A researcher blocks the IKr channel (hERG channel) in cardiac myocytes. Which phase of the ventricular action potential will be most directly prolonged, and what is the principal clinical risk?

• A Phase 0 prolonged; risk of conduction block
• B Phase 4 prolonged; risk of bradycardia
• C Phase 1 prolonged; risk of ventricular fibrillation through re-entry
• D Phase 2 plateau prolonged; risk of early afterdepolarizations and Torsades de Pointes ✓

Explanation

IKr (the rapid component of the delayed rectifier K⁺ current, encoded by hERG/KCNH2) contributes importantly to phase 3 repolarization; its blockade prolongs the action potential duration and the QT interval. This creates conditions for early afterdepolarizations (EADs) during the prolonged plateau, which can trigger Torsades de Pointes (TdP), a polymorphic ventricular tachycardia. Many drugs (e.g., sotalol, dofetilide, some antihistamines) cause acquired long QT syndrome by this mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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