Rate dependence in outer hair cell mediated active processes: Determining Prestin’s Speed Limit

Abstract

The electromotility of the outer hair cell (OHC) contributes to the sensitivity of the mammalian cochlea by amplifying traveling waves through electrical-to-mechanical energy conversion realized at the molecular level by an electromotile protein called prestin. Rate-dependent effects, including viscous damping, transmembrane electrical impedance, and state-dependent conformal transitions, hold the potential to attenuate OHC-mediated active processes at high frequencies thereby rendering prestin ineffective in high frequency cycle-by-cycle amplification. Determining the upper frequency limit of prestin remains a central challenge in cochlear biophysics. In this study, we will build a simplified OHC model to explore the influence of the rate dependence on active force generation and power deposition. Through numerical investigations, the proposed model can be used to model charge and electromotility data from in vitro experiments, but subtle variations in the rate parameters significantly change the predictions of electromechanical force as well as the power deposition. Based on these theoretical considerations, we propose an experimental approach to consistently determine the rate dependence and other OHC response parameters by characterizing the electrical and mechanical behavior about a resting position. This approach holds the potential to conclusively determine the upper frequency limit of prestin under physiological resting conditions.