Complex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension

Abstract

Outer hair cell (OHC) nonlinear capacitance (NLC) represents voltage sensor charge movements of prestin (SLC26a5), the protein responsible for OHC electromotility. Previous measures of NLC frequency response have employed methods which did not assess the influence of dielectric loss (sensor charge movements out of phase with voltage) that may occur, and such loss conceivably may influence prestin’s frequency dependent activity. Here we evaluate prestin’s complex capacitance out to 30 kHz and find that prestin’s frequency response determined using this approach coincides with all previous estimates. We also show that membrane tension has no effect on prestin’s frequency response, despite substantial shifts in its voltage operating range, indicating that prestin transition rate alterations do not account for the shifts. The magnitude roll-off of prestin activity across frequency surpasses the reductions of NLC caused by salicylate treatments that are known to abolish cochlear amplification. Such roll-off likely limits the effectiveness of prestin in contributing to cochlear amplification at the very high acoustic frequencies processed by some mammals.

The cochlear outer hair cell speed paradox

“…High-frequency experimental results of Frank et al ( 2 ) are reproduced in Fig. 2 A and B , and low-frequency roll-off of NLC reported by Santos-Sacchi and Tan ( 13 ) are reproduced in Fig. 3 D using exactly the same physics.…”

“…If the piezoelectric domain had zero compliance, it would not deform under load and Eq. 7 would predict zero frequency dependence of Re NLC, which is known not to be the case ( 13 ). The fact that is frequency dependent means the piezoelectric domain is compliant, and the magnitude of compliance can be estimated from the frequency dependence of NLC.…”

“…The present report is focused primarily on resolving the OHC speed paradox, a paradox most clearly exemplified by disparity between the ultrafast cycle-by-cycle isometric force generated by OHCs ( 2 ) vs. the slow low-pass-filtered characteristics of electrical charge displacement in OHC membranes ( 13 ). The paradox is resolved using first principles to show how the piezoelectric behavior of OHCs explains both results.…”

“…Evidence that OHCs can modulate voltage at auditory frequencies is compelling, but whether or not the motor mechanism can be driven by voltage cycle-by-cycle is less clear. Direct experimental measurement of electrical charge displacement and motility in OHCs and membrane patches suggests prestin-dependent electromotility is too slow to support cycle-by-cycle amplification ( 6 , 11 – 13 ).…”

“…The paradox is resolved by accounting for the reversible interplay between charge displacement, voltage, stress, and temperature using first principles set forth by Maxwell, Seebeck, Currie, and Newton. Results explain high-frequency force generation in isolated OHCs ( 2 ), low-pass nonlinear capacitance (NLC) in membrane patches ( 13 ), and OHC power output in the cochlea across the frequency bandwidth of hearing. Fundamental mechanisms are revealed through examination of load-dependent electrical charge displacement in the piezoelectric membrane complex.…”