Deletion of the Ca2+-activated potassium (BK) alpha-subunit but not the BK-beta-1-subunit leads to progressive hearing loss

  • 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.

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Author: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 Pfaff, Alfons Rüsch, Peter RuthGND, Marlies Knipper
Pubmed Id:
Parent Title (English):Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Acad. of Sciences
Place of publication:Washington, DC
Contributor(s):Ramon Latorre
Document Type:Article
Date of Publication (online):2005/06/27
Year of first Publication:2004
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2005/06/27
Tag:KCNQ4; cochlea
Page Number:6
First Page:12922
Last Page:12927
Copyright © 2004, The National Academy of Sciences
Source:Proc Natl Acad Sci U S A. 2004 August 31; 101(35): 12922-12927,
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoDeutsches Urheberrecht