Study of Mechanotransduction in Hair Cell

Functional studies of inner ear hair cells of mammals, birds, and other vertebrates are limited by the difficulty in accessing the inner ear which is embedded in the temporal bone. Zebrafish lateral line was recently reported to be a useful in vivo model for studying hair cells and ototoxicity. We have demonstrated that the scanning ion-electrode technique (SIET) to be a sensitive approach for functionally assaying mechanotransducer channel (MET channel) in zebrafish. We also showed that ototoxin (neomycin and gentamicin) effectively block MET channel mediated Ca 2+ influx within 10 min. In this project, we will extend our study to mechanotransduction of hair bundle and examine the Ca 2+ and pH regulation mechanism after Ca 2+ influx through MET channel. This proposal will designed as a three years project: The first year: To know the role of PMCA in Ca 2+ regulation in hair bundle. The prupose in the first year is to examine if PMCA (membrane Ca 2+ ATPase) pump out Ca 2+ to maintain Ca 2+ concentration in hair bundle after Ca 2+ influx through MET channel. The second year: To know the role of NHE in pH regulation in hair bundle. The purpose in the second year is to examine if NHE (Na + /H + exchanger) mediated H + influx in hair cell to regulate pH in hair bundle. The third year: To know the effect of ototoxin (neomycin, gentamicin) on PMCA and NHE. The purpose in the third year is to examine if ototoxins inhibit function of PMCA and NHE.