Digoxin exerts its inotropic effect by which mechanism?

Digoxin exerts its inotropic effect by which mechanism?

• A. Block Na+/K+ ATPase to increase intracellular Ca2+
• B. Inhibit Na+/Ca2+ exchanger
• C. Block beta-adrenergic receptors
• D. Open voltage-gated potassium channels

Answer: (A)

Digoxin increases the force of cardiac contraction by inhibiting the Na+/K+ ATPase pump in heart muscle cells. This raises intracellular sodium, which reduces the driving force for the Na+/Ca2+ exchanger that normally removes Ca2+ from the cell. With less Ca2+ being expelled (or even Ca2+ entering in reverse mode), more calcium stays inside the cell during systole. The extra intracellular Ca2+ enhances calcium-induced calcium release and strengthens cross-bridge cycling, producing a positive inotropic effect. This mechanism is distinct from effects on conduction that come from increasing vagal tone, and it differs from actions like blocking beta receptors or opening potassium channels, which would not enhance contractility.

Digoxin increases the force of cardiac contraction by inhibiting the Na+/K+ ATPase pump in heart muscle cells. This raises intracellular sodium, which reduces the driving force for the Na+/Ca2+ exchanger that normally removes Ca2+ from the cell. With less Ca2+ being expelled (or even Ca2+ entering in reverse mode), more calcium stays inside the cell during systole. The extra intracellular Ca2+ enhances calcium-induced calcium release and strengthens cross-bridge cycling, producing a positive inotropic effect.

This mechanism is distinct from effects on conduction that come from increasing vagal tone, and it differs from actions like blocking beta receptors or opening potassium channels, which would not enhance contractility.