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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | De Zeeuw, Chris I. Spitzmaul, Guillermo Tolosa, Leonardo Frens, Maarten A. Jentsch, Thomas J. Winkelman, Beerend H. J. Heidenreich, Matthias Chabbert, Christian |
| Description | Author Affiliation: Spitzmaul G ( Leibniz-Institut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin (MDC), 13125 Berlin, Germany.) |
| 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 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 Kcnq4(dn/dn) and Kcnq5(dn/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(-/-), Kcnq5(dn/dn) nor Kcnq4(-/-)/Kcnq5(dn/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(-/-)/Kcnq5(dn/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 present predominantly 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. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 13 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-03-29 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Deafness Metabolism KCNQ Potassium Channels Animals Ear, Inner Electrophysiology Genotype Hair Cells, Auditory, Inner Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Microscopy, Fluorescence Models, Biological Neurons Potassium Channels Synaptic Transmission Vestibule, Labyrinth Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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