Physiology · Renal Physiology (GFR, Tubular Function, Acid-Base, Concentration)

In the thick ascending limb of the loop of Henle, the NKCC2 cotransporter moves ions with a fixed stoichiometry. The exact stoichiometry and the driving force for this transporter are:

  • A 2Na⁺:1K⁺:3Cl⁻ (electrogenic); driven by lumen-positive transepithelial potential
  • B 1Na⁺:1K⁺:2Cl⁻ (electroneutral); driven by basolateral Na⁺/K⁺-ATPase maintaining low intracellular Na⁺
  • C 1Na⁺:2K⁺:1Cl⁻ (electroneutral); driven by intracellular K⁺ gradient via ROMK channel
  • D 1Na⁺:1K⁺:1Cl⁻ (electrogenic); driven by aldosterone-stimulated apical H⁺-ATPase
Correct answer: B. 1Na⁺:1K⁺:2Cl⁻ (electroneutral); driven by basolateral Na⁺/K⁺-ATPase maintaining low intracellular Na⁺

Explanation

NKCC2 in the thick ascending limb cotransports 1 Na⁺, 1 K⁺, and 2 Cl⁻ simultaneously and is electroneutral (net charge transport = 0). The primary driving force is the low intracellular Na⁺ concentration maintained by the basolateral Na⁺/K⁺-ATPase. K⁺ recycled back into the lumen via ROMK channels maintains substrate availability and generates a lumen-positive voltage that drives paracellular reabsorption of Ca²⁺, Mg²⁺, and Na⁺. This is the target of loop diuretics (furosemide), which block NKCC2.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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