A 68-year-old woman with heart failure with reduced ejection fraction and stage 3 chronic kidney disease presents with a 2-day history of nausea, vomiting, and yellow-green visual disturbances. She has been taking digoxin 0.25 mg daily for 8 months. Vital signs: temperature 37.1°C, blood pressure 108/72 mmHg, heart rate 42 bpm with regular rhythm. Laboratory results: serum creatinine 2.1 mg/dL, potassium 3.2 mEq/L, serum digoxin level 3.2 ng/mL (therapeutic range 0.5–2.0 ng/mL). ECG shows sinus bradycardia without atrioventricular block. Which of the following best explains the mechanism by which digoxin toxicity is producing this patient's bradycardia?

1. A)Competitive inhibition of beta-1 adrenergic receptors on nodal tissue, reducing cAMP-dependent pacemaker activity
2. B)Increased intracellular calcium in sinoatrial node cells, which directly hyperpolarizes the membrane potential
3. C)Inhibition of the Na+/K+-ATPase pump, leading to increased vagal acetylcholine sensitivity and enhanced parasympathetic effects at the sinoatrial nodeGABARITO
4. D)Direct blockade of L-type calcium channels in pacemaker cells of the sinoatrial node, decreasing spontaneous depolarization
5. E)Inhibition of adenosine deaminase, increasing extracellular adenosine which activates inhibitory A1 receptors on nodal tissue