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Physiology · General physiology: Na+-K+ ATPase and digoxin
Sample itemA 68-year-old man with chronic heart failure is started on digoxin. Which sequence best explains its positive inotropic effect on the myocardium?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Na+-K+ ATPase inhibition raises intracellular Na+, slowing Na+-Ca2+ exchange and leaving more Ca2+ for contraction
The Na+-K+ ATPase pumps 3 Na+ out and 2 K+ in per ATP. Digoxin inhibits it, so intracellular Na+ rises and the Na+ gradient that drives the Na+-Ca2+ exchanger falls. Less Ca2+ is extruded, the sarcoplasmic reticulum stores more Ca2+, and contractility increases.
Option by option
A. Beta-1 receptor stimulation raises cAMP and phosphorylates the L-type Ca2+ channel
Beta-1 stimulation is the mechanism of dobutamine and adrenaline, not digoxin.
B. Direct opening of L-type Ca2+ channels increases Ca2+ entry with each action potential
Digoxin does not open Ca2+ channels directly; agents such as Bay K8644 do this experimentally.
C. Na+-K+ ATPase inhibition raises intracellular Na+, slowing Na+-Ca2+ exchange and leaving more Ca2+ for contraction (correct)
Reduced Ca2+ extrusion through the exchanger raises cytosolic and stored Ca2+, which strengthens contraction.
D. Phosphodiesterase 3 inhibition raises cAMP and increases Ca2+ uptake into the sarcoplasmic reticulum
Phosphodiesterase 3 inhibition is the mechanism of milrinone, not digoxin.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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