A 58-year-old man from Delhi presents to the emergency department with palpitations and syncope. His ECG shows a prolonged QT interval (520 ms) and he is found to have hypokalaemia (K+ 2.8 mEq/L). On further questioning, he has been taking a new antiarrhythmic drug for atrial fibrillation. Which phase of the cardiac action potential is most critically affected by this electrolyte disturbance, leading to early afterdepolarizations and torsades de pointes?

Explanation

## Understanding the Cardiac Action Potential in Hypokalaemia ### Phase 3 and Repolarization Dynamics **Key Point:** Phase 3 (repolarization) is the phase during which K+ efflux through delayed rectifier potassium channels (IK) restores the negative resting membrane potential. Hypokalaemia reduces the K+ concentration gradient, slowing repolarization and prolonging the action potential duration (APD). ### Mechanism of QT Prolongation and Afterdepolarizations 1. **Normal Phase 3:** K+ channels open, K+ flows out, membrane potential becomes more negative, action potential terminates. 2. **In Hypokalaemia:** - Reduced extracellular K+ decreases the driving force for K+ efflux. - Repolarization slows, APD lengthens → **prolonged QT interval**. - L-type Ca²⁺ channels (which normally inactivate by end of Phase 2) remain open longer. - Continued inward Ca²⁺ current during late Phase 3 → **early afterdepolarizations (EADs)**. - EADs trigger ectopic beats → **torsades de pointes** (polymorphic VT). ### Why Phase 2 Alone Is Not the Answer Although Phase 2 (plateau) is maintained by the balance of inward Ca²⁺ and outward K+ currents, the **critical defect** in hypokalaemia is the **impaired K+ efflux during Phase 3**, not Phase 2 dysfunction per se. **Clinical Pearl:** Hypokalaemia + QT prolongation + antiarrhythmic drugs (Class IA, III) = **high risk of torsades de pointes**. Always check K+ and Mg²⁺ before starting antiarrhythmics. **High-Yield:** The mnemonic **"ABCDEFG"** for causes of long QT: - **A**ntiarrhythmics (Class IA, III) - **B**radycardia - **C**alcium channel blockers (rarely) - **D**rugs (macrolides, fluoroquinolones, antipsychotics) - **E**lectrolyte disturbances (↓K⁺, ↓Mg²⁺, ↓Ca²⁺) - **F**emale sex - **G**enetic (congenital LQTS) ### Phases of Cardiac Action Potential Summary | Phase | Duration | Key Ions | Channels | Clinical Relevance | |-------|----------|----------|----------|--------------------| | 0 | ~1 ms | Na⁺ in, K⁺ out | Fast Na⁺, early K⁺ | Depolarization velocity; Class I antiarrhythmics block Na⁺ | | 1 | Brief | K⁺ out | Transient K⁺ | Notch on ECG | | 2 | 200–300 ms | Ca²⁺ in, K⁺ out | L-type Ca²⁺, delayed K⁺ | Plateau; Class IV antiarrhythmics block Ca²⁺ | | 3 | 150–200 ms | K⁺ out | Delayed rectifier K⁺ (IK) | **Repolarization; hypokalaemia prolongs this** | | 4 | Variable | Minimal | Leak K⁺, inward rectifier | Resting potential; pacemaker activity | **Warning:** Do not confuse Phase 2 prolongation (which occurs in hypercalcaemia) with Phase 3 prolongation (hypokalaemia). The **QT interval** reflects Phases 0–3; prolongation in hypokalaemia is due to **delayed Phase 3**, not Phase 2 extension. [cite:Guyton & Hall Textbook of Medical Physiology 14e Ch 10]