Skeletal muscle fibers are quite different from the "typical" cells we described in Chapter 3. One obvious difference is size: Skeletal muscle fibers are enormous. A muscle fiber from a thigh muscle could have a diameter of 100 µm and a length equal to that of the entire muscle (up to 30 cm, or 12 in.). A second obvious difference is that skeletal muscle fibers are multinucleate: Each skeletal muscle fiber contains hundreds of nuclei just internal to the cell membrane (Figure 10-2). The genes in these nuclei direct the production of enzymes and structural proteins required for normal muscle contraction, and the presence of multiple copies of these genes speeds up the process. This feature is important because metabolic turnover tends to be very rapid in skeletal muscle fibers.

The distinctive features of size and multiple nuclei are related. During development, groups of embryonic cells called myoblasts fuse, forming individual skeletal muscle fibers (Figure 10-2a). Each nucleus in a skeletal muscle fiber reflects the contribution of a single myoblast. Some myoblasts, however, do not fuse with developing muscle fibers. These unfused cells remain in adult skeletal muscle tissue as the satellite cells seen in Figures 10-1 and 10-2a. After an injury, satellite cells may enlarge, divide, and fuse with damaged muscle fibers, thereby assisting in the regeneration of the tissue.

The Sarcolemma and Transverse Tubules

The sarcolemma, or cell membrane of a muscle fiber, surrounds the sarcoplasm, or cytoplasm of the muscle fiber (Figure 10-3a). Like other cell membranes, the sarcolemma has a characteristic transmembrane potential due to the unequal distribution of positive and negative charges across the membrane. In a skeletal muscle fiber, a sudden change in the transmembrane potential is the first step that leads to a contraction.

A skeletal muscle fiber is very large, but all regions of the cell must contract simultaneously. Thus, the signal to contract must be distributed quickly throughout the interior of the cell. This signal is conducted through the transverse tubules. Transverse tubules, or T tubules, are narrow tubes that are continuous with the sarcolemma and extend into the sarcoplasm at right angles to the cell surface (Figure 10-3b). Filled with extracellular fluid, T tubules form passageways through the muscle fiber, like a series of tunnels through a mountain. The T tubules have the same general properties as the sarcolemma. Electrical impulses conducted by the sarcolemma travel along the T tubules. These impulses, or action potentials, are the trigger for muscle fiber contraction.

Myofibrils

Inside the muscle fiber, branches of the transverse tubules encircle cylindrical structures called myofibrils (Figure 10-3). A myofibril is 1-2 µm in diameter and as long as the entire cell. Each skeletal muscle fiber contains hundreds to thousands of myofibrils.

Myofibrils consist of bundles of myofilaments, protein filaments composed primarily of actin and myosin. The actin forms the bulk of thin filaments, and the myosin forms thick filaments. We introduced both types of filaments in Chapter 3.  Myofibrils, which can actively shorten, are responsible for skeletal muscle fiber contraction. At each end of the skeletal muscle fiber, the myofibrils are anchored to the inner surface of the sarcolemma. In turn, the outer surface of the sarcolemma is attached to collagen fibers of the tendon or aponeurosis of the skeletal muscle. As a result, when the myofibrils contract, the entire cell shortens. In doing so, it pulls on the tendon. Scattered among and around the myofibrils are mitochondria and granules of glycogen, the storage form of glucose. Glucose breakdown through glycolysis and mitochondrial activity provides the ATP needed to power muscular contractions.

The Sarcoplasmic Reticulum

Wherever a transverse tubule encircles a myofibril, the tubule is tightly bound to the membranes of the sarcoplasmic reticulum. The sarcoplasmic reticulum (SR) is a membrane complex similar to the smooth endoplasmic reticulum of other cells. In skeletal muscle fibers, the SR forms a tubular network around each individual myofibril (Figure 10-3b). On either side of a T tubule, the tubules of the SR enlarge, fuse, and form expanded chambers called terminal cisternae. The combination of a pair of terminal cisternae plus a transverse tubule is known as a triad. Although the membranes of the triad are tightly bound together, their fluid contents are separate and distinct.

In Chapter 3, we noted the existence of special ion pumps that keep the intracellular concentration of calcium ions (Ca²⁺) very low.  Most cells pump the calcium ions across their cell membranes and into the extracellular fluid. Although skeletal muscle fibers do pump Ca²⁺ out of the cell in this way, they also remove calcium ions from the sarcoplasm by actively transporting them into the terminal cisternae of the sarcoplasmic reticulum. The sarcoplasm of a resting skeletal muscle fiber contains very low concentrations of Ca²⁺, around 10^–7 mmol/l. The free Ca²⁺ concentration inside the terminal cisternae may be as much as 1000 times higher. In addition, cisternae contain the protein calsequestrin, which reversibly binds Ca²⁺. Including both the free calcium and the bound calcium, the total concentration of Ca²⁺ inside cisternae can be 40,000 times that of the surrounding sarcoplasm.

A muscle contraction begins when stored calcium ions are released into the sarcoplasm. These ions then diffuse into individual contractile units called sarcomeres.

Sarcomeres

As we have seen, myofibrils are bundles of thin and thick filaments. These myofilaments are organized into repeating functional units called sarcomeres.

Sarcomere Organization A myofibril consists of approximately 10,000 sarcomeres end to end. Each sarcomere has a resting length of 1.6-2.6 µm. Sarcomeres are the smallest functional units of the muscle fiber. Interactions between the thick and thin filaments of sarcomeres are responsible for muscle contraction. A sarcomere contains (1) thick filaments, (2) thin filaments, (3) proteins that stabilize the positions of the thick and thin filaments, and (4) proteins that regulate the interactions between thick and thin filaments.

Differences in the size, density, and distribution of thick filaments and thin filaments account for the banded appearance of each myofibril (Figure 10-4). There are dark bands (A bands) and light bands (I bands). The names of these bands are derived from anisotropic and isotropic, which refer to the appearance of these bands when they are viewed under polarized light. You may find it helpful to remember that A bands are dArk and that I bands are lIght in a typical light micrograph.

The A Band The thick filaments are located at the center of a sarcomere, in the A band. The length of the A band is equal to the length of a typical thick filament. The A band, which also includes portions of thin filaments, contains the following three subdivisions (Figure 10-4):

1.The M line. The central portion of each thick filament is connected to its neighbors by proteins of the M line. These dark-staining proteins help stabilize the positions of the thick filaments.

2.The H zone. In a resting sarcomere, the H zone, or H band, is a lighter region on either side of the M line. The H zone contains thick filaments but no thin filaments.

3.The zone of overlap. In the zone of overlap, thin filaments are situated between the thick filaments. In this region, each thin filament is surrounded by three thick filaments, and each thick filament is surrounded by six thin filaments.

The cross-sectional views in Figure 10-5 should help you visualize these features of the three dimensional structure of the sarcomere.

The I Band Each I band, which contains thin filaments but not thick filaments, extends from the A band of one sarcomere to the A band of the next sarcomere. Z lines mark the boundary between adjacent sarcomeres. The Z lines consist of proteins called connectins, which interconnect thin filaments of adjacent sarcomeres. From the Z lines at either end of the sarcomere, thin filaments extend toward the M line and into the zone of overlap. Strands of the protein titin extend from the tips of the thick filaments to attachment sites at the Z line (Figure 10-5b). Titin helps keep the thick and thin filaments in proper alignment; it also helps the muscle fiber resist extreme stretching that would otherwise disrupt the contraction mechanism.

Two transverse tubules encircle each sarcomere, and triads are located on each side of the M line at the zone of overlap. As a result, calcium ions released by the SR enter the regions where thick and thin filaments can interact.

Each Z line is surrounded by a meshwork of intermediate filaments that interconnect adjacent myofibrils. The myofibrils closest to the sarcolemma are bound to attachment sites on the inside of the membrane. Because the Z lines of all the myofibrils are aligned in this way, the muscle fiber as a whole has a banded appearance (Figure 10-2b). These bands, or striations, are visible with the light microscope, so skeletal muscle tissue is also known as striated muscle.

Figure 10-6 reviews the levels of organization we have discussed so far. We shall now consider the molecular structure of the myofilaments responsible for muscle contraction.

Thin Filaments A typical thin filament is 5–6 nm in diameter and 1 µm in length (Figure 10-7a ). A single thin filament contains four proteins: F actin, nebulin, tropomyosin, and troponin:

1. F actin is a twisted strand composed of two rows of 300–400 individual globular molecules of G actin (Figure 10-7b). A long strand of nebulin spirals along the F actin strand in the cleft between the rows of G actin molecules. Nebulin holds the F actin strand together; as thin filaments develop, the length of the nebulin molecule probably determines the length of the F actin strand. Each molecule of G actin contains an active site that can bind to a thick filament much as a substrate molecule binds to the active site of an enzyme.  Under resting conditions, myosin binding is prevented by the troponin–tropomyosin complex.

2.Strands of tropomyosin cover the active sites and prevent actin–myosin interaction (Figure 10-7b). A tropomyosin molecule is a double-stranded protein that covers seven active sites. It is bound to one molecule of troponin midway along its length.

3.A troponin molecule consists of three globular subunits. One subunit binds to tropomyosin, locking them together as a troponin–tropomyosin complex; a second subunit binds to one G actin, holding the troponin–tropomyosin complex in position; the third subunit has a receptor that binds a calcium ion. In a resting muscle, intracellular Ca²⁺ concentrations are very low and that binding site is empty.

A contraction cannot occur unless the position of the troponin–tropomyosin complex changes, exposing the active sites on F actin. The necessary change in position occurs when calcium ions bind to receptors on the troponin molecules.

At either end of the sarcomere, the thin filaments are attached to the Z line (Figure 10-7a). Although it is called a line because it looks like a dark line on the surface of the myofibril, the Z line in sectional view is more like an open meshwork (Figure 10-5b). For this reason, the Z line is often called the Z disc.

Thick Filaments Thick filaments are 10–12 nm in diameter and 1.6 µm long (Figure 10-7c). Each thick filament consists of roughly 500 myosin molecules. Each myosin molecule consists of a pair of myosin subunits twisted around one another (Figure 10-7d). The long, attached tail is bound to other myosin molecules in the thick filament. The free head, which projects outward toward the nearest thin filament, consists of two globular protein subunits. Because myosin heads interact with thin filaments during a contraction, they are also known as cross-bridges. The connection between the head and the tail functions as a hinge that lets the head pivot at its base. When pivoting occurs, the head swings toward or away from the M line. As we will see in a later section, this pivoting is the key step in muscle contraction.

All the myosin molecules are arranged with their tails pointing toward the M line (Figure 10-7c). The H zone includes a central region where there are no myosin heads. Elsewhere, the myosin heads are arranged in a spiral, each facing one of the surrounding thin filaments.

Each thick filament has a core of titin. On either side of the M line, a strand of titin extends the length of the thick filament and then continues across the I band to the Z line on that side. The portion of the titin strand exposed within the I band is highly elastic and will recoil after stretching. In the normal resting sarcomere, the titin strands are completely relaxed; they become tense only when some external force stretches the sarcomere.

 How would severing the tendon attached to a muscle affect the muscle's ability to move a body part?

 Why does skeletal muscle appear striated when viewed through a microscope?

 Where would you expect the greatest concentration of Ca²⁺ in resting skeletal muscle to be?

Abnormalities in the genes that code for structural and functional proteins in muscle fibers are responsible for a number of inherited diseases collectively known as the muscular dystrophies. These conditions, which cause a progressive muscular weakness and deterioration, are the result of abnormalities in the sarcolemma or in the structure of internal proteins. The best-known example is Duchenne’s muscular dystrophy, which typically develops in males from 3 to 7 years old. The Muscular Dystrophies