Learning Objective: After completing this section, medical students should be able to describe the mechanism, physiological role, and clinical relevance of the Na⁺/K⁺-ATPase pump, and explain how digitalis (digoxin) affects cardiac contractility through modulation of intracellular ion exchange.
Overview
The Na⁺/K⁺-ATPase pump is a primary active transporter found in the plasma membrane of all cells. It maintains electrochemical gradients essential for neuronal excitability, muscle contraction, and osmotic balance.
Mechanism of Action
| Step | Event | Result |
|---|---|---|
| 1 | 3 Na⁺ ions bind on the cytosolic side | Pump gets phosphorylated (ATP → ADP + P) |
| 2 | Pump changes conformation | 3 Na⁺ ions are transported out of the cell |
| 3 | 2 K⁺ ions bind on the extracellular side | Pump gets dephosphorylated |
| 4 | Pump returns to its original conformation | 2 K⁺ ions are brought into the cell |
Net Effect: 3 Na⁺ out, 2 K⁺ in → electrogenic, making the inside of the cell more negative.
Clinical Correlation: Digoxin and the Na⁺/K⁺-ATPase
| Drug | Mechanism | Effect |
|---|---|---|
| Digoxin | Directly inhibits Na⁺/K⁺-ATPase | ↓ Na⁺ efflux → ↑ intracellular Na⁺ |
| ↓ Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺ | ||
| ↑ Ca²⁺ → ↑ cardiac contractility (positive inotropy) |
Key Points Summary
- Located in the plasma membrane, the ATP-binding site faces the cytosol.
- Uses 1 ATP → moves 3 Na⁺ out, 2 K⁺ in.
- Maintains resting membrane potential and cell volume.
- Digoxin inhibits the pump → ↑ [Ca²⁺]i → stronger cardiac contraction.
