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The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion

Item Type:Article
Title:The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion
Creators Name:Roepke, T.K. and Anantharam, A. and Kirchhoff, P. and Busque, S.M. and Young, J.B. and Geibel, J.P. and Lerner, D.J. and Abbott, G.W.
Abstract:Genes in the KCNE family encode single transmembrane domain ancillary subunits that co-assemble with voltage-gated potassium (Kv) channel alpha subunits to alter their function. KCNE2 (also known as MiRP1) is expressed in the heart, is associated with human cardiac arrhythmia, and modulates cardiac Kv alpha subunits hERG and KCNQ1 in vitro. KCNE2 and KCNQ1 are also expressed in parietal cells, leading to speculation they form a native channel complex there. Here, we disrupted the murine kcne2 gene and found that kcne2 (-/-) mice have a severe gastric phenotype with profoundly reduced parietal cell proton secretion, abnormal parietal cell morphology, achlorhydria, hypergastrinemia, and striking gastric glandular hyperplasia arising from an increase in the number of non-acid secretory cells. KCNQ1 exhibited abnormal distribution in gastric glands from kcne2 (-/-) mice, with increased expression in non-acid secretory cells. Parietal cells from kcne2 (+/-) mice exhibited normal architecture but reduced proton secretion, and kcne2 (+/-) mice were hypochlorhydric, indicating a gene-dose effect and a primary defect in gastric acid secretion. These data demonstrate that KCNE2 is essential for gastric acid secretion, the first genetic evidence that a member of the KCNE gene family is required for normal gastrointestinal function.
Keywords:Achlorhydria, Cultured Cells, Gastric Acid, Gastric Mucosa, Gastric Parietal Cells, Gastrins, Gene Targeting, Hyperplasia, KCNQ1 Potassium Channel, Protein Subunits, Stomach, Up-Regulation, Voltage-Gated Potassium Channels, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:281
Number:33
Page Range:23740-23747
Date:18 August 2006
Official Publication:https://doi.org/10.1074/jbc.M604155200
PubMed:View item in PubMed

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