10.3 Contraction and Relaxation of Skeletal Muscle Fibers

What are the three functions of ATP in muscle contraction?

(1) Its hydrolysis by an ATPase activates the myosin head so it can bind to actin and rotate (2) Its binding to myosin causes detachment from actin after the power stroke; (3) It powers the pumps that transport calcium ions from the cytosol back into the sarcoplasmic reticulum.

3. Power stroke

After a cross‐bridges form, 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 1). Once the power stroke occurs, ADP is released from the myosin head.

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.

As the thin filaments slide inward, the_______________narrow and eventually disappear altogether when the muscle is maximally contracted. However, the width of the _______________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______________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.

I band and H zone A band Z discs

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.

production of ATP in muscle fibers

creatine phosphate, anaerobic cellular respiration, aerobic cellular respiration

Excitation‐contraction coupling occurs at the triads of the skeletal muscle fiber. Recall that a triad consists of a transverse (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 .__________________channels are located in the T tubule membrane; they arranged in clusters of four known as tetrads.

Voltage‐gated Ca2+

axon terminal

end of axon

If another nerve impulse releases more acetylcholine, steps 2 and 3 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.

. However, a huge amount of Ca2+ is stored inside the sarcoplasmic reticulum. 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

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.

ACh receptors

muscarinic and nicotinic

Acetylcholine (ACh) (neurotransmitter)

muscle contractions; transmitter at neuromuscular junction; important for memory

acetylcholine receptors

nicotinic and muscarinic

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.

Why is tension maximal at a sarcomere length of 2.2 μm?

-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.

contraction cycle

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 en ergy. 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. 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. 3Power stroke. After a cross‐bridges form, 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 1). Once the power stroke occurs, ADP is released from the myosin head. 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.

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

1Release of acetylcholine. 2Activation of ACh receptors. 3Production of muscle action potential. 4Termination of ACh activity.

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.

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.

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 en ergy. 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.

Which numbered steps in this figure are part of excitation-contraction coupling? Several plant products and drugs selectively block certain events at the NMJ. _________________________, 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. Yet 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. The plant derivative ______________, 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 __________________________ 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 Neostigmine is also used as an antidote for curare poisoning and to terminate the effects of curare‐like drugs after surgery.

Botulinum toxin curare anticholinesterase

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. __________________ 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

Ca2+ release channels

Neurotransmitters

Chemicals that transmit information from one neuron to another

The terminal cisternal membrane of the sarcoplasmic reticulum also contains ____________________ that use ATP to constantly transport Ca2+ from the sarcoplasm into the SR . 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 _____________________ 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.

Ca2+‐ATPase pumps calsequestrin

Ca2+ release channels

Channels located in the sarcoplasmic reticulum; opening of these channels is triggered by the opening of voltage-gated Ca2+ channels located in T-tubules</font

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. 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

motor end plate (neuromuscular junction)

The Ach binds with receptors on the ___________________of a muscle cell.

_________________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

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.

Termination of ACh activity

The effect of ACh binding lasts only briefly because ACh is rapidly broken down by an enzyme called acetylcholinesterase (AChE) ( This enzyme is located on the extracellular side of the motor end plate membrane. AChE breaks down ACh into acetate and choline, products that cannot activate the ACh receptor.

Attachment of myosin on 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.

At the NMJ, the end of the motor neuron, called the________________ divides into a cluster of synaptic end bulbs , 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 __________________) the neurotransmitter released at the NMJ. The region of the sarcolemma opposite the synaptic end bulbs, called the __________________ (Figure 10.9b, c), is the muscular part of the NMJ. Within each motor end plate are 30 million to 40 million ________________________ integral transmembrane proteins to which ACh specifically binds. These receptors are abundant in _______________, deep grooves in the motor end plate that provide a large surface area for ACh. As you will see, the _________________ 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.

axon terminal acetylcholine (ACh) motor end plate acetylcholine receptors junctional folds ACh receptors

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

As noted earlier in the chapter, the neurons that stimulate skeletal muscle fibers to contract are called_____________________. 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 _____________________ the synapse between a somatic motor neuron and a skeletal muscle fiber (Figure 10.9a). A _____________________ 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 ________________, 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_________________.

somatic motor neurons neuromuscular junction (NMJ) synapse synaptic cleft neurotransmitter

When a skeletal muscle fiber is excited and an action potential travels along the T tubule, the __________________ channels detect the change in voltage and undergo a conformational change that ultimately causes the Ca2+ release channels to open . 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__________________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.

voltage‐gated Ca2+ Ca2+ concentration