title: Fast adaptation in vestibular hair cells requires myosin-1c activity.
abstract: In sensory hair cells of the inner ear, mechanical amplification of small stimuli requires fast adaptation, the rapid closing of mechanically activated transduction channels. In frog and mouse vestibular hair cells, we found that the rate of fast adaptation depends on both channel opening and stimulus size and that it is modeled well as a release of a mechanical element in series with the transduction apparatus. To determine whether myosin-1c molecules of the adaptation motor are responsible for the release, we introduced the Y61G mutation into the Myo1c locus and generated mice homozygous for this sensitized allele. Measuring transduction and adaptation in the presence of NMB-ADP, an allele-specific inhibitor, we found that the inhibitor not only blocked slow adaptation, as demonstrated previously in transgenic mice, but also inhibited fast adaptation. These results suggest that mechanical activity of myosin-1c is required for fast adaptation in vestibular hair cells.
authors.affiliation: Department of Neuroscience and Department of Otolaryngology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stauffer
authors.forename: John D
authors.initials: JD
authors.lastname: Scarborough
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Hirono
authors.forename: Emilie D
authors.initials: ED
authors.lastname: Miller
authors.forename: Kavita
authors.initials: K
authors.lastname: Shah
authors.forename: John A
authors.initials: JA
authors.lastname: Mercer
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Holt
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gillespie
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000483:Alleles; D000818:Animals; D001001:Anura; D018069:Hair Cells, Vestibular / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D024461:Myosin Type I; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D004856:Postural Balance / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011930:Reaction Time / Q000502:physiology*; D013997:Time Factors
chemical_list: C470422:Myo1c protein, mouse; D011500:Protein Synthesis Inhibitors; D024461:Myosin Type I; D009218:Myosins