Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells

Chengtao Yang, Vivian Gonzalez-Perez, Taro Mukaibo, James E. Melvin, Xiao Ming Xia, Christopher J. Lingle

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca2+, suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KOmicewith a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva. LRRC26-containing BK channels are competent to contribute to resting K+ efflux at normal cell membrane potentials with resting cytosolic Ca2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.

Original languageEnglish
Pages (from-to)E3739-E3747
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number18
DOIs
StatePublished - May 2 2017

Keywords

  • BK channels
  • LRRC26
  • SLO1
  • Salivary glands
  • Secretory epithelium

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