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
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).