A ventricular myocyte is held at its resting membrane potential of −90 mV. Tetrodotoxin (TTX) is applied, which blocks fast voltage-gated Na⁺ channels. Which phase of the cardiac action potential will be most directly abolished?

• A Phase 1 (early rapid repolarization)
• B Phase 2 (plateau)
• C Phase 4 (spontaneous depolarization)
• D Phase 0 (rapid depolarization) ✓

Explanation

Phase 0 of the ventricular action potential depends entirely on rapid inward Na⁺ current through fast TTX-sensitive channels, producing the steep upstroke from −90 to +30 mV. TTX blocks these channels, preventing depolarization. Phase 2 relies on L-type Ca²⁺ channels (TTX-insensitive), and SA nodal Phase 4 depends on If (funny current) and ICaL, not fast Na⁺ channels.

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

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