The role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss

J. Chen, H. B. Zhao

Research output: Contribution to journalReview articlepeer-review

67 Scopus citations

Abstract

The KCNJ10 gene which encodes an inwardly rectifying K+ channel Kir4.1 subunit plays an essential role in the inner ear and hearing. Mutations or deficiency of KCNJ10 can cause hearing loss with EAST or SeSAME syndromes. This review mainly focuses on the expression and function of Kir4.1 potassium channels in the inner ear and hearing. We first introduce general information about inwardly rectifying potassium (Kir) channels. Then, we review the expression and function of Kir4.1 channels in the inner ear, especially in endocochlear potential (EP) generation. Finally, we review KCNJ10 mutation-induced hearing loss and functional impairments. Kir4.1 is strongly expressed on the apical membrane of intermediate cells in the stria vascularis and in the satellite cells of cochlear ganglia. Functionally, Kir4.1 has critical roles in cochlear development and hearing through two distinct aspects of extracellular K+ homeostasis: First, it participates in the generation and maintenance of EP and high K+ concentration in the endolymph inside the scala media. Second, Kir4.1 is the major K+ channel in satellite glial cells surrounding spiral ganglion neurons to sink K+ ions expelled by the ganglion neurons during excitation. Kir4.1 deficiency leads to hearing loss with the absence of EP and spiral ganglion neuron degeneration. Deafness mutants show loss-of-function and reduced channel membrane-targeting and currents, which can be rescued upon by co-expression with wild-type Kir4.1. This review provides insights for further understanding Kir potassium channel function in the inner ear and the pathogenesis of deafness due to KCNJ10 deficiency, and also provides insights for developing therapeutic strategies targeting this deafness.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalNeuroscience
Volume265
DOIs
StatePublished - Apr 18 2014

Bibliographical note

Funding Information:
Dr Jing Chen was supported by China Scholarship Council, Scholarship of Chinese Young Science Foundation of CTGU ( KJ2011A007 ), and Yichang Science & Technology Bureau ( A12301-50 ). This work was supported by a grant (R01) from the National Institute on Deafness and Other Communication Disorders DC 05989.

Keywords

  • Deafness
  • EAST
  • Endocochlear potential
  • KCNJ10
  • SeSAME
  • Spiral ganglion

ASJC Scopus subject areas

  • General Neuroscience

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