Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion

1 Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles 2 Department of Physiology, David Geffen School of Medicine, University of California Los Angeles 3 Department of Medicine, David Geffen School of Medicine, University of California Los Angeles 4 Membrane Biology Laboratory, West Los Angeles Veterans Affairs Medical Center, Los Angeles, California Genomic microarray analysis of genes specifically expressed in a pure cell isolate from a heterocellular organ identified the likely K efflux channel associated with the gastric H-K-ATPase. The function of this channel is to supply K to the luminal surface of the pump to allow H for K exchange. KCNQ1-KCNE2 was the most highly expressed and significantly enriched member of the large variety of K channels expressed in the gastric epithelium. The function of this K channel in acid secretion was then shown by inhibition of secretion in isolated gastric glands with specific KCNQ inhibitors and by colocalization of the channel with the H-K-ATPase in the secretory canaliculus of the parietal cell. KCNQ1-KCNE2 appears to be the K efflux channel that is essential for gastric acid secretion. parietal cell; oligonucleotide expression microarray; potassium channel; KCNQ1; KCNE2