期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：35
页码：12922-12927
DOI：10.1073/pnas.0402660101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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}-(BK{alpha}-/-) and {beta}1-subunit (BK{beta}1-/-) knockout mice, we demonstrate normal hearing function and cochlear structure of BK{beta}1-/- mice. During the first 4 postnatal weeks also, BK{alpha}-/- mice most surprisingly did not show any obvious hearing deficits. High-frequency hearing loss developed in BK{alpha}-/- mice only from {approx}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.
