Abstract
The cochlea converts sound vibration into electrical impulses and amplifies the low-level sound signal. Urethane, a widely used anesthetic in animal research, has been shown to reduce the neural responses to auditory stimuli. However, the effects of urethane on cochlea, especially on the function of outer hair cells, remain largely unknown. In the present study, we compared the cochlear microphonic responses between awake and urethane-anesthetized rats. The results revealed that the amplitude of the cochlear microphonic was decreased by urethane, resulting in an increase in the threshold at all of the sound frequencies examined. To deduce the possible mechanism underlying the urethane-induced decrease in cochlear sensitivity, we examined the electrical response properties of isolated outer hair cells using whole-cell patch-clamp recording. We found that urethane hyperpolarizes the outer hair cell membrane potential in a dose-dependent manner and elicits larger outward current. This urethane-induced outward current was blocked by strychnine, an antagonist of the α9 subunit of the nicotinic acetylcholine receptor. Meanwhile, the function of the outer hair cell motor protein, prestin, was not affected. These results suggest that urethane anesthesia is expected to decrease the responses of outer hair cells, whereas the frequency selectivity of cochlea remains unchanged.
Highlights
Under general anesthetics, decreased hearing sensitivity is common in both animal research and clinical settings
By comparing the cochlear microphonic (CM) responses between awake and urethane-anesthetized rats, we found that the activity of outer hair cells (OHCs) was significantly reduced by urethane
Our results indicate that urethane hyperpolarizes the OHC membrane potential, which is at least partially mediated by the ACh receptors (AChR)
Summary
Under general anesthetics, decreased hearing sensitivity is common in both animal research and clinical settings. Several studies have demonstrated that different anesthetics increase auditory brainstem response thresholds [1,2,3] and depress neural excitability in the auditory midbrain [4, 5] and cortex [6,7,8]. The sensitivity of the auditory system could be changed by anesthetics at two levels: the cochlea and the auditory neurons. Because any change in cochlear function may influence the response of central auditory neurons, the effects on the cochlea are essential for the anesthetic-induced reduction in hearing sensitivity. Urethane has been reported to depress the sound-evoked activity of the auditory system [4,5,6], its direct effect on the cochlea, sensory hair cells, remains unknown
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