The positive inotropic effect of digoxin results directly from which intracellular change?
- A Increased cyclic AMP through adenylate cyclase stimulation
- B Direct opening of L-type calcium channels
- C Inhibition of the sarcolemmal Na+/K+-ATPase leading to reduced Ca2+ extrusion via the sodium-calcium exchanger ✓
- D Inhibition of phosphodiesterase type 3 in cardiomyocytes
Correct answer: C. Inhibition of the sarcolemmal Na+/K+-ATPase leading to reduced Ca2+ extrusion via the sodium-calcium exchanger
Explanation
Digoxin inhibits Na+/K+-ATPase, raising intracellular sodium. The sodium-calcium exchanger then extrudes less calcium, so sarcoplasmic reticulum calcium stores increase and more calcium is released per beat. This distinguishes it from milrinone (option D), which raises cAMP by blocking PDE-3, and from beta-agonists acting through adenylate cyclase (option A). The exchanger link between sodium loading and calcium retention is the single fact that defines digitalis inotropy.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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