What is the primary mechanism by which digoxin increases cardiac contractility?

• A. Inhibition of Na+/K+ ATPase leading to increased intracellular calcium
• B. Activation of beta-adrenergic receptors
• C. Inhibition of calcium channels
• D. Vasodilation of smooth muscle

Answer: (A)

Digoxin increases contractility mainly by inhibiting the Na+/K+ ATPase pump in cardiac muscle cells. This raises intracellular sodium, which reduces the driving force for the Na+/Ca2+ exchanger to remove calcium. As a result, calcium accumulates in the cytosol during each heartbeat, allowing more calcium to bind to troponin C, increasing cross-bridge formation and producing a stronger contraction.

The other ideas don’t fit this effect: activating beta-adrenergic receptors would boost contractility via cAMP and PKA but digoxin isn’t a beta-agonist; blocking calcium channels would decrease calcium entry and weaken contraction; vasodilation affects afterload and vascular tone rather than directly increasing the force of contraction.