Which best describes the mechanism by which digoxin increases cardiac contractility?

Which best describes the mechanism by which digoxin increases cardiac contractility?

• A. Blocks L-type calcium channels
• B. Decreases AV nodal conduction by reducing calcium influx
• C. Inhibits Na-K ATPase leading to increased intracellular Na and Ca
• D. Activates beta-adrenergic receptors

Answer: (C)

Digoxin increases contractility mainly by inhibiting the Na+/K+ ATPase pump in cardiac myocytes. This raises intracellular sodium, which reduces the driving force for the Na+/Ca2+ exchanger to remove calcium from the cell. As a result, intracellular calcium accumulates, and more calcium is available to trigger strong cross-bridge cycling during systole, producing a stronger, more forceful contraction. The extra calcium can also be taken up into the sarcoplasmic reticulum, further enhancing calcium availability for future contractions. Digoxin does have another effect—increasing vagal tone to slow AV nodal conduction—but that is separate from the mechanism that boosts contractility. Other proposed mechanisms, like blocking L-type calcium channels or primarily activating beta-adrenergic receptors, would affect calcium handling in ways that don’t explain the distinctive inotropic effect produced by Na+/K+ ATPase inhibition.

Digoxin increases contractility mainly by inhibiting the Na+/K+ ATPase pump in cardiac myocytes. This raises intracellular sodium, which reduces the driving force for the Na+/Ca2+ exchanger to remove calcium from the cell. As a result, intracellular calcium accumulates, and more calcium is available to trigger strong cross-bridge cycling during systole, producing a stronger, more forceful contraction. The extra calcium can also be taken up into the sarcoplasmic reticulum, further enhancing calcium availability for future contractions.

Digoxin does have another effect—increasing vagal tone to slow AV nodal conduction—but that is separate from the mechanism that boosts contractility. Other proposed mechanisms, like blocking L-type calcium channels or primarily activating beta-adrenergic receptors, would affect calcium handling in ways that don’t explain the distinctive inotropic effect produced by Na+/K+ ATPase inhibition.