Department of Anesthesiology

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

TitleGenetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo.
Publication TypeJournal Article
Year of Publication2011
AuthorsRoepke TK, King EC, Purtell K, Kanda VA, Lerner DJ, Abbott GW
JournalFASEB J
Volume25
Issue2
Pagination727-36
Date Published2011 Feb
ISSN1530-6860
KeywordsAnimals, Female, Gene Deletion, Gene Expression Regulation, Hyperplasia, KCNQ1 Potassium Channel, Male, Mice, Parietal Cells, Gastric, Protein Subunits, Protein Transport, Stomach, Stomach Diseases
Abstract

Targeted deletion of the Kcne2 potassium channel β subunit gene ablates gastric acid secretion and predisposes to gastric neoplasia in mice. Here, we discovered that Kcne2 deletion basolaterally reroutes the Kcnq1 α 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 α subunit polarized trafficking and the existence and consequences of potassium channel β subunit remodeling.

DOI10.1096/fj.10-173682
Alternate JournalFASEB J.
PubMed ID21084694
PubMed Central IDPMC3023397
Grant ListR01 HL079275 / HL / NHLBI NIH HHS / United States
R01 HL079275 / HL / NHLBI NIH HHS / United States
T32GM073546 / GM / NIGMS NIH HHS / United States