Endocochlear potential depends on Cl- channels: mechanism underlying deafness in Bartter syndrome IV.
Standard
Endocochlear potential depends on Cl- channels: mechanism underlying deafness in Bartter syndrome IV. / Rickheit, Gesa; Maier, Hannes; Strenzke, Nicola; Andreescu, Corina E; Zeeuw, De; Münscher, Adrian; Muenscher, Adrian; Zdebik, Anselm A; Jentsch, Thomas J.
in: EMBO J, Jahrgang 27, Nr. 21, 21, 05.11.2008, S. 2907-2917.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Endocochlear potential depends on Cl- channels: mechanism underlying deafness in Bartter syndrome IV.
AU - Rickheit, Gesa
AU - Maier, Hannes
AU - Strenzke, Nicola
AU - Andreescu, Corina E
AU - Zeeuw, De
AU - Münscher, Adrian
AU - Muenscher, Adrian
AU - Zdebik, Anselm A
AU - Jentsch, Thomas J
PY - 2008/11/5
Y1 - 2008/11/5
N2 - Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a beta-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K(+)-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd(-/-) mice thus demonstrate a novel function of Cl(-) channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV.
AB - Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a beta-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K(+)-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd(-/-) mice thus demonstrate a novel function of Cl(-) channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV.
KW - Animals
KW - Bartter Syndrome
KW - Chloride Channels
KW - Cochlea
KW - DNA-Binding Proteins
KW - Deafness
KW - Endolymph
KW - Evoked Potentials
KW - Gene Deletion
KW - Hair Cells, Auditory
KW - High Mobility Group Proteins
KW - Humans
KW - Integrases
KW - Membrane Proteins
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Models, Biological
KW - SOXE Transcription Factors
KW - Stria Vascularis
KW - Transcription Factors
KW - Vestibule, Labyrinth
U2 - 10.1038/emboj.2008.203
DO - 10.1038/emboj.2008.203
M3 - SCORING: Journal article
C2 - 18833191
VL - 27
SP - 2907
EP - 2917
JO - EMBO J
JF - EMBO J
SN - 0261-4189
IS - 21
M1 - 21
ER -