In proximal renal tubular acidosis (type 2 RTA), the primary biochemical defect is failure of bicarbonate reabsorption in the proximal tubule. Which transporter is principally responsible for basolateral HCO3⁻ exit from the proximal tubular cell?

• A NHE3 (Na⁺/H⁺ exchanger-3) on the apical membrane
• B NBC1 (electrogenic Na⁺-HCO3⁻ cotransporter) on the basolateral membrane ✓
• C AE1 (Cl⁻/HCO3⁻ exchanger) on the basolateral membrane
• D V-type H⁺-ATPase on the apical membrane

Explanation

In proximal tubular cells, HCO3⁻ enters via apical carbonic anhydrase IV + NHE3 (lumenal H⁺ secretion regenerates HCO3⁻ from CO2 inside the cell). The HCO3⁻ generated intracellularly exits via the basolateral electrogenic Na⁺-HCO3⁻ cotransporter NBC1 (SLC4A4), which carries 1 Na⁺ + 3 HCO3⁻ into peritubular blood. Mutations in NBC1 cause autosomal recessive proximal RTA with ocular abnormalities. AE1 (Cl⁻/HCO3⁻ exchanger) and V-type H⁺-ATPase are the principal transporters in alpha-intercalated cells of the collecting duct, relevant to distal (type 1) RTA.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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