BIOPHYSICS AND DEVELOPMENT OF COCHLEAR OUTER HAIR CELLS

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DESCRIPTION: (Adapted from applicant's abstract): The outer hair cell (OHC) is one of two receptor cells in the mammalian hearing organ, the organ of Corti, and plays a critical role in hearing. OHCs enhance basilar membrane motion through a local mechanical feedback process within the cochlea, termed the 'cochlear amplifier'. It is generally believed that he basis of cochlear amplification is a voltage-dependent somatic length change of OHCs. This amplification process is apparently responsible for high sensitivity, broad dynamic range, exquisite frequency selectivity, and a host of nonlinear behaviors seen in the normal ear. The long-term goal of the proposal is to study the development and biophysics of OHCs. Specifically, our aims are: 1) to determine how OHC membrane conductances influence the dynamic characteristics of motile responses by simultaneously recording membrane conductances influences the dynamic characteristics of motile responses by simultaneously recording membrane potential changes and motility with a combination of whole-cell voltage-clamp and microchamber techniques in isolated guinea pig OHCs 2) to determine how mechanical load and initial cell length affect the magnitude, frequency response characteristics, and asymmetry of OHC motility, using microchamber technique with OHCs isolated from Guinea pig cochleae. 3) To study how potassium conductances are differentially expressed among the three rows of OHCs, using whole cells voltage clamp techniques on the newly developed gerbil hemicochlea preparation. 4) To determine how OHC potassium currents develop after birth, using whole-cell voltage-clamp technique on the hemicochlea preparation. 5) To determine whether the functional maturation of OHC ACh receptors is regulated by efferent innervation. The experiments will be carried out with whole-cell voltage-clamp techniques on OHCs obtained from tissue cultures of the organ of Corti, deprived of efferent innervation. The experiments will be carried out with whole cell voltage clamp techniques on PHCs obtained from tissue cultures of the organ of Corti, deprived of efferent innervation. Neonatal Mongolian gerbils are chosen for the two development studies, since an important period of hair cell development occurs after birth. Studying development and biophysics of OHCs will delineate the motor function of these putative effectors and thus, will lead to a greater understanding of their role in cochlear mechanics. Because the majority of Americans with hearing loss, some 30 million in all, have some kind of hair cell damage, understanding the operation of OHCs is essential to the biological remediation and prevention of hair cell-related hearing loss and deafness.