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Active cochlear amplification is dependent on supporting cell gap junctions.

Zhu Y, Liang C, Chen J, Zong L, Chen GD, Zhao HB - Nat Commun (2013)

Bottom Line: Here we describe the novel finding that gap junctions between cochlear supporting cells also have a critical role in active cochlear amplification in vivo.We find that targeted-deletion of connexin 26 in Deiters cells and outer pillar cells, which constrain outer hair cells standing on the basilar membrane, causes a leftward shift in outer hair cell electromotility towards hyperpolarization, and reduces active cochlear amplification with hearing loss.Our study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, University of Kentucky Medical School, Lexington, Kentucky 40536, USA.

ABSTRACT
Mammalian hearing relies upon active cochlear mechanics, which arises from outer hair cell electromotility and hair bundle movement, to amplify acoustic stimulations increasing hearing sensitivity and frequency selectivity. Here we describe the novel finding that gap junctions between cochlear supporting cells also have a critical role in active cochlear amplification in vivo. We find that targeted-deletion of connexin 26 in Deiters cells and outer pillar cells, which constrain outer hair cells standing on the basilar membrane, causes a leftward shift in outer hair cell electromotility towards hyperpolarization, and reduces active cochlear amplification with hearing loss. Coincident with large reduction in distortion product otoacoustic emission and severe hearing loss at high frequencies, the shift is larger in shorter outer hair cells. Our study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions. These new findings also show that connexin 26 deficiency can reduce active cochlear amplification to induce hearing loss.

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Left-shift of OHC NLC in Cx26 cKO mice. a: NLC recorded from Cx26 cKO and WT mice.Smooth lines represent fitting by the first derivative of Boltzmann equation.b–e: Parameters of NLC fitting. WT littermates served as a control group. Micewere P50–60 old. **: P < 0.001 as determined by one-way ANOVA with aBonferroni correction. Data are expressed as mean ± S.D;
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Figure 6: Left-shift of OHC NLC in Cx26 cKO mice. a: NLC recorded from Cx26 cKO and WT mice.Smooth lines represent fitting by the first derivative of Boltzmann equation.b–e: Parameters of NLC fitting. WT littermates served as a control group. Micewere P50–60 old. **: P < 0.001 as determined by one-way ANOVA with aBonferroni correction. Data are expressed as mean ± S.D;

Mentions: OHC electromotility associated NLC in Cx26 cKO mice retained a normal bell-shape but wasshifted to the left in the hyperpolarization direction (Fig.6a). The voltage of peak capacitance (Vpk) was significantly shifted from−73.8±2.14 mV in WT mice to − 90.9±2.22 mV in homozygous mice (Fig. 6b, P=0.00004, one-way ANOVA with a Bonferronicorrection). Vpk in heterozygous mice was −82.9±2.37 mV and also had asignificant left-shift by ~10 mV (P=0.0003, one-way ANOVA with a Bonferroni correction). TheVpk-shifting is larger in shorter OHCs (Fig. 7).Linear regression analysis shows that the slope of Vpk-shift with cell length is2.33±0.55 (mean±SD, r2=0.22) and1.60±0.49 mV/ μm (r2=0.32) in Cx26 cKO and WTmice, respectively (Fig. 7a). The slopes had significantdifference between Cx26 cKO and WT mice (P=0.004, Univariate analysis of variance). TheVpk at OHC lengths <15, 15–20, and >20 μm was left-shifted by−20.8±4.25, −14.6±2.72, and −10.37±3.81 mV,respectively, in Cx26 cKO mice (Fig. 7b, P < 0.05, one-wayANOVA with a Bonferroni correction).


Active cochlear amplification is dependent on supporting cell gap junctions.

Zhu Y, Liang C, Chen J, Zong L, Chen GD, Zhao HB - Nat Commun (2013)

Left-shift of OHC NLC in Cx26 cKO mice. a: NLC recorded from Cx26 cKO and WT mice.Smooth lines represent fitting by the first derivative of Boltzmann equation.b–e: Parameters of NLC fitting. WT littermates served as a control group. Micewere P50–60 old. **: P < 0.001 as determined by one-way ANOVA with aBonferroni correction. Data are expressed as mean ± S.D;
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Related In: Results  -  Collection

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Figure 6: Left-shift of OHC NLC in Cx26 cKO mice. a: NLC recorded from Cx26 cKO and WT mice.Smooth lines represent fitting by the first derivative of Boltzmann equation.b–e: Parameters of NLC fitting. WT littermates served as a control group. Micewere P50–60 old. **: P < 0.001 as determined by one-way ANOVA with aBonferroni correction. Data are expressed as mean ± S.D;
Mentions: OHC electromotility associated NLC in Cx26 cKO mice retained a normal bell-shape but wasshifted to the left in the hyperpolarization direction (Fig.6a). The voltage of peak capacitance (Vpk) was significantly shifted from−73.8±2.14 mV in WT mice to − 90.9±2.22 mV in homozygous mice (Fig. 6b, P=0.00004, one-way ANOVA with a Bonferronicorrection). Vpk in heterozygous mice was −82.9±2.37 mV and also had asignificant left-shift by ~10 mV (P=0.0003, one-way ANOVA with a Bonferroni correction). TheVpk-shifting is larger in shorter OHCs (Fig. 7).Linear regression analysis shows that the slope of Vpk-shift with cell length is2.33±0.55 (mean±SD, r2=0.22) and1.60±0.49 mV/ μm (r2=0.32) in Cx26 cKO and WTmice, respectively (Fig. 7a). The slopes had significantdifference between Cx26 cKO and WT mice (P=0.004, Univariate analysis of variance). TheVpk at OHC lengths <15, 15–20, and >20 μm was left-shifted by−20.8±4.25, −14.6±2.72, and −10.37±3.81 mV,respectively, in Cx26 cKO mice (Fig. 7b, P < 0.05, one-wayANOVA with a Bonferroni correction).

Bottom Line: Here we describe the novel finding that gap junctions between cochlear supporting cells also have a critical role in active cochlear amplification in vivo.We find that targeted-deletion of connexin 26 in Deiters cells and outer pillar cells, which constrain outer hair cells standing on the basilar membrane, causes a leftward shift in outer hair cell electromotility towards hyperpolarization, and reduces active cochlear amplification with hearing loss.Our study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, University of Kentucky Medical School, Lexington, Kentucky 40536, USA.

ABSTRACT
Mammalian hearing relies upon active cochlear mechanics, which arises from outer hair cell electromotility and hair bundle movement, to amplify acoustic stimulations increasing hearing sensitivity and frequency selectivity. Here we describe the novel finding that gap junctions between cochlear supporting cells also have a critical role in active cochlear amplification in vivo. We find that targeted-deletion of connexin 26 in Deiters cells and outer pillar cells, which constrain outer hair cells standing on the basilar membrane, causes a leftward shift in outer hair cell electromotility towards hyperpolarization, and reduces active cochlear amplification with hearing loss. Coincident with large reduction in distortion product otoacoustic emission and severe hearing loss at high frequencies, the shift is larger in shorter outer hair cells. Our study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions. These new findings also show that connexin 26 deficiency can reduce active cochlear amplification to induce hearing loss.

Show MeSH
Related in: MedlinePlus