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@ARTICLE{Tan:829983,
author = {Tan, Hua and Bungert, Stefanie and Fahlke, Christoph and
Stölting, Gabriel},
title = {{R}educed {M}embrane {I}nsertion of {CLC}-{K} by {V}33{L}
{B}arttin {R}esults in {L}oss of {H}earing, but {L}eaves
{K}idney {F}unction {I}ntact},
journal = {Frontiers in physiology},
volume = {8},
issn = {1664-042X},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {FZJ-2017-03585},
pages = {269},
year = {2017},
abstract = {In the mammalian ear, transduction of sound stimuli is
initiated by K+ entry through mechano-sensitive channels
into inner hair cells. K+ entry is driven by a positive
endocochlear potential that is maintained by the marginal
cell layer of the stria vascularis. This process requires
basolateral K+ import by NKCC1 Na+−2Cl−−K+
co-transporters as well as Cl− efflux through
ClC-Ka/barttin or ClC-Kb/barttin channels. Multiple
mutations in the gene encoding the obligatory CLC-K subunit
barttin, BSND, have been identified in patients with Bartter
syndrome type IV. These mutations reduce the endocochlear
potential and cause deafness. As CLC-K/barttin channels are
also expressed in the kidney, patients with Bartter syndrome
IV typically also suffer from salt-wasting hyperuria and
electrolyte imbalances. However, there was a single report
on a BSND mutation that resulted only in deafness, but not
kidney disease. We herein studied the functional
consequences of another recently discovered BSND mutation
that predicts exchange of valine at position 33 by leucine.
We combined whole-cell patch clamp, confocal microscopy and
protein biochemistry to analyze how V33L affects distinct
functions of barttin. We found that V33L reduced membrane
insertion of CLC-K/barttin complexes without altering
unitary CLC-K channel function. Our findings support the
hypothesis of a common pathophysiology for the selective
loss of hearing due to an attenuation of the total chloride
conductance in the stria vascularis while providing enough
residual function to maintain normal kidney function.},
cin = {ICS-4},
ddc = {610},
cid = {I:(DE-Juel1)ICS-4-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000403229100001},
pubmed = {pmid:28555110},
doi = {10.3389/fphys.2017.00269},
url = {https://juser.fz-juelich.de/record/829983},
}