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Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo

Item Type:Article
Title:Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo
Creators Name:Roepke, T.K. and King, E.C. and Purtell, K. and Kanda, V.A. and Lerner, D.J. and Abbott, G.W.
Abstract:Targeted deletion of the Kcne2 potassium channel {beta} subunit gene ablates gastric acid secretion and predisposes to gastric neoplasia in mice. Here, we discovered that Kcne2 deletion basolaterally reroutes the Kcnq1 {alpha} subunit in vivo in parietal cells (PCs), in which the normally apical location of the Kcnq1-Kcne2 channel facilitates its essential role in gastric acid secretion. Quantitative RT-PCR and Western blotting revealed that Kcne2 deletion remodeled fundic Kcne3 (2.9±0.8-fold mRNA increase, n=10; 5.3±0.4-fold protein increase, n=7) but not Kcne1, 4, or 5, and resulted in basolateral Kcnq1-Kcne3 complex formation in Kcne2(-/-) PCs. Concomitant targeted deletion of Kcne3 (creating Kcne2(-/-)Kcne3(-/-) mice) restored PC apical Kcnq1 localization without Kcne1, 4, or 5 remodeling (assessed by quantitative RT-PCR; n=5-10), indicating Kcne3 actively, basolaterally rerouted Kcnq1 in Kcne2(-/-) PCs. Despite this, Kcne3 deletion exacerbated gastric hyperplasia in Kcne2(-/-) mice, and both hypochlorhydria and hyperplasia in Kcne2(+/-) mice, suggesting that Kcne3 up-regulation was beneficial in Kcne2-depleted PCs. The findings reveal, in vivo, Kcne-dependent {alpha} subunit polarized trafficking and the existence and consequences of potassium channel {beta} subunit remodeling.
Keywords:Gastric Acid, MiRP1, Potassium Channel, Animals, Mice
Source:FASEB Journal
ISSN:0892-6638
Publisher:Federation of American Societies for Experimental Biology (U.S.A.)
Volume:25
Number:2
Page Range:727-736
Date:February 2011
Official Publication:https://doi.org/10.1096/fj.10-173682
PubMed:View item in PubMed

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