Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion

Citation
R. Estevez et al., Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion, NATURE, 414(6863), 2001, pp. 558-561
Citations number
29
Categorie Soggetti
Multidisciplinary,Multidisciplinary,Multidisciplinary
Journal title
NATURE
ISSN journal
00280836 → ACNP
Volume
414
Issue
6863
Year of publication
2001
Pages
558 - 561
Database
ISI
SICI code
0028-0836(20011129)414:6863<558:BIACCB>2.0.ZU;2-G
Abstract
Renal salt loss in Bartter's syndrome is caused by impaired transepithelial transport in the loop of Henle. Sodium chloride is taken up apically by th e combined activity of NKCC2 (Na+-K--2Cl(-) cotransporters) and ROMK potass ium channels. Chloride ions exit from the cell through basolateral ClC-Kb c hloride channels. Mutations in the three corresponding genes have been iden tired(1-3) that correspond to Bartter's syndrome types(1-3). The gene(4) en coding the integral membrane protein barttin is mutated in a form of Bartte r's syndrome that is associated with congenital deafness and renal failure. Here we show that barttin acts as an essential beta -subunit for ClC-Ka an d ClC-Kb chloride channels, with which it colocalizes in basolateral membra nes of renal tubules and of potassium-secreting epithelia of the inner ear. Disease-causing mutations in either ClC-Kb or barttin compromise currents through heteromeric channels. Currents can be stimulated further by mutatin g a proline-tyrosine (PY) motif on barttin. This work describes the first k nown beta -subunit for CLC chloride channels and reveals that heteromers fo rmed by ClC-K and barttin are crucial for renal salt reabsorption and potas sium recycling in the inner ear(5).