Muscle Histology 1. Skeletal and cardiac muscle, which are both striated, at resting length contain an A band in each sarcomere. This A band contains: (A) Essentially all the contractile protein myosin, but no actin (B) Essentially all the contractile protein actin, but no myosin (C) Essentially all the myosin, plus some actin (D) Essentially all the actin, plus some myosin (E) Troponin and tropomyosin, but no actin Answer. C. The A band is the region of the thick (myosin) filaments. Since at resting length there will be some overlap between the m yosin and actin filaments, the A band will also contain some actin.
2. When skeletal muscle shortens in response to stimulation, there is... (A) A decrease in the width of the I band (B) A decrease in the width of the A band (C) An increase in the width of the H zone
(D) All of the above (E) A and B (F) None (F) None of the above
Answer: A. A band: the length of thick filament, remain unchanged during contraction. The width of both I band and H zone decrease during contraction due to cross-bridge interaction between thin and thick filaments.
3. Which of the following decreases in length during the contraction of a skeletal muscle fiber? (A) A band of the sarcomere (B) I band of the sarcomere (C) Thick filaments
(D) Thin filaments (E) Z discs of the sarcomere
Answer: B. The physical lengths of the actin and myosin filaments do not change during contraction. Therefore, the A band, which is composed of myosin filaments, does not change either. either. The distance between Z discs decreases, bu t the Z discs themselves do not change. Only the I band decreases in length as the muscle contracts.
4. A person lifting up their physiology textbook contracts their bicep muscle isotonically i sotonically.. Which one of the following does not change its length in this process when compared comp ared to when the muscle is at rest? (A) I band (B) A band
(C) H zone (D) Sarcomere
(E) Biceps tendon
Answer: B. The A band represents the area of the sarcomere that is made up of the thick filaments. The length of the thick filaments filaments do not change during any type of contraction. Therefore the A band does not change length during an isotonic contraction of the
biceps muscle. 5. A cross-s cross-section ectional al view of a skeletal skeletal muscle muscle fiber through through the H zone would would reveal the presence presence of what? (A) Actin and titin (B) Actin, but no myosin (C) Actin, myosin, and titin
(D) Myosin and actin (E) Myosin, but no actin
Answer: E. The H zone is the region in the center of the sarcomere composed of the lighter bands on either side of and including the M line. In this region, the myosin filaments are centered on the M line, and there are no overlapping actin filaments. Therefore, a cross-section through this region would reveal only myosin. 2+
6. Which Which of of the the foll followi owing ng binds binds Ca Ca in order to uncover the active site on F-actin? (A) Actin monomer (B) Myosin
(C) Tropomyosin (D) Troponin
(E) Crossbridge
Answer: D. Troponin (Tn) is a complex made up of three subunits; Tn T bound to the tropomyosin protein, Tn I that is believed to inhibit the active site and Tn C that binds to calcium. Depolarization of the muscle membrane membrane leads to an elevation in intracellular intracellular calcium levels (via different different mechanisms in skeletal and cardiac muscle). This increases the number of Tn C bound to calcium, which in turn increases the number of o f active sites on the thin filament available for binding to the myosin m yosin heads of the thick filament.
7. A 64-year-old 64-year-old man man was admitted admitted to the the hospital hospital with with edema and and congestive congestive heart failure. failure. He was found to have diastolic dysfunction characterized by inadequate filling of the heart during diastole. The decrease in ventricular filling is due to a decrease in ventricular muscle compliance. Which of the following proteins determines the normal stiffness of ventricular muscle? (A) Calmodulin (B) Troponin
(C) Tropomyosin (D) Titin
(E) Myosin kinase
light
chain
Answer: D. Titin is a large protein that connects the Z lines to the M lines, thereb y providing a scaffold for the sarcomere. Titin Titin contains two types of folded domains d omains that provide muscle with its elasticity. elasticity. The resistance to stretch increases throughout a contraction, which protects the th e structure of the sarcomere and prevents excess stretch.
Excitation-Contraction Coupling 8. In skeletal muscle, which of the following events o ccurs before depolarization of the T tubules in the mechanism of excitation-contraction coupling? (A) Depolarization of the sarcrolemmal membrane 2+ (B) Opening of Ca release channels on the sarcoplasmic reticulum 2+ 2+ (C) Uptake of Ca into the sarcoplasmic reticulum by Ca -ATPase 2+ (D) Binding of Ca to troponin C (E) Binding of actin and myosin ex citation-contraction coupling, excitation always precedes Answer: A. In the mechanism of excitation-contraction contraction. Excitation refers to the electrical activation of the muscle cell, which begins with an action potential in the sarcrolemmal membrane that spreads to the T tubules. Depolarization of 2+ the T tubules then leads to the release of Ca from the nearby sarcoplasmic reticulum, followed 2+ 2+ by an increase in intracellular Ca concentration, binding of Ca to troponin C, and then contraction. 9. Which of the following best describes the action p otential of skeletal muscle upon stimulation? (A) It spreads inward to all parts of the muscle via v ia the T-tubules (B) It has a prolonged plateau phase 2+ (C) It causes the immediate uptake of Ca into the lateral sacs of SR (D) It is longer than the action potential of cardiac muscle (E) It is not essential for contraction Answer: A. Depolarization of the muscle fiber is essential for initiating muscle contraction. The 2+ action potential transmitted to all a ll of the fibrils along T-tubules, triggering the release of Ca from the lateral sacs of the SR next nex t to T-system. T-system. It is shorter than the action potential of cardiac muscle and doesn't have a prolonged plateau phase.
10. The action potential of skeletal muscle: (A) Has a prolonged plateau phase (B) Spreads inward to all parts of the muscle via T-tubules T-tubules (C) Causes the immediate uptake of calcium into the lateral sacs of sarcoplasmic reticulum (D) Is longer than the action potential of cardiac muscle (E) Is not essential for muscle contraction in the intact muscle ca n contract as a unit. All other choices are Answer: B. Because of this spread, the muscle can opposite.
2+
11. Depolarization of the T tubule is directly linked to the opening of Ca channels on the sarcoplasmic reticulum (SR) of… (A) Skeletal muscle (B) Cardiac muscle
(C) Both A and B (D) None (D) None of the above
2+
2+
Answer: A. Ca released from SR depends on voltage-gated Ca channels in skeletal muscle, 2+ 2+ and Ca -induced Ca channels in cardiac muscle.
12. In a normal, healthy muscle, what occurs oc curs as a result of propagation of an action potential to the terminal membrane of a motor neuron? (A) (B) (C) (D) (E)
2+
Opening of voltage-gated Ca channels in the presynaptic membrane Depolarization of the T tubule membrane follows Always results in muscle contraction 2+ Increase in intracellular Ca concentration in the motor neuron terminal All of the above are correct
Answer: E. The neuromuscular junction is equipped with a so -called safety factor that ensures that every nerve impulse that travels to the terminal of a motor neuron results in an action potential in the sarcolemma. Given a normal, healthy muscle, contraction is also ensured. The 2+ voltage sensitivity of the Ca channels in the presynaptic membrane and the high concentration 2+ 2+ of extracellular Ca ensure an influx of Ca sufficient to stimulate the fusion of synaptic vesicles to the presynaptic membrane and the release of acetylcholine. The overabundance of acetylcholine released guarantees a depolarization of the postsynaptic membrane and the firing of an action potential.
13. At the muscle end- plate, acetylcholine (ACh) caused the opening of… +
(A) Na (A) Na channels and depolarization toward the E Na + (B) K channels and depolarization toward the EK 2+ (C) Ca channels and depolarization toward the ECa + + (D) Na (D) Na and K channels and depolarization to a value halfway between the E Na and EK + + (E) Na (E) Na and K channels and hyperpolarization to a value halfway between the E Na and EK Answer: D. Binding of ACh to receptors in the muscle end plate opens channels that allow + + passage of both Na and K down their chemical/concentration gradient. The resulting membrane potential will be depolarized to a value that is approximately halfway between their respective equilibrium potentials.
14. Which of the following is true about the synaptic channels on the endplate of skeletal muscle? +
(A) They are highly selective for Na (B) They are opened when the cell membrane depolarizes (C) They are activated by acetylcholine (ACh) (D) They are inhibited by atropine (E) They are responsible for the relative refractory period Answer: C. ACh is released from the alpha motoneuron nerve terminal and activates the synaptic channels (Nm receptors) on the skeletal muscle end plate. These channels, unlike the channels produced action potential, are not affected by changes in the membrane potential. Atropine blocks muscarinic (M) receptors, not Nm receptors. These channels are equally + + permeable to Na and K .
15. The end-plate of a normally innervated skeletal muscle cell can be distinguished from the rest of the cell membrane in that only the end-plate: (A) Will initiate a contraction in response to the local application of acetylcholine + (B) Will depolarize when exposed to an excess of extracellular K 2+ (C) Will depolarize in response to an excess of extracellular Ca (D) Has all of the above characteristics (E) Has none of the above characteristics Answer: A. The end-plate region of the skeletal muscle cell is the only region with receptors to acetylcholine. The end-plate potential produced in this region can lead to an action potential and muscle contraction. All region of the muscle membrane will be depolarized by increases in + 2+ extracellular K and least if not none; region will be dramatically affected by Ca .
16. The end-plate potential of skeletal muscle is best characterized as: (A) A local reversal of charge originating at the end-plate (B) A reversal of charge originating at the end-plate and propagated throughout the cell (C) A decrease in the transmembrane potential that is propagated throughout the cell (D) A local decrease in the transmembrane potential that is caused by an increased permeability + + to Na and K (E) A local decrease in the transmembrane potential that is associated with little or no increase in + Na conductance +
Answer: D. An end-plate potential is a local depolarization caused b y an influx of Na . The + + channels that open to allow the passage of Na (mainly) also permit the passage of K . The depolarization is not great enough to produce a reversal of the membrane charge.
17. Which one of the following is directly associated with the motor endplate potential? 2+
(A) Ca entry through voltage-dependent channels on the axon terminal (B) Acetylcholine release from the nerve terminal + (C) Na entry through nicotinic channels on the muscle membrane + (D) Na entry through voltage-dependent channels on the muscle membrane 2+ (E) Ca entry through dihydropyridine channels in the transverse tubule Answer: C. The motor endplate potential is produced in the muscle. Therefore you require ionic movement through channels that are found on the muscle membrane. The motor endplate + potential is also caused by Na entry into the muscle. The release of acetylcholine from the motorneuron leads to its binding to nicotinic receptors found at the motor endplate. This leads to + opening of the associated ion channel that allows for the simultaneous movement of Na into the + + + cell and K out. More Na moves in than K out so you get depolarization of the muscle cell membrane. This graded potential is the motor endplate potential.
18. Mary has just found out that she is suffering from myasthenia gravis, an autoimmune disease that decreases the number of nicotinic receptors on th e muscle membrane of the neuromuscular junction. She has been told to take a cholinesterase inhibitor which increases the concentration of acetylcholine at the neuromuscular junction. The binding of acetylcholine to the nicotinic receptors at the neuromuscular junction stimulate the influx o f what ion into the muscle cell? (A) Potassium (B) Sodium
(C) Calcium (D) Chlorine +
+
(E) Nicotine +
Answer: B. Both Na and K can go through NM. But, K will go out (efflux), and the influx of + + Na more than the efflux of K .
19. A 30-year-old woman is running the Boston marathon. In regard to the physiology of her different muscle tissue types, an increase in sodium conductanc e is associated with which of the following? (A) The plateau phase of the ventricular muscle action potential in heart (B) The downstroke of the skeletal muscle action potential (C) The upstroke of the smooth muscle action potential (D) The refractory period of the nerve cell action potential (E) The end-plate potential of the skeletal muscle fiber Answer: E. The end-plate potential in skeletal muscle is produced b y an influx of sodium into the cell, which results from the increase in sodium permeability that occurs with acetylcholine binding to the nicotinic receptors on the membrane of the motor end plate. Acetylcholine binding at the motor end plate also increases the potassium conductance of the membrane. The plateau phase of ventricular muscle action potentials and the upstroke of smooth muscle action potentials are produced by an increase in calcium conductance. An increase in potassium conductanc e is responsible for the downstroke of the action po tential. The refractory period is caused by an increase in potassium conductance and a decrease in the number of sodium channels available to
produce an action potential (i.e., sodium channel inactivation). 20. Which of the following temporal sequences is correct for ex citation-contraction coupling in skeletal muscle? 2+
(A) Increased intracellular [Ca ]; action potential in the muscle membrane; cross-bridge formation 2+ (B) Action potential in the muscle membrane; depolarization of the T tubules; release of Ca from the sarcoplasmic reticulum (SR) (C) Action potential in the muscle membrane; splitting of adenosine triphosphate (ATP); binding 2+ of Ca to troponin C 2+ (D) Release of Ca from the sarcoplasmic reticulum (SR); depolarization of the T tubules; 2+ binding of Ca to troponin C Answer: B. The correct sequence is action potential in the muscle membrane; depolarization of 2+ 2+ the T tubules; release of Ca from the sarcoplasmic reticulum; binding of Ca to troponin C; cross-bridge formation; and splitting of adenosine triphosphate.
21. Which of the following statements about smooth muscle contraction is most accurate? (A) (B) (C) (D)
2+
Ca independent Does not require an action potential Requires more energy compared to skeletal muscle Shorter in duration compared to skeletal muscle
Answer: B. In contrast to skeletal muscle, smooth muscle can be stimulated to contract without the generation of an action potential. For example, smooth muscle contracts in response to any 2+ 2+ stimulus that increases the cytosolic Ca concentration. This includes Ca channel openers, subthreshold depolarization, and a variety of tissue factors and circulating hormones that 2+ stimulate the release of intracellular Ca stores. Smooth muscle contraction uses less energy and 2+ lasts longer compared to that of skeletal muscle. Smoo th muscle contraction is heavily Ca dependent.
Muscle Contraction 22. Which of the following best defines contraction? (A) A series of chemical reactions that cause the muscle to pull (B) A series of chemical reactions that cause the muscle to shorten (C) A series of chemical reaction in which the muscle respond to stimulate (D) Shortening (E) Production of tension Answer: A. In both isometric and an isotonic contraction the muscle is attempting to pull a load. Muscle shortening does not occur during isometric contraction. Chemical reactions could be something totally unrelated to “contraction.” Production of tension will occur with the application of preload (not contraction, or active force).
23. Skeletal muscle contraction... (A) Equals the duration of the action potential (B) Equals the duration of the absolute refractory period (C) Precedes the refractory period (D) Ends immediately after the refractory period is over (E) All of the above (F) A and C (G) None of the above Answer: G. The action potential and the absolute refractory period are extremely short and are over for a significant time interval before mechanical contraction be gins.
24. Check each of the following statements about skeletal muscle contraction that is true. 2+
(A) The major function of the T system (transverse tubules) is to store and release Ca 2+ (B) The intracellular release of Ca causes the formation of bonds between actin and myosin 2+ (C) The bonds between actin and myosin are maintained until the Ca is sequestered (D) All of the above (E) B and C (F) None of the above Answer: B. The sarcoplasmic reticulum is the major intracellular storage and release site for calcium. The free calcium then attaches to troponin, causing the movement of tropomyosin and exposing the cross-bridge attachment sites on the actin. Thu s, statement B is correct. However, the bonds are not maintained; rather, there is cycling of the crossbridges. Cycling means the bonds form then break and continue this cycling during contraction. Every time a single cross bridge goes through one cycle, 1 ATP is hydrolyzed.
25. Which of the following best describes the contractile response of skeletal muscle? (A) It starts after the action potential (B) It does not last as long as the action potential (C) It produces more tension when the muscle contract isometrically than isotonically (D) It produces more tension when the muscle contract isotonically than isometrically (E) It decreases in magnitude with repeated stimulation Answer: C. The duration of the contractile response of skeletal muscle exceeds the duration of the action potential, and the contraction starts around the same time the action potential starts. Because the muscle contractile mechanism does no t have a refractory period, repeated stimulation before relaxation causes greater tension development than du ring a single muscle twitch (summation, or temporal summation). Isometrical tension is more than isotonical tension. (during an isotonical contraction, the force is constant, and it doesn't reach/exceed the peak of isometrical contraction force/tension.)
26. During an isometric contraction in vivo... (A) The total tension in the muscle is generated from actin-myosin cross-bridge 2+ (B) Intracellular free Ca is lower than under resting conditions (C) ATPase activity of the sarcoplasmic reticulum is inhibited 2+ (D) Troponin-bound Ca is required to maintain active tension + + (E) The Na /K -ATPase pump is actively inhibited 2+
Answer: D. Ca must remain bound to the troponin to maintain cross-bridge cycling. If the 2+ 2+ 2+ Ca detached from troponin (because of lower intracellular [Ca ] or removal by Ca -ATPase to SR), the troponin will cover the attachment site on the actin and cycling will be terminated. During an isometric contraction cross-bridges will generate active tension/force. The total + + tension will be the sum of the active (cross-bridge) and passive (preload) tension. The Na /K ATPase pump is not inhibited or at least it is not “actively.”
27. In a series of experiments, it is noted that in a skeletal muscle fiber an intracellular concentration 2+ – 6.5 of Ca of 10 mol/L is the threshold value needed for inducing contraction. On this basis, one – 5.5 2+ would expect a concentration of 10 mol/L of Ca to cause: (A) A more forceful contraction (B) A less forceful contraction
(C) A contraction of equal force (D) Relaxation – 5.5
– 6.5
Answer: A. A calcium concentration of 10 mol/L is greater than a concentration of l0 mol/L. More free calcium means more activated and cycling cross-bridges. The more cross bridges that cycle, the greater the force of contraction.
28. A newly discovered toxin incapacitated skeletal muscle by preventing the binding of ATP to the myosin cross-bridges. Which of the following would be expected in the affected muscle? (A) Decreased resting muscle compliance 2+ (B) A reduced sequestration of Ca by the sarcoplasmic reticulum 2+ (C) Reduced Ca release by the sarcoplasmic reticulum (D) Enhanced binding of ADP to myosin (E) A 50% reduction in the ability to develop active tension Answer: A. Under resting condition, the myosin cross-bridges are not linked to the actin of the thin filament. This permits the sliding of the thin and thick filaments past one another (easy to stretch or good compliance). During cross-bridge cycling (contraction), ATP is not required to form the cross-link between actin and myosin. Rather, the attachment of ATP to bind to the cross bridge head (myosin light chain) is required to break the cross-link. Inability of ATP attachment (or resetting myosin head position) terminate cycling with the actin and myosin cross-link. (i.e. 2+ 2+ rigor motis) The cycling of Ca independent from myosin cross-bridge cycling, (but Ca ATPase). ADP can be found on myosin, but it is ATP bound to myosin and it get hydrolyzed. Since cross-bridge cycling terminated, there would be 100% reduction of active tension.
29. Which one of the following groups matches the following statement? This group of muscles requires calcium to bind to troponin C to initiate the contractile state. (A) Skeletal muscle only (B) Skeletal and cardiac muscle only (C) Cardiac muscle only
(D) Cardiac and smooth muscle only (E) Smooth muscle only
Answer: B. Smooth muscle doesn’t have troponin C.
30. Which one of the following proteins is important for skeletal muscle contraction but not for smooth muscle contraction? (A) Actin (B) Myosin
(C) Troponin (D) Myosin-ATPase
2+
(E) Ca -ATPase
Answer: C. Smooth muscle does not have troponin.
31. You are comparing the structure of skeletal and smooth muscle. Which one of the following is only associated with skeletal muscle? (A) Myosin (B) Actin
(C) Myosin light chains (D) Troponin
(E) Tropomyosin
Answer: D. Troponin (Tn) is found in skeletal muscle and is a complex made up of three subunits; Tn T bound to the tropomyosin protein, Tn I that is believed to inhibit the active site and Tn C that binds to calcium. Depolarization of the muscle membrane leads to an elevation in intracellular calcium levels increasing the number of Tn C bound to calcium, which in turn
increases the number of active sites on the thin filament available for binding to the myosin heads of the thick filament. Troponin is not found in smooth muscle, a similar molecular calponin has been reported, but it can be stated that skeletal muscle has troponin while smooth muscle does not. 32. In order to initiate the processes involved in smooth muscle contraction calcium must bind to which one of the following proteins? (A) Troponin C (B) Myosin light chain kinase (C) Calsequestrin
(D) Calmodulin (E) Ryanodine receptor
Answer: D. On the elevation of calcium levels to initiate contraction the calcium binds to calmodulin. Calmodulin is a protein found in the muscle cytoplasm associate with a MLCK enzyme and when bound to 4 calcium ions it is activated. When activated this MLCK phosphorylates the regulatory light chains on the myosin head allowing crossbridge binding and hence contraction.
33. Calmodulin is most closely related, both structurally and functionally, to which of the following proteins? (A) G-actin (B) Myosin light chain
(C) Tropomyosin (D) Troponin C 2+
Answer: D. In smooth muscle, the binding of four Ca ions to the protein calmodulin permits 2+ the interaction of the Ca -calmodulin complex with myosin light chain kinase. This interaction activates myosin light chain kinase, resulting in the phosphor ylation of the myosin light chains 2+ and, ultimately, muscle contraction. In skeletal muscle, the activating Ca signal is received by the protein troponin C. Like calmodulin, each molecule of troponin C can bind with up to four 2+ Ca ions. Binding results in a conformational change in th e troponin C protein that dislodges the tropomyosin molecule and exposes the active sites on the actin filament.
34. Excitation-contraction coupling in skeletal muscle involves all o f the following events EXCEPT one. Which one is this EXCEPTION? (A) (B) (C) (D) (E)
ATP hydrolysis 2+ Binding of Ca to calmodulin Conformational change in dihydropyridine receptor Depolarization of the transverse tubule (T tubule) membrane Increased Na+ conductance of sarcolemma
Answer: B. Excitation-contraction coupling in skeletal muscle begins with an excitatory depolarization of the muscle fiber membrane (sarcolemma). This depolarization triggers the all+ or-none opening of voltage-sensitive Na channels and an action potential that travels deep into the muscle fiber via the T tubule network. At the T tubule-sarcoplasmic reticulum “triad” the depolarization of the T tubule causes a conformational change in the dihydropyridine receptor
and subsequently in the ryanodine receptor on the sarcoplasmic reticulum. The latter causes the 2+ 2+ release of Ca into the sarcoplasm and the binding of Ca to troponin C (not to calmodulin) on the actin filament. 35. The functions of tropomyosin in skeletal muscle include: (A) Sliding on actin to produce shortening (B) Releasing calcium after initiation of contraction (C) Binding of myosin during contraction (D) Covering up the sites where myosin binds to actin in resting muscle (E) Generating ATP, which it passes to the contractile mechanism Answer: D. Tropomyosin is an important regulator of the interaction of actin with the myosin crossbridge. Troponin I is bound to actin and holds the troponin-tropomyosin in a position that prevents the myosin crossbridge access to the binding site on the actin molecule.
Calcium and Muscle 36. Malignant hyperthermia is a potentially fatal genetic disorder characterized b y a hyperresponsiveness to inhaled anesthetics and results in elevated bod y temperature, skeletal muscle rigidity, and lactic acidosis. Which of the following molecular changes could account for these clinical manifestations? (A) (B) (C) (D)
2+
Decreased voltage sensitivity of the dihydropyridine receptor (L-type Ca channel) 2+ Enhanced activity of the sarcoplasmic reticulum Ca -ATPase Prolonged opening of the ryanodine receptor channel + Reduction in the density of voltage-sensitive Na channels in the T tubule membrane
Answer: C. As long as the ryanodine receptor channel on the sarcoplasmic reticulum remains 2+ open, Ca will continue to flood the sarcoplasm and stimulate contraction. This prolonged contraction results in heat production, muscle rigidity, and lactic acidosis. In contrast, factors that 2+ 2+ either inhibit Ca release or stimulate Ca uptake into the sarcoplasmic reticulum, or that prevent either the depolarization of the T tubule membrane or the transduction of the 2+ depolarization into Ca release, would favor muscle relaxation.
37. A 32-year-old woman undergoing surgery developed malignant hyperthermia following halothane anesthesia. The life-threatening increase in metabolic rate and body temperature is attributed to a mutation of the ryanodine receptor in skeletal muscle, resulting in which of the following? 2+
(A) Excess Ca release from the SR during muscle contraction (B) Rapid repetitive firing of presynaptic terminals of motorneurons (C) Inability of skeletal muscle cells to repolarize (D) An increase in the refractory period of the motoneurons (E) Production of endogenous muscle pyrogens
2+
Answer: A. Because of the mutation, there will be massive amount of Ca released intracellularly from SR, and the cell has to pu sh them back to SR repeatedly and consumes large amount of ATPs, which ultimately leads to increase body temperature. This question is beyond of your requirement, yet you should know what the ryanodine receptor does. (This is the receptor 2+ responsible for “voltage-induced Ca release) 2+
38. The rate at which Ca is sequestered by the sarcoplasmic reticulum of skeletal muscle du ring a twitch is directly related to: (A) The rate of tension development (B) The rate of ATP hydrolysis by myosin (C) The rate of relaxation
(D) The height of the action potential (E) All of the above (F) None of the above 2+
Answer: C. Sequestration means the movement of Ca back into the sarcoplasmic reticulum. This is an energy-dependent process that terminates contraction.
39. A single contraction of skeletal muscle is most likely to be terminated by which of the following actions? (A) (B) (C) (D) (E)
Closure of the postsynaptic nicotinic acetylcholine receptor Removal of acetylcholine from the neuromuscular junction 2+ Removal of Ca from the terminal of the motor neuron 2+ Removal of sarcoplasmic Ca Return of the dihydropyridine receptor to its resting conformation 2+
Answer: D. Skeletal muscle contraction is tightly regulated by the concentration of Ca in the 2+ sarcoplasm. As long as sarcoplasmic Ca is sufficiently high, none of the remaining events2+ removal of acetylcholine from the neuromuscular junction, removal of Ca from the presynaptic terminal, closure of the acetylcholine receptor channel, and return of the dihydropyridine receptor to its resting conformation-would have any effect on the con tractile state of the muscle.
40. Smooth muscle contraction is terminated by which of the following? (A) (B) (C) (D) (E)
Dephosphorylation of myosin kinase Dephosphorylation of myosin light chain 2+ Efflux of Ca ions across the plasma membrane Inhibition of myosin phosphatase 2+ Uptake of Ca ions into the sarcoplasmic reticulum 2+
Answer: B. Smooth muscle contraction is regulated by both Ca and myosin light chain 2+ phosphorylation. When the cytosolic Ca concentration decreases following the initiation of contraction, myosin kinase becomes inactivated. Ho wever, cross-bridge formation continues, 2+ even in the absence of Ca , until the myosin light chains are dephosphorylated through the action of myosin light chain phosphatase.
41. You are charged with the responsibility of developing a new drug to treat muscle spasticity following spinal cord injury. Which of the following characteristics would be most useful in treating this condition? (A) Inhibition of protein kinases 2+ (B) Inhibition of the Ca -dependent ATPase of the sarcoplasmic reticulum 2+ (C) Blocking the opening of Ca channels in the cell membrane 2+ (D) Inhibition of Ca release from the sarcoplasmic reticulum 2+ (E) Activation of voltage-gated Ca channels of the T-tubular membrane system Answer: D. Muscle spasticity is a consequence of convulsive muscle contractions. Thus, treatment should focus on reducing the ability of the muscle to contract. It can be done by reducing/inhibiting any part of muscle contraction mechanism (or cross-bridge c ycling). 2+ Inhibition of PK may or may not affect it (not enough information here). Inhibition of the Ca 2+ dependent ATPase of the SR will increase intracellular [Ca ] and then contraction, so worsening 2+ the condition. Skeletal muscle doesn't have Ca channels on the surface membrane, but 2+ 2+ inhibiting voltage-gated Ca channels will help the condition (reduces intracellular [Ca ]).
42. When comparing the contractile responses in smooth and skeletal muscle, which of the following is most different? 2+
(A) The source of activator Ca 2+ (B) The role of Ca in initiating contraction (C) The mechanism of force generation
(D) The source of energy used during contraction (E) The nature of the contractile proteins
2+
Answer: B. In smooth muscle, Ca binds to and activates calmodulin, which activates MLCK which phosphorylates myosin light chain, and the n a cross-bridge can happen. In skeletal muscle, 2+ Ca binds to troponin, which causes the shift of tropomyosin from the attachment site of myosin, and then a cross-bridge can happen. Choice C, D, and E are same in both muscles, and choice A varies in smooth muscles depends on how much SR is well developed. 2+
2+
43. Which of the following best represents the muscle type(s) that require Ca -induced Ca release in order to initiate contraction? (A) Cardiac muscle (B) Skeletal muscle (C) Smooth muscle
(D) Cardiac and skeletal muscle (E) Cardiac and smooth muscle 2+
2+
Answer: E. Both cardiac and smooth muscle require Ca -induced Ca release in order to 2+ initiate a contraction. Intracellular Ca levels must be elevated in order to bind TnC or 2+ calmodulin in cardiac and smooth muscle respectively. The binding of Ca to these two proteins initiates the contraction process using two completely different mechanisms. Depolarization of 2+ 2+ the muscle membrane leads to Ca entering the muscle cell. This Ca binds to the ryanadine 2+ receptor on the SR causing it to open and allow Ca to rush out of the SR into the intracellular 2+ fluid increasing concentration dramatically. This elevation in Ca levels means greater number of proteins (TnC and calmodulin) are bound leading to more crossbridge interactions and hence
the production of contractile force. 44. Similarities between smooth and cardiac muscle include which of the following? (A) (B) (C) (D) (E)
Ability to contract in the absence of an action potential 2+ Dependence of contraction on Ca ions Presence of a T tubule network Role of myosin kinase in muscle contraction Striated arrangement of the actin and myosin filaments
Answer: B. The strongest common denominator among smooth, skeletal, a nd cardiac muscle 2+ contraction is their shared dependence on Ca for the initiation of contraction. Cardiac and skeletal muscles exhibit several characteristics not shared by smooth muscle. For example, the contractile proteins in both cardiac and skeletal mu scles are organized into discrete sarcomeres. Both muscle types also possess some semblance of a T tubule s ystem and are dependent on the generation of action potentials for their contraction. Smooth muscle, in contrast, is relatively less organized, is uniquely regulated by myosin light chain phosphorylation, and can contract in vivo in the absence of action potentials.
45. The delayed onset and prolonged duration of smooth muscle contraction, as well as the greater force generated by smooth muscle compared with skeletal muscle, are all consequences of which of the following? (A) (B) (C) (D) (E)
Greater amount of myosin filaments present in smooth muscle Higher energy requirement of smooth muscle Physical arrangement of actin and myosin filaments Slower cycling rate of the smooth muscle myosin cross-bridges 2+ Slower uptake of Ca ions following contraction
Answer: D. The slower cycling rate of the cross-bridges in smooth muscle means that a higher percentage of possible cross-bridges is active at any point in time. The more active cross-bridges there are, the greater the force that is generated. Although the relatively slow cycling rate means that it takes longer for the myosin head to attach to the actin filament, it also means that the myosin head remains attached longer, prolonging muscle contraction. Because of the slow cross bridge cycling rate, smooth muscle actually requires less energy to maintain a contraction compared with skeletal muscle.
46. Which of the following best describes an attribute of v isceral smooth muscle not shared by skeletal muscle? (A) Contraction is ATP dependent (B) Contracts in response to stretch (C) Does not contain actin filaments
(D) High rate of cross-bridge cycling (E) Low maximal force of contraction
Answer: B. An important characteristic of visceral smooth muscle is its ability to contract in response to stretch. Stretch results in depolarization and potentially the ge neration of action
potentials. These action potentials, coupled with normal slow-wave potentials, stimulate rhythmical contractions. Like skeletal muscle, smooth muscle contraction is both actin and ATP dependent. However, the cross-bridge cycle in smooth muscle is co nsiderably slower than in skeletal muscle, which allows for a higher maximal force of contraction. 47. Smooth muscle that exhibits rhythmical contraction in the absence of external stimuli also necessarily exhibits which of the following? (A) (B) (C) (D) (E)
2+
“Slow” voltage-sensitive Ca channels Intrinsic pacemaker wave activity 2+ Higher resting cytosolic Ca concentration Hyperpolarized membrane potential Action potentials with “plateaus”
Answer: B. For a muscle to contract spontaneously and rhythmically, there must be an intrinsic rhythmical “pacemaker.” Intestinal smooth muscle, for example, exhibits a rhythmical slowwave potential that transiently depolarizes and repolarizes the muscle membrane. This slow wave does not stimulate contraction itself, but if the amplitude is sufficient, it can trigger one or more 2+ action potentials that result in Ca influx and contraction. Although they are typical of smooth 2+ muscle, neither “slow” voltage-sensitive Ca channels nor action potentials with “plateaus” play 2+ a necessary role in rhythmical contraction. A high resting cytosolic Ca concentration would support a sustained contraction, and hyperpolarization would favor relaxation.
48. The sensitivity of the smooth muscle contractile apparatus to calcium is known to increase in the steady-state under normal conditions. This increase in calcium sensitivity can be attributed to a decrease in the levels of which of the following substances? (A) Actin (B) Adenosine Triphosphate (ATP) (C) Calcium-calmodulin complex
(D) Calmodulin (E) Myosin light chain phosphatase (MLCP)
Answer: E. Smooth muscle is unique in its ability to generate various degrees of tension at a constant concentration of intracellular calcium. This change in calcium sensitivity of smooth muscle can be attributed to differences in the activity of MLCP. Smooth muscle contracts when the myosin light chain is phosphorylated by the actions of myosin light chain kinase (MLCK). MLCP is a phosphatase that can dephosphorylate the m yosin light chain, rendering it inactive and therefore attenuating the muscle contraction. Choice A: Both actin and myosin are important components of the smooth muscle contractile apparatus much like that of skeletal muscle and cardiac muscle, but these do not play a role in calcium sensitivity. Choice B: ATP is required for smooth muscle contraction. Decreased ATP levels would be expected to decrease the ability of smooth muscle to contract even in the face of high calcium levels. Choice C: The calciumcalmodulin complex binds with MLCK, which lead s to phosphorylation of the myosin light chain. A decrease in the calcium-calmodulin complex should attenuate the contraction of smooth muscle. Choice D: Again, the binding of calcium ions to calmodulin is an initial step in the activation of the smooth muscle contractile apparatus.
49. A 32-year-old man is diagnosed with primary h ypertension. His physician recommends a drug for hypertension that acts by decreasing vascular smoo th muscle contractile activity without affecting ventricular contractility. Which of the following is the most likely site of action f or the drug? (A) β- receptors (B) Calmodulin
(C) Troponin (D) Tropomyosin
(E) Protein kinase A
Answer: B. Smooth muscle contraction is regulated by a series of reactions that begins with the binding of calcium to calmodulin, in contrast to cardiac (and skeletal) muscle, where contraction 2+ is triggered by the binding of Ca to troponin C, which by altering the position of tropomyosin on the thin filament, allows cross-bridge cycling to begin. The calcium-calmodulin complex in smooth muscle binds to and activates a protein kinase called myosin light chain kinase (MLCK), which catalyzes the phosphorylation of the myosin light chains (LC20). Once these light chains are phosphorylated, myosin and actin interaction can occur and vascular smooth muscle shortens and develops tension. Although β-adrenergic receptor agonists (which will increase PKA) may lower blood pressure by relaxing vascular smooth muscle, they also increase the rate and strength of the heart beat.
ANS and Muscle 50. An experimental drug is being tested as a potential therapeutic treatment for asthma. Preclinical studies have shown that this drug induces the relaxation of cultured porcine tracheal smooth muscle cells pre-contracted with acetylcholine. Which of the following mechanisms of action is most likely to induce this effect? (A) (B) (C) (D) (E)
2+
Decreased affinity of troponin C for Ca + Decreased plasma membrane K permeability + Increased plasma membrane Na permeability 2+ Inhibition of the sarcoplasmic reticulum Ca -ATPase Stimulation of adenylate cyclase
Answer: E. The stimulation of either adenylate or guanylate c yclase induces smooth muscle relaxation. The cyclic nucleotides produced by these enzymes stimulate cAMP- and cGMPdependent kinases, respectively. These kinases phosphorylate, among other things, enzymes that 2+ remove Ca from the cytosol, and in doing so they inhibit contraction. In contrast, either a + + decrease in K permeability or an increase in Na permeability results in membrane 2+ depolarization and contraction. Likewise, inhibition of the sarcoplasmic reticulum Ca -ATPase, one of the enzymes activated by cyclic nucleotide-dependent kinases, would also favor muscle contraction. Smooth muscle does not express troponin.
2+
51. In smooth muscle, Ca is release from the sarcoplasmic reticulum (SR) by which of the following? (A) Diacylglycerol (DAG) (B) The guanosine triphosphate (GTP) binding protein (G protein)
(C) Phospholipase C (PLC) (D) Inositol triphosphate (IP3) (E) Adenylate cyclase
2+
Answer: D. In smooth muscle, Ca is released from SR by an IP3-activated channel. In striated 2+ muscle, Ca is released from SR by ryanodine receptor that is activated by depolarization in 2+ skeletal muscle and by (extracellular) Ca in cardiac muscle. DAG, GTP, and PLC all pray a 2+ role in excitation-contraction coupling but do no t directly cause the release of Ca into the cytoplasm. Adenylate cyclase generates cAMP and it activates PKA, which phosphorylates 2+ 2+ phospholamban, leading to an increase in Ca sequestration by the SR Ca -ATPase.
Preload/Afterload 52. Increasing the afterload on skeletal muscle fiber… (A) Decreases the force produced by the muscle during shortening (B) Decreases the interval between excitation and shortening (C) Increases the velocity of shortening (D) Increases the amount of shortening (E) None of the above Answer: E. When the afterload on an isotonically contracting skeletal muscle is increased, th e velocity of shortening slows, the amount of force p roduced by the muscle increases, the interval between excitation and shortening increases, and the amount of shortening decreases.
53. All of the following will occur when an unstimulated muscle is stretched except... (A) Increased preload (B) Increased afterload
(C) Increased muscle length (D) Increased passive tension
Answer: B. Stretch = increase muscle length, and this cause increased preload ( = passive tension).
54. Which of the following statements is true? (A) A muscle at resting length exerts its maximum force during an isotonic contraction (B) The maximum velocity of shortening during contraction occurs when there is no afterload (C) The preload is the weight the muscle moves before it starts to relax (D) In most form of muscle contraction in an intact in dividual, the preload and afterload are equal (E) All of the above (F) A and B (G) C and D (H) B and D (I) None of the above Answer: B. Afterload decreases the velocity of shortening. When there is n o load, velocity will be maximal. During isotonic contraction, force is determined by afterload. The greatest force is developed by a maximal stimulation during an isometric contraction. In an intact individual the preload is constant in most cases (muscles are nearly at their ideal length), while the afterload varies (represents the load the muscle is attempting to lift.)
55. Alteration in preload alters the force of contractions in which of the following muscle type of types? (A) Cardiac muscle (B) Skeletal muscle (C) Smooth and cardiac muscle
(D) Smooth and skeletal muscle (E) Smooth, cardiac, and skeletal muscle
Answer: E. All muscle types are able to influence the force of contraction b y varying the initial length (≈ preload) of their sarcomeres.
56. The diagram shows the force-velocity relationship for isotonic contractions of skeletal muscle. The differences in the three curves result from differences in which of the following?
(A) (B) (C) (D) (E)
Frequency of muscle contraction Hypertrophy Muscle mass Myosin ATPase activity Recruitment of motor units
Answer: D. The diagram shows that the maximum velocity of shortening (Vmax) occurs when there is no afterload on the muscle (force = 0). Increasing afterload decreases the velocity of shortening until a point is reached where shortening do es not occur (isometric contraction) and contraction velocity is thus 0 (where curves intersect X-axis). 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 contraction 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.
57. Illustrates differences in the force-velocity relationship of skeletal muscle caused by changes in myosin ATPase activity.
(A) Figure A
(B) Figure B
(C) Neither figure
Answer: B. These two graphs show the force-velocity relationship for isotonic contractions. The starting point for each curve on the У 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 figure A all three curves start at the same point on the У axis, therefore they all have the same ATPase activity. In figure B the three curves start at different points on the У axis, thus they all have different ATPase activities. Muscle V1 has the greatest ATPase activity, therefore it is the fastest muscle, and V3 has the least ATPase activity (slowest muscle).
58. In the diagram below, the shift from curve X to curve Y could be produced by:
(A) (B) (C) (D) (E)
Changes in afterload Changes in preload Changes in myosin ATPase activity Changes in # of active cross-bridges Spatial summation of fibers
Answer: C. A shift from curve X to curve Y produces a higher intersection point on the У axis. This means a greater ATPase activity and a faster muscle, i.e., a greater velocity of shortening. Since the point on the χ axis is the same, the two muscles can generate the same maximum force during contraction, i.e., they have the same muscle mass.
59. The following diagram shows the chart records taken from an isolated skeletal muscle contracting against various loads. Both the length and force produced by the muscle were measured, the X-axis represents time. An upward deflection indicates shortening on the length trace. The muscle resting length was kept constant throughout the data recording. In which diagram does the muscle produce the fastest shortening velocity?
Answer: 4. The chart shows an isotonic contraction and it can be observed that the muscle does shorten after lifting the load. In order to determine the shortening velocity you need to determine the gradient at the point where the muscle is shortening at its fastest, this is at at the beginning of the shortening phase. In this question it is difficult to determine this gradient as no values are given on the x and y axis and it is hard to look at the three different isotonic chart records and decide which has the fastest shortening via this method. The way to look at this question is to think of the force-velocity relationship and compare where the data from these 4 chart records sit. The following diagram shows this:
As you can see the light afterload that has to be generated by the muscle in Chart 4 allows for a quite high level of shortening and hence shortening velocity. As this afterload is the lightest of the 4 charts this is the one that would have the greatest shortening velocity.
60. The following diagram shows the force velocity relationship obtained from a single skeletal muscle fibre. All data is taken on the ascending limb of the length tension curve. The numbers identify the curve to their right. Which one of the following curves is produced when the muscle is at the shortest length?
Answer: 1. You are told in the question that all data is taken from the ascending limb of the length-tension relationship. From this information you can assume that an increase in muscle length will produce an increase in crossbridge cycling when the muscle is contracting. This in turn would mean that the shorter the muscle length the less crossbridge cycling during the
contraction and therefore the maximum force developed by the muscle would be less. As passive tension is negligible in skeletal muscle when you are on the ascending limb of the length tension relationship the load value (X-axis) when shortening velocity is z ero is indicative of the isometric force the muscle can develop at that particular length. Curve No. 1 meets the X-axis at the lowest value of load, so it represents the data from the muscle at its shortest length. Another way of looking at this with respect to the amount of crossbridge cycling is to compare the shortening velocity of the muscle at the same load at different lengths. If there is less crossbridge cycling at the shortest length then you would expect the muscle not to be able to shorten as much once it had lifted its load (there would be less crossbridge cycling "left over" after the afterload had been produced), therefore the length of shortening (and shortening velocity) would be less at shorter lengths at the same load. Again you can observe that Curve No. 1 does have the least shortening velocity at all loads when compared to the other curves, hence it represents the data of the muscle at its shortest length. 61. Use the force-velocity diagrams, from the same muscle, below to answer the following question. Which one of the following statements must be true when comparing Point 1 to Point 2?
(A) Point 1 is at a shorter resting muscle length (B) Point 1 is on a curve that has a greater maximum velocity of shortening (C) Point 1 is lifting a greater load (D) Point 1 utilizes less energy (E) At Point 1 no shortening occurs
Answer: C. If you look at the graph you can see that Point 1 sits further to the right of the Y-axis than Point 2. Point 1 is therefore lifting a greater load.
62. Using the two force-velocity curves, taken at muscle len gths on the ascending limb of the lengthtension relationship, shown in the graph below which one of the following statements is true under all circumstances?
(A) The two curves are from two different muscles (B) The curve on which you find Point B is of a muscle that will always produce more isometric force than that indicated by the curve with Point A (C) The shortening is quicker at Point B than at Point A (D) The afterload at point A is less than at point B (E) Curve B is taken from a fast-twitch muscle
Answer: D. Both curves have the same Vmax, thus they are the same muscle. Curve A is above Curve B, thus it produces more force. Point B has more load than Point A, thus the velocity is slower. There is no enough information to tell if they are fast-twitch or slow-twitch muscles.
63. Illustrates differences in the force-velocity relationship of skeletal muscle caused by changes in recruitment of additional motor units.
(A) Figure A
(B) Figure B
(C) Neither figure
Answer: A. The point where each curve crosses the χ axis is the maximum force the muscle can generate during contraction. This is determined by the muscle mass or the number of motor units activated during contraction. In figure A the maximum force that can be generated increases
from F1 through F3, thus activated muscle mass also increases. In figure B all three curves end at the same point on the χ axis, thus all three muscles have the same muscle mass. Also, with each curve the maximum velocity occurs when there is no load, and as load increases, velocity during shortening decreases. When the curve crosses the χ axis, there is zero velocity, which means the muscle is unable to lift the load (isometric contraction). 64. Use the following diagram of the active length ten sion curve from an in vitro skeletal muscle preparation to answer the question. Which circle is at a sarcomere length where there is the most crossbridge attachment occurring during contraction?
Answer: 3. Looking at the diagram you can see that Point 3 is at the plateau of the active lengthtension curve. At this length there is maximum overlap between the thick and thin filaments and no physical interference caused by the thin filaments on opposite ends of the sarcomere. Therefore there will be maximum crossbridge attachment during muscle contraction at this length.
Another way of looking at this is to realize that you will observe maximum force production when you have the most crossbridge attachment. Point 3 shows the highest force development.
65. During the resting state, a single skeletal muscle sarcomere can exist at a number of lengths. During an isometric contraction, the length at which it can exert its maximum force in response to stimulation is:
(A) 1.7 µm (B) 2.2 µm
(C) 3.0 µm (D) All of the them
(E) Both B and C
Answer: B. Maximum force during an isometric contraction is achieved when all cross-bridges are cycling. This can only be achieved when the system is saturated with c alcium and there is the ideal overlap between actin and myosin. The figure with a sarcomere length of 2.2 µm demonstrates this ideal overlap. The first figure with a sarcomere length of 1.7 µm shows an overlap of actin filaments. This would decrease the number of potential cycling cross-bridges and thus decrease the maximum achievable force during contraction. The bottom figure shows an overstretched sarcomere that has a decreased ov erlap between the actin and myosin. This also will decrease the number of potential cycling cross-bridges. Remember, when the sarcomere is stretched to the point where there is no overlap between actin and myosin, no cycling between the actin and myosin is possible. Under these conditions there will be no active tension following stimulation.
66. The figure below depicts the isometric length-tension relationship of skeletal muscle. Identify the region where actin and myosin overlap is the least.
Answer: E. This curve demonstrates the relationship between the max imum possible active tension during an isometric contraction and muscle length. The active tension achieved is determined by the number of cross-bridges cycling, wh ich in turn is determined by the relationship between actin and myosin filaments. At point C, which represents the greatest achievable active tension from this muscle, there is the ideal overlap between the actin and myosin. This is the resting length of most skeletal muscles in vivo. When muscle length increases there is less overlap between the actin a nd myosin, fewer cross-bridges can cycle, and less active tension will develop. The least overlap is at the greatest muscle length; the far right in the graph. To the left of point C the decrease in muscle length destroys the relationship between the actin and myosin; actin filaments overlap and eventually the myosin hits the Z lines.
67. The diagram shows the length-tension relationship for a single sarcomere. Why is the tension development maximal between points B and C?
(A) Actin filaments are overlapping each other (B) Myosin filaments are overlapping each other (C) The myosin filament is at its minimal length (D) The Z discs of the sarcomere abut the ends of the myosin filament (E) There is optimal overlap between the actin and myosin filaments (F) There is minimal overlap between the actin and myosin filaments
Answer: E. 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, whe re 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.
68. Use the figure below for this question: A change in resting skeletal muscle length from “c” to “e” results in:
(A) A decrease in actin and myosin interaction 2+ (B) Reduced Ca sensitivity of tropomyosin (C) Bending and folding of the thick filaments 2+ (D) Increased release of Ca from terminal cisternae 2+ (E) Reduced entry of Ca into the fiber during the action potential 2+
Answer: A. This is skeletal muscle, not cardiac, won’t change Ca sensitivity by preload, and its 2+ contraction is not depend on extracellular Ca entry. Choice C occurs between “E” and “D”. Choice D occurs from “e” to “c”.
The diagram illustrates the isometric length-tension relationship in a representative intact skeletal muscle. When answering the following three questions, use the letters in the diagram to identify each of the following.
69. So-called “active” or contraction-dependent tension. Answer: B. In this diagram, “active” or contraction-dependent tension is the difference between total tension (trace A) and the passive tension contributed by noncontractile elements (trace C). The length-tension relationship in intact muscle resembles the biphasic relationship observed in individual sarcomeres and reflects the same physical interactions between actin and myosin filaments.
70. The muscle length at which active tension is maximal. Answer: E. “Active” tension is maximal at normal physiological muscle lengths. At this point, there is optimal overlap between actin and myosin filaments to support maximal cross-bridge formation and tension development.
71. The contribution of non-contractile muscle elements to total tension. Answer: C. Trace C represents the passive tension contributed by noncontractile elements, including fascia, tendons, and ligaments. This passive tension accounts for a n increasingly large portion of the total tension recorded in intact muscle as it is stretched beyond its normal length.
The following length-tension diagram was obtained on a muscle. Supramaximal tetanic stimuli were used to initiate a contraction at each muscle length studied. Use this for next 4 questions.
72. Which point represents a preload of 40 g? (A) Point 3 (B) Point 4
(C) Point 8 (D) Points 4 and 8
(E) Points 3, 4, and 8
Answer: B. This length-tension graph depicts the three basic curves discussed in class. The curve that starts at point 6 and goes through point 1 is the passive or preload curve. The active tension curve starts at point 7, reaches a peak at point 9, and then declines and crosses the χ axis as the dashed line. The line between points 9 and 2 represents the total tension developed by adding the passive and active tensions together. The point that represents a preload of 40 g is on the passive curve at point 4. If this point is taken across to the У axis, it represents a tension of 40 g.
73. Maximal active tension in the diagram is developed by skeletal muscle at point(s): (A) Point 1 (B) Point 2
(C) Point 4 (D) Points 3 and 4
(E) Point 9
Answer: E. Active tension curve starts from point 7 to point 9 . The solid curve from point 9 to 2 is total tension curve. The dashed curve from point 9 to 3 is the descending limb of the active tension curve. Point 1 shows the highest tension in the choices, yet it is not active tension (likely, passive tension).
74. Which point(s) in the diagram represent(s) no overlap between most of the muscle’s thick and thin filaments? Point(s): (A) Point 2 (B) Point 3
(C) Point 6 (D) Point 7
(E) Points 6 and 7
Answer: A. No overlap between actin and myosin means no active tension upon stimulation. This is represented by the point (muscle length) where the active tension curve crosses the χ axis. This point is not labeled, but the same length is represented by the point on the preload curve directly above; point 2. If a muscle is at point 2 on the preload curve (or beyond it, like point 1), no active tension will be developed when the muscle is stimulated. Point 2 or 1 is a better answer than point 7 because there the loss of active tension was produced by destroying the geometric relationship between the actin and myosin.
75. If a muscle length was at point 4 on the passive curve, what is the active tension generated during stimulation? (A) Less than 40 g
(B) 40 to 60 g (C) 60 to 80 g
(D) 80 to 100 g
Answer: B. If a relaxed muscle at point 4 on the passive curve is stimulated maximally, it will generate active tension, depicted by the point on the dashed curve directly above. This point on the У axis would represent a tension of approximately 50 g. The answer is not point l0; this represents the total tension in the muscle during stimulation (passive plus active)
76. The length-tension diagram shown here was obtained from a skeletal muscle with equal numbers of red and white fibers. Supramaximal tetanic stimuli were used to initiate an isometric contraction at each muscle length studied. The resting length was 20 cm. What is the maximum amount of active tension that the muscle is capable of generating at a preload of 100 grams?
(A) (B) (C) (D) (E)
145-155 grams 25-35 grams 55-65 grams 95-105 grams Cannot be determined
Answer: C. The diagram shows the relationship between preload o r 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, the student must first find where 100 grams intersects the preload curve (passive tension cu rve) and then move down to the active tension curve, One can see that a preload 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, as discussed above. Drawing these three curves in a manner that is mathematically correct is not an easy task. The student should thus recognize that active tension may not equal total tension minus passive tension at all points on the diagram shown here as well as on USMLE diagrams. 77. Use the following diagram of the length tension c urve from an in vitro skeletal muscle preparation to answer the question. The dark blue line represents active tension, the green line passive tension. Which circle is at a sarcomere length where there is the greatest total tension produced during a contraction?
Answer: 5. The total tension produced during a contraction is equal to the passive + active tension. Point 5 has the lowest active tension but an extremely high passive tension. It can be observed that stretching the muscle past the optimal length h as a dramatic effect on passive tension with it rising at a much greater rate than the decline in active tension due to decreased filament overlap. This means that the total tension increases with sarcomere length on the above diagram somewhere between Points 3 and 4 and continues to do so until you physically damage the muscle. Therefore Point 5 has the highest total tension.
78. A severe laceration to a wrist completely severed a major muscle tendon. To reattach the tendon, the severed ends were overlapped b y 7.5 cm before suturing. After recovery, which of the following could be expected compared with the preinjured muscle? (A) Increased passive tension and decreased maximal active tension (B) Decreased passive tension and decreased maximal active tension (C) Increased passive tension and increased maximal active tension (D) Increased passive tension and same maximal active tension (E) Same passive tension and same maximal active tension
Answer: A. In vivo, under resting conditions, skeletal muscle is pre-streched to its ideal or near ideal length. That means, there will be nearly max imum overlapping of actins and myosins available, and thus they will generate maximum active force, theoretically. Since the muscle is stretched, therefore, passive tension “increased,” and it is over -stretched from the ideal length, there are less actin/myosin interaction or overlapping, thus, the active force “decreased.”
79. A 24-year-old woman is admitted as an emergency to University Hospital following an automobile accident in which severe lacerations to the left wrist severed a major muscle tendon. The severed ends of the tendon were overlapped by 6 cm to facilitate suturing and reattachment. Which of the following would be expected after 6 weeks compared to the preinjured muscle? Assume that series growth of sarcomeres cannot be completed within 6 weeks. Passive tension (A) Decrease (B) Decrease (C) Increase (D) Increase (E) No change
Maximal active tension Decrease Increase Increase Decrease No change
Answer: D. Stretching the muscle to facilitate reattachment of the tendons leads to an increase in passive tension or preload. This increase in passive tension increases the muscle length beyond its ideal length, which in turn leads to a decrease in the maximal active tension that can be generated by the muscle. The reason that maximal active tension decreases is that interdigitation of actin and myosin filaments decreases when the muscle is stretched; the interdigitation of a muscle is normally optimal at its resting length.
80. The following diagram shows the chart records taken from an isolated skeletal muscle contracting against various loads. Both the length and force produced by the muscle were measured, the X-axis represents time. An upward deflection indicates shortening on the length trace. The muscle resting length was kept constant throughout the data recording. Which one of the chart recordings show the muscle undergoing isometric contractions?
Answer: 1. An isometric contraction is one in which there is development of force without any shortening occurring. As can be seen in the chart record abov e the length of the muscle stays constant throughout the whole process, no shortening has taken place. The force record shows that during this time two muscle contractions have taken place with the associated force production being recorded with no associated contraction. This therefore is the ISOMETRIC contraction.
81. If the gastrocnemius muscle is removed from the body, it will achieve a length... (A) Greater than it had in the body, because it is more relaxed (B) Shorter than it had in the body, because it is less relaxed (C) Shorter than it had in the body, because it its elastic characteristics (D) The same as it had in the body Answer: C. Relaxed skeletal muscle in vivo is stretched close to the ideal passive length. Thus, if the muscle is removed from the body, preload will be eliminated and muscle will shorten.
Motor Unit & Summation/Tetany 82. In an isometric contraction of a skeletal muscle, force of contraction cannot be altered by... (A) Changing the resting length of the muscle (B) Increasing stimulation frequency (C) Increasing the number of sarcomeres in parallel in the muscle (D) Increasing the number of sarcomeres in series in the mu scle Answer: D. By altering resting length, overlap between the actin and myosin will change, and this will affect the number of cross-bridge that can cycle during stimulation. Increasing 2+ stimulation frequency will cause increase the Ca released from the SR and this will increase the number of cross-bridge cycling (temporal summation). Increasing the number of sarcomeres in parallel is similar to activating additional motor units (spatial summation). Adding sarcomeres in series does not increase the strength of contraction. i.e. longer rope is not a stronger rope, thicker rope is.
83. Weightlifting can result in a dramatic increase in skeletal muscle mass, This increase in muscle mass is primarily attributable to which of the following? (A) (B) (C) (D) (E)
Fusion of sarcomeres between adjacent myofibrils Hypertrophy of individual muscle fibers Increase in skeletal muscle blood supply Increase in the number of motor neurons Increase in the number of neuromuscular junctions
Answer: B. Prolonged or repeated maximal contraction results in a concomitant increase in the synthesis of contractile proteins and an increase in muscle mass. This increase in mass, or
hypertrophy, is observed at the level of individual muscle fibers. 84. A 17-year-old soccer player suffered a fracture to the left tibia. After her lower leg has been in a cast for 8 weeks, she is surprised to find that the left gastrocnemius muscle is significantly smaller in circumference than it was before the fracture. What is the most likel y explanation? (A) (B) (C) (D) (E)
Decrease in the number of individual muscle fibers in the left gastrocnemius Decrease in blood flow to the muscle caused by constriction from the cast Temporary reduction in actin and myosin protein synthesis Increase in glycolytic activity in the affected muscle Progressive denervation
Answer: C. Skeletal muscle continuously remodels in response to its level of use. When a muscle is inactive for an extended period, the rate of synthesis of the contractile proteins in individual muscle fibers decreases, resulting in an overall reduction in muscle mass. This reversible reduction in muscle mass is called atrophy.
85. Which of the following characteristics of skeletal muscle make tetanic contraction po ssible? (A) The motor neurons to skeletal muscle have a short refractory period and are therefore capable of delivering a high frequency of stimuli to a muscle fiber (B) The cell membrane of the skeletal muscle fiber re covers its excitability well before the cell ceases its contraction (C) The prolonged exposure of the muscle end plate to high concentrations of acetylcholine throughout the tetanus (D) The action potential of skeletal muse outlasts the period of contraction (E) All of the above (F) A and B (G) A, B and C (H) None of the above Answer: F. Tetanus in skeletal muscle is possible because multiple action potentials can be delivered before and during the mechanical event (contraction). Multiple action potentials will 2+ saturate the troponin with Ca , resulting in continuous cycling of all available cross-bridges. This is possible only because of the very short refractory period of the neuronal and skeletal muscle action potentials. During tetanus, the muscle end plate is not exposed to ACh “throughout”.
86. The amount of force produced by a skeletal muscle can be increased by which of the following? 2+
(A) Increasing extracellular Ca 2+ (B) Decreasing extracellular Ca (C) Increasing the activity of AChE (D) Decreasing the interval between contractions (E) Increasing the preload (in vivo)
Answer: D. When the interval between skeletal muscle contractions is small, the force produced by the two successive contractions will summate. The shorter the interval between the contractions, the greater the summation will be. (The max imum summation is called tetanus.) 2+ 2+ Changing extracellular Ca level affect the force little if any because extracellular Ca do not participate in troponin interaction. Increasing the activity of AChE decreases ACh at NMJ and thus less stimuli to the muscle. In vivo, a skeletal muscle is at (near) ideal length, thus increasing preload will have decreased the active force/tension.
87. The force produced by a single skeletal muscle fiber can be increased by which of the following? (A) (B) (C) (D) (E)
+
Decreasing extracellular K concentration Increasing the amplitude of the depolarizing stimulus Increasing the frequency of stimulation of the fiber + Increasing the number of voltage-gated Na channels in the sarcolemma + Increasing the permeability of the sarcolemma to K 2+
Answer: C. Increasing the sarcoplasmic Ca concentration can increase force generation in a single muscle fiber. This can be accomplished by increasing the frequency of stimulation of the fiber. Neither increasing the amplitude of the depolarization at the postsynaptic membrane of the + neuromuscular junction nor increasing the number of voltage-gated Na channels is likely to 2+ affect the release of Ca from the sarcoplasmic reticulum. In contrast, both a decrease in the + + extracellular K concentration and an increase in the permeability of the muscle membrane to K would decrease excitability of the muscle cell.
88. Repetitive stimulation of a skeletal muscle fiber will cause an increase in contractile strength due to an increase in which of the following? (A) The duration of cross-bridge cycling 2+ (B) The concentration of Ca in the myoplasm during contraction (C) The magnitude of the end-plate potential (D) The number of muscle myofibrils generating tension (E) The velocity of muscle contraction Answer: A. The velocity of muscle is determined by afterload. The magnitude of end-plate potential (action potential) is passed on in “all or none” fashion, thus as long as it reaches the threshold, it doesn't matter. Increasing the number of muscle fibers generating tension is not 2+ caused by “repetitive” stimulation. During contraction, the amount of Ca in the cell is 2+ “maximally” released from SR. Repetitive stimulation sustains this [Ca ], and thus the duration of cross-bridge cycling prolonged.
89. Which of the following best describes the reason wh y you can tetanize skeletal muscle but not cardiac muscle? (A) (B) (C) (D) (E)
The myosin ATPase activity is greater in skeletal muscle when compared to cardiac muscle 2+ 2+ Ca -induced Ca -release does not allow for tetanization to take p lace in cardiac muscle The length tension relationship for cardiac muscle is shorter than that of skeletal muscle The duration of muscle contraction is longer in skeletal muscle The ratio of action potential duration to twitch duration is much less in skeletal muscle
Answer: E. This statement is true, the timecourse of a skeletal muscle action potential is a few msec at most whereas the shortest contraction time is at least 100msec. In cardiac muscle the action potential is approximately of the same duration as the contraction. In order to produce tetany you need to stimulate the muscle at a high enough frequency to keep the series elastic 2+ component continuously stretched as well as to increase intracellular Ca levels to increase the available active sites on the thin filament producing a contraction of greater force. In cardiac muscle the duration of the action potential leads to the absolute refractory period spanning the timecourse of the contraction making it impossible to p roduce a continuous tetanic contraction.
When you think about the function of these two muscle types it is not surprising that you can only produce tetanic contractions in skeletal muscle. Skeletal muscle is there to provide support to the skeletal system, therefore long sustained contractions are required for the maintenance of posture and for the regulation of movement in a smooth manner. You can imagine what walking would look like if you could only produce single twitches. Cardiac muscle on the other hand needs to contract then relax in a regular fashion. To allow for blood to enter the heart (relaxed) and then be pumped out (contract) ... if we had a sustained contraction of the muscle of the heart then blood would be squeezed out into the aorta but none would be able to return to the ventricle and your cardiac output would decrease to nothing. Not a good situation to be in. 90. Tetanic contraction of a skeletal muscle fiber results from a cumulative increase in the intracellular concentration of which of the following? (A) ATP 2+ (B) Ca
+
(C) K + (D) Na
(E) Troponin 2+
Answer: B. Muscle contraction is dependent on an elevation of intracellular Ca concentration. As the twitch frequency increases, the initiation of a subsequent twitch can occur before the previous twitch has subsided. As a result, the amplitude of the individual twitches is summed. At very high twitch frequencies, the muscle exhibits tetanic contraction. Under these conditions, 2+ intracellular Ca accumulates and supports sustained maximal contraction.
91. Post-tetanic facilitation is thought to be the result of… (A) (B) (C) (D)
Opening voltage-gated sodium channels Opening transmitter gated potassium channels A buildup of calcium in the presynaptic terminal Electrotonic conduction
Answer: C. Post-tetanic facilitation is the neuronal phenomenon in which a neuron is more easily excited following a brief period of activity. T his is thought to be due to the buildup of calcium in the presynaptic membrane caused by the prior neuronal activity. Subsequent neuronal impulses release neurotransmitter more readily as a result of this preplaced calcium from the prior stimulus.
92. During a demonstration for medical students, a neurologist uses magnetic c ortical stimulation to trigger firing of the ulnar nerve in a volunteer. At relatively low-amplitude stimulation, action potentials are recorded only from muscle fibers in the index finger. As the amplitude of the stimulation is increased, action potentials are recorded from muscle fibers in both the index finger and the biceps muscle. What is the fundam ental principle underlying this amplitudedependent response? (A) (B) (C) (D) (E)
Large motor neurons that innervate large motor units require a larger depolarizing stimulus Recruitment of multiple motor units requires a larger depolarizing stimulus The biceps muscle is innervated by more motor neurons The motor units in the biceps are smaller than those in the muscles of the fingers The muscles in the fingers are innervated only by the ulnar nerve
Answer: A. Muscle fibers involved in fine motor control are generally innervated by small motor neurons with relatively small motor units, including those that innervate single fibers. These neurons fire in response to a smaller depolarizing stimulus compared with motor neurons with larger motor units. As a result, during weak contractions, increases in muscle contraction can occur in small steps, allowing for fine motor con trol. This concept is called the size principle.
Muscle Fiber Types The diagram illustrates the single isometric twitch characteristics of two skeletal m uscles, A and B, in response to a depolarizing stimulus. Refer to it when answering the next two questions.
93. Which of the following best describes muscle B, when compared to muscle A? (A) Adapted for rapid contraction (B) Composed of larger muscle fibers (C) Fewer mitochondria
(D) Innervated by smaller nerve fibers (E) Less extensive blood supply
Answer: D. Muscle B is characteristic of a slow twitch muscle (Type 1) composed of predominantly slow twitch muscle fibers. These fibers are smaller in size and are innervated by smaller nerve fibers. They typically have a more ex tensive blood supply, a greater number of mitochondria, and large amounts of myoglobin, all of which support high levels of oxidative phosphorylation.
94. The delay between the termination of the transient depolarization of the muscle membrane and the onset of muscle contraction observed in bo th muscles A and B reflects the time necessary for which of the following events to occur? (A) (B) (C) (D) (E)
ADP to be released from the myosin head ATP to be synthesized 2+ Ca to accumulate in the sarcoplasm G-actin to polymerize into F-actin Myosin head to complete one cross-bridge cycle
2+
Answer: C. Muscle contraction is triggered by an increase in sarcoplasmic Ca concentration. The delay between the termination of the depolarizing pulse and the onset of muscle contraction, also called the “lag,” reflects the time nec essary for the depolarizing pulse to be translated into 2+ an increase in sarcoplasmic Ca concentration. This process involves a conformational change in the voltage-sensing, or dihydropyridine receptor, located on the T tubule membrane; the subsequent conformational change in the ryanodine receptor on the sarcoplasmic reticulum; and 2+ the release of Ca from the sarcoplasmic reticulum.
95. The slow twitch muscle fiber differs from the fast twitch fiber because the slow twitch fiber... (A) Has a smaller number of muscle fibers in each mo tor unit but equally powerful (B) Has a higher concentration of myoglobin and mitochondria (C) Has a higher ATPase activity (D) In a large limb serves as a reserve which can b e recruited if there is a forceful contraction (E) Is more readily fatigued (F) Is part of a motor unit that consists mainly of red fibers Answer: B. A slow twitch is associated with a red endurance muscle. It does have a smaller number of muscle fibers but it is generally not as powerful as a white muscle (fast twitch). It has greater myoglobin (makes it red) and mitochondria b ecause it works mainly aerobically. It metabolizes ATP slowly (lower ATPase activity). It is not kept in reserve for very forceful contraction (large fast muscle motor units are). The slow red muscle is endurance muscle, and fatigues less than fast white muscle.
Muscle Energy Sources 96. A 16-year-old adolescent boy on the track team asks his pediatrician if he can take creatine on a regular basis in order to increase his muscle strength prior to a track meet. Which of the following most likely explains why he wants to take creatine? (A) Creatine increases plasma glucose concentrations (B) Creatine prevents dehydration (C) Creatine increases muscleglycogen concentrations (D) Creatine is converted to phosphocreatine (E) Creatine delays the metabolism of fatty acids Answer: D. Phosphocreatine is rapidly converted to ATP in muscle. It causes dehydration, and may increase the muscle glycogen concentration, may accelerate fatty acids metabolism. It doesn't seem to affect plasma glucose level.
