Question

The positive inotropic effect of digitalis is due to inhibition of $Na^+/K^+$ ATPase pump in cardiac muscle cell membrane leading to

• A. Decreased activity of $Na^+/Ca^{++}$ exchanger causing decreased influx of $Na^+$ and decreased efflux of $Ca^{++}$ in the sarcolemma
• B. Decreased efflux of $Na^+$ leading to less negative resting membrane potential and opening of voltage gated $Ca^{++}$ channels on the T tubules
• C. Increased intracellular $Na^+$ causing increased efflux of $Na^+$ and increased influx of $Ca^{++}$ through $Na^+/Ca^{++}$ exchanger in the sarcolemma
• D. Increased intracellular $Na^+$ decreasing the activity of $Ca^{++}$ pump in the sarcoplasmic reticulum

Hint:

Remember the cascade: Inhibition of $Na^+/K^+$ ATPase $\rightarrow$ Increased intracellular $Na^+$ $\rightarrow$ Decreased activity of $Na^+/Ca^{++}$ exchanger $\rightarrow$ Decreased $Ca^{++}$ efflux $\rightarrow$ Increased intracellular $Ca^{++}$ $\rightarrow$ Positive inotropy.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Digitalis (a cardiac glycoside) increases myocardial contractility (positive inotropic effect) by modulating intracellular ion concentrations.
Its primary target is the sarcolemmal $Na^+/K^+$-ATPase pump.
Detailed Explanation:
Under physiological conditions, the $Na^+/K^+$-ATPase actively pumps $Na^+$ out of the cell and $K^+$ into the cell, maintaining a high extracellular $Na^+$ gradient.
This $Na^+$ gradient drives the forward activity of the $Na^+/Ca^{++}$ exchanger (NCX), which expels $Ca^{++}$ from the cytoplasm in exchange for extracellular $Na^+$ entering the cell.
When digitalis binds to and inhibits the $Na^+/K^+$-ATPase pump, intracellular $Na^+$ concentration increases.
This elevation in intracellular $Na^+$ reduces the transmembrane sodium gradient.
As a result, the driving force for the $Na^+/Ca^{++}$ exchanger is diminished, leading to decreased influx of $Na^+$ and a corresponding decreased efflux of $Ca^{++}$ from the cell.
The decreased extrusion of $Ca^{++}$ causes intracellular $Ca^{++}$ levels to rise.
This excess $Ca^{++}$ is sequestered into the sarcoplasmic reticulum (SR).
During the next action potential, a larger pool of $Ca^{++}$ is released from the SR, enhancing actin-myosin cross-bridge formation and producing a stronger contraction.

Step 2: Final Answer:
The reduced sodium gradient directly decreases the activity of the $Na^+/Ca^{++}$ exchanger, leading to decreased efflux of $Ca^{++}$ as stated in option (A).