The countercurrent multiplier in the loop of Henle depends on active NaCl reabsorption without water in the thick ascending limb (TAL). Which transporter on the apical membrane of TAL cells performs this function and is the target of loop diuretics?

• A Na⁺-Cl⁻ cotransporter (NCC)
• B Epithelial Na⁺ channel (ENaC)
• C Na⁺-H⁺ exchanger (NHE3)
• D Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) ✓

Explanation

NKCC2 (SLC12A1) on the apical membrane of TAL cells cotransports 1 Na⁺, 1 K⁺, and 2 Cl⁻ into the cell, with the driving force provided by basolateral Na⁺-K⁺-ATPase. The TAL is impermeable to water, so solute reabsorption without water dilutes tubular fluid and concentrates the medullary interstitium. Furosemide (a loop diuretic) blocks NKCC2, abolishing the medullary concentration gradient. NCC is the thiazide target in the distal convoluted tubule. Bartter syndrome type 1 is caused by loss-of-function NKCC2 mutations.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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