KCNQ1 is the luminal K+ recycling channel during stimulation of gastric acid secretion

摘要

Parietal cell (PC) proton secretion via H+/K+-ATPase requires apical K+ recycling. A variety of K+ channels and transporters are expressed in the PC and the molecular nature of the apical K+ recycling channel is under debate. This study was undertaken to delineate the exact function of KCNQ1 channels in gastric acid secretion. Acid secretory rates and electrophysiological parameters were determined in gastric mucosae of 7- to 8-day-old KCNQ1+/+, +/– and −/− mice. Parietal cell ultrastructure, abundance and gene expression levels were quantified. Glandular structure and PC abundance, and housekeeping gene expression did not differ between the KCNQ1−/− and +/+ mucosae. Microvillar secretory membranes were intact, but basal acid secretion was absent and forskolin-stimulated acid output reduced by ∼90% in KCNQ1−/− gastric mucosa. Application of a high K+ concentration to the luminal membrane restored normal acid secretory rates in the KCNQ1−/− mucosa. The study demonstrates that the KCNQ1 channel provides K+ to the extracellular K+ binding site of the H+/K+-ATPase during acid secretion, and no other gastric K+ channel can substitute for this function.