Unravelling a role for KCNQ1 in K~+ recycling and gastric acid secretion

摘要

Gastric acid,, secretion by the luminal H~+/K~+-ATPase is dependent on recycling of K~+ from the cell to the lumen to supply K~+ for the H~+-K~+ exchange mechanism. Several different K~+ channels, depending on the species studied, have been suggested to support gastric acid secretion, including KCNQ1 and the inward rectifying channels Kirl.l, Kir2.1, Kir4.1 and Kir5.1. KCNQ1 has been speculated to be the primary recycling K~+ channel in gastric parietal cells for almost a decade, and several lines of evidence point to a pivotal role of KCNQ1 in gastric acid secretion. KCNQ1 is a member of a large family of voltage-activated K~+ channels and regulates key physiological functions such as shaping the cardiac action potential and controlling water and salt homeostasis in several epithelial tissues. As such, it has been shown to be abundantly expressed in stomach, small and large intestine, kidneys and pancreas. KCNQ1 and the regulatory subunit KCNE2 are highly expressed and co-localize in gastric parietal cells. The assembly of KCNQ1 with KCNE2 in the apical membrane of the parietal cell is of special importance considering the extreme condition of pH 1 at the luminal side. KCNE2 changes the biophysical properties of KCNQ1 and confers activation by external acidification on KCNQ1. This is essential because KCNQ1 alone is inhibited by low extracellular pH and would not be able to conduct K~+ under such conditions.