TY  - JOUR
A1  - Rüttiger, Lukas
A1  - Sausbier, Matthias
A1  - Zimmermann, Ulrike
A1  - Winter, Harald
A1  - Braig, Claudia
A1  - Engel, Jutta
A1  - Knirsch, Martina
A1  - Arntz, Claudia
A1  - Langer, Patricia
A1  - Hirt, Bernhard
A1  - Müller, Marcus
A1  - Köpschall, Iris
A1  - Pfister, Markus
A1  - Münkner, Stefan
A1  - Rohbock, Karin
A1  - Pfaff, Imke
A1  - Rüsch, Alfons
A1  - Ruth, Peter
A1  - Knipper, Marlies
T1  - Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BK-beta-1-subunit leads to progressive hearing loss
T2  - Proceedings of the National Academy of Sciences of the United States of America
N2  - The large conductance voltage- and Ca2+-activated potassium (BK) channel has been suggested to play an important role in the signal transduction process of cochlear inner hair cells. BK channels have been shown to be composed of the pore-forming alpha-subunit coexpressed with the auxiliary beta-1-subunit. Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha–/–) and beta-1-subunit (BKbeta-1–/–) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta-1–/– mice. During the first 4 postnatal weeks also, BKalpha–/– mice most surprisingly did not show any obvious hearing deficits. High-frequency hearing loss developed in BKalpha–/– mice only from ca. 8 weeks postnatally onward and was accompanied by a lack of distortion product otoacoustic emissions, suggesting outer hair cell (OHC) dysfunction. Hearing loss was linked to a loss of the KCNQ4 potassium channel in membranes of OHCs in the basal and midbasal cochlear turn, preceding hair cell degeneration and leading to a similar phenotype as elicited by pharmacologic blockade of KCNQ4 channels. Although the actual link between BK gene deletion, loss of KCNQ4 in OHCs, and OHC degeneration requires further investigation, data already suggest human BK-coding slo1 gene mutation as a susceptibility factor for progressive deafness, similar to KCNQ4 potassium channel mutations. © 2004, The National Academy of Sciences. Freely available online through the PNAS open access option.
KW  - cochlea
KW  - KCNQ4
Y1  - 2005
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/4319
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-11712
SN  - 1091-6490
SN  - 0027-8424
N1  - Copyright © 2004, The National Academy of Sciences
VL  - 101
IS  - 35
SP  - 12922
EP  - 12927
PB  - National Acad. of Sciences
CY  - Washington, DC
ER  -