What is the principal mechanism of action of Cardiac glycosides?

• A. Stimulate the release of Calcium from the sarcoplasmic reticulum leading to an increase in intracellular Calcium
• B. Inhibit the cell membrane outward calcium transporter preventing Calcium extrusion
• C. Inhibit Na-K-ATPase leading to increase in intracellular Sodium and preventing Calcium extrusion
• D. Inhibit Na-Ca exchanger in the sarcoplasmic reticulum leading to increase in intracellular Calcium

Answer: (C)

Cardiac glycosides block the Na+/K+-ATPase pump on the cardiac cell membrane. This causes sodium to accumulate inside the cell, which reduces the driving force for the Na+/Ca2+ exchanger to remove Ca2+. As a result, intracellular calcium builds up, increasing calcium availability for contraction and producing a stronger (positive inotropic) effect. The other options misstate either the transporter involved or its location, whereas the key action is inhibition of Na+/K+-ATPase leading to higher intracellular Na+ and consequently higher intracellular Ca2+.