fiber.

4. MECHANICS OF SINGLE-FIBER CONTRACTION
   1. Contraction refers to the turning on of the cross-bridge cycle. Whether there is an accompanying change in muscle length depends upon the external forces acting on the muscle.
   2. Three types of contractions can occur following activation of a muscle fiber: (1) an isometric contraction: the muscle generates tension but does not change length; (2) an isotonic contraction: the muscle shortens, moving a load; and (3) a lengthening contraction: the external load on the muscle is greater than the muscle tension, causing the muscle to lengthen during the period of contractile activity.
   3. Increasing the frequency of action potentials in a muscle fiber increases the mechanical response (tension or shortening), up to the level of maximal tetanic tension.
   4. Maximum isometric tetanic tension is produced when there is a maximal overlap of thick and thin filaments, that is at the optimal length l. Stretching a fiber beyond its optimal length decreases the filament overlap and decreases the tension produced, whereas decreasing the fiber length below l also decreases the tension generated for several reasons.
   5. The velocity of muscle fiber shortening decreases with increases in load. Maximum velocity occurs at zero load.

5. SKELETAL-MUSCLE ENERGY METABOLISM
   1. Muscle fibers form ATP by the transfer of phosphate from creatine phosphate to ADP, by oxidative phosphorylation of ADP in mitochondria, and by substrate-level phosphorylation of ADP in the glycolytic pathway.
   2. At the beginning of exercise, muscle glycogen is the major fuel consumed. As the exercise proceeds, glucose and fatty acids from the blood provide most of the fuel, fatty acids becoming progressively more important during prolonged exercise. When the intensity of exercise exceeds about 70 percent of maximum, glycolysis begins to contribute an increasing fraction of the total ATP generated.
   3. Muscle fatigue is caused by a variety of factors, including internal changes in acidity, phosphate concentration, glycogen depletion, and excitation-contraction coupling failure, not by a lack of ATP.

6. TYPES OF SKELETAL-MUSCLE FIBERS
   1. Three types of skeletal-muscle fibers (slow-oxidative, fast oxidative, and fast-glycolytic fibers) can be distinguished by their maximal shortening velocities and the predominant pathway used to form ATP.
      1. Differences in maximal shortening velocities are the result of different myosin isozymes with high or low ATPase activities, giving rise to fast and slow fibers.
      2. Fast-glycolytic fibers have a larger average diameter than oxidative fibers and therefore produce greater tension, but they also fatigue more rapidly.
   2. All the muscle fibers in a single motor unit belong to the same fiber type, and most muscles contain all three types.
   3. Table 11-3 summarizes the characteristics of the three types of skeletal-muscle fibers.

7. WHOLE-MUSCLE CONTRACTION
   1. The tension produced by whole-muscle contraction depends on the amount of tension developed by each fiber and the number of active fibers in the muscle.
   2. Muscles that produce delicate movements have a small number of fibers per motor unit, whereas large postural muscles have much larger motor units.
   3. Fast-glycolytic motor units not only have large-diameter fibers but also tend to have large numbers of fibers per motor unit.
   4. Increases in muscle tension are controlled primarily by increasing the number of active motor units in a muscle, a process known as recruitment. Slow-oxidative motor units are recruited first during weak contractions, then fast-oxidative motor units, and finally fast-glycolytic motor units during very strong contractions.
   5. Increasing motor unit recruitment increases the velocity at which a muscle will move a given load.
   6. The strength and susceptibility to fatigue of a muscle can be altered by exercise.
      1. Long-duration, low-intensity exercise increases a fiber's capacity for oxidative ATP production by increasing the number of mitochondria and blood vessels in the muscle, resulting in increased endurance.
      2. Short-duration, high-intensity exercise increases fiber diameter as a result of increased synthesis of actin and myosin, resulting in increased strength.

   7. Movement around a joint requires two antagonistic groups of muscles: One flexes the limb at the joint, and the other extends the limb.
   8. The lever system of muscles and bones requires muscle tensions far greater than the load in order to sustain a load in an isometric contraction. The advantage of the lever system is that it produces a shortening velocity at the end of the lever arm that is greater than the muscle-shortening velocity.

SECTION B: SMOOTH MUSCLE

1. STRUCTURE
   1. Smooth-muscle fibers are spindle-shaped cells that lack striations, have a single nucleus, and are capable of cell division. They contain actin and myosin filaments and contract by a sliding-filament mechanism.

2. CONTRACTION AND ITS CONTROL
   1. An increase in cytosolic calcium leads to the binding of calcium by calmodulin. The calcium-calmodulin complex then binds to myosin light-chain kinase, activating the enzyme, which uses ATP to phosphorylate smooth-muscle myosin. In smooth muscle only phosphorylated myosin is able to bind to actin and undergo cross-bridge cycling.
   2. Smooth-muscle myosin has a low rate of ATP splitting, resulting in a much slower shortening velocity than found in striated muscles. However, the tension produced per unit cross-sectional area is equivalent to that of skeletal muscle.
   3. The two sources of the cytosolic calcium ions that initiate smooth-muscle contraction are the sarcoplasmic reticulum and extracellular calcium. The opening of calcium channels in the smooth-muscle plasma membrane and sarcoplasmic reticulum, mediated by a variety of factors, allows calcium ions to enter the cytosol.
   4. The increase in cytosolic calcium resulting from most stimuli does not activate all the cross bridges in smooth muscle. Therefore smooth-muscle tension can be increased by agents that increase the concentration of cytosolic calcium ions.
   5. Table 11-5 summarizes the types of stimuli that can initiate smooth-muscle contraction by opening or closing calcium channels in the plasma membrane or sarcoplasmic reticulum.
   6. Most, but not all, smooth-muscle cells can generate action potentials in their plasma membrane upon membrane depolarization. The rising phase of the smooth-muscle action potential is due to the influx of calcium ions into the cell through open calcium channels.
   7. Some smooth muscles generate action potentials spontaneously, in the absence of any external input, because of pacemaker potentials in the plasma membrane that repeatedly depolarize the membrane to threshold.
   8. Smooth-muscle cells do not have a specialized end-plate region. A number of smooth-muscle fibers may be influenced by neurotransmitters released by a single nerve ending, and a single smooth-muscle fiber may be influenced by neurotransmitters from more than one neuron. Neurotransmitters may have either excitatory or inhibitory effects on smooth-muscle contraction.
   9. Smooth muscles can be classified broadly as single-unit or multiunit smooth muscle.