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GRAVITATIONAL EFFECTS ON MECHANOTRANSDUCTION AND ADAPTATION IN SENSORY HAIR CELLS OF A MAMMALIAN VESTIBULAR ORGAN.  Jeffrey R. Holt.   Departments of Neuroscience and Otolaryngology, University of Virginia, Charlottesville, Virginia.

   The vestibular hair cells of the mammalian inner ear transduce head movements and gravitational stimuli into electrical signals that are transmitted to the brain.  They are exquisitely sensitive, signaling deflections of their mechanosensitive hair bundles as small as 1-2 nanometers.  Remarkably, they are able to preserve this level of sensitivity even when confronted with large tonic stimuli, such as gravity, which may impose hair bundle offsets as large as a micron.  To accomplish this feat hair cells have devised an adaptation process that repositions the mechanotransduction apparatus on a millisecond time scale thus allowing high sensitivity over a broad operating range.

   We have been investigating mechanotransduction and adaptation in the hair cells of the mouse utricle, a gravity-sensitive, vestibular organ. The sensory epithelium is excised from neonatal mouse utricles and placed in a recording chamber.  We use glass micropipettes mounted on piezoelectric bimorphs to deflect the hair bundles and whole-cell, tight-seal pipettes to record the current response.  We find rapid sub-millisecond current activation with amplitudes up to several hundred picoAmperes.  In response to sustained hair bundle deflections, the current decays over the subsequent 10-100 milliseconds.  The current decay, or adaptation, has been hypothesized to result from the activity of an adaptation motor that continually adjusts its position regulating tension in the mechanotransduction apparatus.

   We have recently identified myosin Ic as a molecular component of the adaptation motor.  With our collaborators, we generated a transgenic mouse that carried a mutant form of the gene for myosin Ic.  A substitution mutation (tyrosine to glycine at position 61) rendered myosin Ic sensitive to inhibition by an ADP analog.  We found that addition of the analog abolished the hair cell’s ability to adapt to tonic stimuli in transgenic but not wild-type cells, confirming a role for myosin Ic in hair-cell adaptation.

(Supported by NIH grant DC03279)

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