TY - JOUR T1 - Functional Mechanotransduction Is Required for Cisplatin-Induced Hair Cell Death in the Zebrafish Lateral Line JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4405 LP - 4414 DO - 10.1523/JNEUROSCI.3940-12.2013 VL - 33 IS - 10 AU - Andrew J. Thomas AU - Dale W. Hailey AU - Tamara M. Stawicki AU - Patricia Wu AU - Allison B. Coffin AU - Edwin W Rubel AU - David W. Raible AU - Julian A. Simon AU - Henry C. Ou Y1 - 2013/03/06 UR - http://www.jneurosci.org/content/33/10/4405.abstract N2 - Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner (myo7aa) and sputnik (cad23) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analog of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line. ER -