⚡ The Sodium-Potassium ATPase pump (Na⁺/K⁺-ATPase) is an essential membrane protein found in nearly all animal cells. It maintains the electrochemical gradient across the plasma membrane, which underpins nerve impulse transmission, muscle contraction, nutrient absorption, and fluid balance. 🧪 For each ATP hydrolysed: 3 Na⁺ ions are pumped out and 2 K⁺ ions are pumped in. This makes the pump electrogenic, contributing to the resting membrane potential.

🧬 Structure

The Na⁺/K⁺-ATPase pump is a heterodimer:
- 🅰️ Alpha (α) subunit: Catalytic unit – binds Na⁺, K⁺, ATP; performs ion transport.
- 🅱️ Beta (β) subunit: Ensures correct folding, stability, and membrane localisation.
- ➕ In some tissues, a Gamma (γ) subunit (FXYD protein family) modulates activity and tissue-specific function.

⚙️ Mechanism of Action

Uses ATP hydrolysis to transport ions against their concentration gradients.
Located in the plasma membrane with the ATP-binding site on the cytosolic side.
For each ATP:
- 🚫 3 Na⁺ out (pump phosphorylated)
- ➕ 2 K⁺ in (pump dephosphorylated)
This unequal exchange makes the pump electrogenic, generating a net negative charge inside the cell.

🔄 Step-by-Step Cycle

1️⃣ Na⁺ Binding: 3 Na⁺ ions bind intracellularly.
2️⃣ ATP Hydrolysis & Phosphorylation: ATP donates phosphate → conformational change.
3️⃣ Na⁺ Release: Pump opens outwards, releasing 3 Na⁺ ions.
4️⃣ K⁺ Binding: 2 extracellular K⁺ ions bind to their sites.
5️⃣ Dephosphorylation: Phosphate released, pump returns to original shape.
6️⃣ K⁺ Release: 2 K⁺ ions delivered into the cytoplasm → cycle restarts.

📌 Key Functions

⚡ Resting Membrane Potential: Maintains negative charge inside neurons and muscle cells.
💧 Cell Volume Regulation: Prevents osmotic swelling/shrinkage by controlling intracellular solute concentration.
🍞 Secondary Active Transport: Drives uptake of glucose (via SGLT) and amino acids by maintaining Na⁺ gradient.
🔥 Thermogenesis: Contributes to basal metabolic rate and heat production (especially in brown adipose tissue).

🩺 Clinical Significance

🧠 Neurological disorders: Pump dysfunction implicated in epilepsy, migraine with aura, and familial hemiplegic migraine.
❤️ Cardiac glycosides (e.g. digoxin): Inhibit Na⁺/K⁺-ATPase → ↑ intracellular Na⁺ → ↓ Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺ → stronger cardiac contraction (positive inotropy).
🩸 Hypertension: Altered pump activity may increase vascular tone and sodium retention.
💀 Cell death risk: Complete inhibition causes osmotic swelling, electrolyte collapse, and apoptosis/necrosis.

📝 Summary

🔑 The Na⁺/K⁺ pump is vital for cell physiology – generating membrane potential, enabling nutrient transport, and protecting cell volume.
🚨 Dysfunction → wide-ranging pathology (neurological, cardiovascular, renal).
💊 Pharmacology: exploited by drugs like digoxin for therapeutic benefit.

📚 References

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Sodium Potassium ATPase pump