contraction and relaxation

10.3 Contraction and Relaxation of Skeletal Muscle Fibers

OBJECTIVES

Outline the steps involved in the sliding filament mechanism of muscle contraction.

Describe how muscle action potentials arise at the neuromuscular junction.

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 Sliding Filament Mechanism

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. 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.

A three-part figure shows the sliding filament mechanism of muscle contraction. Each part includes an orientation diagram of a lateral view of the arm, a diagram of two sarcomeres, and a micrograph to show the changes in the I band and H band during muscle contraction. Diagram (a) shows relaxed muscle. The H band is a bit smaller than the I band and the A band, which are the same size. Diagram (b) shows partially contracted muscle. The H band and I band are thinner because of the overlap of the thin and thick filaments. Diagram (c) shows maximally contracted muscle. The A band is the same size but the I band and H band have disappeared.

FIGURE 10.5 Sliding filament mechanism of muscle contraction, as it occurs in two adjacent sarcomeres.

During muscle contractions, thin filaments move toward the M line of each sarcomere.

Q What happens to the I band and H zone as muscle contracts? Do the lengths of the thick and thin filaments change?

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 10.6):

ATP 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.

Attachment 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.

Power 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 ). Once the power stroke occurs, ADP is released from the myosin head.

Detachment 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.

A diagram shows the contraction cycle in 4 steps. Step 1. Myosin head hydrolyzes A T P and becomes energized and oriented. The myosin head lifts at a 90-degree angle to attach to the actin. Step 2. Myosin head binds to actin, forming a cross-bridge. Step 3. Myosin head pivots, pulling the thin filament past the thick filament toward center of the sarcomere in a power stroke. The myosin head is lifted at a 45-degree angle. Step 4. As myosin head binds A T P, the cross-bridge detaches from actin.

FIGURE 10.6 The contraction cycle. Sarcomeres exert force and shorten through repeated cycles during which the myosin heads attach to actin (forming cross-bridges), rotate, and detach.

During the power stroke of contraction, cross-bridges rotate and move the thin filaments past the thick filaments toward the center of the sarcomere.

Q What would happen if ATP suddenly were not available after the sarcomere had started to shorten?

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.

As the contraction cycle continues, movement of cross-bridges applies the force that draws the Z discs toward each other, and the sarcomere shortens. 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 fibers of a skeletal muscle start to shorten, they first pull on their connective tissue coverings and tendons. 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).

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.

Excitation-contraction coupling occurs at the triads of the skeletal muscle fiber. Recall that a triad consists of a T tubule and two opposing terminal cisterns of the sarcoplasmic reticulum (SR). At a given triad, the T tubule and terminal cisterns are mechanically linked together by two groups of integral membrane proteins: voltage-gated Ca2+ channels and Ca2+ release channels (Figure 10.7a). Voltage-gated Ca2+ channels are located in the T tubule membrane; they arranged in clusters of four known as tetrads. The main role of these voltage-gated Ca2+ channels in excitation-contraction coupling is to serve as voltage sensors that trigger the opening of the Ca2+ release channels. Ca2+ release channels are present in the terminal cisternal membrane of the SR. When a skeletal muscle fiber is at rest, the part of the Ca2+ release channel that extends into the sarcoplasm is blocked by a given cluster of voltage-gated Ca2+ channels, preventing Ca2+ from leaving the SR (Figure 10.7a). When a skeletal muscle fiber is excited and an action potential travels along the T tubule, the voltage-gated Ca2+ channels detect the change in voltage and undergo a conformational change that ultimately causes the Ca2+ release channels to open (Figure 10.7b). Once these channels open, large amounts of Ca2+ flow out of the SR into the sarcoplasm around the thick and thin filaments. As a result, the Ca2+ concentration in the sarcoplasm rises tenfold or more. The released calcium ions combine with troponin, which in turn undergoes a conformational change that causes tropomyosin to move away from the myosin-binding sites on actin. Once these binding sites are free, myosin heads bind to them to form cross-bridges, and the muscle fiber contracts.

The terminal cisternal membrane of the sarcoplasmic reticulum also contains Ca2+-ATPase pumps that use ATP to constantly transport Ca2+ from the sarcoplasm into the SR (Figure 10.7a,b). As long as muscle action potentials continue to propagate along the T tubules, the Ca2+ release channels remain open and Ca2+ flows into the sarcoplasm faster than it is transported back into the SR by the Ca2+-ATPase pumps. After the last action potential has propagated throughout the T tubules, the Ca2+ release channels close. As the Ca2+-ATPase pumps move Ca2+ back into the SR, the Ca2+ level in the sarcoplasm rapidly decreases. Inside the SR, molecules of a protein known as calsequestrin bind to Ca2+, allowing even more Ca2+ to be sequestered (stored) within the SR. In a relaxed muscle fiber, the concentration of Ca2+ is 10,000 times higher in the SR than in the sarcoplasm. As the Ca2+ level in the sarcoplasm decreases, Ca2+ is released from troponin, tropomyosin covers the myosin-binding sites on actin, and the muscle fiber relaxes.

Clinical Connection

Electrodiagnostic Medicine

Electrodiagnostic medicine is a branch of medicine concerned with the diagnosis of neuromuscular disorders. Nerve conduction velocity studies and muscle response studies, both of which are usually performed together, are tests that are components of electrodiagnostic medicine.

Nerve conduction velocity (NCV) tests measure the speed of nerve impulses conducted through nerves outside the brain and spinal cord; for example, those of your limbs. These studies involve stimulating a nerve with an electrical impulse applied to the skin and recording the response from a muscle (contraction) or another portion of a nerve through patches placed on the skin. NCV tests are used to diagnose conditions such as carpal tunnel syndrome, herniated discs, and sciatica.

Following a nerve conduction velocity test, a complimentary test called electromyography (e-lek′-trō-mĪ-OG-ra-fē; electro = electricity; myo = muscle; graph = to write) or EMG is performed. In this test, a very thin needle, which serves as a recording device, is placed through the skin into a muscle. The needle is connected by a wire to the screen of a device (an oscilloscope). Resting muscle produces no electrical activity as there are no muscle action potentials. The more forceful the contraction, the higher the level of electrical activity. Once the needle is in place, the client is asked to contract a muscle and the activity is recorded on the screen and may also be detected audibly with a speaker. EMG is used to diagnose disorders such as muscular dystrophy, myasthenia gravis, and amyotrophic lateral sclerosis.

A photo shows a physician performing nerve conduction velocity test on a patient. Recording patches are attached on the patient’s palm below the thumb and a stimulator is placed on the skin over the wrist.

A photo of an oscilloscope shows a waveform with low altitude resting muscle followed by high altitude contracting muscle. Another photo shows a physician performing electromyography on a patient by inserting a recording needle on the skin over the wrist.

Length–Tension Relationship

Figure 10.8 shows the length–tension relationship for skeletal muscle, which indicates how the forcefulness of muscle contraction depends on the length of the sarcomeres within a muscle before contraction begins. At a sarcomere length of about 2.0–2.4 µm (which is very close to the resting length in most muscles), the zone of overlap in each sarcomere is optimal, and the muscle fiber can develop maximum tension. Notice in Figure 10.8 that maximum tension (100%) occurs when the zone of overlap between a thick and thin filament extends from the edge of the H zone to one end of a thick filament.

A two-part diagram shows the events of excitation-contraction coupling. Diagram (a) shows relaxation. Sarcolemma with transverse tubule indentations cover the muscle fiber, which is filled with sarcoplasm. Terminal cisterns of S R containing C a 2 plus ions appear between the transverse tubules and have C a 2 plus active transport pumps at their borders. Their C a 2 plus release channels are closed. Two detailed views of the sarcomeres appear below showing troponin holding tropomyosin in position to block myosin-binding sites on actin.

Diagram (b) shows contraction. The C a 2 plus channels open to release C a 2 plus into the sarcoplasm. The C a 2 plus binds to troponin which changes the shape of the troponin-tropomyosin complex and uncovers the myosin-binding sites on actin, allowing the myosin heads to move and the muscle to contract.

FIGURE 10.7 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 T 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.

An increase in the Ca2+ level in the sarcoplasm starts the sliding of thin filaments. When the level of Ca2+ in the sarcoplasm declines, sliding stops.

Q What are the three functions of ATP in muscle contraction?

The Neuromuscular Junction (Synapse)

As noted earlier in the chapter, the neurons that stimulate skeletal muscle fibers to contract are called 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. A muscle fiber contracts in response to one or more action potentials propagating along its sarcolemma and through its system of T tubules. Muscle action potentials arise at the neuromuscular junction (NMJ) or neuromuscular synapse (NMS) (noo-rō-MUS-kū-lar), the synapse between a somatic motor neuron and a skeletal muscle fiber (Figure 10.9a). A synapse is a region where communication occurs between two neurons, or between a neuron and a target cell—in this case, between a somatic motor neuron and a muscle fiber. At most synapses a small gap, called the synaptic cleft, separates the two cells. Because the cells do not physically touch, the action potential cannot “jump the gap” from one cell to another. Instead, the first cell communicates with the second by releasing a chemical messenger called a neurotransmitter.

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

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.

A nerve impulse (nerve action potential) elicits a muscle action potential in the following way (Figure 10.9c):

Release of acetylcholine. Arrival of the nerve impulse at the synaptic end bulbs stimulates voltage-gated channels to open. Because calcium ions are more concentrated in the extracellular fluid, Ca2+ flows inward through the open channels. The entering Ca2+ in turn stimulates the synaptic vesicles to undergo exocytosis. During exocytosis, the synaptic vesicles fuse with the motor neuron’s plasma membrane, liberating ACh into the synaptic cleft. The ACh then diffuses across the synaptic cleft between the motor neuron and the motor end plate.

Activation 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.

Production 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.

Termination 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.

If another nerve impulse releases more acetylcholine, steps and and repeat. When action potentials in the motor neuron cease, ACh is no longer released, and AChE rapidly breaks down the ACh already present in the synaptic cleft. This ends the production of muscle action potentials, the Ca2+ moves from the sarcoplasm of the muscle fiber back into the sarcoplasmic reticulum, and the Ca2+ release channels in the sarcoplasmic reticulum membrane close.

A series of three diagrams and a micrograph illustrate the neuromuscular junction. Diagram (a) shows the structure of the neuromuscular junction. The branching axon collateral of a somatic motor neuron ends in four axon terminals at the neuromuscular junction, with a synaptic end bulb adjacent to the motor end plate of a muscle fiber. The muscle fiber shows a sarcolemma wrapped around myofibrils. Diagram (b) is an enlarged view of the neuromuscular junction showing the details of a synaptic end bulb and a motor end plate. An arrow indicates a nerve impulse descending through the axon terminal toward the synaptic end bulb. The synaptic end bulb is filled with synaptic vesicles containing A C h. Voltage gated C a 2 plus channels on its surface transmit C a 2 plus ions into the synaptic end bulb. Some of the synaptic vesicles are releasing A C h into the synaptic cleft, the space between the bulb and the motor end plate. Diagram (c) shows the four-step process of binding of acetylcholine to A C h receptors in the motor end plate. Step 1. A C h is released from synaptic vesicle and passes through the cleft. Step 2. A C h binds to A C h receptor in the junction fold of the plate. Step 3. Muscle action potential is produced. Step 4. A C h is broken down. An S E M micrograph (d) at 1650 times magnification shows two neuromuscular junctions. The somatic motor neuron is connected to the axon collateral which leads to axon terminal then the synaptic end bulbs which are on the skeletal muscle fibers. Blood capillaries are also entwined in the muscles.

FIGURE 10.9 Structure of the neuromuscular junction (NMJ).

Synaptic end bulbs at the tips of axon terminals contain synaptic vesicles filled with acetylcholine (ACh).

Q What part of the sarcolemma contains acetylcholine receptors?

A skeletal muscle fiber has only one NMJ and it is usually located near the midpoint of the fiber. Muscle action potentials that arise at the NMJ propagate toward both ends of the muscle fiber. This arrangement permits nearly simultaneous activation (and thus contraction) of all parts of the muscle fiber.

Figure 10.10 summarizes the events that occur during contraction and relaxation of a skeletal muscle fiber.

Several plant products and drugs selectively block certain events at the NMJ. Botulinum toxin (bot-u-LĪN-um), produced by the bacterium Clostridium botulinum, blocks exocytosis of synaptic vesicles at the NMJ. As a result, ACh is not released, and muscle contraction does not occur. The bacteria proliferate in improperly canned foods, and their toxin is one of the most lethal chemicals known. A tiny amount can cause death by paralyzing skeletal muscles. Breathing stops due to paralysis of respiratory muscles, including the diaphragm. However, it is also the first bacterial toxin to be used as a medicine (Botox®). Injections of Botox into the affected muscles can help patients who have strabismus (crossed eyes), blepharospasm (uncontrollable blinking), or spasms of the vocal cords that interfere with speech. It is also used to alleviate chronic back pain due to muscle spasms in the lumbar region and as a cosmetic treatment to relax muscles that cause facial wrinkles.

A multi-part diagram summarizes the events of contraction and relaxation in a skeletal muscle fiber in 9 steps. Step 1. A nerve action potential in a somatic motor neuron triggers the release of acetylcholine or A C h. Step 2. A C h binds to receptors in the motor end plate, ultimately triggering a muscle action potential. Step 3. Acetylcholinesterase destroys A C h so another muscle action potential does not arise unless more A C h is released from the somatic motor neuron. Step 4. A muscle action potential traveling along a transverse tubule triggers a change in the voltage-gated C a 2 plus channels that causes the C a 2 plus release channels to open, allowing the release of calcium ions into the sarcoplasm. Step 5. C a 2 plus binds to troponin on the thin filament, exposing the myosin-binding sites on actin. Step 6. Contraction: Myosin heads bind to actin, undergo power strokes, and release; thin filaments are pulled toward center of sarcomere. Step 7. C a 2 plus release channels close and C a 2 plus A T Pase pumps use A T P to restore low levels of C a 2 plus in the sarcoplasm. Step 8. Tropomyosin slides back into position where it blocks the myosin-binding sites on actin. Step 9. Muscle relaxes.

FIGURE 10.10 Summary of the events of contraction and relaxation in a skeletal muscle fiber.

Acetylcholine released at the neuromuscular junction triggers a muscle action potential, which leads to muscle contraction.

Q Which numbered steps in this figure are part of excitation–contraction coupling?

The plant derivative curare, a poison used by South American Indians on arrows and blowgun darts, causes muscle paralysis by binding to and blocking ACh receptors. In the presence of curare, the ion channels do not open. Curare-like drugs are often used during surgery to relax skeletal muscles.

A family of chemicals called anticholinesterase agents has the property of slowing the enzymatic activity of acetylcholinesterase, thus slowing removal of ACh from the synaptic cleft. At low doses, these agents can strengthen weak muscle contractions. One example is neostigmine, which is used to treat patients with myasthenia gravis (see the Disorders: Homeostatic Imbalances section at the end of this chapter). Neostigmine is also used as an antidote for curare poisoning and to terminate the effects of curare-like drugs after surgery.

Checkpoint

What roles do contractile, regulatory, and structural proteins play in muscle contraction and relaxation?

How do calcium ions and ATP contribute to muscle contraction and relaxation?

How does sarcomere length influence the maximum tension that is possible during muscle contraction?

How is the motor end plate different from other parts of the sarcolemma?