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The Journal of Neuroscience, November 1, 2002, 22(21):9643-9650

Effects of Furosemide Applied Chronically to the Round Window: A Model of Metabolic Presbyacusis

Richard A. Schmiedt¹, Hainan Lang¹, Hiro-oki Okamura², and Bradley A. Schulte^{1, 2}

Departments of ¹ Otolaryngology and Head-Neck Surgery and ² Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425

Hearing thresholds in elderly humans without a history of noise exposure commonly show a profile of a flat loss at low frequencies coupled with a loss that increases with frequency above ~2 kHz. This profile and the relatively robust distortion product otoacoustic emissions that are found in elderly subjects challenge the common belief that age-related hearing loss (presbyacusis) is based primarily on sensory-cell disorders. Here, we examine a model of presbyacusis wherein the endocochlear potential (EP) is reduced by means of furosemide applied chronically to one cochlea of a young gerbil. The model results in an EP that is reduced from 90 to ~60 mV, a value often seen in quiet-aged gerbils, with no concomitant loss of hair cells. Resulting measures of cochlear and neural function are quantitatively similar to those seen in aging gerbils and humans, e.g., a flat threshold loss at low frequencies with a high-frequency roll-off of approximately 8.4 dB/octave. The effect of the EP on neural thresholds can be parsimoniously explained by the known gain characteristics of the cochlear amplifier as a function of cochlear location: in the apex, amplification is limited to ~20 dB, whereas in the base, the gain can be as high as 60 dB. At high frequencies, amplification is directly proportional to the EP on an ~1 dB/mV basis. This model suggests that the primary factor in true age-related hearing loss is an energy-starved cochlear amplifier that results in a specific audiogram profile.

Key words: hearing; aging; gerbil; endocochlear potential; otoacoustic emissions; compound action potentials; presbyacusis

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22219643-08$05.00/0

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