Thapsigargin suppresses cochlear potentials and DPOAEs and is toxic to hair cells

Document Type

Article

Publication Date

7-23-2003

Publication Title

Hearing Research

Abstract

Thapsigargin, a drug that inhibits sarco-endoplasmic reticulum Ca2+ ATPases (SERCAs), was infused into the perilymph compartment of the guinea pig cochlea in increasing concentrations (0.1–10 μM) while sound evoked cochlear potentials were monitored. Thapsigargin significantly suppressed the compound action potential of the auditory nerve, cochlear microphonics, and increased N1 latency at low (56 dB SPL) and high intensity (92 dB SPL) levels of sound, suppressed low intensity sound evoked summating potential (SP) and greatly increased the magnitude of the high intensity sound evoked SP. At 10 μM, the drug suppressed the cubic distortion product otoacoustic emissions (2f1−f2=8 kHz, f2=12 kHz) evoked by both high and low intensity primaries (45, 60, 70 dB SPL). Thapsigargin (10 μM; 30 min) increased the endocochlear potential slightly (5 mV). In chronic animals, thapsigargin (10 μM; 60 min) destroyed many outer hair cells and some inner hair cells, especially in the basal turns. These effects are consistent with the hypothesis that the inhibition of the SERCAs affects the function of the cochlear amplifier and outer hair cells to a greater degree than it affects other functions of the cochlea.

First Page

51

Last Page

60

PubMed ID

14553903

Volume

184

Publisher

Elsevier

Rights

© 2003 Elsevier B.V. All rights reserved.

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