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

In the thick ascending limb (TAL) of the loop of Henle, the Na⁺-K⁺-2Cl⁻ (NKCC2) cotransporter is energized indirectly by the Na⁺/K⁺-ATPase. Which ion's recycling via the ROMK channel on the apical membrane is essential to maintain NKCC2 activity, and why?

  • A Na⁺ recycling, to prevent hyperpolarization of the apical membrane
  • B K⁺ recycling back into the tubular lumen, to prevent luminal K⁺ depletion that would otherwise limit NKCC2 transport
  • C Cl⁻ recycling, to maintain electroneutral transport across the apical membrane
  • D Ca²⁺ recycling, to activate the cotransporter's regulatory domain
Correct answer: B. K⁺ recycling back into the tubular lumen, to prevent luminal K⁺ depletion that would otherwise limit NKCC2 transport

Explanation

NKCC2 co-transports 1 Na⁺, 1 K⁺, and 2 Cl⁻; however, luminal K⁺ concentration is relatively low compared to Na⁺ and Cl⁻. The ROMK (Kir1.1) channel on the apical membrane recycles K⁺ back into the lumen, maintaining adequate luminal K⁺ to sustain NKCC2 function. This K⁺ recycling also generates a lumen-positive transepithelial potential that drives paracellular reabsorption of Ca²⁺ and Mg²⁺. Loop diuretics (furosemide) block NKCC2, and ROMK mutations cause Bartter syndrome type II.

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

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