Document Detail

Bestrophin 1 and 2 are components of the Ca(2+) activated Cl(-) conductance in mouse airways.
MedLine Citation:
PMID:  18652850     Owner:  NLM     Status:  MEDLINE    
Ca(2+) 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 Ca(2+) activated Cl(-) channels (CaCC) in the airways is still obscure. Bestrophin proteins were described to form CaCC and to regulate voltage gated Ca(2+) 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 muM). As two paralogs, best1 and best2, are present in mouse tracheal epithelium, we examined the contribution of each paralog to Ca(2+) 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 Ca(2+) was also reduced in whole cell recordings of vmd2(-/-) cells. These results clearly suggest a role of bestrophin 1 and 2 for Ca(2+) dependent Cl(-) secretion in mouse airways.
René Barro-Soria; Rainer Schreiber; Karl Kunzelmann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-03
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1783     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-09     Completed Date:  2008-11-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1993-2000     Citation Subset:  IM    
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany.
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MeSH Terms
Calcium / metabolism*
Cells, Cultured
Chloride Channels / deficiency,  genetics,  metabolism*
Chlorine / metabolism*
Eye Proteins / genetics,  metabolism*
Mice, Knockout
Patch-Clamp Techniques
Trachea / metabolism*
Reg. No./Substance:
0/Best-2 protein, mouse; 0/Chloride Channels; 0/Eye Proteins; 0/Vmd2 protein, mouse; 7440-70-2/Calcium; 7782-50-5/Chlorine

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