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PMID: 17003041 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bestrophin-1 enables Ca2+-activated Cl- conductance in epithelia.

The Journal of biological chemistry ·Vol. 284 ·No. 43 ·2009-10-23 ·Pages 29405-12

Barro Soria R, Spitzner M, Schreiber R, Kunzelmann K

Abstract

Epithelial cells express calcium-activated Cl(-) channels of unknown molecular identity. These Cl(-) channels play a central role in diseases such as secretory diarrhea, polycystic kidney disease, and cystic fibrosis. The family of bestrophins has been suggested to form calcium-activated Cl(-) channels. Here, we demonstrate molecular and functional expression of bestrophin-1 (BEST1) in mouse and human airways, colon, and kidney. Endogenous calcium-activated whole cell Cl(-) currents coincide with endogenous expression of the Vmd2 gene product BEST1 in murine and human epithelial cells, whereas calcium-activated Cl(-) currents are absent in epithelial tissues lacking BEST1 expression. Blocking expression of BEST1 with short interfering RNA or applying an anti-BEST1 antibody to a patch pipette suppressed ATP-induced whole cell Cl(-) currents. Calcium-dependent Cl(-) currents were activated by ATP in HEK293 cells expressing BEST1. Thus, BEST1 may form the Ca2+-activated Cl(-) current, or it may be a component of a Cl(-) channel complex in epithelial tissues.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Bestrophins Calcium/metabolism Cell Line Chloride Channels/genetics,metabolism Chlorides/metabolism Epithelial Cells/metabolism Epithelium/metabolism Eye Proteins/genetics,metabolism Humans Ion Channels Mice Organ Specificity/physiology
Chemicals
BEST1 protein, human Best1 protein, mouse Bestrophins Chloride Channels Chlorides Eye Proteins Ion Channels Adenosine Triphosphate Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Barro Soria René
Institut für Physiologie, Universität Regensburg, Universitätsstrabetae 31, D-93053 Regensburg, Germany.
Spitzner Melanie
Schreiber Rainer
Kunzelmann Karl
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M605716200
Published
2009-10-23
Epub
2006-00-26
Pages
29405-12
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2785573
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M605716200 PMC Full Text View journal details
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