Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness

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Item Type:	Article
Title:	Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness
Creators Name:	Kharkovets, T., Dedek, K., Maier, H., Schweizer, M., Khimich, D., Nouvian, R., Vardanyan, V., Leuwer, R., Moser, T. and Jentsch, T.J.
Abstract:	KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2 dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is strongly expressed in vestibular hair cells, vestibular function appeared normal. Auditory function was only slightly impaired initially. It then declined over several weeks in Kcnq4-/- mice and over several months in mice carrying the dominant negative allele. This progressive hearing loss was paralleled by a selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the I(K,n) current of OHCs. The ensuing depolarization of OHCs impaired sound amplification. Inner hair cells and their afferent synapses remained mostly intact. These cells were only slightly depolarized and showed near-normal presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly caused by a slow degeneration of OHCs resulting from chronic depolarization.
Keywords:	Capacitance, Channelopathy, KCNQ5, Ribbon, Animals, Mice
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	Nature Publishing Group
Volume:	25
Number:	3
Page Range:	642-652
Date:	8 February 2006
Official Publication:	https://doi.org/10.1038/sj.emboj.7600951
PubMed:	View item in PubMed

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