| First Author | Barro-Soria R | Year | 2008 |
| Journal | Biochim Biophys Acta | Volume | 1783 |
| Issue | 10 | Pages | 1993-2000 |
| PubMed ID | 18652850 | Mgi Jnum | J:140865 |
| Mgi Id | MGI:3814760 | Doi | 10.1016/j.bbamcr.2008.06.016 |
| Citation | Barro-Soria R, et al. (2008) Bestrophin 1 and 2 are components of the Ca(2+) activated Cl(-) conductance in mouse airways. Biochim Biophys Acta 1783(10):1993-2000 |
| abstractText | 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. |
