Chapter10 Muscle Tissue

Skeletal Muscle Fibres

Because skeletal muscle cells are long and cylindrical, they are commonly referred to as muscle fibres. Skeletal muscle fibres can be quite large for human cells, with diameters up to 100 µm and lengths up to 30 cm (11.8 in) in the sartorius of the upper leg. During early development each myoblast, with its own nucleus, fuses with up to hundreds of other myoblasts to form the multinucleated skeletal muscle fibres. Multiple nuclei mean multiple copies of genes, permitting the production of the large amounts of proteins and enzymes needed for muscle contraction.

The plasma membrane of muscle fibres is called the sarcolemma, the cytoplasm is referred to as sarcoplasm, and the specialized smooth endoplasmic reticulum—which stores, releases, and retrieves calcium ions (Ca⁺⁺)—is called the sarcoplasmic reticulum (SR; Figure 10.3). As will soon be described, the functional unit of a skeletal muscle fibre is the sarcomere, a highly organized arrangement of the contractile myofilaments actin (thin filament) and myosin (thick filament), along with other support proteins.

The Sarcomere

The striated appearance of skeletal muscle fibres is due to the arrangement of the myofilaments of actin and myosin in sequential order from one end of the muscle fibre to the other. Each packet of these microfilaments and their regulatory proteins, troponin and tropomyosin (along with other proteins), is called a sarcomere.

The sarcomere is the functional unit of the muscle fibre. The sarcomere itself is bundled within the myofibril that runs the entire length of the muscle fibre and attaches to the sarcolemma at its end. As myofibrils contract, the entire muscle cell contracts. Because myofibrils are only approximately 1.2 µm in diameter, hundreds to thousands (each with thousands of sarcomeres) can be found inside one muscle fibre. Each sarcomere is approximately 2 µm in length with a three-dimensional cylinder-like arrangement and is bordered by structures called Z discs (also called Z lines, because pictures are two-dimensional), to which the actin myofilaments are anchored (Figure 10.4).

The components of a sarcomere are organized into a variety of bands and zones. The darker middle part of the sarcomere is the A band, which extends the entire length of the thick filaments. Toward each end of the A band is a zone of overlap, where the thick and thin filaments lie side by side. The I band is a lighter, less dense area that contains the rest of the thin filaments but no thick filaments, and a Z disc passes through the centre of each I band. The alternating dark A bands and light I bands create the striations that can be seen in both myofibrils and whole skeletal and cardiac muscle fibres. A narrow H band in the centre of each A band contains thick but not thin filaments. A mnemonic that will help you remember the composition of the I and H bands is as follows: The letter I is thin (contains thin filaments), while the letter H is thick (contains thick filaments). Supporting proteins that hold the thick filaments together at the centre of the H band form the M line, so named because it is at the middle of the sarcomere.

Because the actin and its troponin-tropomyosin complex (projecting from the Z discs toward the centre of the sarcomere) form strands that are thinner than the myosin, it is called the thin filament of the sarcomere. Likewise, because the myosin strands and their multiple heads (projecting from the centre of the sarcomere, toward but not all the way to the Z discs) have more mass and are thicker, they are called the thick filaments of the sarcomere.

The Neuromuscular Junction

Another specialization of skeletal muscle is the site where a motor neuron’s terminal meets the muscle fibre—called the neuromuscular junction (NMJ). This is where the muscle fibre first responds to signalling by the motor neuron. Every skeletal muscle fibre in every skeletal muscle is innervated by a motor neuron at the NMJ. Excitation signals from the neuron are the only way to functionally activate the fibre to contract.

Excitation-Contraction Coupling

All living cells have membrane potentials, or electrical gradients across their membranes. The inside of the membrane is usually around −60 to −90 mV relative to the outside. This is the cell’s membrane potential. Neurons and muscle cells can use their membrane potentials to generate electrical signals. They do this by controlling the movement of charged particles, called ions, across their membranes to create electrical currents. This is achieved by opening and closing specialized proteins in the membrane called ion channels. Although the currents generated by ions moving through these channel proteins are very small, they form the basis of both neural signalling and muscle contraction.

Both neurons and skeletal muscle cells are electrically excitable, meaning that they are able to generate action potentials. An action potential is a special type of electrical signal that can travel along a cell membrane as a wave. This allows a signal to be transmitted quickly and faithfully over long distances. Excitation-contraction coupling comes down to this: For a skeletal muscle fibre to contract, its membrane must first be “excited”—in other words, it must be stimulated to fire an action potential. The muscle fibre action potential, which sweeps along the sarcolemma as a wave, is “coupled” to the actual contraction through the release of calcium ions (Ca⁺⁺) from the SR. Once released, the Ca⁺⁺ interacts with the shielding proteins, forcing them to move aside so that the actin-binding sites are available for attachment by myosin heads. The myosin then pulls the actin filaments toward the centre, shortening the muscle fibre. In skeletal muscle, this sequence begins with signals from the somatic motor division of the nervous system. In other words, the “excitation” step in skeletal muscles is always triggered by signalling from the nervous system (Figure 10.5).

The motor neurons that tell the skeletal muscle fibres to contract originate in the spinal cord, with a smaller number located in the brain stem for activation of skeletal muscles of the face, head, and neck. These neurons have long processes, called axons, which are specialized to transmit action potentials long distances—in this case, all the way from the spinal cord to the muscle itself (which may be up to 1 m away). The axons of multiple neurons bundle together to form nerves, like wires bundled together in a cable. Signalling begins when a neuronal action potential travels along the axon of a motor neuron, and then along the individual branches to terminate at the NMJ. At the NMJ, the axon terminal releases a chemical messenger, or neurotransmitter, called acetylcholine (ACh). The ACh molecules diffuse across a minute space called the synaptic cleft and bind to ACh receptors located within the motor end-plate of the sarcolemma on the other side of the synapse. Once ACh binds, a channel in the ACh receptor opens, and positively charged ions can pass through into the muscle fibre, causing it to depolarize, meaning that the membrane potential of the muscle fibre becomes less negative (closer to zero).

As the membrane depolarizes, another set of ion channels called voltage-gated sodium channels is triggered to open. Sodium ions enter the muscle fibre, and an action potential rapidly spreads (or “fires”) along the entire membrane to initiate excitation-contraction coupling.

Things happen very quickly in the world of excitable membranes (just think about how quickly you can snap your fingers as soon as you decide to do it). Immediately following depolarization of the membrane, it repolarizes, reestablishing the negative membrane potential. Meanwhile, the ACh in the synaptic cleft is degraded by the enzyme acetylcholinesterase (AChE) so that the ACh cannot rebind to a receptor and reopen its channel, which would cause unwanted extended muscle excitation and contraction.

Propagation of an action potential along the sarcolemma is the excitation portion of excitation-contraction coupling. Recall that this excitation actually triggers the release of calcium ions (Ca⁺⁺) from their storage in the cell’s SR. For the action potential to reach the membrane of the SR, there are periodic invaginations in the sarcolemma, called T-tubules (“T” stands for “transverse”). You will recall that the diameter of a muscle fibre can be up to 100 µm, so these T-tubules ensure that the membrane can get close to the SR in the sarcoplasm. The arrangement of a T-tubule with the membranes of SR on either side is called a triad (Figure 10.6). The triad surrounds the cylindrical structure called a myofibril, which contains actin and myosin.

The T-tubules carry the action potential into the interior of the cell, which triggers the opening of calcium channels in the membrane of the adjacent SR, causing Ca⁺⁺ to diffuse out of the SR and into the sarcoplasm. It is the arrival of Ca⁺⁺ in the sarcoplasm that initiates contraction of the muscle fibre by its contractile units, or sarcomeres.

The Sliding Filament Model of Contraction

When signalled by a motor neuron, a skeletal muscle fibre contracts as the thin filaments are pulled and then slide past the thick filaments within the fibre’s sarcomeres. This process is known as the sliding filament model of muscle contraction (Figure 10.9). The sliding can only occur when myosin-binding sites on the actin filaments are exposed by a series of steps that begins with Ca⁺⁺ entry into the sarcoplasm.

Tropomyosin is a protein that winds around the chains of the actin filament and covers the myosin-binding sites to prevent actin from binding to myosin. Tropomyosin binds to troponin to form a troponin-tropomyosin complex. The troponin-tropomyosin complex prevents the myosin “heads” from binding to the active sites on the actin microfilaments. Troponin also has a binding site for Ca⁺⁺ ions.

To initiate muscle contraction, tropomyosin has to expose the myosin-binding site on an actin filament to allow cross-bridge formation between the actin and myosin microfilaments. 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. This allows the myosin heads to bind to these exposed binding sites and form cross-bridges. The thin filaments are then pulled by the myosin heads to slide past the thick filaments toward the centre of the sarcomere. But each head can only pull a very short distance before it has reached its limit and must be “recocked” before it can pull again, a step that requires ATP.

ATP and Muscle Contraction

For thin filaments to continue to slide past thick filaments during muscle contraction, myosin heads must pull the actin at the binding sites, detach, recock, attach to more binding sites, pull, detach, recock, and so on. This repeated movement is known as the cross-bridge cycle. This motion of the myosin heads is similar to the motion of oars when an individual rows a boat: The paddles of the oars (the myosin heads) pull, then they are lifted from the water (detach), repositioned (recocked), and immersed again to pull (Figure 10.10). Each cycle requires energy, and the action of the myosin heads in the sarcomeres repetitively pulling on the thin filaments also requires energy, which is provided by ATP.

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 10.10a and 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. As actin is pulled, the filaments move approximately 10 nm toward the M line. This movement is called the power stroke, as movement of the thin filament occurs at this step (Figure 10.10c). 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 the head has another binding site for ATP.

ATP binding causes the myosin head to detach from the actin (Figure 10.10d). 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 10.10e). 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, and 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 the sarcomeres in one myofibril, all the myofibrils in one muscle fibre, and all the muscle fibres in one skeletal muscle, and you can understand why so much energy (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 actin-binding sites, so the cross-bridges stay in place, causing rigidity in the skeletal muscles.

Sources of ATP

ATP supplies the energy for muscle contraction to take place. In addition to its direct role in the cross-bridge cycle, ATP also provides the energy for the active transport Ca⁺⁺ 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 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.

As the ATP produced by creatine phosphate is depleted, muscles turn to glycolysis as an ATP source. Glycolysis is an anaerobic (oxygen-independent) 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 ATPs and two molecules of pyruvic acid, which can be used in aerobic respiration or, when oxygen levels are low, converted to lactic acid.

If oxygen is available, pyruvic acid is used in aerobic respiration. However, if oxygen is not available (anaerobic metabolism), 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 the muscle. Glycolysis itself cannot be sustained for very long (approximately one 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. 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. The exact causes of muscle fatigue are not fully known, although certain factors have been correlated with the decreased muscle contraction that occurs during fatigue. ATP is needed for normal muscle contraction, and 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. Lactic acid buildup may lower intracellular pH, affecting enzyme and protein activity. Imbalances in Na⁺ and K⁺ levels as a result of membrane depolarization may disrupt Ca⁺⁺ flow out of the SR. Long periods of sustained exercise may damage the SR and the sarcolemma, resulting in impaired Ca⁺⁺ 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 convert lactic acid into glucose or glycogen in the liver. Other systems used during exercise also require oxygen, and all these combined processes result in the increased breathing rate that occurs with exercise. Until the oxygen debt has been met, oxygen intake is elevated, even after exercise has stopped.

Relaxation of a Skeletal Muscle

Relaxing skeletal muscle fibres, and ultimately, the skeletal muscle, begins with the motor neuron, which stops releasing its chemical signal, ACh, into the synapse at the NMJ. The muscle fibre will repolarize, which closes the gates in the SR where Ca⁺⁺ was being released. ATP-driven pumps will move Ca⁺⁺ out of the sarcoplasm back into the SR. This results in the “reshielding” of the actin-binding sites on the thin filaments. Without the ability to form cross-bridges between the thin and thick filaments, the muscle fibre loses its tension and relaxes.

Muscle Strength

The number of skeletal muscle fibres in a given muscle is genetically determined and does not change. Muscle strength is directly related to the amount of myofibrils and sarcomeres within each fibre. Factors, such as hormones and stress (and artificial anabolic steroids), acting on the muscle can increase the production of sarcomeres and myofibrils within the muscle fibres, a change called hypertrophy, which results in the increased mass and bulk in a skeletal muscle. Likewise, decreased use of a skeletal muscle results in atrophy, where the number of sarcomeres and myofibrils is significantly reduced (but not the number of muscle fibres). It is common for a limb in a cast to show atrophied muscles when the cast is removed, and certain diseases, such as polio, also cause atrophied muscles.

Motor Units

As you have learned, every skeletal muscle fibre must be innervated by the axon terminal of a motor neuron in order to contract. Each muscle fibre is innervated by only one motor neuron. The actual group of muscle fibres in a muscle innervated by a single motor neuron is called a motor unit. The size of a motor unit is variable depending on the nature of the muscle.

A small motor unit is an arrangement where a single motor neuron supplies a small number of muscle fibres in a muscle. Small motor units permit very fine motor control of the muscle. The best example in humans is the small motor units of the extraocular eye muscles that move the eyeballs. There are thousands of muscle fibres in each muscle, but every six or so fibres are supplied by a single motor neuron, as the axons branch to form synaptic connections at their individual NMJs. This allows for exquisite control of eye movements so that both eyes can quickly focus on the same object. Small motor units are also involved in the many fine movements of the fingers and thumb of the hand for grasping, texting, and so on.

A large motor unit is an arrangement where a single motor neuron supplies a large number of muscle fibres in a muscle. Large motor units are concerned with simple, or “gross,” movements, such as powerfully extending the knee joint. The best example is the large motor units of the thigh muscles or back muscles, where a single motor neuron will supply thousands of muscle fibres in a muscle, as its axon splits into thousands of branches.

There is a wide range of motor units within many skeletal muscles, which gives the nervous system a wide range of control over the muscle. The small motor units in the muscle will have smaller, lower-threshold motor neurons that are more excitable, firing first to their skeletal muscle fibres, which also tend to be the smallest. Activation of these smaller motor units results in a relatively small degree of contractile strength (tension) generated in the muscle. As more strength is needed, larger motor units with bigger, higher-threshold motor neurons are enlisted to activate larger muscle fibres. This increasing activation of motor units produces an increase in muscle contraction known as recruitment. As more motor units are recruited, the muscle contraction grows progressively stronger. In some muscles, the largest motor units may generate a contractile force 50 times greater than the smallest motor units in the muscle. This allows a feather to be picked up using the biceps brachii arm muscle with minimal force, and a heavy weight to be lifted by the same muscle by recruiting the largest motor units.

When necessary, the maximal number of motor units in a muscle can be recruited simultaneously, producing the maximum force of contraction for that muscle, but this cannot last for very long because of the energy requirements to sustain the contraction. To prevent complete muscle fatigue, motor units are generally not all simultaneously active, but instead some motor units rest while others are active, which allows for longer muscle contractions. The nervous system uses recruitment as a mechanism to efficiently utilize a skeletal muscle.

The Length-Tension Range of a Sarcomere

When a skeletal muscle fibre contracts, myosin heads attach to actin to form cross-bridges, followed by the thin filaments sliding over the thick filaments as the heads pull the actin, and this results in sarcomere shortening, creating the tension of the muscle contraction. The cross-bridges can only form where thin and thick filaments already overlap, so that the length of the sarcomere has a direct influence on the force generated when the sarcomere shortens. This is called the length-tension relationship.

The ideal length of a sarcomere to produce maximal tension occurs at 80 percent to 120 percent of its resting length, with 100 percent being the state where the medial edges of the thin filaments are just at the most-medial myosin heads of the thick filaments (Figure 10.12). This length maximizes the overlap of actin-binding sites and myosin heads. If a sarcomere is stretched past this ideal length (beyond 120 percent), thick and thin filaments do not overlap sufficiently, which results in less tension produced. If a sarcomere is shortened beyond 80 percent, the zone of overlap is reduced, with the thin filaments jutting beyond the last of the myosin heads, and shrinks the H zone, which is normally composed of myosin tails. Eventually, there is nowhere else for the thin filaments to go, and the amount of tension is diminished. If the muscle is stretched to the point where thick and thin filaments do not overlap at all, no cross-bridges can be formed, and no tension is produced in that sarcomere. This amount of stretching does not usually occur, as accessory proteins and connective tissue oppose extreme stretching.

The Frequency of Motor Neuron Stimulation

A single action potential from a motor neuron will produce a single contraction in the muscle fibres of its motor unit. This isolated contraction is called a twitch. A twitch can last for a few milliseconds (ms) or 100 ms, depending on the muscle type. The tension produced by a single twitch can be measured by a myogram, an instrument that measures the amount of tension produced over time (Figure 10.13). Each twitch undergoes three phases. The first phase is the latent period, during which the action potential is being propagated along the sarcolemma and Ca⁺⁺ ions are released from the SR. This is the phase during which excitation and contraction are being coupled but contraction has yet to occur. The contraction phase occurs next. The Ca⁺⁺ ions in the sarcoplasm have bound to troponin, tropomyosin has shifted away from actin-binding sites, cross-bridges have formed, and sarcomeres are actively shortening to the point of peak tension. The last phase is the relaxation phase, when tension decreases as contraction stops. Ca⁺⁺ ions are pumped out of the sarcoplasm into the SR, and cross-bridge cycling stops, returning the muscle fibres to their resting state.

Although a person can experience a muscle “twitch,” a single twitch does not produce any significant muscle activity in a living body. A series of action potentials to the muscle fibres is necessary to produce a muscle contraction that can produce work. Normal muscle contraction is more sustained, and it can be modified by input from the nervous system to produce varying amounts of force; this is called a graded muscle response. The frequency of action potentials (nerve impulses) from a motor neuron and the number of motor neurons transmitting action potentials both affect the tension produced in skeletal muscle.

The rate at which a motor neuron fires action potentials affects the tension produced in the skeletal muscle. If the fibres are stimulated while a previous twitch is still occurring, the second twitch will be stronger. This response is called wave summation because the excitation-contraction coupling effects of successive motor neuron signalling are summed, or added together (Figure 10.14a). At the molecular level, summation occurs because the second stimulus triggers the release of more Ca⁺⁺ ions, which become available to activate additional sarcomeres while the muscle is still contracting from the first stimulus. Summation results in greater contraction of the motor unit.

If the frequency of motor neuron signalling increases, summation and subsequent muscle tension in the motor unit continue to rise until they reach a peak point. The tension at this point is about three to four times greater than the tension of a single twitch, a state referred to as incomplete tetanus. During incomplete tetanus, the muscle goes through quick cycles of contraction with a short relaxation phase for each. If the stimulus frequency is so high that the relaxation phase disappears completely, contractions become continuous in a process called complete tetanus (Figure 10.14b).

During tetanus, the concentration of Ca⁺⁺ ions in the sarcoplasm allows virtually all the sarcomeres to form cross-bridges and shorten, so that a contraction can continue uninterrupted (until the muscle fatigues and can no longer produce tension).

Treppe

When a skeletal muscle has been dormant for an extended period and then activated to contract, with all other things being equal, the initial contractions generate about half the force of later contractions. The muscle tension increases in a graded manner that, to some, looks like a set of stairs. This tension increase is called treppe, a condition where muscle contractions become more efficient. It’s also known as the “staircase effect” (Figure 10.15).

It is believed that treppe results from a higher concentration of Ca⁺⁺ in the sarcoplasm from the steady stream of signals from the motor neuron. It can only be maintained with adequate ATP.

Muscle Tone

Skeletal muscles are rarely completely relaxed, or flaccid. Even if a muscle is not producing movement, it is contracted a small amount to maintain its contractile proteins and produce muscle tone. The tension produced by muscle tone allows muscles to continually stabilize joints and maintain posture.

Muscle tone is accomplished by a complex interaction between the nervous system and skeletal muscles that results in the activation of a few motor units at a time, most likely in a cyclical manner. In this manner, muscles never fatigue completely, as some motor units can recover while others are active.

The absence of the low-level contractions that lead to muscle tone is referred to as hypotonia, and it can result from damage to parts of the central nervous system (CNS), such as the cerebellum, or from loss of innervations to a skeletal muscle, as in poliomyelitis. Hypotonic muscles have a flaccid appearance and display functional impairments, such as weak reflexes. Conversely, excessive muscle tone is referred to as hypertonia, accompanied by hyperreflexia (excessive reflex responses), often the result of damage to upper motor neurons in the CNS. Hypertonia can present with muscle rigidity (as seen in Parkinson’s disease) or spasticity, a phasic change in muscle tone, where a limb will “snap” back from passive stretching (as seen in some strokes).

Hyperplasia in Smooth Muscle

Similar to skeletal and cardiac muscle cells, smooth muscle can undergo hypertrophy to increase in size. Unlike other muscle, smooth muscle can also divide to produce more cells, a process called hyperplasia. This can most evidently be observed in the uterus at puberty, which responds to increased estrogen levels by producing more uterine smooth muscle fibres and greatly increasing the size of the myometrium.

10.1 Overview of Muscle Tissues

Muscle is the tissue in animals that allows for active movement of the body or materials within the body. There are three types of muscle tissue: skeletal muscle, cardiac muscle, and smooth muscle. Most of the body’s skeletal muscle produces movement by acting on the skeleton. Cardiac muscle is found in the wall of the heart and pumps blood through the circulatory system.

Smooth muscle is found in the skin, where it is associated with hair follicles; it is also found in the walls of internal organs, blood vessels, and internal passageways, where it assists in moving materials.

10.2 Skeletal Muscle

Skeletal muscles contain connective tissue, blood vessels, and nerves. There are three layers of connective tissue: epimysium, perimysium, and endomysium. Skeletal muscle fibres are organized into groups called fascicles. Blood vessels and nerves enter the connective tissue and branch in the cell. Muscles attach to bones directly or through tendons or aponeuroses. Skeletal muscles maintain posture, stabilize bones and joints, control internal movement, and generate heat.

Skeletal muscle fibres are long, multinucleated cells. The membrane of the cell is the sarcolemma; the cytoplasm of the cell is the sarcoplasm. The sarcoplasmic reticulum (SR) is a form of endoplasmic reticulum. Muscle fibres are composed of myofibrils. The striations are created by the organization of actin and myosin, resulting in the banding pattern of myofibrils.

10.3 Muscle Fibre Contraction and Relaxation

A sarcomere is the smallest contractile portion of a muscle. Myofibrils are composed of thick and thin filaments. Thick filaments are composed of the protein myosin; thin filaments are composed of the protein actin. Troponin and tropomyosin are regulatory proteins.

Muscle contraction is described by the sliding filament model of contraction. ACh is the neurotransmitter that binds at the neuromuscular junction (NMJ) to trigger depolarization, and an action potential travels along the sarcolemma to trigger calcium release from the SR. The actin sites are exposed after Ca⁺⁺ enters the sarcoplasm from its SR storage to activate the troponin-tropomyosin complex so that the tropomyosin shifts away from the sites. The cross-bridging of myosin heads docking into actin-binding sites is followed by the “power stroke”—the sliding of the thin filaments by thick filaments. The power strokes are powered by ATP. Ultimately, the sarcomeres, myofibrils, and muscle fibres shorten to produce movement.

10.4 Nervous System Control of Muscle Tension

The number of cross-bridges formed between actin and myosin determines the amount of tension produced by a muscle. The length of a sarcomere is optimal when the zone of overlap between thin and thick filaments is greatest. Muscles that are stretched or compressed too greatly do not produce maximal amounts of power. A motor unit is formed by a motor neuron and all the muscle fibres that are innervated by that same motor neuron. A single contraction is called a twitch. A muscle twitch has a latent period, a contraction phase, and a relaxation phase. A graded muscle response allows variation in muscle tension. Summation occurs as successive stimuli are added together to produce a stronger muscle contraction. Tetanus is the fusion of contractions to produce a continuous contraction. Increasing the number of motor neurons involved increases the number of motor units activated in a muscle, which is called recruitment. Muscle tone is the constant, low-level contractions that allow for posture and stability.

10.5 Types of Muscle Fibres

ATP provides the energy for muscle contraction. The three mechanisms for ATP regeneration are creatine phosphate, anaerobic glycolysis, and aerobic metabolism. Creatine phosphate provides about the first 15 seconds of ATP at the beginning of muscle contraction. Anaerobic glycolysis produces small amounts of ATP in the absence of oxygen for a short period. Aerobic metabolism utilizes oxygen to produce much more ATP, allowing a muscle to work for longer periods. Muscle fatigue, which has many contributing factors, occurs when a muscle can no longer contract. An oxygen debt is created as a result of muscle use. The three types of muscle fibre are slow oxidative (SO), fast oxidative (FO), and fast glycolytic (FG). SO fibres use aerobic metabolism to produce low-power contractions over long periods and are slow to fatigue. FO fibres use aerobic metabolism to produce ATP but produce higher tension contractions than SO fibres. FG fibres use anaerobic metabolism to produce powerful, high-tension contractions but fatigue quickly.

10.6 Cardiac Muscle Tissue

Cardiac muscle is striated muscle that is present only in the heart. Cardiac muscle fibres have a single nucleus, are branched, and joined to one another by intercalated discs that contain gap junctions for depolarization between cells and desmosomes to hold the fibres together when the heart contracts.

Contraction in each cardiac muscle fibre is triggered by Ca⁺⁺ ions in a similar manner as skeletal muscle, but here the Ca⁺⁺ ions come from SR and through voltage-gated calcium channels in the sarcolemma. Pacemaker cells stimulate the spontaneous contraction of cardiac muscle as a functional unit, called a syncytium.

10.7 Smooth Muscle

Smooth muscle is found throughout the body around various organs and tracts. Smooth muscle cells have a single nucleus and are spindle-shaped. Smooth muscle cells can undergo hyperplasia, mitotically dividing to produce new cells. The smooth cells are nonstriated, but their sarcoplasm is filled with actin and myosin, along with dense bodies in the sarcolemma to anchor the thin filaments and a network of intermediate filaments involved in pulling the sarcolemma toward the fibre’s middle, shortening it in the process. Ca⁺⁺ ions trigger contraction when they are released from SR and enter through opened voltage-gated calcium channels. Smooth muscle contraction is initiated when the Ca⁺⁺ binds to intracellular calmodulin, which then activates an enzyme called myosin kinase that phosphorylates myosin heads so they can form the cross-bridges with actin and then pull on the thin filaments. The fibres in some smooth muscle have latch-bridges, cross-bridges that cycle slowly without the need for ATP; these muscles can maintain low-level contractions for long periods. Single-unit smooth muscle tissue contains gap junctions to synchronize membrane depolarization and contractions so that the muscle contracts as a single unit. Single-unit smooth muscle in the walls of the viscera, called visceral muscle, has a stress-relaxation response that permits the muscle to stretch, contract, and relax as the organ expands. Multiunit smooth muscle cells do not possess gap junctions, and contraction does not spread from one cell to the next.