R Dieler1, C Davies, W E Shehata-Dieler. 1. Bayerische Julius-Maximilians-Universität, Klinik und Poliklinik für Hals-, Nasen- und Ohrenkranke, Germany. r.dieler@mail.uni-wuerzburg.de
Abstract
BACKGROUND: Large doses of quinine (as well as of salicylate) are known to produce reversible hearing loss and tinnitus. Cochlear outer hair cells seem to be the common site for the ototoxic effect of both drugs. METHODS: Isolated outer hair cells from the guinea pig cochlea were exposed to ototoxic doses of quinine hydrochloride (0.05-1.5 mmol/l). The cells were examined using tight-seal whole-cell recording techniques and transmission electron microscopy. RESULTS: Quinine exposure led to a hyperpolarization followed by a depolarization of the hair cells' membrane potential. It also caused a diminution of evoked rapid motile responses that was more apparent in response to hyperpolarizing than to depolarizing pulses. These effects were largely dose dependent and reversible. Ototoxic doses of quinine were not found to induce changes in turgor, shape or fine structure of outer hair cells such as those reported with ototoxic doses of salicylates in vitro. CONCLUSIONS: The present in vitro findings show that quinine (as well as salicylate) directly and reversibly affects cochlear outer hair cells. They also indicate that the underlying mechanisms of quinine ototoxicity are considerably different to that of salicylate although both substances clinically lead to identical symptoms.
BACKGROUND: Large doses of quinine (as well as of salicylate) are known to produce reversible hearing loss and tinnitus. Cochlear outer hair cells seem to be the common site for the ototoxic effect of both drugs. METHODS: Isolated outer hair cells from the guinea pig cochlea were exposed to ototoxic doses of quinine hydrochloride (0.05-1.5 mmol/l). The cells were examined using tight-seal whole-cell recording techniques and transmission electron microscopy. RESULTS:Quinine exposure led to a hyperpolarization followed by a depolarization of the hair cells' membrane potential. It also caused a diminution of evoked rapid motile responses that was more apparent in response to hyperpolarizing than to depolarizing pulses. These effects were largely dose dependent and reversible. Ototoxic doses of quinine were not found to induce changes in turgor, shape or fine structure of outer hair cells such as those reported with ototoxic doses of salicylates in vitro. CONCLUSIONS: The present in vitro findings show that quinine (as well as salicylate) directly and reversibly affects cochlear outer hair cells. They also indicate that the underlying mechanisms of quinineototoxicity are considerably different to that of salicylate although both substances clinically lead to identical symptoms.