Effect of Salicylate on Outer Hair Cell Piezoelectricity for Tinnitus

Tinnitus is a conscious perception of a sound without real acoustic stimulation, and can be induced by many factors, such as intense noise and ototoxic drugs. Salicylate (aspirin) is a well-known ototoxic drug that can cause severe tinnitus and hearing loss. Although the salicylate can induce alterations of neural activity in the auditory centers, the significant pathophysiological changes locate in the cochlear outer hair cells (ORCs). A mammalian OHC has electromotility and piezoelectricity. Salicylate can eliminate OHC electromotility to induce hearing loss. However, the mechanism of its induced tinnitus remains unclear. Recent experiments revealed that ORC piezoelectricity could induce lateral inhibition in the cochlea. We hypothesize that salicylate may also diminishes the OHC piezoelectricity induced lateral inhibition and results in overactivity of hair cells to generate tinnitus. In this project, the effect of salicylate on OHC piezoelectricity and lateral inhibition will be recorded using a patch clamp technique, and the counteraction of chlorpromazine to the salicylate effect will be tested. These experiments will elucidate the cellular and biophysical mechanisms underlying the salicylate-induced tinnitus, and will also provide information about the role of OHC piezoelectricity induced cochlear lateral inhibition in tinnitus generation.