Muscle Physiology and Contraction · USMLE Step 1

During prolonged, repeated contractions (fatigue), which factor contributes to decreased force generation in muscle fibers?

  1. Excessive release of Ca²⁺ from the SR
  2. Build-up of metabolic byproducts and reduced ATP
  3. Increased troponin Ca²⁺ sensitivity
  4. Enhanced rate of filament sliding
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Correct answer: Build-up of metabolic byproducts and reduced ATP

With repeated contraction, ATP depletion and the accumulation of metabolites impair cross-bridge cycling and calcium handling, leading to muscle fatigue and reduced force generation.

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