Biophysics and Development of Cochlear Hair Cells

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DESCRIPTION (provided by applicant): Sensory receptor cells of the mammalian cochlea are morphologically and functionally dichotomized. Inner hair cells (IHCs) transmit auditory information to the brain, while outer hair cells (OHCs) amplify the mechanical signal, which is then transduced by IHCs. Both types of the hair cells respond to basilar membrane (BM) vibration by producing a transducer current through mechanotransducer channels located at the tip of the stereocilia when their hair bundles are deflected. The receptor potential generated by IHCs facilitates the release of neurotransmitters at their synaptic end. The receptor potential produced by OHCs, however, provides the input to their motor activity. Somatic motility of OHCs is generally thought to be responsible for the cochlear amplification in mammals. OHCs are innervated predominantly by efferent fibers originated in the brainstem. The effect of efferent action, mediated by the release of ACh, can alter micromechanical events within the cochlear partition and thereby provides a 'gain control' of the cochlear amplifier. The long-term goal of our laboratory is to study OHC motility, hair cell mechanoelectric transduction, and the mechanisms underlying the mechanical amplification. Specifically, our aims are: 1) to study the mechanical properties of OHCs in wild-type and prestin-mutant mice; 2) to study the effects of efferent activation by electrical stimulation on receptor currents and receptor potentials of the OHCs; 3) to study mechanoelectric transduction of adult IHCs. Isolated mouse OHCs will be used for Aim 1, while gerbil hemicochlea preparations will be used for Aim 2, and Aim 3. The hemicochlea preparation will allow us to measure hair cell receptor currents (or receptor potentials) and BM motion simultaneously at various cochlear locations while the BM is mechanically stimulated and/or the efferent terminals are electrically stimulated. Studying the mechanoelectrical and electromechanical transduction of hair cells will delineate the function of the sensory cells in hearing. Because the majority of Americans with hearing loss, some 30 millions in all, have some kind of hair cell damage, understanding the operation of hair cells is essential to the biological remediation and prevention of hair cell-related hearing loss and deafness.