title: Reduced climbing and increased slipping adaptation in cochlear hair cells of mice with Myo7a mutations.
abstract: Mutations in Myo7a cause hereditary deafness in mice and humans. We describe the effects of two mutations, Myo7a(6J) and Myo7a(4626SB), on mechano-electrical transduction in cochlear hair cells. Both mutations result in two major functional abnormalities that would interfere with sound transduction. The hair bundles need to be displaced beyond their physiological operating range for mechanotransducer channels to open. Transducer currents also adapt more strongly than normal to excitatory stimuli. We conclude that myosin VIIA participates in anchoring and holding membrane-bound elements to the actin core of the stereocilium. Myosin VIIA is therefore required for the normal gating of transducer channels.
authors.affiliation: School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK. c.j.kros@sussex.ac.uk
authors.forename: C J
authors.initials: CJ
authors.lastname: Kros
authors.forename: W
authors.initials: W
authors.lastname: Marcotti
authors.forename: S M
authors.initials: SM
authors.lastname: van Netten
authors.forename: T J
authors.initials: TJ
authors.lastname: Self
authors.forename: R T
authors.initials: RT
authors.lastname: Libby
authors.forename: S D M
authors.initials: SD
authors.lastname: Brown
authors.forename: G P
authors.initials: GP
authors.lastname: Richardson
authors.forename: K P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D000199:Actins / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D003638:Deafness / Q000235:genetics; D004096:Dihydrostreptomycin Sulfate / Q000494:pharmacology; D004398:Dyneins; D004594:Electrophysiology; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000502:physiology; D051379:Mice; D020409:Molecular Motor Proteins / Q000502:physiology; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D013016:Sound; D014638:Vanadates / Q000494:pharmacology
chemical_list: D000199:Actins; D007473:Ion Channels; C000631455:MYO7A protein, human; D020409:Molecular Motor Proteins; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D014638:Vanadates; D009218:Myosins; D004398:Dyneins; D004096:Dihydrostreptomycin Sulfate