Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti

Jun-Ping Bai,Joseph Santos-Sacchi,Dhasakumar Navaratnam

doi:10.1038/s41598-019-52965-1

Abstract

Several studies have documented the early development of OHC electromechanical behavior. The mechanical response (electromotility, eM) and its electrical correlate (nonlinear capacitance, NLC), resulting from prestin’s voltage-sensor charge movement, increase over the course of several postnatal days in altricial animals. They increase until about p18, near the time of peripheral auditory maturity. The correspondence of auditory capabilities and prestin function indicates that mature activity of prestin occurs at this time. One of the major requirements of eM is its responsiveness across auditory frequencies. Here we evaluate the frequency response of prestin charge movement in mice over the course of development up to 8 months. We find that in apical turn OHCs prestin’s frequency response increases during postnatal development and stabilizes when mature hearing is established. The low frequency component of NLC, within in situ explants, agrees with previously reported results on isolated cells. If prestin activity is independent of cochlear place, as might be expected, then these observations suggest that prestin activity somehow influences cochlear amplification at high frequencies in spite of its low pass behavior.

Highlights

Prestin drives outer hair cells (OHCs) electromotility, known to be responsible for cochlear amplification (CA) in mammals[7]
With our Boltzmann fit (Eq 1) we obtain the usual Boltzmann parameters while extracting nonlinear capacitance (NLC), and determine Csa, a component of capacitance that we believe arises from changes in membrane surface area or membrane thickness as prestin alters its conformational state across voltage[17,18,19,20]
The plots highlight a substantial roll-off of peak NLC across frequency, which we investigate in more detail further below

Summary

Introduction

Prestin drives OHC electromotility (eM), known to be responsible for cochlear amplification (CA) in mammals[7]. The electrical signature of eM is a bell-shaped nonlinear capacitance (NLC), the first derivative of prestin sensor charge vs membrane voltage (dQp/dVm), which peaks at a characteristic membrane voltage (Vh)[8,9]. We have previously studied the development of NLC in OHCs of the mouse[10]. Those studies demonstrated that increases in prestin charge (Qmax) continued after stabilization of linear capacitance (at p10), which corresponds to total membrane surface area (sum of membrane and embedded prestin surface area). Though the number of prestin molecules appeared to stabilize, additional changes in NLC characteristics ensued, indicating some sort of maturational events. Specific motor charge density (a metric for prestin density within the membrane) remains fairly constant

Methods

Results

Conclusion