A 72-year-old woman with a history of atrial fibrillation is on digoxin therapy. She presents with nausea, visual disturbances (yellow-green halos), and a heart rate of 35 bpm. An ECG shows a prolonged PR interval and a characteristic 'sagging' ST segment. Which phase of the cardiac action potential is most directly affected by digoxin toxicity in the AV node?

Explanation

## Digoxin Toxicity and AV Nodal Conduction **Key Point:** Digoxin toxicity primarily affects phase 4 of the AV nodal action potential by enhancing vagal tone and increasing AV nodal refractoriness, leading to bradycardia and AV block. ### Mechanism of Digoxin Action on Phase 4 Digoxin acts through two pathways: 1. **Direct effect:** Inhibition of Na⁺/K⁺-ATPase → increased intracellular Na⁺ and Ca²⁺ 2. **Indirect effect (at toxic levels):** Enhanced vagal (parasympathetic) tone via increased acetylcholine sensitivity **High-Yield:** In the AV node, phase 4 is mediated by slow L-type Ca²⁺ channels (not fast Na⁺ channels). Digoxin toxicity increases vagal tone, which: - Decreases the slope of phase 4 diastolic depolarization - Increases the threshold potential (makes it more negative) - Prolongs the PR interval and can cause AV block ### Comparison of AV Node vs. Ventricular Myocyte Phase 4 | Feature | AV Node (Slow Response) | Ventricular Myocyte (Fast Response) | |---------|------------------------|-------------------------------------| | Phase 0 depolarization | L-type Ca²⁺ channels (slow) | Fast Na⁺ channels (rapid) | | Phase 4 pacemaker activity | Prominent (automatic) | Absent (non-automatic) | | Digoxin effect on Phase 4 | **Decreased slope** (↓ automaticity) | Minimal direct effect | | Vagal sensitivity | High | Low | | Clinical effect of digoxin toxicity | **Bradycardia, AV block** | Ectopy, arrhythmias | **Clinical Pearl:** The characteristic "sagging" ST segment (resembling a reversed tick mark or "digitalis effect") reflects the altered repolarization in ventricular tissue due to increased intracellular Ca²⁺, but the primary conduction abnormality (prolonged PR interval, bradycardia) is from phase 4 effects in the AV node. **Mnemonic:** **DIGOXIN = AV Node SLOW-DOWN** — digoxin slows AV nodal conduction by decreasing the slope of phase 4 diastolic depolarization via enhanced vagal tone. ### Why Bradycardia and AV Block Occur When the slope of phase 4 decreases and the threshold becomes more negative, it takes longer for the membrane potential to reach threshold, delaying AV nodal conduction and reducing the intrinsic rate of AV nodal pacemaker cells.