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Vestibular role of KCNQ4 and KCNQ5 K(+) channels revealed by mouse models

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Item Type:Article
Title:Vestibular role of KCNQ4 and KCNQ5 K(+) channels revealed by mouse models
Creators Name:Spitzmaul, G. and Tolosa, L. and Winkelman, B.H.J. and Heidenreich, M. and Frens, M.A. and Chabbert, C. and de Zeeuw, C.I. and Jentsch, T.J.
Abstract:The function of sensory hair cells of the cochlea and vestibular organs depends on an influx of K+ through apical mechanosensitive ion channels and its subsequent removal over their basolateral membrane. The KCNQ4 (Kv7.4) K+ channel, which is mutated in DFNA2 human hearing loss, is expressed in the basal membrane of cochlear outer hair cells (OHCs) where it may mediate K+ efflux. Like the related K+ channel KCNQ5 (Kv7.5), KCNQ4 is also found at calyx terminals ensheathing type I vestibular hair cells where it may be localized pre- or postsynaptically. Making use of Kcnq4-/- mice lacking KCNQ4, as well as Kcnq4dn/dn and Kcnq5dn/dn mice expressing dominant negative channel mutants, we now show unambiguously that in adult mice both channels reside in postsynaptic calyx-forming neurons, but cannot be detected in the innervated hair cells. Accordingly whole-cell currents of vestibular hair cells did not differ between genotypes. Neither Kcnq4-/-, Kcnq5dn/dn nor Kcnq4-/-/Kcnq5dn/dn double mutant mice displayed circling behavior found with severe vestibular impairment. However, a milder form of vestibular dysfunction was apparent from altered vestibulo-ocular reflexes in Kcnq4-/-/Kcnq5dn/dn and Kcnq4-/- mice. The larger impact of KCNQ4 may result from its preferential expression in central zones of maculae and cristae, which are innervated by phasic neurons that are more sensitive than the tonic neurons predominantly present in the surrounding peripheral zones where KCNQ5 is found. The impact of postsynaptic KCNQ4 on vestibular function may be related to K+ removal and modulation of synaptic transmission.
Keywords:Electrophysiology, Hair Cell, Neurobiology, Potassium Channels, Synapses, M-Current, Calyx Terminal, Gene Disruption, Knock-Out Mouse, Utricle, Animals, Mice
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:9334-9344
Date:29 March 2013
Official Publication:https://doi.org/10.1074/jbc.M112.433383
PubMed:View item in PubMed

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