Effects of Gap Junction Uncoupling in the Gerbil Cochlea

Spiess, Adam C.; Lang, Hainan; Schulte, Bradley A.; Spicer, Samuel S.; Schmiedt, Richard A.

doi:10.1097/00005537-200209000-00020

Cited by 33 publications

(31 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this finding, Engel-Yeger et al [2002,2003] detected small OAEs in narrow frequency ranges in homozygotes and compound heterozygotes for the 35delG, W77R, and V37I mutations. Spiess et al [2002] found that uncoupling gap junctions in the Mongolian gerbil inner ear leads to large decreases in OAE magnitudes, but the OAEs, particularly in the low frequencies, do not disappear completely. Also, studies of mice lacking connexin 26 in the inner ear epithelial gap junction network suggest that the cochlear hair cells develop normally in utero, then many, but not all, begin to die postnatally [Cohen-Salmon et al, 2002].…”

Section: Discussionmentioning

confidence: 92%

Connexin 26 variants and auditory neuropathy/dys‐synchrony among children in schools for the deaf

Cheng

Brashears

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Genetic and auditory studies of 731 children with severe-to-profound hearing loss in US schools for the deaf and 46 additional children receiving clinical services for hearing loss ranging from moderate to profound demonstrated that mutations in the connexin 26 (GJB2) and connexin 30 (GJB6) genes explain at least 12% of those with nonsyndromic sensorineural deafness. Otoacoustic emissions (OAEs) testing to detect functional outer hair cells indicated that 76 of the children had emissions and therefore may have (as yet unconfirmed) auditory neuropathy/dys-synchrony (AN/AD). Five of these children with OAEs were GJB2 homozygotes or compound heterozygotes with the genotypes 35delG/35delG, W77X/W77X, 35delG/360delGAG, 35delG/V95M, and V84M/M34T. In particular, unilateral AN/AD was confirmed in a child with moderate hearing loss and the 35delG/V95M genotype. Detecting OAEs in individuals with GJB2 mutations suggests that lack of functional gap junctions as a result of GJB2 mutations does not necessarily destroy all outer hair cell function.

show abstract

Section: Discussionmentioning

confidence: 92%

Connexin 26 variants and auditory neuropathy/dys‐synchrony among children in schools for the deaf

Cheng

Brashears

et al. 2005

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…In patients with connexin mutations, auditory function tests demonstrate a reduced or absent distortion product of otoacoustic emission (DPOAE; Engel-Yeger et al, 2002. Local cochlear application of gap junctional blockers also causes a large reduction in DPOAE in the gerbil (Spiess et al, 2002). The DPOAE arises from the active cochlear mechanics, contributed mainly by outer hair cell electromotility in mammals (Liberman et al, 2002;Cheatham et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Distinct and gradient distributions of connexin26 and connexin30 in the cochlear sensory epithelium of guinea pigs

Zhao

2006

J of Comparative Neurology

108

144

View full text Add to dashboard Cite

Connexin26 (Cx26) and Cx30 are predominant isoforms of gap junction channels in the cochlea and play a critical role in hearing. In this study, the cellular distributions of Cx26 and Cx30 in the cochlear sensory epithelium of guinea pigs were examined by immunofluorescent staining and confocal microscopy in whole mounts of the cochlear sensory epithelium and dissociated cell preparations. The expression of Cx26 and Cx30 demonstrated a longitudinal gradient distribution in the epithelium and was reduced threefold from the cochlear apex to base. The reduction was more pronounced in the Deiters cells and pillar cells than in the Hensen cells. Cx26 was expressed in all types of supporting cells, but little Cx30 labeling was seen in the Hensen cells. Cx26 expression in the Hensen cells was concentrated mainly in the second and third rows, forming a distinct band along the sensory epithelium at its outer region. In the dissociated Deiters cells and pillar cells, Cx30 showed dense labeling at the cell bodies and processes in the reticular lamina. Cx26 labeling largely overlapped that of Cx30 in these regions. Cx26 and Cx30 were also coexpressed in the gap junctional plaques between Claudius cells. Neither Cx26 nor Cx30 labeling was seen in the hair cells and spiral ganglion neurons. These observations demonstrate that Cx26 and Cx30 have a longitudinal gradient distribution and distinct cellular expression in the auditory sensory epithelium. This further supports our previous reports that Cx26 and Cx30 can solely and concertedly perform different functions in the cochlea. Indexing termsgap junction; cochlear supporting cells; reticular lamina; spiral ganglion; inner ear; nonsyndromic hearing lossThe connexin gene family encodes gap junction channels in mammals. So far, more than 20 connexin genes and their corresponding isoforms have been identified . Each connexin shows tissue-or cell-specific expression, and most organs and tissues express more than one connexin (for reviews see Harris, 2001; Evans and Martin, 2002;Willecke et al., 2002). Connexin gap junctions perform electronic and metabolic communications between cells and play important roles in many aspects of cellular and physiological functions. In particular, gap junctions are known to play a critical role in hearing function. Connexin mutations can cause hearing loss and account for 70 -80% of nonsyndromic hearing loss in children (Kelsell et al., 1997;Denoyelle et al., 1997;Grifa et al., 1999 The mammalian cochlea is the auditory organ and contains sensory hair cells and nonsensory supporting cells. Gap junctional coupling is extensive in the cochlea (for reviews see Kikuchi et al., 2000;Zhao et al., 2006). In early histological studies, electron microscopy and dye injection demonstrated that intercellular communications existed in the organ of Corti (Jahnke, 1975;Gulley and Reese, 1976;Iurato et al., 1976Iurato et al., , 1977Hama and Saito, 1977;Santos-Sacchi and Dallos, 1983;Santos-Sacchi, 1987;Zwislocki et al., 1992). Kikuchi et al. (1995), using ...

show abstract

“…Yet this need not promote overt strial pathology. Notably, mitochondrial inhibitors applied in guinea pigs reproduce many of the features of noise injury (Hoya et al 2004;Okamoto et al 2005), while gap junction inhibitors only somewhat reproduce the effects of noise (Spiess et al 2002). In any event, the appearance of the lateral wall does not readily indicate which cells or genes may drive phenotypic differences.…”

Section: Genes and Processes That Establish Or Modulate The Epmentioning

confidence: 97%

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

Ohlemiller

Kiener

Gagnon

2016

JARO

View full text Add to dashboard Cite

We reported earlier that the endocochlear potential (EP) differs between C57BL/6J (B6) and BALB/cJ (BALB) mice, being lower in BALBs by about 10 mV (Ohlemiller et al. Hear Res 220: 10-26, 2006). This difference corresponds to strain differences with respect to the density of marginal cells in cochlear stria vascularis. After about 1 year of age, BALB mice also tend toward EP reduction that correlates with further marginal cell loss. We therefore suggested that early sub-clinical features of the BALB stria vascularis may predispose these mice to a condition modeling Schuknecht's strial presbycusis. We further reported (Ohlemiller et al. J Assoc Res Otolaryngol 12: 45-58, 2011) that the acute effects of a 2-h 110 dB SPL noise exposure differ between B6 and BALB mice, such that the EP remains unchanged in B6 mice, but is reduced by 40-50 mV in BALBs. In about 25 % of BALBs, the EP does not completely recover, so that permanent EP reduction may contribute to noise-induced permanent threshold shifts in BALBs. To identify genes and alleles that may promote natural EP variation as well as noiserelated EP reduction in BALB mice, we have mapped related quantitative trait loci (QTLs) using 12 recombinant inbred (RI) strains formed from B6 and BALB (CxB1-CxB12). EP and strial marginal cell density were measured in B6 mice, BALB mice, their F1 hybrids, and RI mice without noise exposure, and 1-3 h after broadband noise (4-45 kHz, 110 dB SPL, 2 h). For unexposed mice, the strain distribution patterns for EP and marginal cell density were used to generate preliminary QTL maps for both EP and marginal cell density. Six QTL regions were at least statistically suggestive, including a significant QTL for marginal cell density on chromosome 12 that overlapped a weak QTL for EP variation. This region, termed Maced (Marginal cell density QTL) supports the notion of marginal cell density as a genetically influenced contributor to natural EP variation. Candidate genes for Maced notably include Foxg1, Foxa1, Akap6, Nkx2-1, and Pax9. Noise exposure produced significant EP reductions in two RI strains as well as significant EP increases in two RI strains. QTL mapping of the EP in noise-exposed RI mice yielded four suggestive regions. Two of these overlapped with QTL regions we previously identified for noise-related EP reduction in CBA/J mice (Ohlemiller et al. Hear Res 260: 47-53, 2010) on chromosomes 5 and 18 (Nirep). The present map may narrow the Nirep interval to a~10-Mb region of proximal Chr. 18 that includes Zeb1, Arhgap12, Mpp7, and Gjd4. This study marks the first exploration of natural gene variants that modulate the EP. Their orthologs may underlie some human hearing loss that originates in the lateral wall.Electronic supplementary material The online version of this article

show abstract

Effects of Gap Junction Uncoupling in the Gerbil Cochlea

Cited by 33 publications

References 26 publications

Connexin 26 variants and auditory neuropathy/dys‐synchrony among children in schools for the deaf

Connexin 26 variants and auditory neuropathy/dys‐synchrony among children in schools for the deaf

Distinct and gradient distributions of connexin26 and connexin30 in the cochlear sensory epithelium of guinea pigs

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

Contact Info

Product

Resources

About