Quinine-induced alterations of electrically evoked otoacoustic emissions and cochlear potentials in guinea pigs

Quinine is a well-known ototoxic drug which may affect portions of the auditory system with different biochemical effects, causing reversible hearing loss and tinnitus. Recent investigations indicate that quinine at high concentrations can act directly on cochlear outer hair cells to affect their motility and the mechanical response of the basilar membrane. This study aimed to investigate the effect of quinine on the electromotility of outer hair cells in vivo by means of measuring the electrically evoked otoacoustic emissions (EEOAEs), and the relationship between EEOAE and hearing sensitivity alterations in guinea pigs. Quinine was infused into the scala tympani with concentrations between 0.05 and 5 mM. An alternating current (35 μA RMS) swept from 400 Hz to 40 kHz was applied to the round window to evoke the EEOAE. The compound action potential (CAP), cochlear microphonic (CM) and summating potential (SP) were also measured. Results show that quinine affects the EEOAE in a dose-dependent manner and that its effects are reversible. Two aspects of the EEOAE were affected by quinine, depending on concentration: (1) the 'fine structure' only for concentrations below 0.1 mM and (2) the overall amplitude and the 'fine structure' for concentrations above 0.1 mM. At 5 mM the fine structure was completely absent and the mean amplitude of the EEOAE greatly decreased. Multiple component analysis shows the short delay component of the EEOAE is related to the mean value of the amplitude spectrum while the long delay component is related to the fine structure. The alterations of the EEOAE are roughly comparable to that of the cochlear potentials. A 'threshold concentration' for quinine's effects was found at 25 μM. CAP was significantly affected at 25 μM while EEOAE, CM and SP were not. Enhancement of the EEOAE amplitude was noticed in five out of 20 animals in the current study. The enhancement appears only related to the EEOAE mean level or short delay component. The results suggest that quinine can affect in vivo electromotility of outer hair cells at low concentration and therefore change the cochlear amplifier performance via an effect on electro-mechanical transduction. Its effects on the cochlear spiral ganglion neurons and/or their presynaptic process are also suggested, and these are speculated to be the primary sites for quinine's effects on the auditory system.