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Review
. 2019 Mar 16:695:40-45.
doi: 10.1016/j.neulet.2017.09.020. Epub 2017 Sep 14.

Connexin hemichannels and cochlear function

Vytas K Verselis  1
Affiliations
Review

Connexin hemichannels and cochlear function

Vytas K Verselis. Neurosci Lett. .

Abstract

Connexins play vital roles in hearing, including promoting cochlear development and sustaining auditory function in the mature cochlea. Mutations in connexins expressed in the cochlear epithelium, Cx26 and Cx30, cause sensorineural deafness and in the case of Cx26, is one of the most common causes of non-syndromic, hereditary deafness. Connexins function as gap junction channels and as hemichannels, which mediate intercellular and transmembrane signaling, respectively. Both channel configurations can play important, but very different roles in the cochlea. The potential roles connexin hemichannels can play are discussed both in normal cochlear function and in promoting pathogenesis that can lead to hearing loss.

Keywords: Atp; Connexins; Deafness; Hemichannels; Pannexins.

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Figures

Figure 1
Figure 1
Illustrations of the cochlear ducts and epithelial cell networks depicting proposed functions of hemichannels. A) Expanded view of the sensory epithelium. Hemichannels in supporting cells can release ATP to modulate hair cell electromotility, activate K+ channels, reduce K+ accumulation and initiate Ca2+ waves. Ca2+ signaling could also involve hemichannel-mediated IP3 release and direct Ca2+ entry. B) Expanded view of the stria vascularis in the lateral wall. Hemichannels can depolarize the multi-cell layer consisting of fibrocytes (FC), basal cells (BC) and intermediate cells (IC). These cells are separated from the marginal cells (MC) by an electrically-insulated intrastrial space. Shown are the key pumps, transporters, ion channels, the potentials and K+ concentrations of the cellular and extracellular compartments that move K+ from perilymph to endolymph; Na/K ATPases, N/K/Cl (NKCC) co-transporters, ClC chloride channels, Kir4.1 and KCNQ1/KCNE K+ channels, Cx hemichannels (HC) and gap junctions (GJs), Panx1 channels (Px1) and tight junctions (TJs).
Figure 2
Figure 2
Cx26 syndromic deafness mutants. A) Topology of a Cx subunit consisting of four transmembrane domains (TM1-TM4), two extracellular loops (E1, E2), a cytoplasmic loop (CL) and amino (NT) and carboxy (CT) termini. Denoted are the 18 residues with mutations causing syndromic deafness; those associated with KID syndrome are indicated in red. B) Representation of six subunits (in green) around a central aqueous pore from the atomic structure of Cx26 (Protein Data Bank accession no. 2ZW3) published by [44]. The structure is displayed using the PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC. KID mutant residues are shown as spherical renditions. Shown are end views from the extracellular and cytoplasmic sides a side view. The KID mutations often occur at residues facing the pore and at subunit interfaces.
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