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Protection from noise-induced hearing loss by Kv2.2 potassium currents in the central medial olivocochlear system

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journal contribution
posted on 24.09.2014, 13:28 by Huaxia Tong, Cornelia Kopp-Scheinpflug, Nadia Pilati, Susan W. Robinson, James L. Sinclair, Joern R. Steinert, Margaret Barnes-Davies, Rebecca Allfree, Blair D. Grubb, Samuel M. Young, Ian D. Forsythe
The central auditory brainstem provides an efferent projection known as the medial olivocochlear (MOC) system, which regulates the cochlear amplifier and mediates protection on exposure to loud sound. It arises from neurons of the ventral nucleus of the trapezoid body (VNTB), so control of neuronal excitability in this pathway has profound effects on hearing. The VNTB and the medial nucleus of the trapezoid body are the only sites of expression for the Kv2.2 voltage-gated potassium channel in the auditory brainstem, consistent with a specialized function of these channels. In the absence of unambiguous antagonists, we used recombinant and transgenic methods to examine how Kv2.2 contributes to MOC efferent function. Viral gene transfer of dominant-negative Kv2.2 in wild-type mice suppressed outward K(+) currents, increasing action potential (AP) half-width and reducing repetitive firing. Similarly, VNTB neurons from Kv2.2 knock-out mice (Kv2.2KO) also showed increased AP duration. Control experiments established that Kv2.2 was not expressed in the cochlea, so any changes in auditory function in the Kv2.2KO mouse must be of central origin. Further, in vivo recordings of auditory brainstem responses revealed that these Kv2.2KO mice were more susceptible to noise-induced hearing loss. We conclude that Kv2.2 regulates neuronal excitability in these brainstem nuclei by maintaining short APs and enhancing high-frequency firing. This safeguards efferent MOC firing during high-intensity sounds and is crucial in the mediation of protection after auditory overexposure.

History

Citation

Journal of Neuroscience, 2013, 33 (21), pp. 9113-9121

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and Pharmacology

Version

VoR (Version of Record)

Published in

Journal of Neuroscience

Publisher

Society for Neuroscience

issn

0270-6474

eissn

1529-2401

Copyright date

2013

Available date

24/09/2014

Publisher version

http://www.jneurosci.org/content/33/21/9113

Language

en