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.
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