Gentamicin causes cochlear hair cell loss in a dose-dependent manner.

<p>A) Low magnification image of a postnatal 3-day-old (P3) mouse cochlea immunolabeled for myosin7a, a specific marker for inner and outer hair cells. B) Cochleae were isolated from P3 mice and cultured overnight. The following day, cultures were bathed in gentamicin (0–0.5 mM) for 1 hr at 37°C followed by a 48 hr recovery period in AG-free culture media. C) Schematic of aminoglycoside (AG, red) entry into hair cells via mechanotransduction channels (MET, green) located at the apical end of stereocilia, and proposed mechanism of MET channel closure preventing AG entry following tip-link (yellow) breakage. D–G) Representative images of the middle turn of cochleae treated with varying doses of gentamicin and labeled with anti-myosin7a. (D) Control. (E) 0.1 mM gentamicin (F) 0.25 mM gentamicin (G) 0.5 mM gentamicin. H) Myosin7a-positive hair cells per 400 µm middle turn were counted and 0.23 mM gentamicin was determined to cause a 50% hair cell loss, mostly among outer hair cells. Error bars = S.D., scale bars = 100 µm in A, 25 µm in D–G.