skeletal muscle physiology

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A 66-year-old man who lives alone has a severe myocardial infarction and dies during the night. The medical examiner's office is called the following morning and describes the man's body as being in rigor mortis. This state of rigor mortis is most likely due to which of the following? A. A lack of action potentials in motor neurons B. Failure of tropomyosin and troponin to move away from the actin binding sites on myosin C. Increased intracellular Ca2+concentration D. Inhibition of Ca2+ entry from the extracellular fluid and sarcoplasmic reticulum E. Prevention of detachment of the myosin heads from actin

Answer: E Explanation. Rigor is a state of permanent contraction that occurs in skeletal muscle when adenosine triphosphate (ATP) levels are depleted. With no ATP bound, myosin remains attached to actin and the cross-bridge cycle cannot continue. If there were no action potentials in motor neurons, the muscle fibers they innervate would not contract at all, since action potentials are required for release of Ca2+ from the sarcoplasmic reticulum (SR). When intracellular Ca2+ concentration increases, Ca2+ binds troponin C, permitting the cross-bridge cycle to occur. Decreases in intracellular Ca2+ concentration cause relaxation.

Which of the following statements best describes how the length of a skeletal muscle cell in vivo relates to the force it can generate? A. The longer a skeletal muscle cell is when it begins to contract, the stronger the force generation will be B. The shorter a skeletal muscle cell is when it begins to contract, the stronger the force generation will be C. The tension in a skeletal muscle cell is greatest when contractions occur at either very short or very long lengths D. Skeletal muscle cells generate the most force when the contraction occurs at an intermediate length E. Skeletal muscle cells generate the same amount of force, regardless of their length.

Answer: D. Explanation: When a skeletal muscle fiber contracts, myosin heads attach to actin to form crossbridges. The thin filaments slide 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 overlap. Therefore, 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 (~2-2.2 m). This length maximizes the overlap of actin-binding sites and myosin heads. 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 >3 m (>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 length by firm attachments of skeletal muscle to bones (via their tendons) and to other inelastic tissues.

A 28-year-old woman qualifies to run in the New York marathon. She undertakes an endurancetraining regimen designed to improve marathon performance. Which of the following properties is greater in type I (slow oxidative) compared to type IIb (fast-glycolytic) muscle fibers, thereby promoting distance-running success? A. Glycogen content B. Myosin ATPase activity C. Glycolytic capacity D. Oxidative capacity E. Speed of contraction

Answer: D. Explanation: Skeletal muscle is a heterogeneous tissue made up of 3 different fiber types - type I (slow oxidative), type IIa (fast oxidative) and type IIb (fast glycolytic). Compared to type IIb, type I fibers also have less fatigability, decreased force of contraction, and decreased speed of contraction.

A healthy 32-year-old man lifts weights regularly as part of his workout. In one of his bicep muscle fibers at rest, the length of the I band is 1.0 μm and the A band is 1.5 μm. Contraction of that muscle fiber results in a 10% shortening of the length of the sarcomere. What is the length of the A band after the shortening produced by muscle contraction? A. 0.45 μm B. 1.00 μm c. 1.35 μm D. 1.50 μm E. 1.90 μm

Answer: D. Explanation: The A band, the region of the sarcomere where thick And thin filaments overlap. It encompasses the width of the thick filament and this does not change during contraction.

. In skeletal muscle at rest, myosin cross-bridges are prevented from binding to actin molecules by which of the following? A. Calmodulin B. Myosin phosphatase C. Titin D. Troponin E. Tropomyosin

tropomyosin Answer: E. Explanation: When skeletal muscle fibers are at rest, tropomyosin inhibits the interaction between actin and myosin. The inhibition is removed when Ca2+ binds to troponin C. The binding of Ca2+ to troponin causes troponin to undergo a conformational change, during which tropomyosin is moved from its resting position to a position where it no longer blocks the interaction between the myosin and actin. In smooth muscle, calcium binds calmodulin activating myosin light chain kinase (MLCK) which phosphorylates myosin light chains. This is necessary for cross-bridge formation in smooth muscle. Myosin phosphatase (also called myosin light chain phosphatase, MLCP) dephosphorylates myosin light chains permitting relaxation.

Which of the following characterizes the event(s) which occur during the latent period of an isometric twitch in skeletal muscle? . Ca2+ binds to troponin T B. Dihydropyridine receptors open and conduct Ca2+ into the sarcoplasmic reticulum C. Myosin hydrolyzes ATP and releases from actin D. Ryanodine receptors open and Ca2+ enters the cytoplasm E. Tropomyosin moves to block myosin-binding sites on actin

A muscle twitch is divided into three phases: 1) the latent period; 2) the contraction phase; 3) the relaxation phase. A brief delay occurs between application of the stimulus (black arrow) and the beginning of contraction (contraction phase, increase in tension). 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. The second phase, the contraction period, lasts 10-100 msec. During this time, Ca2+ binds to troponin C, myosin‐binding sites on actin are exposed, and cross‐bridges form. Peak tension develops in the muscle fiber. During the third phase, 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, 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.

Which of the following best characterizes a skeletal muscle sarcomere at rest (not contracting)? A. ADP+P are bound to myosin B. ATP is bound to actin . Calcium is bound to troponin C D. Myosin and actin are attached E Myosin is inactivated

A.ADP+P are bound to myosin Explanation: At rest, there is no calcium in the cytoplasm to bind to troponin C. The myosin binding sites on actin are covered by tropomyosin and myosin and actin are unable to interact. Myosin is bound to ADP+P. The myosin head is energized and ready to bind to actin once calcium levels in the cytoplasm increase. In skeletal muscle, myosin is constitutively active and always ready to bind to actin. It is unlike smooth muscle in this regard, where myosin light chains must be phosphorylated by myosin light chain kinase in order for myosin to bind to actin. Actin does not bind ATP. ATP binds to ATP binding sites in the myosin head. When ATP binds to myosin, myosin and actin detach from each other.

. The attached diagram shows the force-velocity relationship for isotonic contractions of five different muscles (A-E). Which of the muscle fibers depicted in the force-velocity relationship diagram most likely exhibits the highest rate of ATP hydrolysis?

Answer: A. Explanation: During a contraction the rate at which the muscle is able to break down ATP (ATP hydrolysis) determines a fast versus a slow muscle. The rate of hydrolysis of ATP is determined by the myosin ATPase activity. This is reflected by the maximum velocity of shortening, i.e., the rate of crossbridge cycling when lifting no load. It corresponds to the point on the "Y" axis. A decrease in ATPase activity would decrease Vmax.

A 25-year old woman works out on a daily basis. She combines strength training and cardio in her routine. She uses 20 lb. dumbbells to do bicep curls. Which of the following signifies the isometric contraction of the muscle during a bicep curl? A. Bringing the dumbbell down. B. Holding the weight stationary after the lift is complete. C. Lifting the dumbbell up. D. When the muscle is in the relaxed state. E. When the weight is released and it drops.

Answer: B Explanation: During isometric contraction, the length of the muscle does not change, nor is any movement (velocity of shortening = 0) or joint motion involved (work = 0) (e.g. trying to lift a car). During a bicep curl, isometric contraction corresponds to the time where the weight is held stationary. Bringing the weight up or down involves changing the length of the muscle. This is isotonic contraction. When the muscle is in the relaxed state, it is not contracting. When the weight is released, the muscle is not contracting.

. A severe laceration to a wrist completely severed a major muscle tendon. To suture the ends of the tendon together, the surgeon had to overlap the severed ends by 1.7 cm. In doing so, the muscle is stretched beyond the original resting length. What change (if any) in passive and active tension would be expected in the stretched muscle? Maximum Active Tension During Contraction/Passive Tension A Decrease Decrease B Decrease Increase C No change Decrease D Decrease No change E No change No change F Increase Decrease G Increase Increase H No change Increase I Increase No change

Answer: B Explanation: In the body, (in vivo) skeletal muscle is prestretched to its optimal length (Lo). This length also corresponds to the resting length of skeletal muscle. At this length, there is an optimum prestretch (or preload) on the sarcomere such that if troponin is saturated with calcium, all of the cross-bridges will cycle, producing greatest force of contraction. If the tendons are overlapped before they are sutured, the muscle will be stretched beyond Lo. This will decrease the overlap of the actin and myosin, and fewer cross-bridges can cycle. Fewer potential cross-bridges for cycling means a decrease in the maximum force that can be generated during contraction (decreased active tension). Overlapping the tendons will increase the passive tension in the muscle.

The length-tension diagram shown here was obtained from a skeletal muscle. Supramaximal tetanic stimuli were used to initiate an isometric contraction at each muscle length studied. What is the maximum amount of active tension that the muscle is capable of generating at a passive tension of 100 grams? A. 25-35 grams B. 55-65 grams C. 95-105 grams D. 145-155 grams E. Cannot be determined

Answer: B Explanation: The diagram shows the relationship between passive tension (curve Z), total tension (curve X), and active tension (curve Y). Active tension cannot be measured directly: it is the difference between total tension and passive tension. To answer this question, first find where 100 grams intersects the passive tension curve and then move down to the active tension curve. One can see that a passive tension of 100 grams is associated with a total tension of a little more than 150 grams, and an active tension of a little more than 50 grams. Note that active tension equals total tension minus passive tension

What is the function of the structure indicated by the arrow in the following image: A. Sequester calcium ions during muscle relaxation B. Allow action potentials to propagate into the muscle fiber C. Provide energy for contraction D. Bind to calcium to initiate contraction . Anchor thin filaments at the sarcomere terminal

Answer: B Explanation: The structure indicated by the arrow is a tranverse- or t-tubule. These invaginations of the plasma membrane permit propagation of action potentials into the muscle fiber where depolarization ultimately leads to calcium release from the sarcoplasmic reticulum. A is incorrect since calcium is sequestered in the sarcoplasmic reticulum. C is incorrect since energy for contraction is provided by ATP and this is not stored in the t-tubules. D is incorrect since calcium binds to troponin to initiate contraction. Thin filaments are anchored to the Z-line in the sarcomere, not t-tubules making E incorrect.

In skeletal muscle, which of the following events occurs immediately before depolarization of the Ttubules in the mechanism of excitation-contraction coupling? A. Binding of actin and myosin B. Binding of Ca2+ to troponin C C. Depolarization of the sarcolemma D. Opening of Ca2+ release channels on the sarcoplasmic reticulum E. Uptake of Ca2+ into the sarcoplasmic reticulum by Ca2+ - ATPase

Answer: C Explanation: In the mechanism of excitation-contraction coupling, excitation always precedes contraction. Excitation refers to the electrical activation of the muscle cell, which begins with an action potential (depolarization) in the sarcolemma (muscle plasma membrane) that spreads to the T-tubules. Depolarization of the T-tubules leads to the release of Ca2+ from the nearby sarcoplasmic reticulum (SR), followed by an increase in intracellular Ca2+ concentration, binding of Ca2+ to troponin C, and then contraction.

The length-tension diagram shown here was obtained from a skeletal muscle. Supramaximal tetanic stimuli were used to initiate an isometric contraction at each muscle length studied. Looking at the attached diagram, what is the most likely approximate resting length of this muscle? A. 0 cm B. 10 cm C. 20 cm D. 30 cm E. 40 cm

Answer: C Explanation: The resting length of a skeletal muscle is its length when at rest in the body. When a skeletal muscle is stretched from its resting length, it develops passive tension. This passive tension arises from resistance of titin, collagen and other connective tissue elements to stretch. Line Z on the graph corresponds to the passive tension of this muscle as it is stretched. Since passive tension begins to increase at ~20 cm, this is likely the best estimate of the resting length of this muscle.

During the process of excitation-contraction coupling in skeletal muscle, which of the following stimulates calcium release from the sarcoplasmic reticulum? A. Activation of troponin C B. An increase in intracellular calcium concentration C. Inositol trisphosphate (IP3) D. Membrane depolarization E. Protein Kinase A

Answer: D Explanation: Depolarization of the t-tubules in skeletal muscle fibers causes the calcium release channels of the sarcoplasmic reticulum (SR) to open, allowing calcium to enter the cytoplasm. Depolarization activates the voltage-sensitive dihydropyridine receptors (DHPR) on the T-tubular membrane. The DHPR are linked to calcium release channels in the SR membrane called ryanodine receptors (RYR). The AP in the T-tubule causes a conformational change in the DHPR which mechanically opens RYR in the SR membrane. Once these channels open, calcium is released from the SR into the cytoplasm.

The attached diagram shows the force-velocity relationship for isotonic contractions of five different muscles (A-E). Looking at curves B and C, the primary difference between these curves results from a difference in which of the following Frequency of muscle stimulation B. Hypertrophy C. Muscle mass D. Myosin ATPase activity E. Recruitment of motor units

Answer: D. Explanation: Looking at the force-velocity curves for all the fiber types, it is apparent that the maximum velocity of shortening (Vmax) occurs when there is no load on the muscle (force = 0). Increasing load decreases the velocity of shortening until a point is reached where shortening does not occur (isometric contraction) and contraction velocity is thus 0 (where curves intersect X axis). The primary difference between curves B and C is that the maximum velocity of shortening is lower in for fiber C compared to fiber B. The maximum velocity of shortening is dictated by the ATPase activity of the muscle, increasing to high levels when the ATPase activity is elevated. Choice A: Increasing the frequency of muscle stimulation will increase the load that a muscle can lift within the limits of the muscle, but will not affect the velocity of contraction. Choices B, C, and E: Muscle hypertrophy, increasing muscle mass, and recruiting additional motor units will increase the maximum load that a muscle can lift, but these will not affect the maximum velocity of contraction.

Which of the following statements best describes a motor unit? A. All of the fibers of a particular fiber type in a given muscle B. All of the muscles that contract to complete a particular body movement C. A particular muscle and all of its synergistic and antagonistic muscles D. A small group of connecting muscle fibers E. A single motor neuron and all of the muscle fibers that it innervates F. A group of muscle fibers and all of the motor neurons that innervate them

Answer: E. Explanation: A motor unit is defined as a single motor neuron and all the muscle fibers that it innervates. Muscle fibers are typically innervated by one motor neuron and one motor neuron innervates > 1 muscle fiber. A single muscle typically has many motor units. 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 process in which the number of active motor units increases is called motor unit recruitment.

This diagram shows the length-tension relationship for a single sarcomere. Why is tension development lowest at point D? A. Actin filaments are overlapping each other B. Myosin filaments are overlapping each other C. The myosin filament is at its minimal length D. There is optimal overlap between the actin and myosin filaments E. There is minimal overlap between the actin and myosin filaments F. The Z discs of the sarcomere touch the ends of the myosin filament

Answer: E. Explanation: Tension development in a single sarcomere is directly proportional to the number of active myosin cross-bridges attached to actin filaments. Overlap between the myosin and actin filaments is optimal at sarcomere lengths of about 2.0 to 2.5 micrometers, which allows maximal contact between myosin heads and actin filaments. At lengths less than 2.0 micrometers, the actin filaments protrude into the H band, where no myosin heads exist. At lengths greater than 2.5 micrometers, the actin filaments are pulled toward the ends of the myosin filaments, again reducing the number of possible cross-bridges.

The diagram shows the force-velocity relationship for isotonic contractions of two skeletal muscle preparations (X and Y). The muscle preparations used to generate these curves were isolated from the same muscle, were the same size and were prepared in the same manner. Looking at curves X and Y, the primary difference between these curves results from a difference in which of the following? .AMyosin ATPase activity B. Myosin light chain kinase activity C. Myosin light chain phosphatase activity D. The rate of calcium-calmodulin interaction E. The degree of overlap of actin-myosin filaments

Answer: E. Explanation: This graph depicts the force-velocity relationship for isotonic contractions. The starting point for each curve on the y axis represents the maximum velocity of contraction, i.e. the velocity with no load. This parameter is determined by the muscle's ATPase activity. In this graph, both curves start at the same point on the y -axis, therefore they have the same ATPase activity. The point where each curve crosses the x axis is the maximum force (Fmax) that muscle can generate during contraction. When the velocity of shortening is = 0, this means that the weight applied is too much for the muscle to lift (isometric contraction). Fmax is greater for muscle X than muscle Y. If we think back to the length-tension relationship, we remember that force exerted by a muscle is a function of length. When a muscle is stimulated to contract at its resting length, force generated is greatest. When a muscle is stimulated to contract at greater or lesser lengths than resting, force generated will be lower than at resting length. As such, we can say that compared to muscle X, muscle Y was likely shortened too much or stretched too much leading to sub-optimal overlap between actin and myosin filaments and a reduction in maximum tension generated. Myosin light chain kinase, myosin light chain phosphatase and calmodulin are associated with smooth, not skeletal, muscle.

When the cell membrane of a skeletal muscle is depolarized, ryanodine receptors change configuration and permit flow of Ca2+ through which of the following mechanisms? A. Actively, from the extracellular fluid to the cytoplasm. B. Actively, from the cytoplasm to the sarcoplasmic reticulum. C. Actively, from the sarcoplasmic reticulum to the cytoplasm. D. Passively, from the extracellular fluid to the cytoplasm. E. Passively, from the sarcoplasmic reticulum to the cytoplasm.

E. Passively, from the sarcoplasmic reticulum to the cytoplasm.

Repeated stimulation of a skeletal muscle fiber causes a sustained contraction (tetanus). Accumulation of which of the following in intracellular fluid is responsible for tetanus? A. Adenosine triphosphate (ATP) . Calmodulin C. Ca2+ D. Cl− E. K + F. Mg2+ G. Na+ H. Troponin

c Explanation: A single action potential in a skeletal muscle fiber briefly releases enough Ca2+ to saturate troponin, and all the myosin-binding sites on the thin filaments are therefore initially available. However, the binding of energized cross-bridges to these sites (step 1 of the cross-bridge cycle) takes time, whereas the Ca2+ released into the cytosol begins to be pumped back into the sarcoplasmic reticulum almost immediately. Thus, after a single action potential, the Ca2+ concentration begins to decrease and the troponin-tropomyosin complex re-blocks many binding sites before cross-bridges have had time to attach to them. This means that a single action potential results in a single twitch. In contrast, during a tetanic contraction, the successive action potentials each release Ca2+ from the sarcoplasmic reticulum before all the Ca2+ from the previous action potential has been pumped back into the sarcoplasmic reticulum. This results in a persistent elevation of cytosolic Ca2+concentration. Under these conditions, more binding sites remain available and many more cross-bridges become bound to the thin filaments.


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