Cochlear effects of locally applied inhibitors

Abstract

The round window has been used as a route for introducing ototoxic substances into the inner ear in order to bypass barriers between the systemic circulation and the inner ear. We have used this method to administer locally sodium potassium-ATPase inhibitors and chloride transport inhibitors to the inner ear of the chinchilla. Drugs dissolved in saline solution were applied on the round window membrane. Endocochlear potential (EP) was recorded from the basal turn using the round window approach. The EP was not altered following application of saline solution as a control. Following application of ouabain (1 mM), the EP steadily declined. After vanadate (27 mM), the EP initially increased, and subsequently declined. Sanguiarine did not alter the EP. The loop diuretics furosemide and piretanide caused a marked decline in the EP after local application. However, the stilbene derivative DIDS did not alter the EP after topical application. These findings raise questions about whether the loop diuretics have any effect on chloride transport in the cochlea and make appear unlikely that active chloride transport contributes to the normal EP.