Chapter 10

4Detachment of myosin from actin.

At the end of the power stroke, the cross-bridge remains firmly attached to actin until it binds another molecule of ATP. As ATP binds to the ATP-binding site on the myosin head, the myosin head detaches from actin.

Nerve and Blood Supply

Each muscle receives a nerve, artery, and veins Consciously controlled skeletal muscle has nerves supplying every fiber to control activity Contracting muscle fibers require huge amounts of oxygen and nutrients Also need waste products removed quickly Skeletal muscles are well supplied with nerves and blood vessels.

Structure of Skeletal Muscle Tissue

Each of your skeletal muscles is a separate organ composed of hundreds to thousands of cells, which are called muscle fibers (myocytes) because of their elongated shapes. Thus, muscle cell and muscle fiber are two terms for the same structure. Skeletal muscle also contains connective tissues surrounding muscle fibers, and blood vessels and nerves (Figure 10.1). To understand how contraction of skeletal muscle can generate tension, you must first understand its gross and microscopic anatomy.

Whole muscles that control precise movements consist of many small motor units

For instance, muscles of the larynx (voice box) that control voice production have as few as two or three muscle fibers per motor unit, and muscles controlling eye movements may have 10 to 20 muscle fibers per motor unit. In contrast, skeletal muscles responsible for large-scale and powerful movements, such as the biceps brachii muscle in the arm and the gastrocnemius muscle in the calf of the leg, have as many as 2000 to 3000 muscle fibers in some motor units. Because all of the muscle fibers of a motor unit contract and relax together, the total strength of a contraction depends, in part, on the size of the motor units and the number that are activated at a given time.

Control of Muscle Tension

Motor unit, muscle twitch, frequency of stimulation, strength stimulus A single nerve impulse in a somatic motor neuron elicits a single muscle action potential in all skeletal muscle fibers with which it forms synapses. Action potentials always have the same size in a given neuron or muscle fiber. In contrast, the force of muscle fiber contraction does vary; a muscle fiber is capable of producing a much greater force than the one that results from a single action potential. The total force or tension that a single muscle fiber can produce depends mainly on the rate at which nerve impulses arrive at the neuromuscular junction

2.Stabilizing body positions.

Skeletal muscle contractions stabilize joints and help maintain body positions, such as standing or sitting. Postural muscles contract continuously when you are awake; for example, sustained contractions of your neck muscles hold your head upright when you are listening intently to your anatomy and physiology lecture.

2Attachment of myosin to actin

The energized myosin head attaches to the myosin-binding site on actin and releases the previously hydrolyzed phosphate group. When a myosin head attaches to actin during the contraction cycle, the myosin head is referred to as a cross-bridge. Although a single myosin molecule has a double head, only one head binds to actin at a time.

muscle tone (tonos = tension),

a small amount of tautness or tension in the muscle due to weak, involuntary contractions of its motor units. Recall that skeletal muscle contracts only after it is activated by acetylcholine released by nerve impulses in its motor neurons. Hence, muscle tone is established by neurons in the brain and spinal cord that excite the muscle's motor neurons.

Myasthenia gravis

autoimmune neuromuscular disorder characterized by weakness of voluntary muscles is an autoimmune disease that causes chronic, progressive damage of the neuromuscular junction. The immune system inappropriately produces antibodies that bind to and block some ACh receptors, thereby decreasing the number of functional ACh receptors at the motor end plates of skeletal muscles (see Figure 10.9). Because 75% of patients with myasthenia gravis have hyperplasia or tumors of the thymus, it is thought that thymic abnormalities cause the disorder. As the disease progresses, more ACh receptors are lost. Thus, muscles become increasingly weaker, fatigue more easily, and may eventually cease to function.

When the connective tissue elements extend as a broad, flat sheet, it is

called an aponeurosis (ap-ō-noo-RŌ-sis; apo- = from; -neur- = a sinew). An example is the epicranial aponeurosis on top of the skull between the frontal and occipital bellies of the occipitofrontalis muscle (shown in Figure

The result is a sustained but wavering contraction

called unfused (incomplete) tetanus (tetan- = rigid, tense; Figure 10.14c). When a skeletal muscle fiber is stimulated at a higher rate of 80 to 100 times per second, it does not relax at all. The result is fused (complete) tetanus, a sustained contraction in which individual twitches cannot be detected (Figure 10.14d).

Microscopic blood vessels called

capillaries are plentiful in muscular tissue; each muscle fiber is in close contact with one or more capillaries (see Figure 10.9d). The blood capillaries bring in oxygen and nutrients and remove heat and the waste products of muscle metabolism. Especially during contraction, a muscle fiber synthesizes and uses considerable ATP (adenosine triphosphate). These reactions, which you will learn more about later on, require oxygen, glucose, fatty acids, and other substances that are delivered to the muscle fiber in the blood.

Properties of Muscular Tissue

Muscular tissue has four special properties that enable it to function and contribute to homeostasis: 1. Electrical excitability 2. Contractility 3. Extensibility 4. Elasticity

Abnormal Contractions of Skeletal Muscle

One kind of abnormal muscular contraction is a spasm, a sudden involuntary contraction of a single muscle in a large group of muscles. A painful spasmodic contraction is known as a cramp. Cramps may be caused by inadequate blood flow to muscles, overuse of a muscle, dehydration, injury, holding a position for prolonged periods, and low blood levels of electrolytes, such as potassium. A tic is a spasmodic twitching made involuntarily by muscles that are ordinarily under voluntary control. Twitching of the eyelid and facial muscles are examples of tics

The coverings and tendons

stretch and then become taut, and the tension passed through the tendons pulls on the bones to which they are attached. The result is movement of a part of the body. You will soon learn, however, that the contraction cycle does not always result in shortening of the muscle fibers and the whole muscle. In some contractions, the cross-bridges rotate and generate tension, but the thin filaments cannot slide inward because the tension they generate is not large enough to move the load on the muscle (such as trying to lift a whole box of books with one hand).

The epimysium, perimysium, and endomysium are all continuous with the connective tissue that attaches skeletal muscle to other structures, such as

such as bone or another muscle. For example, all three connective tissue layers may extend beyond the muscle fibers to form a ropelike tendon that attaches a muscle to the periosteum of a bone. An example is the calcaneal (Achilles) tendon of the gastrocnemius (calf) muscle, which attaches the muscle to the calcaneus (heel bone) (shown in Figure 11.22c).

At the NMJ, the end of the motor neuron, called the

the axon terminal, divides into a cluster of synaptic end bulbs (Figure 10.9a, b), the neural part of the NMJ. Suspended in the cytosol within each synaptic end bulb are hundreds of membrane-enclosed sacs called synaptic vesicles. Inside each synaptic vesicle are thousands of molecules of acetylcholine (ACh) (as′-ē-til-KŌ-lēn), the neurotransmitter released at the NMJ.

During a maximal muscle contraction

the distance between two Z discs can decrease to half the resting length. The Z discs in turn pull on neighboring sarcomeres, and the whole muscle fiber shortens. Some of the components of a muscle are elastic: They stretch slightly before they transfer the tension generated by the sliding filaments. The elastic components include titin molecules, connective tissue around the muscle fibers (endomysium, perimysium, and epimysium), and tendons that attach muscle to bone. As the cells of a skeletal muscle start to shorten, they first pull on their connective tissue coverings and tendons

During the third phase, the

the relaxation period, also lasting 10-100 msec, Ca2+ is actively transported back into the sarcoplasmic reticulum, myosin-binding sites are covered by tropomyosin, myosin heads detach from actin, and tension in the muscle fiber decreases. The actual duration of these periods depends on the type of skeletal muscle fiber. Some fibers, such as the fast-twitch fibers that move the eyes (described shortly), have contraction periods as brief as 10 msec and equally brief relaxation periods. Others, such as the slow-twitch fibers that move the legs, have contraction and relaxation periods of about 100 msec each.

In an isotonic contraction (ī′-sō-TON-ik; iso- = equal; -tonic = tension)

the tension (force of contraction) developed in the muscle remains almost constant while the muscle changes its length. Isotonic contractions are used for body movements and for moving objects. The two types of isotonic contractions are concentric and eccentric.

In an isometric contraction (ī′-sō-MET-rik; metro = measure or length

the tension generated is not enough to exceed the resistance of the object to be moved, and the muscle does not change its length. An example would be holding a book steady using an outstretched arm (Figure 10.15c). These contractions are important for maintaining posture and for supporting objects in a fixed position. Although isometric contractions do not result in body movement, energy is still expended. The book pulls the arm downward, stretching the shoulder and arm muscles. The isometric contraction of the shoulder and arm muscles counteracts the stretch. Isometric contractions are important because they stabilize some joints as others are moved. Most activities include both isotonic and isometric contractions.

The contraction cycle repeats as the

myosin ATPase hydrolyzes the newly bound molecule of ATP, and continues as long as ATP is available and the Ca2+ level near the thin filament is sufficiently high. The cross-bridges keep rotating back and forth with each power stroke, pulling the thin filaments toward the M line. Each of the 600 cross-bridges in one thick filament attaches and detaches about five times per second. At any one instant, some of the myosin heads are attached to actin, forming cross-bridges and generating force, and other myosin heads are detached from actin, getting ready to bind again.

motor neuron

neurons that carry outgoing information from the brain and spinal cord to the muscles and glands A motor neuron and all the skeletal muscle fibers it innervates are a motor unit. Within the muscle, the axon of a motor neuron divides into many branches or axon terminals, each of which forms a neuromuscular junction with a skeletal muscle fiber

When the motor neurons serving a skeletal muscle are damaged or cut, the muscle becomes

flaccid (FLAK-sid or FLAS-sid = flabby), a state of limpness in which muscle tone is lost. To sustain muscle tone, small groups of motor units are alternatively active and inactive in a constantly shifting pattern. Muscle tone keeps skeletal muscles firm, but it does not result in a force strong enough to produce movement. For example, when you are awake, the muscles in the back of the neck are in normal tonic contraction; they keep the head upright and prevent it from slumping forward on the chest. Muscle tone also is important in smooth muscle tissues, such as those found in the gastrointestinal tract, where the walls of the digestive organs maintain a steady pressure on their contents. The tone of smooth muscle fibers in the walls of blood vessels plays a crucial role in maintaining blood pressure.

In DMD, the gene that codes

for the protein dystrophin is mutated, so little or no dystrophin is present in the sarcolemma. Without the reinforcing effect of dystrophin, the sarcolemma tears easily during muscle contraction, causing muscle fibers to rupture and die. The dystrophin gene was discovered in 1987, and by 1990 the first attempts were made to treat DMD patients with gene therapy. The muscles of three boys with DMD were injected with myoblasts bearing functional dystrophin genes, but only a few muscle fibers gained the ability to produce dystrophin. Similar clinical trials with additional patients have also failed. An alternative approach to the problem is to find a way to induce muscle fibers to produce the protein utrophin, which is similar to dystrophin. Experiments with dystrophin-deficient mice suggest this approach may work.

A fasciculation (fa-sik-ū-LĀ-shun) is an

involuntary, brief twitch of an entire motor unit that is visible under the skin; it occurs irregularly and is not associated with movement of the affected muscle. Fasciculations may be seen in multiple sclerosis (see Disorders: Homeostatic Imbalances in Chapter 12) or in amyotrophic lateral sclerosis (Lou Gehrig's disease;

Fascia (FASH-ē-a = bandage)

is a dense sheet or broad band of irregular connective tissue that lines the body wall and limbs and supports and surrounds muscles and other organs of the body. As you will see, fascia holds muscles with similar functions together (see Figure 11.21). Fascia allows free movement of muscles; carries nerves, blood vessels, and lymphatic vessels; and fills spaces between muscles.

A fibrillation

is a spontaneous contraction of a single muscle fiber that is not visible under the skin but can be recorded by electromyography. Fibrillations may signal destruction of motor neurons.

Such delayed onset muscle soreness (DOMS)

is accompanied by stiffness, tenderness, and swelling. Although the causes of DOMS are not completely understood, microscopic muscle damage appears to be a major factor. In response to exercise-induced muscle damage, muscle fibers undergo repair: new regions of sarcolemma are formed to replace torn sarcolemmas, and more muscle proteins (including those of the myofibrils) are synthesized in the sarcoplasm of the muscle fibers.

•Perimysium(peri- = around)

is also a layer of dense irregular connective tissue, but it surrounds groups of 10 to 100 or more muscle fibers, separating them into bundles called fascicles (FAS-i-kuls = little bundles). Many fascicles are large enough to be seen with the naked eye. They give a cut of meat its characteristic "grain"; if you tear a piece of meat, it rips apart along the fascicles.

If the tension generated in a concentric isotonic contraction (kon-SEN-trik)

is great enough to overcome the resistance of the object to be moved, the muscle shortens and pulls on another structure, such as a tendon, to produce movement and to reduce the angle at a joint. Picking up a book from a table involves concentric isotonic contractions of the biceps brachii muscle in the arm (Figure 10.15a). By contrast, as you lower the book to place it back on the table, the previously shortened biceps lengthens in a controlled manner while it continues to contract

Smooth muscle tissue(A tissue specialized for contraction, composed of smooth muscle fibers (cells), located in the walls of hollow internal organs, and innervated by autonomic motor neurons.)

is located in the walls of hollow internal structures, such as blood vessels, airways, and most organs in the abdominopelvic cavity. It is also found in the skin, attached to hair follicles. Under a microscope, this tissue lacks the striations of skeletal and cardiac muscle tissue. For this reason, it looks nonstriated, which is why it is referred to as smooth

2.Contractility

is the ability of muscular tissue to contract forcefully when stimulated by an action potential. When a skeletal muscle contracts, it generates tension (force of contraction) while pulling on its attachment points. If the tension generated is great enough to overcome the resistance of the object to be moved, the muscle shortens and movement occurs.

3.Extensibility

is the ability of muscular tissue to stretch, within limits, without being damaged. The connective tissue within the muscle limits the range of extensibility and keeps it within the contractile range of the muscle cells. Normally, smooth muscle is subject to the greatest amount of stretching. For example, each time your stomach fills with food, the smooth muscle in the wall is stretched. Cardiac muscle also is stretched each time the heart fills with blood.

A twitch contraction

is the brief contraction of all muscle fibers in a motor unit in response to a single action potential in its motor neuron. In the laboratory, a twitch can be produced by direct electrical stimulation of a motor neuron or its muscle fibers. The record of a muscle contraction, called a myogram (MĪ-ō-gram), is shown in Figure 10.13. Twitches of skeletal muscle fibers last anywhere from 20 to 200 msec. This is very long compared to the brief 1-2 msec* that a muscle action potential lasts.

As the sarcomeres

of a muscle fiber are stretched to a longer length, the zone of overlap shortens, and fewer myosin heads can make contact with thin filaments. Therefore, the tension the fiber can produce decreases. When a skeletal muscle fiber is stretched to 170% of its optimal length, there is no overlap between the thick and thin filaments. Because none of the myosin heads can bind to thin filaments, the muscle fiber cannot contract, and tension is zero. As sarcomere lengths become increasingly shorter than the optimum, the tension that can develop again decreases. This is because thick filaments crumple as they are compressed by the Z discs, resulting in fewer myosin heads making contact with thin filaments. Normally, resting muscle fiber length is held very close to the optimum by firm attachments of skeletal muscle to bones (via their tendons) and to other inelastic tissues.

Endomysium(endo- = within)

penetrates the interior of each fascicle and separates individual muscle fibers from one another. The endomysium is mostly reticular fibers

At the neuromuscular junction

point of contact between a motor neuron and a skeletal muscle cell each axon terminal divides into synaptic end bulbs. Within the synaptic end bulbs are synaptic vesicles filled with acetylcholine (neurotransmitter molecules). When a nerve impulse reaches the synaptic end bulb, acetylcholine is released and diffuses across the synaptic cleft (the space between the synaptic end bulb and the sarcolemma). Acetylcholine molecules bind to receptors in the motor end plate, the region of the sarcolemma directly across from the synaptic end bulb. If enough acetylcholine binds, an action potential is generated, stimulating the skeletal muscle fiber to contract.

The action of smooth muscle is

produce involuntary contractions, weak and slow usually involuntary, and some smooth muscle tissue, such as the muscles that propel food through your gastrointestinal tract, has autorhythmicity. Both cardiac muscle and smooth muscle are regulated by neurons that are part of the autonomic (involuntary) division of the nervous system and by hormones released by endocrine glands.

Anticholinesterase drugs such as

pyridostigmine (Mestinon) or neostigmine, the first line of treatment, act as inhibitors of acetylcholinesterase, the enzyme that breaks down ACh. Thus, the inhibitors raise the level of ACh that is available to bind with still-functional receptors. More recently, steroid drugs such as prednisone have been used with success to reduce antibody levels. Another treatment is plasmapheresis, a procedure that removes the antibodies from the blood. Often, surgical removal of the thymus (thymectomy) is helpful.

When a muscle fiber receives enough stimulation to contract, it temporarily loses its excitability and cannot respond for a time. The period of lost excitability, called the

refractory period (rē-FRAK-tō-rē), is a characteristic of all muscle and nerve cells. The duration of the refractory period varies with the muscle involved. Skeletal muscle has a short refractory period of about 1 msec; cardiac muscle has a longer refractory period of about 250 msec.

Recruitment is one factor

responsible for producing smooth movements rather than a series of jerks. As mentioned, the number of muscle fibers innervated by one motor neuron varies greatly. Precise movements are brought about by small changes in muscle contraction. Therefore, the small muscles that produce precise movements are made up of small motor units. For this reason, when a motor unit is recruited or turned off, only slight changes occur in muscle tension. By contrast, large motor units are active when a large amount of tension is needed and precision is less important. Clinical ConnectionClinical Connection: Anaerobic Training versus Aerobic Training

4Termination of ACh activity.

The effect of ACh binding lasts only briefly because ACh is rapidly broken down by an enzyme called acetylcholinesterase (AChE) (as′-ē-til-kō′-lin-ES-ter-ās). This enzyme is located on the extracellular side of the motor end plate membrane. AChE breaks down ACh into acetyl and choline, products that cannot activate the ACh receptor.

3Production of muscle action potential.

The inflow of Na+ (down its electrochemical gradient) makes the inside of the muscle fiber more positively charged. This change in the membrane potential triggers a muscle action potential. Each nerve impulse normally elicits one muscle action potential. The muscle action potential then propagates along the sarcolemma into the system of T tubules. This causes the sarcoplasmic reticulum to release its stored Ca2+ into the sarcoplasm, and the muscle fiber subsequently contracts.

Connective tissue surrounds and protects muscular tissue

The subcutaneous layer or hypodermis, which separates muscle from skin (see Figure 11.21), is composed of areolar connective tissue and adipose tissue. It provides a pathway for nerves, blood vessels, and lymphatic vessels to enter and exit muscles.

Frequency of Stimulation

A single neural stimulation produces: A single contraction or twitch Which lasts about 7-100 msec. Sustained muscular contractions Require many repeated stimuli When a second stimulus occurs after the refractory period of the first stimulus is over, but before the skeletal muscle fiber has relaxed, the second contraction will actually be stronger than the first

Motor Units

1 motor neuron and all the muscle fibers it innervates Even though each skeletal muscle fiber has only a single neuromuscular junction, the axon of a somatic motor neuron branches out and forms neuromuscular junctions with many different muscle fibers

1.Electrical excitability

a property of both muscle and nerve cells. Action potentials in muscles are referred to as muscle action potentials; those in nerve cells are called nerve action potentials. For muscle cells, two main types of stimuli trigger action potentials. One is autorhythmic electrical signals arising in the muscular tissue itself, as in the heart's pacemaker. The other is chemical stimuli, such as neurotransmitters released by neurons, hormones distributed by the blood, or even local changes in pH.

Myasthenia gravis occurs in

about 1 in 10,000 people and is more common in women, typically ages 20 to 40 at onset; men usually are ages 50 to 60 at onset. The muscles of the face and neck are most often affected. Initial symptoms include weakness of the eye muscles, which may produce double vision, and weakness of the throat muscles that may produce difficulty in swallowing. Later, the person has difficulty chewing and talking. Eventually the muscles of the limbs may become involved. Death may result from paralysis of the respiratory muscles, but often the disorder does not progress to that stage.

Maximum tension is also affected by the

amount of stretch before contraction (see Figure 10.8) and by nutrient and oxygen availability. The total tension a whole muscle can produce depends on the number of muscle fibers that are contracting in unison.

Generally, an artery

and one or two veins accompany each nerve that penetrates a skeletal muscle. The neurons that stimulate skeletal muscle to contract are somatic motor neurons. Each somatic motor neuron has a threadlike axon that extends from the brain or spinal cord to a group of skeletal muscle fibers (see Figure 10.9d). The axon of a somatic motor neuron typically branches many times, each branch extending to a different skeletal muscle fiber.

This built-in rhythm is termed

autorhythmicity(The ability to repeatedly generate spontaneous action potentials) Several hormones and neurotransmitters can adjust heart rate by speeding or slowing the pacemaker.

When the length of a muscle increases during a contraction, the contraction is an

eccentric isotonic contraction (ek-SEN-trik) (Figure 10.15b). During an eccentric contraction, the tension exerted by the myosin cross-bridges resists movement of a load (the book, in this case) and slows the lengthening process. For reasons that are not well understood, repeated eccentric isotonic contractions (for example, walking downhill) produce more muscle damage and more delayed-onset muscle soreness than do concentric isotonic contractions.

The term neuromuscular disease

encompasses problems at all three sites; the term myopathy (mī-OP-a-thē; -pathy = disease) signifies a disease or disorder of the skeletal muscle tissue itself.

The number of impulses per second is the

frequency of stimulation.

If two stimuli are applied,

have contraction periods as brief as 10 msec and equally brief relaxation periods. Others, such as the slow-twitch fibers that move the legs, have contraction and relaxation periods of about 100 msec each. If two stimuli are applied, one immediately after the other, the muscle will respond to the first stimulus but not to the second

Exercise-Induced Muscle Damage

Including torn sarcolemmas in some muscle fivers, damaged myofibrils, and disrupted Z discs

exercise-induced muscle damage

including torn sarcolemmas in some muscle fibers, damaged myofibrils, and disrupted Z discs. Microscopic muscle damage after exercise also is indicated by increases in blood levels of proteins, such as myoglobin and the enzyme creatine kinase, which are normally confined within muscle fibers. From 12 to 48 hours after a period of strenuous exercise, skeletal muscles often become sore

1. Producing body movements

Movements of the whole body such as walking and running, and localized movements such as grasping a pencil, keyboarding, or nodding the head rely on the integrated functioning of skeletal muscles, bones, and joints.

This phenomenon, in which stimuli arriving at different times cause larger contractions

is called wave summation. When a skeletal muscle fiber is stimulated at a rate of 20 to 30 times per second, it can only partially relax between stimuli.

Note that a brief delay occurs between application of the stimulus (time zero on the graph) and the beginning of contraction. The delay, which lasts about 2 msec,

is termed the latent period. During the latent period, the muscle action potential sweeps over the sarcolemma and calcium ions are released from the sarcoplasmic reticulum

4.Elasticity

is the ability of muscular tissue to return to its original length and shape after contraction or extension.

•Epimysium (epi- = upon)

is the outer layer, encircling the entire muscle. It consists of dense irregular connective tissue.

The region of the sarcolemma opposite the synaptic end bulbs, called the

motor end plate (Figure 10.9b, c), is the muscular part of the NMJ. Within each motor end plate are 30 million to 40 million acetylcholine receptors, integral transmembrane proteins to which ACh specifically binds. These receptors are abundant in junctional folds, deep grooves in the motor end plate that provide a large surface area for ACh. As you will see, the ACh receptors are ligand-gated ion channels. An NMJ thus includes all of the synaptic end bulbs on one side of the synaptic cleft, the synaptic cleft itself, plus the motor end plate of the muscle fiber on the other side.

Each skeletal muscle fiber is stimulated to contract by a

motor neuron

The process in which the number of active motor units increases is called

motor unit recruitment

As the contraction cycle continues,

movement of cross-bridges applies the force that draws the Z discs toward each other, and the sarcomere shortens.

Even at rest, a skeletal muscle exhibits

muscle tone (tonos = tension),

Muscle contraction occurs because

myosin heads attach to and "walk" along the thin filaments at both ends of a sarcomere, progressively pulling the thin filaments toward the M line (Figure 10.5). As a result, the thin filaments slide inward and meet at the center of a sarcomere. They may even move so far inward that their ends overlap (Figure 10.5c). As the thin filaments slide inward, the I band and H zone narrow and eventually disappear altogether when the muscle is maximally contracted

The term muscular dystrophy (DIS-trō-fē′; dys- = difficult; -trophy = nourishment)

refers to a group of inherited muscle-destroying diseases that cause progressive degeneration of skeletal muscle fibers. The most common form of muscular dystrophy is Duchenne muscular dystrophy (DMD) (doo-SHĀN). Because the mutated gene is on the X chromosome, and because males have only one X chromosome, DMD strikes boys almost exclusively. (Sex-linked inheritance is described in Chapter 29.) Worldwide, about 1 in every 3500 male babies—about 21,000 in all—are born with DMD each year. The disorder usually becomes apparent between the ages of 2 and 5, when parents notice the child falls often and has difficulty running, jumping, and hopping. By age 12 most boys with DMD are unable to walk. Respiratory or cardiac failure usually causes death by age 20.

A tremor is a

rhythmic, involuntary, purposeless contraction that produces a quivering or shaking movement.

However, the width of the A band and the individual lengths of the thick and thin filaments remain unchanged

Since the thin filaments on each side of the sarcomere are attached to Z discs, when the thin filaments slide inward, the Z discs come closer together, and the sarcomere shortens. Shortening of the sarcomeres causes shortening of the whole muscle fiber, which in turn leads to shortening of the entire muscle.

The three types of muscular tissue

skeletal, cardiac, and smooth

Typically, the different motor units of an entire muscle are not

stimulated to contract in unison. While some motor units are contracting, others are relaxed. This pattern of motor unit activity delays muscle fatigue and allows contraction of a whole muscle to be sustained for long periods. The weakest motor units are recruited first, with progressively stronger motor units added if the task requires more force.

The Neuromuscular Junction

the junction between a nerve fiber and the muscle it supplies

The adipose tissue of the subcutaneous layer stores most of the body's

triglycerides, serves as an insulating layer that reduces heat loss, and protects muscles from physical trauma.

Only the heart contains cardiac muscle tissue

which forms most of the heart wall. Cardiac muscle is also striated, but its action is involuntary. The alternating contraction and relaxation of the heart is not consciously controlled. Rather, the heart beats because it has a natural pacemaker that initiates each contraction

Three layers of connective tissue extend from the fascia to protect and strengthen skeletal muscle (

•Epimysium •Perimysium Endomysium

Mechanism of excitation-contraction coupling in a skeletal muscle fiber

(a) During relaxation, the level of Ca2+ in the sarcoplasm is low, only 0.1 μM (0.0001 mM), because calcium ions are pumped into the sarcoplasmic reticulum by Ca2+-ATPase pumps. (b) A muscle action potential propagating along a transverse tubule causes voltage-gated Ca2+ channels to undergo a conformational change that opens Ca2+ release channels in the sarcoplasmic reticulum, calcium ions flow into the sarcoplasm, and contraction begins.

Myograms showing the effects of different frequencies of stimulation

(a) Single twitch. (b) When a second stimulus occurs before the muscle fiber has relaxed, the second contraction is stronger than the first, a phenomenon called wave summation. (The solid black line indicates the force of contraction expected in a single twitch.) (c) Unfused tetanus produces a jagged curve due to partial relaxation of the muscle fiber between stimuli. (d) In fused tetanus, which occurs when there are 80-100 stimuli per second, the myogram line, like the contraction force, is steady and sustained.

DisordersHomeostatic Imbalances

Abnormalities of skeletal muscle function may be due to disease or damage of any of the components of a motor unit: somatic motor neurons, neuromuscular junctions, or muscle fibers.

3Power stroke.

After a cross-bridge forms, the myosin head pivots, changing its position from a 90° angle to a 45° angle relative to the thick and thin filaments. As the myosin head changes to its new position, it pulls the thin filament past the thick filament toward the center of the sarcomere, generating tension (force) in the process. This event is known as the power stroke. The energy required for the power stroke is derived from the energy stored in the myosin head from the hydrolysis of ATP (see step blue1). Once the power stroke occurs, ADP is released from the myosin head.

The Contraction Cycle At the onset of contraction, the sarcoplasmic reticulum releases calcium ions (Ca2+) into the sarcoplasm. There, they bind to troponin. Troponin then moves tropomyosin away from the myosin-binding sites on actin. Once the binding sites are "free," the contraction cycle—the repeating sequence of events that causes the filaments to slide—begins. The contraction cycle consists of four steps (Figure

1. Contraction Cycle Begins 2. Active-Site Exposure 3. Cross-Bridge Formation 4. Myosin Head Pivoting 5. Cross-Bridge Detachment 6. Myosin Reactivation

Functions of Muscular Tissue

1. Producing body movements 2. Stabilizing body positions 3. Storing and moving substances within the body 4. Generating heat

Excitation-Contraction Coupling

An increase in Ca2+ concentration in the sarcoplasm starts muscle contraction, and a decrease stops it. When a muscle fiber is relaxed, the concentration of Ca2+ in its sarcoplasm is very low, only about 0.1 micromole per liter (0.1 μmol/L). However, a huge amount of Ca2+ is stored inside the sarcoplasmic reticulum (Figure 10.7a). As a muscle action potential propagates along the sarcolemma and into the T tubules, it causes the release of Ca2+ from the SR into the sarcoplasm and this triggers muscle contraction. The sequence of events that links excitation (a muscle action potential) to contraction (sliding of the filaments) is referred to as excitation-contraction coupling.

1ATP hydrolysis

As mentioned earlier, a myosin head includes an ATP-binding site that functions as an ATPase—an enzyme that hydrolyzes ATP into ADP (adenosine diphosphate) and a phosphate group. The energy generated from this hydrolysis reaction is stored in the myosin head for later use during the contraction cycle. The myosin head is said to be energized when it contains stored energy. The energized myosin head assumes a "cocked" position, like a stretched spring. In this position, the myosin head is perpendicular (at a 90° angle) relative to the thick and thin filaments and has the proper orientation to bind to an actin molecule. Notice that the products of ATP hydrolysis—ADP and a phosphate group—are still attached to the myosin head.

4.Generating heat

As muscular tissue contracts, it produces heat, a process known as thermogenesis (ther′-mō-JEN-e-sis). Much of the heat generated by muscle is used to maintain normal body temperature. Involuntary contractions of skeletal muscles, known as shivering, can increase the rate of heat production.

1Release of acetylcholine.

Binding of two molecules of ACh to the receptor on the motor end plate opens an ion channel in the ACh receptor. Once the channel is open, small cations, most importantly Na+, can flow across the membrane.

2Activation of ACh receptors

Binding of two molecules of ACh to the receptor on the motor end plate opens an ion channel in the ACh receptor. Once the channel is open, small cations, most importantly Na+, can flow across the membrane.

3.Storing and moving substances within the body

Storage is accomplished by sustained contractions of ringlike bands of smooth muscle called sphincters, which prevent outflow of the contents of a hollow organ Temporary storage of food in the stomach or urine in the urinary bladder is possible because smooth muscle sphincters close off the outlets of these organs Cardiac muscle contractions of the heart pump blood through the blood vessels of the body Contraction and relaxation of smooth muscle in the walls of blood vessels help adjust blood vessel diameter and thus regulate the rate of blood flow Smooth muscle contractions also move food and substances such as bile and enzymes through the gastrointestinal tract, push gametes (sperm and oocytes) through the passageways of the reproductive systems, and propel urine through the urinary system. Skeletal muscle contractions promote the flow of lymph and aid the return of blood in veins to the heart.

Skeletal muscle tissue

Voluntary muscle pulls on bones and causes body movements. skeletal muscle tissue is so named because most skeletal muscles move the bones of the skeleton. (A few skeletal muscles attach to and move the skin or other skeletal muscles.) Skeletal muscle tissue is striated: Alternating light and dark protein bands (striations) are seen when the tissue is examined with a microscope (see Table 4.9). Skeletal muscle tissue works mainly in a voluntary manner. Its activity can be consciously controlled by neurons (nerve cells) that are part of the somatic (voluntary) division of the nervous system

Contraction and Relaxation of Skeletal Muscle Fibers

When scientists examined the first electron micrographs of skeletal muscle in the mid-1950s, they were surprised to see that the lengths of the thick and thin filaments were the same in both relaxed and contracted muscle. It had been thought that muscle contraction must be a folding process, somewhat like closing an accordion. Instead, researchers discovered that skeletal muscle shortens during contraction because the thick and thin filaments slide past one another. The model describing this process is known as the sliding filament mechanism.

The second phase, the

contraction period, lasts 10-100 msec. During this time, Ca2+ binds to troponin, myosin-binding sites on actin are exposed, and cross-bridges form. Peak tension develops in the muscle fiber.

Most skeletal muscles also are

controlled subconsciously to some extent. For example, your diaphragm continues to alternately contract and relax without conscious control so that you don't stop breathing. Also, you do not need to consciously think about contracting the skeletal muscles that maintain your posture or stabilize body positions.

A motor unit consists of a

somatic motor neuron plus all of the skeletal muscle fibers it stimulates (Figure 10.12). A single somatic motor neuron makes contact with an average of 150 skeletal muscle fibers, and all of the muscle fibers in one motor unit contract in unison. Typically, the muscle fibers of a motor unit are dispersed throughout a muscle rather than clustered together.