The internal ear's essential role lies in mechanoelectrical transduction, the conversion of mechanical stimuli into electrical signals. Whether in the cochlea or vestibular labyrinth, this process is mediated by hair cells, the ear's sensory receptors. A sound or an acceleration elicits a response from a hair cell by deflecting its mechanoreceptive hair bundle and thereby permiting the flow of ionic current into the cell. Largely by damaging or killing hair cells, genetic conditions, infections, loud sounds, ototoxic drugs, and ageing cause deficiencies in hearing and balance. The proposed experiments are meant to identify the biochemical constituents of hair bundles and to understand how these proteins participate in the transduction process. Immunological tools will be employed to seek motor proteins, such as myosin, that underlie the ear's capacity to adapt to stimulation. Physiological experiments will explore the hair bundle's ability to produce rapid, active movements and to examine the possibility that such motions underlie the ear's amplification of sound inputs. The spontaneous emission of sounds from the ear will be investigated as another route to learning how hair cells enhance stimuli. Finally, a genetic approach will permit the identificaiton of heretofore unknown proteins from the ear. Beyond contributing to our understanding of the hair cell's structure, these proteins may include some whose abnormalities account for human genetic problems of hearing and balance. This research has two long-term goals. First, by explaining the gating of ion channels by mechanical force, the investigations should shed light on the fundamental nature of mechanosensitivity. The resultant principles may be applicable to other mechanical receptors, such as the touch receptors in skin and the stretch receptors of muscle. The second motivation for studying transduction is to comprehend how this process is compromised by mutations, overstimulation, and ototoxic drugs. An improved understanding of the hair cell's transduction process will yield rational strategies for preventing, ameliorating, or reversing the sensorineural hearing losses and equilibrium problems that afflict nearly thirty million Americans.
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