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Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5.


ABSTRACT: Outer hair cells (OHCs) drive cochlear amplification that enhances our ability to detect and discriminate sounds. The motor protein, prestin, which evolved from the SLC26 anion transporter family, underlies the OHC's voltage-dependent mechanical activity (eM). Here we report on simultaneous measures of prestin's voltage-sensor charge movement (nonlinear capacitance, NLC) and eM that evidence disparities in their voltage dependence and magnitude as a function of intracellular chloride, challenging decades' old dogma that NLC reports on eM steady-state behavior. A very simple kinetic model, possessing fast anion-binding transitions and fast voltage-dependent transitions, coupled together by a much slower transition recapitulates these disparities and other biophysical observations on the OHC. The intermediary slow transition probably relates to the transporter legacy of prestin, and this intermediary gateway, which shuttles anion-bound molecules into the voltage-enabled pool of motors, provides molecular delays that present as phase lags between membrane voltage and eM. Such phase lags may help to effectively inject energy at the appropriate moment to enhance basilar membrane motion.

SUBMITTER: Song L 

PROVIDER: S-EPMC3593883 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5.

Song Lei L   Santos-Sacchi Joseph J  

Proceedings of the National Academy of Sciences of the United States of America 20130219 10


Outer hair cells (OHCs) drive cochlear amplification that enhances our ability to detect and discriminate sounds. The motor protein, prestin, which evolved from the SLC26 anion transporter family, underlies the OHC's voltage-dependent mechanical activity (eM). Here we report on simultaneous measures of prestin's voltage-sensor charge movement (nonlinear capacitance, NLC) and eM that evidence disparities in their voltage dependence and magnitude as a function of intracellular chloride, challengin  ...[more]

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