title: Normal hearing sensitivity at low-to-middle frequencies with 34% prestin-charge density.
abstract: The mammalian outer hair cells (OHCs) provide a positive mechanical feedback to enhance the cochlea's hearing sensitivity and frequency selectivity. Although the OHC-specific, somatic motor protein prestin is required for cochlear amplification, it remains unclear whether prestin can provide sufficient cycle-by-cycle feedback. In cochlear mechanical modeling, varying amounts of OHC motor activity should provide varying degrees of feedback efficiency to adjust the gain of cochlear amplifier at resonant frequencies. Here we created and characterized two new prestin-hypomorphic mouse models with reduced levels of wild-type prestin. OHCs from these mice exhibited length, total elementary charge movement (Q(max)), charge density, and electromotility intermediate between those of wild-type and prestin-null mice. Remarkably, measurements of auditory brainstem responses and distortion product otoacoustic emissions from these mice displayed wild-type like hearing sensitivities at 4-22 kHz. These results indicate that as low as 26.7% Q(max), 34.0% charge density and 44.0% electromotility in OHCs were sufficient for wild-type-like hearing sensitivity in mice at 4-22 kHz, and that these in vitro parameters of OHCs did not correlate linearly with the feedback efficiency for in vivo gain of the cochlear amplifier. Our results thus provide valuable data for modeling cochlear mechanics and will stimulate further mechanistic analysis of the cochlear amplifier.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamashita
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.forename: Jiangang
authors.initials: J
authors.lastname: Gao
authors.forename: Yiling
authors.initials: Y
authors.lastname: Yu
authors.forename: Marcia Mellado
authors.initials: MM
authors.lastname: Lagarde
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
mesh_terms: D000818:Animals; D003051:Cochlea / Q000378:metabolism; D023061:Gene Order; D018390:Gene Targeting; D005838:Genotype; D018072:Hair Cells, Auditory, Outer / Q000502:physiology*; D006309:Hearing / Q000235:genetics*; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020409:Molecular Motor Proteins; C498720:Pres protein, mouse