A patient presents with a prolonged QT interval and episodes of polymorphic ventricular tachycardia (torsades de pointes). The underlying defect is most likely loss-of-function mutation in which channel?
- A KCNQ1 or KCNH2 (IKs or IKr — slowly/rapidly activating rectifier K⁺ channels) ✓
- B SCN5A (cardiac Nav1.5) — fast sodium channel
- C CACNA1C (L-type Ca²⁺ channel Cav1.2)
- D HCN4 (funny current If channel)
Correct answer: A. KCNQ1 or KCNH2 (IKs or IKr — slowly/rapidly activating rectifier K⁺ channels)
Explanation
Torsades de pointes arises from prolonged ventricular repolarization (long QT). Phase 3 repolarization is primarily driven by IKs (KCNQ1) and IKr (KCNH2/hERG) potassium currents; loss-of-function mutations in these genes cause congenital long QT syndromes types 1 and 2 respectively. Reduced outward K⁺ current delays repolarization, allowing triggered early after-depolarizations. SCN5A gain-of-function causes Brugada or LQT3, CACNA1C affects plateau phase, and HCN4 mutations cause sinus node dysfunction.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.