In the stomach, parietal cells secrete HCl via the H⁺/K⁺-ATPase on the apical canalicular membrane. The electrical neutrality during acid secretion is maintained by Cl⁻ efflux through which channel, and the intracellular HCO₃⁻ generated is exported via which mechanism?

• A Cl⁻ exits via voltage-gated ClC-2 channels on the basolateral membrane; HCO₃⁻ is converted back to CO₂ by intracellular carbonic anhydrase
• B Cl⁻ exits via the apical KCNK5 K⁺/Cl⁻ co-transporter; HCO₃⁻ exits via basolateral NBC (sodium-bicarbonate cotransporter)
• C Cl⁻ exits via CFTR channel on the apical canaliculus; HCO₃⁻ exits on the basolateral Cl⁻/HCO₃⁻ exchanger (AE2) ✓
• D Cl⁻ exits via the apical KCNQ1/KCNE2 K⁺ channel replacing recycled K⁺; HCO₃⁻ exits on NBC1 basolaterally

Explanation

For each H⁺ secreted into the canalicular lumen by H⁺/K⁺-ATPase, intracellular carbonic anhydrase generates H⁺ and HCO₃⁻ from CO₂ + H₂O. The H⁺ is pumped into the lumen, while the HCO₃⁻ exits the basolateral side via the Cl⁻/HCO₃⁻ exchanger (AE2, anion exchanger 2) in exchange for Cl⁻ entry. The Cl⁻ then exits apically through CFTR (and KCNK10 ClC channels) to maintain electroneutrality in the canaliculus. Proton pump inhibitors block H⁺/K⁺-ATPase irreversibly; CFTR dysfunction (cystic fibrosis) can impair HCl secretion.

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

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