AbstractThe outer hair cell (OHC) membrane harbors a voltage-dependent protein, prestin (SLC26a5), in high density, whose charge movement is evidenced as a nonlinear capacitance (NLC). NLC is bell-shaped, with its peak occurring at a voltage, Vh, where sensor charge is equally distributed across the plasma membrane. Thus, Vh provides information on the conformational state of prestin. Vh is sensitive to membrane tension, shifting to positive voltage as tension increases and is the basis for considering prestin piezoelectric (PZE). NLC can be deconstructed into real and imaginary components that report on charge movements in phase or 90 degrees out of phase with AC voltage. Here we show in membrane macro-patches of the OHC that there is a partial trade-off in the magnitude of real and imaginary components as interrogation frequency increases, as predicted by a recent PZE model (Rabbitt in Proc Natl Acad Sci USA 17:21880–21888, 2020). However, we find similar behavior in a simple 2-state voltage-dependent kinetic model of prestin that lacks piezoelectric coupling. At a particular frequency, Fis, the complex component magnitudes intersect. Using this metric, Fis, which depends on the frequency response of each complex component, we find that initial Vh influences Fis; thus, by categorizing patches into groups of different Vh, (above and below − 30 mV) we find that Fis is lower for the negative Vh group. We also find that the effect of membrane tension on complex NLC is dependent, but differentially so, on initial Vh. Whereas the negative group exhibits shifts to higher frequencies for increasing tension, the opposite occurs for the positive group. Despite complex component trade-offs, the low-pass roll-off in absolute magnitude of NLC, which varies little with our perturbations and is indicative of diminishing total charge movement, poses a challenge for a role of voltage-driven prestin in cochlear amplification at very high frequencies.
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