Rate Dependent Cochlear Outer Hair Cell Force Generation: Models and Parameter Estimation

The outer hair cells (OHCs) of the mammalian cochlea are the mediators of an active, nonlinear electromechanical process necessary for sensitive, frequency specific hearing. The membrane protein prestin conveys to the OHC a piezoelectric-like behavior hypothesized to actuate a high frequency, cycle-by-cycle conversion of electrical to mechanical energy to boost cochlear responses to low-level sound. This hypothesis has been debated for decades, and we address two key remaining issues: the influence of the rate dependence of conformal changes in prestin and the OHC transmembrane impedance. We develop a theoretical electromechanical model of the OHC that explicitly includes rate dependence of conformal transitions, viscoelasticity, and piezoelectricity. Using this theory, we show the influence of rate dependence and viscoelasticity on electromechanical force generation. Further, we stress the importance of using the correct mechanical boundary conditions when estimating the transmembrane capacitance. Finally, a set of experiments is described to uniquely estimate the constitutive properties of the OHC from whole-cell measurements.