Digoxin exerts its positive inotropic effect by inhibiting which enzyme, and what is the immediate intracellular consequence?
- A Inhibition of Na+/K+ ATPase causing increased intracellular Na+, reduced NCX activity, and increased Ca2+ stores ✓
- B Stimulation of adenylate cyclase causing increased cAMP and enhanced SERCA uptake
- C Inhibition of phosphodiesterase-3 causing increased cAMP and increased Ca2+ influx
- D Blockade of the ryanodine receptor causing prolonged Ca2+ release from the sarcoplasmic reticulum
Correct answer: A. Inhibition of Na+/K+ ATPase causing increased intracellular Na+, reduced NCX activity, and increased Ca2+ stores
Explanation
Digoxin selectively inhibits the alpha subunit of membrane Na+/K+ ATPase. The rise in intracellular Na+ reduces the gradient driving the Na+/Ca2+ exchanger (NCX), so less Ca2+ is extruded and sarcoplasmic reticulum Ca2+ load increases, enhancing contractility. Phosphodiesterase-3 inhibition is the mechanism of milrinone, not digoxin. The ryanodine receptor is not blocked; digoxin may actually increase spontaneous SR Ca2+ release, which underlies delayed afterdepolarizations.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.