Project 12

Do Mammalian Cochlear Tip Links Regenerate?

A popular model of mechanotransduction in hair cells invokes macromolecular “tip links” that act to open the transduction channels when the stereocilia bundles are bent by sound vibration. It has been shown that these tip links are ruptured by lowering the extracellular Ca2+ concentration in their microenvironment, resulting in characteristic disruption to the transduction process. A contentious issue however, is whether or not the tip links can regenerate after rupture, since this would have a bearing on whether or not hearing damage caused by tip link rupture is temporary or permanent. In this project, performed in guinea pigs, the Ca2+ concentration surrounding stereocilia will lowered using the Ca2+ chelating agent BAPTA. A range of measures of cochlear function will be used to confirm loss of hearing. The animals will then be allowed to recover for varying periods before functional measurements are again taken to assess recovery. In addition, scanning electron microscopy and transmission electron microscopy will be used to evaluate the integrity of the stereocila tip links in these same cochleas.