Open AccessDeletion of the Ca2+-activated potassium (BK) α-subunit but not the BKβ1-subunit leads to progressive hearing loss
Author(s) -
Lukas Rüttiger,
Matthias Sausbier,
Ulrike Zimmermann,
Harald Winter,
Claudia Braig,
Jutta Engel,
Martina Knirsch,
Claudia Arntz,
Patricia Langer,
Bernhard Hirt,
Marcus Müller,
Iris Köpschall,
Markus Pfister,
Stefan Münkner,
Karin Rohbock,
Imke L. Pfaff,
Alfons Rüsch,
Peter Ruth,
Marlies Knipper
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0402660101
Subject(s) - bk channel , potassium channel , hair cell , protein subunit , hearing loss , cochlea , chemistry , organ of corti , inner ear , mutant , microbiology and biotechnology , endocrinology , biology , medicine , neuroscience , biochemistry , gene , audiology
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 beta1-subunit. Analyzing the hearing function and cochlear phenotype of BK channel alpha-(BKalpha-/-) and beta1-subunit (BKbeta1-/-) knockout mice, we demonstrate normal hearing function and cochlear structure of BKbeta1-/- 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 approximately 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.