Cell Physiology/Part 1/1.3 Active Transport

1.3 Active Transport

Energy-Dependent Movement Against Electrochemical Gradients

🎯 Learning Objectives

  • •Distinguish between primary and secondary active transport
  • •Describe the structure and function of the Na⁺/K⁺-ATPase
  • •Explain symport and antiport mechanisms
  • •Calculate the free energy required for ion transport

⚡Primary Active Transport

Primary active transport directly uses ATP hydrolysis to move ions against their electrochemical gradient. These transporters are called ATPases or pumps.

🔋 The Na⁺/K⁺-ATPase: The Cell's Power Plant

The sodium-potassium pump is the most important active transporter, consuming ~25% of cellular ATP (up to 70% in neurons).

Stoichiometry (per ATP)

3 Na⁺→ OUT (extracellular)
2 K⁺→ IN (intracellular)
Net: +1 charge OUT(electrogenic)

Pump Cycle (E1-E2 Model)

  1. 1. E1 conformation: 3 Na⁺ bind from cytoplasm
  2. 2. ATP hydrolysis → phosphorylated enzyme (E1-P)
  3. 3. Conformational change to E2-P
  4. 4. Na⁺ released outside, 2 K⁺ bind
  5. 5. Dephosphorylation → E2 to E1 transition
  6. 6. K⁺ released inside, cycle repeats

Pharmacological Inhibitors

Cardiac Glycosides: Digoxin, ouabain—increase cardiac contractility
Mechanism: Block pump → ↑[Na⁺]ᵢ → ↑[Ca²⁺]ᵢ via NCX

Ca²⁺-ATPases

  • SERCA: Sarco/endoplasmic reticulum Ca²⁺-ATPase. Pumps Ca²⁺ into SR (2 Ca²⁺/ATP)
  • PMCA: Plasma membrane Ca²⁺-ATPase. Extrudes Ca²⁺ from cell (1 Ca²⁺/ATP)

H⁺-ATPases

  • H⁺/K⁺-ATPase: Gastric parietal cells, acidifies stomach (target of PPIs)
  • V-type H⁺-ATPase: Lysosomes, endosomes—acidification

🔗Secondary Active Transport

Secondary active transport uses the electrochemical gradient of one ion (usually Na⁺) to drive transport of another molecule against its gradient. The Na⁺ gradient is maintained by the Na⁺/K⁺-ATPase, so secondary transport indirectly depends on ATP.

Symport (Cotransport)

Both substances move in the same direction.

  • SGLT1/2: Na⁺-glucose cotransporter
    Intestine/kidney: 2Na⁺:1Glc (SGLT1) or 1Na⁺:1Glc (SGLT2)
  • NKCC: Na⁺-K⁺-2Cl⁻ cotransporter
    Kidney (loop of Henle), target of furosemide
  • NCC: Na⁺-Cl⁻ cotransporter
    Kidney (DCT), target of thiazides

Antiport (Exchange)

Substances move in opposite directions.

  • NCX: Na⁺/Ca²⁺ exchanger
    3Na⁺ in : 1Ca²⁺ out (electrogenic)
  • NHE: Na⁺/H⁺ exchanger
    1Na⁺ in : 1H⁺ out (electroneutral), pH regulation
  • AE: Cl⁻/HCO₃⁻ exchanger
    RBCs (band 3), kidney—acid-base balance

The Na⁺/Ca²⁺ Exchanger (NCX) in Cardiac Muscle

Forward Mode (Normal)

3 Na⁺ IN, 1 Ca²⁺ OUT

Removes Ca²⁺ during diastole, promotes relaxation

Reverse Mode

3 Na⁺ OUT, 1 Ca²⁺ IN

Occurs when [Na⁺]ᵢ is elevated (e.g., digitalis toxicity)

📐Energetics of Ion Transport

Free Energy for Ion Transport

ΔG = RT ln([X]ᵢ/[X]ₒ) + zFVₘ
Chemical term: RT ln([X]ᵢ/[X]ₒ)
Electrical term: zFVₘ

For Na⁺ at typical cellular conditions: ΔG ≈ +13 kJ/mol (highly unfavorable for entry without energy)

ATP Hydrolysis Energy Budget

-30.5
kJ/mol
Standard ΔG°' for ATP hydrolysis
-50 to -60
kJ/mol
Actual ΔG in cells
~65%
Efficiency
Na⁺/K⁺-ATPase efficiency

📐 Key Equations

Electrochemical Potential
ΔG = RT ln([X]ᵢ/[X]ₒ) + zFVₘ
ATP Hydrolysis
ΔG°' = -30.5 kJ/mol
Na⁺/K⁺-ATPase Stoichiometry
3Na⁺ₒᵤₜ : 2K⁺ᵢₙ : 1ATP
NCX Stoichiometry
3Na⁺ : 1Ca²⁺

🏥 Clinical Relevance

Heart Failure Treatment

Digoxin inhibits Na⁺/K⁺-ATPase → increased contractility via NCX

SGLT2 Inhibitors

Empagliflozin, dapagliflozin—diabetes treatment, cardioprotective

Loop Diuretics

Furosemide blocks NKCC2 in loop of Henle

Proton Pump Inhibitors

Omeprazole inhibits H⁺/K⁺-ATPase—GERD treatment

←1.2 Passive TransportNext: 1.4 Vesicular Transport→