Elsevier

Brain Research Reviews

Volume 32, Issue 1, 24 March 2000, Pages 163-166
Brain Research Reviews

Short review
Gap junction systems in the mammalian cochlea

https://doi.org/10.1016/S0165-0173(99)00076-4Get rights and content

Abstract

Recent findings that a high proportion of non-syndromic hereditary sensorineural hearing loss is due to mutations in the gene for connexin 26 indicate the crucial role that the gene product plays for normal functioning of the cochlea. Excluding sensory cells, most cells in the cochlea are connected via gap junctions and these gap junctions appear to play critical roles in cochlear ion homeostasis. Connexin 26 occurs in gap junctions connecting all cell classes in the cochlea. There are two independent systems of cells, which are defined by interconnecting gap junctions. The first system, the epithelial cell gap junction system, is mainly composed of all organ of Corti supporting cells, and also includes interdental cells in the spiral limbus and root cells within the spiral ligament. The second system, the connective tissue cell gap junction system, consists of strial intermediate cells, strial basal cells, fibrocytes in the spiral ligament, mesenchymal cells lining the bony otic capsule facing the scala vestibuli, mesenchymal dark cells in the supralimbal zone, and fibrocytes in the spiral limbus. One function of these gap junctional systems is the recirculation of K+ ions from hair cells to the strial marginal cells. Interruption of this recirculation, which may be caused by the mutation in connexin 26 gene, would deprive the stria vascularis of K+ and result in hearing loss.

Introduction

The mammalian cochlea has a unique arrangement of extracellular fluid-filled compartments that support the mechanosensory transduction process. The apical surfaces of the cochlear hair cells are bathed in endolymph, which has an ionic composition of high K+ and low Na+. The cochlear endolymph is also characterized by the presence of the endolymphatic potential, of approximately 100 mV. When hair cells are activated by sound, their receptor potentials are generated by the flow of K+ from endolymph into hair cells. The K+ is then released to extracellular space and from here is recirculated back to endolymph. The gap junction systems are most likely the pathway for the recirculation of cochlear K+ [5].

Recent molecular biological studies 2, 3have shown that mutation in connexin 26 gene can cause non-syndromic sensorineural hearing loss, and also strongly support our hypothesis regarding the role of gap junctions in mechanisms of the inner ear.

Section snippets

Distribution of connexin 26 in the cochlea

Immunohistochemical localization of connexin 26 at the light microscopic and ultrastructural levels in the rat inner ear was studied in detail 4, 5. We have since confirmed the immunostaining results in mouse, gerbil, guinea pig, chinchilla, cat, and human, and believe that the initial results are representative of a general organization of mammalian ears.

The mammalian cochlea is comprised of a variety of cell components, including various epithelial and connective tissue cells. Connexin

Epithelial cell gap junction system

All cochlear supporting cells are directly connected to adjacent supporting cells with gap junctions. No definitive gap junctions or connexin 26-like immunoreactivity is detected between the cochlear sensory cells and the supporting cells. In the lateral end of the cochlear supporting cells, gap junctions are observed between Claudius cells and root cells. The root cells extend their cytoplasmic processes, which are also connected by gap junctions, deep into the lower part of the spiral

Connective tissue cell gap junction system

Connective tissue cells in the spiral limbus are coupled to each other and make a large gap junctional network. Mesenchymal cells, which line the scala vestibuli, possess scattered gap junctions, and also have gap junctional connections with fibrocytes in the spiral limbus and with the fibrocytes in the suprastrial zone of the spiral ligament. Fibrocytes in the spiral ligament are classified into the four different type of cells 5, 7. They are composed of types I, II, III, and IV fibrocytes.

Functional significance of gap junction systems in the ion transport mechanism

It is well-established that the high level of K+ in the scala media that is necessary for normal functioning of hair cells is maintained by the activity of marginal cells of the stria vascularis. The marginal cells accumulate K+ using a combination of Na,K-ATPase and Na–K–Cl cotransporter found in their basolateral plasma membranes [8].

It has been established that the K+ accumulated by the stria vascularis come from the perilymphatic space, but K+ in perilymph are prevented direct to access to

Acknowledgements

This work was supported by Research Grant No. 10671581 from the Ministry of Education, Science and Culture, Japan and NIDCD/NIH Grant R01 DC00073.

References (8)

There are more references available in the full text version of this article.

Cited by (222)

  • 2.24 - Physiology and Pharmacology of the Cochlea

    2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
  • Expression pattern of Connexin 26 and Connexin 30 in mature cochlea of the monkey

    2019, Biochemical and Biophysical Research Communications
  • Association of glutamate metabotropic receptor polymorphisms and sensorineural hearing loss in adults of different age groups

    2019, Brazilian Journal of Otorhinolaryngology
    Citation Excerpt :

    In the results of this study, no association between the GRM7 rs11928865 locus and SHL in group A, and no positive results for the rs11920109 locus were observed, reflecting the complexity of SHL due to the involvement of multiple genes, environmental factors, ototoxic drugs, systemic diseases, and lifestyle habits. A number of pathogenic candidate genes including the genes encoding connexin 26 (GJB2),4,11,12 grainyhead-like 2 (GRHL2),5 cadherin (CDH23),6 potassium voltage-gated channel member 4 (KCNQ4),13 N-acetyltransferase (NAT),14–16 apolipoprotein E (APOE),17 and uncoupling protein 2 (UCP2)18,19 have been related to the genetic susceptibility of SHL, and it is likely that these genes interact in the pathogenesis of SHL. In conclusion, rs11928865 was associated with susceptibility to SHL for individuals in group B, but not for individuals in group A.

View all citing articles on Scopus
View full text