title: Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo.
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.
authors.affiliation: Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Torsten K
authors.initials: TK
authors.lastname: Roepke
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: King
authors.forename: Kerry
authors.initials: K
authors.lastname: Purtell
authors.forename: Vikram A
authors.initials: VA
authors.lastname: Kanda
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lerner
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Abbott
mesh_terms: D000818:Animals; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology*; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D010295:Parietal Cells, Gastric / Q000378:metabolism; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology*; D013270:Stomach / Q000473:pathology; D013272:Stomach Diseases / Q000235:genetics / Q000473:pathology
chemical_list: D051657:KCNQ1 Potassium Channel; D021122:Protein Subunits