Gap Junctions and Cochlear Homeostasis

Zhao, Hong-Bo; Kikuchi, Toshihiko; Ngezahayo, Anaclet; White, Thomas W.

doi:10.1007/s00232-005-0832-x

Cited by 147 publications

(135 citation statements)

References 98 publications

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“…12 Recent studies suggested that intercellular communication through GJ is crucial for auditory function. 13,14 In mice, Cx26 and Cx30, apparently the two most abundantly expressed Cxs, are known to co-assemble to form GJ in the cochlea. 15 Mutations of GJB2, which encodes the Cx26 protein, and GJB6, which encodes the Cx30 protein, are implicated in cases of inherited nonsyndromic hearing loss.…”

Section: Introductionmentioning

confidence: 99%

Mutation R184Q of connexin 26 in hearing loss patients has a dominant-negative effect on connexin 26 and connexin 30

Su¹,

et al. 2010

Eur J Hum Genet

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Hearing impairment is the most common sensory disorder worldwide. In a recent study, the authors have shown that a heterozygous missense mutation, p.R184Q, in the connexin 26 (Cx26) is causally related to hearing loss. However, the functional change in the Cx26R184Q mutant remains unknown. This study compared the intracellular distribution and assembly of mutant Cx26R184Q with that of the wild-type (WT) Cx26 and Cx30WT in tet-on HeLa cells and the effect that the mutant protein had on those cells. Fluorescent localization assay of WT Cx26 showed the typical punctuate pattern of gap junction channel between neighboring expression cells. Conversely, the p.R184Q missense mutation resulted in accumulation of the Cx26 mutant protein in the Golgi apparatus rather than in the cytoplasmic membrane. Cx26R184Q coexpressed with either Cx26WT or Cx30WT showed perinuclear localization by bidirectional tet-on expression system, suggesting the impairment of the ability of both WT proteins to intracellular trafficking and targeting to the plasma membrane. Therefore, we proposed that Cx26R184Q has a dominant-negative effect on the function of WT Cx26 and Cx30.

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Section: Introductionmentioning

confidence: 99%

Mutation R184Q of connexin 26 in hearing loss patients has a dominant-negative effect on connexin 26 and connexin 30

Su¹,

et al. 2010

Eur J Hum Genet

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“…Dysfunction of gap junctions can induce a high incidence of hearing loss [1]. For a long time, researchers have hypothesized that the inner ear gap junctions mediate K + transport back to the endolymph [2][3][4][5][7][8][9].…”

Section: Discussionmentioning

confidence: 99%

“…Supporting cells in the cochlea provide physical support and nutrition to hair cells and also play an important role in the maintenance of cochlear ionic homeostasis [1,2]. It has been hypothesized that supporting cells in the cochlea like glia cells in the brain absorb or sink K + ions, which hair cells release during mechano-electrical transduction, and transport them back to the endolymph via intracellular gap junctional communication [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

ATP-mediated potassium recycling in the cochlear supporting cells

Zhu

Zhao

2010

Purinergic Signalling

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Gap junction-mediated K + recycling in the cochlear supporting cell has been proposed to play a critical role in hearing. However, how potassium ions enter into the supporting cells to recycle K + remains undetermined. In this paper, we report that ATP can mediate K + sinking to recycle K + in the cochlear supporting cells. We found that micromolar or submicromolar levels of ATP could evoke a K + -dependent inward current in the cochlear supporting cells. At negative membrane potentials and the resting membrane potential of −80 mV, the amplitude of the ATPevoked inward current demonstrated a linear relationship to the extracellular concentration of K + , increasing as the extracellular concentration of K + increased. The inward current also increased as the concentration of ATP was increased. In the absence of ATP, there was no evoked inward current for extracellular K + challenge in the cochlear supporting cells. The ATP-evoked inward current could be inhibited by ionotropic purinergic (P2X) receptor antagonists. Application of pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS, 50 µM) or pre-incubation with an irreversible P2X7 antagonist oxidized ATP (oATP, 0.1 mM) completely abolished the ATP-evoked inward current at the negative membrane potential. ATP also evoked an inward current at cell depolarization, which could be inhibited by intracellular Cs + and eliminated by positive holding potentials. Our data indicate that ATP can activate P2X receptors to recycle K + in the cochlear supporting cells at the resting membrane potential under normal physiological and pathological conditions. This ATP-mediated K + recycling may play an important role in the maintenance of cochlear ionic homeostasis.

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“…Several different connexin sub-units were reported to be expressed in the mammalian inner ear. 3 Mutations in these genes were responsible for various types of ARNSHI (Hereditary hearing loss homepage: http://webhost.ua.ac.be/hhh/). The second candidate gene screened was FXYD4.…”

Section: Discussionmentioning

confidence: 99%

Re-assigning the DFNB33 locus to chromosome 10p11.23–q21.1

Belguith

Masmoudi²,

Medlej‐Hashim

et al. 2008

Eur J Hum Genet

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Homozygosity mapping is a powerful resource for mapping and identifying loci and genes responsible for autosomal recessive disorders. Nevertheless, it could result in the identification of several homozygous regions unrelated to the disease locus or non-informative regions. Previously, a genome-wide screen in a large consanguineous Jordanian family allowed us to assign the DFNB33 locus to chromosome 9q34.3. Sequencing of 23 candidate genes showed 11 SNPs in a heterozygous state in affected individuals. These results ruled out the candidate region on chromosome 9. Using additional markers, we were able to restrict the disease locus to an approximately 14 cM region at chromosome 10, located between markers D10S193 and D10S1784. A maximum LOD score of 3.99 was obtained with two markers, D10S199 and D10S220. The screening of two candidate genes, CX40.1 and FXYD4, failed to reveal any disease-causing mutations.

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Gap Junctions and Cochlear Homeostasis

Cited by 147 publications

References 98 publications

Mutation R184Q of connexin 26 in hearing loss patients has a dominant-negative effect on connexin 26 and connexin 30

Mutation R184Q of connexin 26 in hearing loss patients has a dominant-negative effect on connexin 26 and connexin 30

ATP-mediated potassium recycling in the cochlear supporting cells

Re-assigning the DFNB33 locus to chromosome 10p11.23–q21.1

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