U01.01.031 Sodium-potassium pump

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Learning Objectives

  • Describe the mechanism and stoichiometry of the \text{Na}^+/\text{K}^+-ATPase.
  • Identify the roles of phosphorylation and dephosphorylation in pump function.
  • Explain the clinical application of Digoxin and its effect on cardiac contractility.

1. Mechanism and Stoichiometry

The \text{Na}^+/\text{K}^+-ATPase is a primary active transporter located in the plasma membrane. It maintains the resting membrane potential by moving ions against their concentration gradients using energy from ATP hydrolysis.

  • The Movement: For every 1 ATP consumed:
    • 3 \text{Na}^+ ions are pumped OUT of the cell.
    • 2 \text{K}^+ ions are pumped IN to the cell.
  • Mnemonic: 2 strikes? K, you’re still IN. 3 strikes? Nah, you’re OUT!

2. Phosphorylation States

The pump cycles between two conformational states driven by the addition and removal of a phosphate group.

  • Phosphorylated State: Occurs when ATP is hydrolyzed; the pump has a high affinity for \text{Na}^+ and releases it extracellularly.
  • Dephosphorylated State: Occurs after $\text{K}^+$ binds; the pump returns to its original conformation to release \text{K}^+ into the cytosol.

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3. Clinical Correlation: Digoxin

Digoxin (a cardiac glycoside) is used in heart failure to increase the force of heart contractions (positive inotropy).

The Digoxin Pathway:
1. Digoxin directly inhibits the \text{Na}^+/\text{K}^+-ATPase.
2. Intracellular [\text{Na}^+] increases.
3. This causes indirect inhibition of the \text{Na}^+/\text{Ca}^{2+} exchanger (which normally uses the Na+ gradient to pump Ca2+ out).
4. Intracellular [\text{Ca}^{2+}] increases.
5. \uparrow Cardiac contractility.

 

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