Physiology · Cardiac Physiology (Cycle, Output, ECG, Electrophysiology)

In the Frank-Starling mechanism, which molecular event explains increased force of contraction with increased preload?

  • A Increased resting myocyte length increases myosin ATPase activity
  • B Sarcomere stretch increases myofilament Ca2+ sensitivity and reduces interfilament lattice spacing, increasing cross-bridge formation
  • C Preload stretches the T-tubule, activating ryanodine receptors directly
  • D Increased end-diastolic volume raises the intracellular Ca2+ transient by triggering more L-type Ca2+ channel openings
Correct answer: B. Sarcomere stretch increases myofilament Ca2+ sensitivity and reduces interfilament lattice spacing, increasing cross-bridge formation

Explanation

The cellular basis of the Frank-Starling law involves two length-dependent mechanisms. First, at optimal sarcomere length (~2.2 µm), actin-myosin overlap is maximal. Second — and now recognised as primary — sarcomere stretch increases the sensitivity of troponin C to Ca2+ (length-dependent activation) and reduces interfilament lattice spacing, increasing the probability of cross-bridge attachment without changing the Ca2+ transient. This explains how the same systolic Ca2+ concentration produces more force at greater preload. Increased Ca2+ release (option D) is the basis of a distinct phenomenon — the Bowditch (Treppe) effect with rate.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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