SITE AND NATURE OF HAIR-CELL TRANSDUCTION

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Hair cells are the sensory receptor cells of the inner ear. They transduce mechanical stimuli in the environment, such as sound, into electrical responses that trigger the nerve fibers going to the brain, a process called mechano-electric transduction. The key event in mechano-electric transduction is thought to be the opening of mechanically-sensitive pores called transduction channels in the hair-cell membrane. The aim of this project is to answer two basic questions about mechano-electric transduction: 1) how does transduction occur, that is, what are the biophysical properties of the transduction channel, and 2) where does transduction occur, that is, where are the channels located in the cell. To determine the biophysical properties of the channel, we will use a newly-developed electrophysiological technique, the whole-cell voltage clamp, to record from single hair cells of the inner ear of the bullfrog. This technique will allow us to measure the minute currents that flow through the transduction channels when a cell is stimulated with a probe. From these measurements, we can estimate such properties as the conductance of a single transduction channel to ionic currents, and the number of channels in a cell. We can also measure directly how the transduction channel's properties are affected by applications of such ototoxic drugs as the aminoglycoside antibiotic, streptomycin. In order to locate the transduction channels in the cell, we will use a novel combination of physiological and morphological techniques. First, we will use the whole-cell voltage-clamp to cause a samll amount of an insoluble compound to form in the transduction channel. Then we will locate this compound using X-ray microanalysis, a electron-microscopic method for detecting extremely small quantities of material. Knowing the location of the transduction channels and their biophysical properties will prove important both in understanding the speed and sensitivity of transduction in normal ears and in understanding how exposure to noise and ototoxic drugs effects transduction.