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Degeneration of sensory outer hair cells following pharmacological blockade of cochlear KCNQ channels in the adult guinea pig.

Abstract : In the inner ear, hair cell function is inextricably linked with intracellular potassium homeostasis. KCNQ potassium channels may play an important role by preventing accumulation of potassium in the hair cells. Linopirdine, a tool useful in targeting native or heterologous KCNQ channels, was used to study the role of KCNQ channels in the guinea pig cochlea. When perfused into intact cochlea, linopirdine transiently increases the summating potential and endocochlear potential, suggesting that it alters K+ homeostasis. The concomitant decrease in cochlear microphonic potential and distortion product otoacoustic emission amplitude indicates that linopirdine has an effect on the outer hair cells (OHCs). To determine the pathological consequences of the inhibition of cochlear KCNQ channels, we developed a hearing loss model based on a chronic intracochlear perfusion of linopirdine via an osmotic minipump. Ultrastructural analysis reveals that KCNQ channel blockade leads to OHC degeneration. Together, these results demonstrate that KCNQ channels, most probably of the KCNQ4 subtype, are crucial for the function and survival of sensory OHCs. Clinically, KCNQ4 channel dysfunction is known to be associated with the DFNA2 form of nonsyndromic dominant deafness. Our study shows that OHC KCNQ4 dysfunction could contribute to the early (40dB) hearing loss, but not for the profound deafness observed at the final stage of this disease.
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https://www.hal.inserm.fr/inserm-00267741
Contributor : Jérôme Ruel <>
Submitted on : Friday, March 28, 2008 - 12:01:19 PM
Last modification on : Saturday, September 7, 2019 - 1:26:48 AM

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  • HAL Id : inserm-00267741, version 1
  • PUBMED : 12823462

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Régis Nouvian, Jérôme Ruel, Jing Wang, Matthieu Guitton, Rémy Pujol, et al.. Degeneration of sensory outer hair cells following pharmacological blockade of cochlear KCNQ channels in the adult guinea pig.. European Journal of Neuroscience, Wiley, 2003, 17 (12), pp.2553-62. ⟨inserm-00267741⟩

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