Bestrophin-1 enables Ca2+-activated Cl- conductance in Epithelia

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 calciumactivated 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. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.