Thomas, A.J., Hailey, D.W., Stawicki, T.M., Wu, P., Coffin, A.B., Rubel, E.W., Raible, D.W., Simon, J.A., and Ou, H.C. (2013) Functional mechanotransduction is required for Cisplatin-induced hair cell death in the zebrafish lateral line. The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(10):4405-4414.
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.