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      State dependent effects on the frequency response of prestin real and imaginary components of nonlinear capacitance

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          The outer hair cell (OHC) harbors the voltage dependent protein prestin (SLC26a5) in high density in its lateral membrane, where voltages sensed by its voltage-sensor are 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, 2020). However, we find similar behavior in a simple kinetic model of prestin that lacks piezoelectric coupling, the meno presto model. 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 intersection frequency; 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 evidences 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, indicative of diminishing total charge movement, poses a challenge for the role of prestin in cochlear amplification at very high frequencies.

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          14 December 2020


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          16 pages, 11 figures

          Molecular biology
          Molecular biology


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