Journal of Neuroscience 2013 Tong.pdf (2.01 MB)
Protection from noise-induced hearing loss by Kv2.2 potassium currents in the central medial olivocochlear system
journal contribution
posted on 2014-09-24, 13:28 authored 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. ForsytheThe 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.
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Citation
Journal of Neuroscience, 2013, 33 (21), pp. 9113-9121Author affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and PharmacologyVersion
- VoR (Version of Record)
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Journal of NeurosciencePublisher
Society for Neuroscienceissn
0270-6474eissn
1529-2401Copyright date
2013Available date
2014-09-24Publisher DOI
Publisher version
http://www.jneurosci.org/content/33/21/9113Language
enAdministrator link
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Keywords
Action PotentialsAnimalsAnimals, NewbornAuditory PathwaysCell Line, TumorCochleaDisease Models, AnimalEvoked Potentials, Auditory, Brain StemFemaleGene Expression RegulationHearing LossMaleMiceMice, Inbred CBAMice, TransgenicMutationNeuroblastomaNoiseOlivary NucleusPatch-Clamp TechniquesShab Potassium ChannelsShaw Potassium ChannelsTransfection
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