Studies in cochlear hair cell transduction

点击翻译按钮获取中文摘要

DESCRIPTION (Adapted from applicant's abstract): In mammals, outer hair cells provide local amplification in the cochlea that is responsible for the ear's remarkable sensitivity and frequency selectivity. While the reliance of the mammalian cochlea on local, outer hair cell based-based amplification is widely accepted, there is no agreement about the amplifying mechanism. One view is that, powered by the cell's receptor potential, somatic shape changes, called electromotility, provide mechanical feedback and thereby amplification. An alternative concept is that amplification arises as an adjunct to the cell's forward transducer process and thus resides in the sterocilia. We have now identified the gene that codes for the specialized motor protein (prestin) that produces electromotility. Thus, it is now possible to test these alternatives. We shall produce a mouse-model that lacks prestin (knockout mouse) and test its hearing. Normal hearing will imply that the second mechanism of amplification is operative, whereas significant hearing loss will show that due to the non-functional prestin, hearing has been degraded. In addition, extensive experiments are conducted on the molecular properties of prestin itself with aims of producing various antibodies against it, to determine its topology and its interaction with various agents that are known to influence outer hair cell motility.