The auditory system?s remarkable sensitivity arises because of an active amplification mechanism termed the active process. One result of the active process is the ability of cochlea to generate otoacoustic emissions (OAEs). Leading theories suggest the active process arises from outer hair cell (OHC) electro-motility. But, limited energy at threshold is a problem of all hair cells. Independent sound amplification mechanisms likely exist because species without OHCs generate OAEs. Movements associated with mechano-electric transducer (MET) channel activation and adaptation have been identified and shown to underlie a mechanical tuning mechanism in hair cells of lower vertebrates. We hypothesize that active hair bundle movements are a universally available amplification and OAE generation mechanism. Salicylate, an OAE antagonist, will be used to identify possible mechanisms of OAE generation in turtle auditory hair cells by experiments designed to determine the sites and mechanisms of drug action. We propose that salicylate affects non-OHC mediated OAEs by acting on active hair bundle movements. Experiments will measure hair bundle movements in the presence of salicylate. Salicylate effects may be direct by altering MET channel activation or adaptation, or indirect by altering basolateral hair cell properties. Therefore the effects of salicylate on MET, calcium and, calcium activated potassium channels will be measured. The physiologic impact of salicylate effects at identified site(s) of action will be investigated by directly measuring active hair bundle movements and (or) electrical resonance properties. Salicylate may act through charge screening and (or) altered membrane stiffness. Measurements of MET and voltage-dependent calcium current responses in the same cell and utilizing other drugs to alter membrane stiffness will aid elucidating the impact of each mechanism. Proposed results will give important new information regarding active hair bundle motion and the cochlear amplifier.
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