104. Physiology | Skeletal Muscle Physiology - Part I

A patient dies suddenly after prolonged immobilization. Several hours later, the body develops marked muscle stiffness due to persistent actin–myosin cross-bridges. Which step of the cross-bridge cycle fails to occur in this setting?

A. Release of inorganic phosphate from myosin
B. Binding of ATP to the myosin head
C. Calcium binding to troponin C
D. Hydrolysis of ATP to ADP and Pi
E. Power stroke of the myosin head

B

• B (✅) ATP binding to myosin is required for detachment from actin. After death, ATP is depleted → myosin remains tightly bound → rigor mortis.

• A Pi release drives the power stroke, not detachment.

• C Calcium binding is irrelevant postmortem; Ca²⁺ is high but detachment still requires ATP.

• D ATP hydrolysis occurs after binding; binding itself is the critical missing step.

• E Power stroke already occurred; the problem is inability to detach afterward.

A genetic mutation causes failure of thin filaments to maintain uniform length across sarcomeres, leading to impaired force generation despite normal calcium signaling. Which protein is most likely defective?

A. Titin
B. Nebulin
C. Tropomyosin
D. α-Actinin
E. Myomesin

B

• B (✅) Nebulin acts as a molecular ruler that regulates thin filament length. Loss → nonuniform sarcomeres and reduced force.

• A Titin anchors thick filaments and provides elasticity.

• C Tropomyosin regulates myosin-binding site exposure, not filament length.

• D α-Actinin anchors actin to the Z-line but does not determine length.

• E Myomesin stabilizes thick filaments at the M-line.

A drug prevents conformational coupling between the dihydropyridine receptor and the ryanodine receptor in skeletal muscle. Which immediate effect would be observed following an action potential?

A. Normal depolarization with absent contraction
B. Reduced acetylcholine release at the neuromuscular junction
C. Prolonged depolarization of the motor end plate
D. Increased calcium reuptake into the sarcoplasmic reticulum
E. Increased ATP hydrolysis by myosin heads

A

• A (✅) Action potential propagation is normal, but no Ca²⁺ release from SR → no contraction → classic excitation–contraction uncoupling.

• B NMJ function is upstream and unaffected.

• C Prolonged depolarization is seen with succinylcholine, not DHP–RyR uncoupling.

• D SERCA activity is unchanged initially.

• E ATP hydrolysis decreases because cross-bridges never form.

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