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Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus

  1. Shuang Li
  2. Bopanna I Kalappa
  3. Thanos Tzounopoulos Is a corresponding author
  1. University of Pittsburgh School of Medicine, United States
Research Article
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Cite as: eLife 2015;4:e07242 doi: 10.7554/eLife.07242

Abstract

Vulnerability to noise-induced tinnitus is associated with increased spontaneous firing rate in dorsal cochlear nucleus principal neurons, fusiform cells. This hyperactivity is caused, at least in part, by decreased Kv7.2/3 (KCNQ2/3) potassium currents. However, the biophysical mechanisms underlying resilience to tinnitus, which is observed in noise-exposed mice that do not develop tinnitus (non-tinnitus mice), remain unknown. Our results show that noise exposure induces, on average, a reduction in KCNQ2/3 channel activity in DCN fusiform cells in noise-exposed mice by 4 days after exposure. Tinnitus is developed in mice that do not compensate for this reduction within the next 3 days. Resilience to tinnitus is developed in mice that show a re-emergence of KCNQ2/3 channel activity and a reduction in HCN channel activity. Our results highlight KCNQ2/3 and HCN channels as potential targets for designing novel therapeutics that may promote resilience to tinnitus.

Article and author information

Author details

  1. Shuang Li

    1. Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Bopanna I Kalappa

    1. Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thanos Tzounopoulos

    1. Departments of Otolaryngology and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, United States
    For correspondence
    1. thanos@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animals were handled, anesthetized and sacrificed according to methods approved by the University of Pittsburgh Institutional Animal Care and Use Committee. The approved IACUC protocol numbers that were employed for this study were: #14125118 and #14094011.

Reviewing Editor

  1. Gary L Westbrook, Reviewing Editor, Vollum Institute, United States

Publication history

  1. Received: February 27, 2015
  2. Accepted: August 22, 2015
  3. Accepted Manuscript published: August 27, 2015 (version 1)
  4. Version of Record published: October 5, 2015 (version 2)

Copyright

© 2015, Li et al

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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