Bestrophin-1 enables Ca2+-activated Cl- conductance in epithelia.
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.
Barro Soria
René
R
Institut für Physiologie, Universität Regensburg, Universitätsstrabetae 31, D-93053 Regensburg, Germany.
Spitzner
Melanie
M
Schreiber
Rainer
R
Kunzelmann
Karl
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000075002:Bestrophins; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels; D051379:Mice; D009928:Organ Specificity / Q000502:physiology
C113133:BEST1 protein, human; C491856:Best1 protein, mouse; D000075002:Bestrophins; D018118:Chloride Channels; D002712:Chlorides; D005136:Eye Proteins; D007473:Ion Channels; D000255:Adenosine Triphosphate; D002118:Calcium