title: A connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics.
abstract: Accelerated age-related hearing loss disrupts high-frequency hearing in inbred CD-1 mice. The p.Ala88Val (A88V) mutation in the gene coding for the gap-junction protein connexin30 (Cx30) protects the cochlear basal turn of adult CD-1Cx30A88V/A88Vmice from degeneration and rescues hearing. Here we report that the passive compliance of the cochlear partition and active frequency tuning of the basilar membrane are enhanced in the cochleae of CD-1Cx30A88V/A88Vcompared to CBA/J mice with sensitive high-frequency hearing, suggesting that gap junctions contribute to passive cochlear mechanics and energy distribution in the active cochlea. Surprisingly, the endocochlear potential that drives mechanoelectrical transduction currents in outer hair cells and hence cochlear amplification is greatly reduced in CD-1Cx30A88V/A88Vmice. Yet, the saturating amplitudes of cochlear microphonic potentials in CD-1Cx30A88V/A88Vand CBA/J mice are comparable. Although not conclusive, these results are compatible with the proposal that transmembrane potentials, determined mainly by extracellular potentials, drive somatic electromotility of outer hair cells.
authors.affiliation: Sensory Neuroscience Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Lukashkina
authors.affiliation: Sensory Neuroscience Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.|Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, UK.
authors.forename: Snezana
authors.initials: S
authors.lastname: Levic
authors.affiliation: Sensory Neuroscience Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lukashkin
authors.affiliation: Department of Otorhinolaryngology, University Medicine Göttingen, Robert-Koch-Strasse 40, Göttingen 37075, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Strenzke
authors.affiliation: Sensory Neuroscience Research Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D001489:Basilar Membrane / Q000378:metabolism / Q000502:physiology; D003051:Cochlea / Q000378:metabolism* / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000235:genetics / Q000502:physiology; D000075302:Connexin 30 / Q000235:genetics* / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism / Q000502:physiology; D006309:Hearing / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D020125:Mutation, Missense; D013045:Species Specificity
chemical_list: D000075302:Connexin 30; D017630:Connexins; C100629:Gjb6 protein, mouse