The objective of the research in this proposal is to understand the molecular mechanism of outer hair cell electromotility. This unique form of cellular motility is responsible for the remarkable sensitivity and exquisite frequency selectivity of mammalian hearing. Loss of electromotility is believed to be responsible for sensioneural hearing loss. Until we understand the molecular mechanism of electromotility, we will be powerless to undertake any clinical efforts to treat people suffering from hearing impairment. The research in this proposal plans to test the novel hypothesis that changes in membrane curvature are responsible for the electromechanical coupling process. This will be accomplished experimentally by testing the effects of various agents known to affect the ability of a membrane to bend on the outer hair cell's voltage dependent capacitance and motility. A theoretical model of electromotility will be developed which includes an analytic expression for the curvature elastic energy. This model will be used to predict the shift in the nonlinear capacitance with membrane tension. The model will also be used to predict the capacitance change expected from membrane bending which will be calculated from the Poisson- Boltzmann equation and membrane electrostatic theory.
