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

Abstract The 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 th...

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Autores principales:	Joseph Santos-Sacchi, Dhasakumar Navaratnam, Winston J. T. Tan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15b01af71fc947e1adf3bda8067adf74
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spelling	oai:doaj.org-article:15b01af71fc947e1adf3bda8067adf742021-12-02T19:06:35ZState dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance10.1038/s41598-021-95121-42045-2322https://doaj.org/article/15b01af71fc947e1adf3bda8067adf742021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95121-4https://doaj.org/toc/2045-2322Abstract The 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.Joseph Santos-SacchiDhasakumar NavaratnamWinston J. T. TanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joseph Santos-Sacchi Dhasakumar Navaratnam Winston J. T. Tan State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
description	Abstract The 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.
format	article
author	Joseph Santos-Sacchi Dhasakumar Navaratnam Winston J. T. Tan
author_facet	Joseph Santos-Sacchi Dhasakumar Navaratnam Winston J. T. Tan
author_sort	Joseph Santos-Sacchi
title	State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
title_short	State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
title_full	State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
title_fullStr	State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
title_full_unstemmed	State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
title_sort	state dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/15b01af71fc947e1adf3bda8067adf74
work_keys_str_mv	AT josephsantossacchi statedependenteffectsonthefrequencyresponseofprestinsrealandimaginarycomponentsofnonlinearcapacitance AT dhasakumarnavaratnam statedependenteffectsonthefrequencyresponseofprestinsrealandimaginarycomponentsofnonlinearcapacitance AT winstonjttan statedependenteffectsonthefrequencyresponseofprestinsrealandimaginarycomponentsofnonlinearcapacitance
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State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance

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