46 Introduction to Skeletal Muscle

Structure and Function of the Muscular System

The muscular system controls numerous functions, which is possible with the significant differentiation of muscle tissue morphology and ability.

The Musculoskeletal System

The muscular system is made up of muscle tissue and is responsible for functions such as maintenance of posture, locomotion and control of various circulatory systems. This includes the beating of the heart and the movement of food through the digestive system. The muscular system is closely associated with the skeletal system in facilitating movement. Both voluntary and involuntary muscular system functions are controlled by the nervous system.

The muscular system: Skeletal muscle of the muscular system is closely associated with the skeletal system and acts to maintain posture and control voluntary movement.

Muscle is a highly-specialized soft tissue that produces tension which results in the generation of force. Muscle cells, or myocytes, contain myofibrils comprised of actin and myosin myofilaments which slide past each other producing tension that changes the shape of the myocyte. Numerous myocytes make up muscle tissue and the controlled production of tension in these cells can generate significant force.

Muscle tissue can be classified functionally as voluntary or involuntary and morphologically as striated or non-striated. Voluntary refers to whether the muscle is under conscious control, while striation refers to the presence of visible banding within myocytes caused by the organization of myofibrils to produce constant tension.

Types of Muscle

The above classifications describe three forms of muscle tissue that perform a wide range of diverse functions.

Skeletal Muscle

Skeletal muscle mainly attaches to the skeletal system via tendons to maintain posture and control movement. For example, contraction of the biceps muscle, attached to the scapula and radius, will raise the forearm. Some skeletal muscle can attach directly to other muscles or to the skin, as seen in the face where numerous muscles control facial expression.

Skeletal muscle is under voluntary control, although this can be subconscious when maintaining posture or balance. Morphologically skeletal myocytes are elongated and tubular and appear striated with multiple peripheral nuclei.

Cardiac Muscle Tissue

Cardiac muscle tissue is found only in the heart, where cardiac contractions pump blood throughout the body and maintain blood pressure.

As with skeletal muscle, cardiac muscle is striated; however it is not consciously controlled and so is classified as involuntary. Cardiac muscle can be further differentiated from skeletal muscle by the presence of intercalated discs that control the synchronized contraction of cardiac tissues. Cardiac myocytes are shorter than skeletal equivalents and contain only one or two centrally located nuclei.

Smooth Muscle Tissue

Smooth muscle tissue is associated with numerous organs and tissue systems, such as the digestive system and respiratory system. It plays an important role in the regulation of flow in such systems, such as aiding the movement of food through the digestive system via peristalsis.

Smooth muscle is non-striated and involuntary. Smooth muscle myocytes are spindle shaped with a single centrally located nucleus.

Types of muscle: The body contains three types of muscle tissue: skeletal muscle, smooth muscle, and cardiac muscle, visualized here using light microscopy. Visible striations in skeletal and cardiac muscle are visible, differentiating them from the more randomised appearance of smooth muscle.

Slow-Twitch and Fast-Twitch Muscle Fibers

Skeletal muscle contains different fibers which allow for both rapid short-term contractions and slower, repeatable long-term contractions.

Skeletal muscle fibers can be further subdivided into slow and fast-twitch subtypes depending on their metabolism and corresponding action. Most muscles are made up of combinations of these fibers, although the relative number substantially varies.

Slow Twitch (Type 1)

Slow-twitch fibers are designed for endurance activities that require long-term, repeated contractions, like maintaining posture or running a long distance. The ATP required for slow-twitch fiber contraction is generated through aerobic respiration (glycolysis and Krebs cycle), whereby 30 molecules of ATP are produced from each glucose molecule in the presence of oxygen. The reaction is slower than anaerobic respiration and thus not suited to rapid movements, but much more efficient, which is why slow-twitch muscles do not tire quickly. However, this reaction requires the delivery of large amounts of oxygen to the muscle, which can rapidly become rate-limiting if the respiratory and circulatory systems cannot keep up.

Due to their large oxygen requirements, slow-twitch fibers are associated with large numbers of blood vessels, mitochondria, and high concentrations of myoglobin, an oxygen-binding protein found in the blood that gives muscles their reddish color. One muscle with many slow-twitch fibers is the soleus muscle in the leg (~80% slow-twitch), which plays a key role in standing.

Fast Twitch (Type II)

Fast-twitch fibers are good for rapid movements like jumping or sprinting that require fast muscle contractions of short duration. Unlike slow-twitch fibers, fast twitch-fibers rely on anaerobic respiration (glycolysis alone) to produce two molecules of ATP per molecule of glucose. While much less efficient than aerobic respiration, it is ideal for rapid bursts of movement since it is not rate limited by need for oxygen. Lactate (lactic acid), a byproduct of anaerobic respiration, accumulates in the muscle tissue reducing the pH (making it more acidic, and producing the stinging feeling in muscles when exercising). This inhibits further anaerobic respiration. While this may seem counter-intuitive, it is a feedback cycle in place to protect the muscles from over-exertion and resultant damage.

As fast-twitch fibers generally do not require oxygenation, they contain fewer blood vessels and mitochondria than slow-twitch fibers and less myoglobin, resulting in a paler color. Muscles controlling eye movements contain high numbers of fast-twitch fibers (~85% fast-twitch).

Determination and Alteration of Muscle Type

While there is evidence that each person has a unique proportion of fast-twitch versus slow-twitch muscles determined by genetics, more research is required. Regardless, repeated exercise that prioritizes one type of muscle fiber use over the other can lead to improvements in an individual’s ability to perform that activity through alterations in the number and composition of fibers associated with improvements in the respiratory and circulatory systems.

Sliding Filament Model of Contraction

In the sliding filament model, the thick and thin filaments pass each other, shortening the sarcomere.

Movement often requires the contraction of a skeletal muscle, as can be observed when the bicep muscle in the arm contracts, drawing the forearm up towards the trunk. The sliding filament model describes the process used by muscles to contract. It is a cycle of repetitive events that causes actin and myosin myofilaments to slide over each other, contracting the sarcomere and generating tension in the muscle.

Sarcomere Structure

To understand the sliding filament model requires an understanding of sarcomere structure. A sarcomere is defined as the segment between two neighboring, parallel Z-lines. Z lines are composed of a mixture of actin myofilaments and molecules of the highly elastic protein titin crosslinked by alpha-actinin. Actin myofilaments attach directly to the Z-lines, whereas myosin myofilaments attach via titin molecules.

Surrounding the Z-line is the I-band, the region where actin myofilaments are not superimposed by myosin myofilaments. The I-band is spanned by the titin molecule connecting the Z-line with a myosin filament.

The region between two neighboring, parallel I-bands is known as the A-band and contains the entire length of single myosin myofilaments. Within the A-band is a region known as the H-band, which is the region not superimposed by actin myofilaments. Within the H-band is the M-line, which is composed of myosin myofilaments and titin molecules crosslinked by myomesin.

Titin molecules connect the Z-line with the M-line and provide a scaffold for myosin myofilaments. Their elasticity provides the underpinning of muscle contraction. Titin molecules are thought to play a key role as a molecular ruler maintaining parallel alignment within the sarcomere. Another protein, nebulin, is thought to perform a similar role for actin myofilaments.

Model of Contraction

The molecular mechanism whereby myosin and acting myofilaments slide over each other is termed the cross-bridge cycle. During muscle contraction, the heads of myosin myofilaments quickly bind and release in a ratcheting fashion, pulling themselves along the actin myofilament.

At the level of the sliding filament model, expansion and contraction only occurs within the I and H-bands. The myofilaments themselves do not contract or expand and so the A-band remains constant.

The sarcomere and the sliding filament model of contraction: During contraction myosin ratchets along actin myofilaments compressing the I and H bands. During stretching this tension is release and the I and H bands expand. The A-band remains constant throughout as the length of the myosin myofilaments does not change.

The amount of force and movement generated generated by an individual sarcomere is small. However, when multiplied by the number of sarcomeres in a myofibril, myofibrils in a myocyte and myocytes in a muscle, the amount of force and movement generated is significant.

ATP and Muscle Contraction

ATP is critical for muscle contractions because it breaks the myosin-actin cross-bridge, freeing the myosin for the next contraction.

ATP and Muscle Contraction

Cross-bridge muscle contraction cycle: The cross-bridge muscle contraction cycle, which is triggered by Ca2+ binding to the actin active site, is shown. With each contraction cycle, actin moves relative to myosin.

Muscles contract in a repeated pattern of binding and releasing between the two thin and thick strands of the sarcomere. ATP is critical to prepare myosin for binding and to “recharge” the myosin.

The Cross-Bridge Muscle Contraction Cycle

ATP first binds to myosin, moving it to a high-energy state. The ATP is hydrolyzed into ADP and inorganic phosphate (P_i) by the enzyme ATPase. The energy released during ATP hydrolysis changes the angle of the myosin head into a “cocked” position, ready to bind to actin if the sites are available. ADP and Pi remain attached; myosin is in its high energy configuration.

The muscle contraction cycle is triggered by calcium ions binding to the protein complex troponin, exposing the active-binding sites on the actin. As soon as the actin-binding sites are uncovered, the high-energy myosin head bridges the gap, forming a cross-bridge. Once myosin binds to the actin, the P_i is released, and the myosin undergoes a conformational change to a lower energy state. As myosin expends the energy, it moves through the “power stroke,” pulling the actin filament toward the M-line. When the actin is pulled approximately 10 nm toward the M-line, the sarcomere shortens and the muscle contracts. At the end of the power stroke, the myosin is in a low-energy position.

After the power stroke, ADP is released, but the cross-bridge formed is still in place. ATP then binds to myosin, moving the myosin to its high-energy state, releasing the myosin head from the actin active site. ATP can then attach to myosin, which allows the cross-bridge cycle to start again; further muscle contraction can occur. Therefore, without ATP, muscles would remain in their contracted state, rather than their relaxed state.

Control of Muscle Tension

Muscle tension is influenced by the number of cross-bridges that can be formed.

Control of Muscle Tension

Neural control initiates the formation of actin – myosin cross-bridges, leading to the sarcomere shortening involved in muscle contraction. These contractions extend from the muscle fiber through connective tissue to pull on bones, causing skeletal movement. The pull exerted by a muscle is called tension. The amount of force created by this tension can vary, which enables the same muscles to move very light objects and very heavy objects. In individual muscle fibers, the amount of tension produced depends primarily on the amount of cross-bridges formed, which is influenced by the cross-sectional area of the muscle fiber and the frequency of neural stimulation.

Muscle tension: Muscle tension is produced when the maximum amount of cross-bridges are formed, either within a muscle with a large diameter or when the maximum number of muscle fibers are stimulated. Muscle tone is residual muscle tension that resists passive stretching during the resting phase.

Cross-bridges and Tension

The number of cross-bridges formed between actin and myosin determine the amount of tension that a muscle fiber can produce. Cross-bridges can only form where thick and thin filaments overlap, allowing myosin to bind to actin. If more cross-bridges are formed, more myosin will pull on actin and more tension will be produced.

Maximal tension occurs when thick and thin filaments overlap to the greatest degree within a sarcomere. If a sarcomere at rest is stretched past an ideal resting length, thick and thin filaments do not overlap to the greatest degree so fewer cross-bridges can form. This results in fewer myosin heads pulling on actin and less muscle tension. As a sarcomere shortens, the zone of overlap reduces as the thin filaments reach the H zone, which is composed of myosin tails. Because myosin heads form cross-bridges, actin will not bind to myosin in this zone, reducing the tension produced by the myofiber. If the sarcomere is shortened even more, thin filaments begin to overlap with each other, reducing cross-bridge formation even further, and producing even less tension. Conversely, if the sarcomere is stretched to the point at which thick and thin filaments do not overlap at all, no cross-bridges are formed and no tension is produced. This amount of stretching does not usually occur because accessory proteins, internal sensory nerves, and connective tissue oppose extreme stretching.

The primary variable determining force production is the number of myofibers (long muscle cells) within the muscle that receive an action potential from the neuron that controls that fiber. When using the biceps to pick up a pencil, for example, the motor cortex of the brain only signals a few neurons of the biceps so only a few myofibers respond. In vertebrates, each myofiber responds fully if stimulated. On the other hand, when picking up a piano, the motor cortex signals all of the neurons in the biceps so that every myofiber participates. This is close to the maximum force the muscle can produce. As mentioned above, increasing the frequency of action potentials (the number of signals per second) can increase the force a bit more because the tropomyosin is flooded with calcium.