Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl- N- tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.

The contention that normally binaural listeners can localize sound under monaural conditions has been challenged by Wightman and Kistler (J. Acoust. Soc. Am. 101:1050-1063, 1997), who found that listeners are almost completely unable to localize virtual sources of sound when sound is presented to only one ear. Wightman and Kistler's results raise the question of whether monaural spectral cues are used by listeners to localize sound under binaural conditions. We have examined the possibility that monaural spectral cues provide useful information regarding sound-source elevation and front-back hemifield when interaural time differences are available to specify sound-source lateral angle. The accuracy with which elevation and front-back hemifield could be determined was compared between a monaural condition and a binaural condition in which a wide-band signal was presented to the near ear and a version of the signal that had been lowpass-filtered at 2.5 kHz was presented to the far ear. It was found that accuracy was substantially greater in the latter condition, suggesting that information regarding sound-source lateral angle is required for monaural spectral cues to elevation and front-back hemifield to be correctly interpreted.

Introduction of adenosine 5'-triphosphate (ATP) into the endolymphatic compartment of the guinea-pig cochlea decreases the endocochlear potential (EP). To determine if this is due to an ATP-induced change in compartment resistance, the cochlear partition resistance (CoPR) was measured using constant current injections into scala media before, during, and after microinjection of ATP into the same compartment. The CoPR (mean = 3.13 +/- 0.13 kOmega) decreased with ATP in a dose-dependent manner (25.1 +/- 3.0% decrease in relation to baseline values) and this was linearly correlated ( R(2) = 0.91) to the magnitude of the ATP-induced decline in EP (41.6 +/- 7.0% decline in relation to the baseline). Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, a P2X receptor antagonist) injected prior to ATP application blocked this ATP-induced reduction in EP and CoPR. This indicates that ATP-gated ion channels (P2X receptors) provide a latent shunt capable of regulating the majority of the electrical potential across the luminal surface of the sensory hair cells, which is necessary for sound transduction. The results suggest a novel sound transduction regulatory mechanism, which, via extracellular ATP, has the capability of adjusting hearing sensitivity.