The response of the nervous system to sounds and accelerations commences with the conversion of mechanical stimuli into electrical signals by hair cells, the sensory receptors of the internal ear. Because this transduction process appears to have a similar mechanism in all vertebrate hair cells that have been studied, we are investigating how transduction occurs in the relatively simple, experimentally accessible internal ears of frogs. In addition to improving our understanding of the biophysical basis for the operation of a major sensory system, our studies will shed light on the derangements of hearing that accompany noise damage and ototoxicity. Transduction by a hair cell is triggered by the application of a mechanical stimulus to its receptive organelle, the hair bundle. We shall first seek an anatomical correlate of the site of transduction within the hair bundle by conducting freeze-fracture electron microscopy on enzymatically isolated, rapid-frozen hair cells. We plan two tests of the hypothesis that transduction occurs at the distal tip of the hair bundle. On the assumption that transduction does not take place at a site so distant from the hair cell's body that the intracellular propagation of signals is inefficient, we shall investigate the feasibility of transduction at the bundle's tip by performing an electrical analysis of the hair cell. We plan additionally to employ an ion-sensitive dye to establish more directly where transduction currents enter the hair cell. Because mechanical inputs to the hair bundle initiate transduction, we wish to characterize the bundle's mechanical characteristics in detail. Specifically, we shall seek, through rapid, sensitive measurements of the bundle's stiffness, mechanical correlates both of sensory adaptation and of the process that opens and closes transduction channels. Finally, we intend to assimilate our results, as well as our previous observations, into a detailed, quantitative model of the electrical response of hair cells. Comparison of this model's predictions with experimental results from our laboratory and others will serve both to test the adequacy of the model and to establish similarities among and differences between the ears of various species.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Hearing Research Study Section (HAR)
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Ghosh, P; Stroud, R M (1991) Ion channels formed by a highly charged peptide. Biochemistry 30:3551-7
Hudspeth, A J (1989) Mechanoelectrical transduction by hair cells of the bullfrog's sacculus. Prog Brain Res 80:129-35;discussion 127-8
Denk, W; Webb, W W; Hudspeth, A J (1989) Mechanical properties of sensory hair bundles are reflected in their Brownian motion measured with a laser differential interferometer. Proc Natl Acad Sci U S A 86:5371-5
Kroese, A B; Das, A; Hudspeth, A J (1989) Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics. Hear Res 37:203-17
Howard, J; Hudspeth, A J (1988) Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the bullfrog's saccular hair cell. Neuron 1:189-99
Howard, J; Roberts, W M; Hudspeth, A J (1988) Mechanoelectrical transduction by hair cells. Annu Rev Biophys Biophys Chem 17:99-124
Roberts, W M; Howard, J; Hudspeth, A J (1988) Hair cells: transduction, tuning, and transmission in the inner ear. Annu Rev Cell Biol 4:63-92
Howard, J; Hudspeth, A J (1987) Mechanical relaxation of the hair bundle mediates adaptation in mechanoelectrical transduction by the bullfrog's saccular hair cell. Proc Natl Acad Sci U S A 84:3064-8
Eatock, R A; Corey, D P; Hudspeth, A J (1987) Adaptation of mechanoelectrical transduction in hair cells of the bullfrog's sacculus. J Neurosci 7:2821-36
Holton, T; Hudspeth, A J (1986) The transduction channel of hair cells from the bull-frog characterized by noise analysis. J Physiol 375:195-227

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