Bestrophin 1 and 2 are components of the Ca2+ activated Cl- conductance in mouse airways

René Barro-Soria, Rainer Schreiber, Karl Kunzelmann

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Ca2+ activated Cl- transport is found in airways and other organs and is abnormal in cystic fibrosis, polycystic kidney disease and infectious diarrhea. The molecular identity of Ca2+ activated Cl- channels (CaCC) in the airways is still obscure. Bestrophin proteins were described to form CaCC and to regulate voltage gated Ca2+ channels. The present Ussing chamber recordings on tracheas of bestrophin 1 knockout (vmd2-/-) mice indicate a reduced Cl- secretion when activated by the purinergic agonist ATP (0.1-1 μM). As two paralogs, best1 and best2, are present in mouse tracheal epithelium, we examined the contribution of each paralog to Ca2+ activated Cl- secretion. In whole cell patch-clamp measurements on primary airway epithelial cells from vmd2-/- tracheas, ATP activated Cl- currents were reduced by 50%. Additional knockdown of mbest2 in vmd2-/- cells by short interfering RNA further suppressed ATP-induced Cl- currents down to 20% of that observed in cells from vmd2+/+ animals. Moreover, RNAi-suppression of both mbest1 and mbest2 reduced CaCC in vmd2+/+ cells. Direct activation of CaCC by increase of intracellular Ca2+ was also reduced in whole cell recordings of vmd2-/- cells. These results clearly suggest a role of bestrophin 1 and 2 for Ca2+ dependent Cl- secretion in mouse airways.

Original languageEnglish (US)
Pages (from-to)1993-2000
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number10
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Keywords

  • Airways
  • Bestrophin 1
  • Bestrophin 2
  • Ca activated Cl channel
  • Cl conductance
  • Epithelium
  • Vmd2

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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