Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig

Volodymyr Rybalchenko, Joseph Santos-Sacchi

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Outer hair cells underlie high frequency cochlear amplification in mammals. Fast somatic motility can be driven by voltage-dependent conformational changes in the motor protein, prestin, which resides exclusively within lateral plasma membrane of the cell. Yet, how a voltage-driven motor could contribute to high frequency amplification, despite the low-pass membrane filter of the cell, remains an enigma. The recent identification of prestin's Cl- sensitivity revealed an alternative mechanism in which intracellular Cl- fluctuations near prestin could influence the motor. We report the existence of a stretch-sensitive conductance within the lateral membrane that passes anions and cations and is gated at acoustic rates. The resultant intracellular Cl- oscillations near prestin may drive motor protein transitions, as evidenced by pronounced shifts in prestin's state-probability function along the voltage axis. The sensitivity of prestin's state probability to intracellular Cl- levels betokens a more complicated role for Cl- than a simple extrinsic voltage sensor. Instead, we suggest an allosteric modulation of prestin by Cl- and other anions. Finally, we hypothesize that prestin sensitivity to anion flux through the mechanically activated lateral membrane can provide a driving force that circumvents the membrane's low-pass filter, thus permitting amplification at high acoustic frequencies.

Original languageEnglish (US)
Pages (from-to)873-891
Number of pages19
JournalJournal of Physiology
Volume547
Issue number3
DOIs
StatePublished - Mar 15 2003

Fingerprint

Outer Auditory Hair Cells
Anions
Guinea Pigs
Acoustics
Membranes
Cell Membrane
Cochlea
Plasma Cells
Cations
Mammals
Proteins

ASJC Scopus subject areas

  • Physiology

Cite this

Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig. / Rybalchenko, Volodymyr; Santos-Sacchi, Joseph.

In: Journal of Physiology, Vol. 547, No. 3, 15.03.2003, p. 873-891.

Research output: Contribution to journalArticle

@article{cf1c50c0768841a9ac5c5642008a35e5,
title = "Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig",
abstract = "Outer hair cells underlie high frequency cochlear amplification in mammals. Fast somatic motility can be driven by voltage-dependent conformational changes in the motor protein, prestin, which resides exclusively within lateral plasma membrane of the cell. Yet, how a voltage-driven motor could contribute to high frequency amplification, despite the low-pass membrane filter of the cell, remains an enigma. The recent identification of prestin's Cl- sensitivity revealed an alternative mechanism in which intracellular Cl- fluctuations near prestin could influence the motor. We report the existence of a stretch-sensitive conductance within the lateral membrane that passes anions and cations and is gated at acoustic rates. The resultant intracellular Cl- oscillations near prestin may drive motor protein transitions, as evidenced by pronounced shifts in prestin's state-probability function along the voltage axis. The sensitivity of prestin's state probability to intracellular Cl- levels betokens a more complicated role for Cl- than a simple extrinsic voltage sensor. Instead, we suggest an allosteric modulation of prestin by Cl- and other anions. Finally, we hypothesize that prestin sensitivity to anion flux through the mechanically activated lateral membrane can provide a driving force that circumvents the membrane's low-pass filter, thus permitting amplification at high acoustic frequencies.",
author = "Volodymyr Rybalchenko and Joseph Santos-Sacchi",
year = "2003",
month = "3",
day = "15",
doi = "10.1113/jphysiol.2002.036434",
language = "English (US)",
volume = "547",
pages = "873--891",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Cl- flux through a non-selective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig

AU - Rybalchenko, Volodymyr

AU - Santos-Sacchi, Joseph

PY - 2003/3/15

Y1 - 2003/3/15

N2 - Outer hair cells underlie high frequency cochlear amplification in mammals. Fast somatic motility can be driven by voltage-dependent conformational changes in the motor protein, prestin, which resides exclusively within lateral plasma membrane of the cell. Yet, how a voltage-driven motor could contribute to high frequency amplification, despite the low-pass membrane filter of the cell, remains an enigma. The recent identification of prestin's Cl- sensitivity revealed an alternative mechanism in which intracellular Cl- fluctuations near prestin could influence the motor. We report the existence of a stretch-sensitive conductance within the lateral membrane that passes anions and cations and is gated at acoustic rates. The resultant intracellular Cl- oscillations near prestin may drive motor protein transitions, as evidenced by pronounced shifts in prestin's state-probability function along the voltage axis. The sensitivity of prestin's state probability to intracellular Cl- levels betokens a more complicated role for Cl- than a simple extrinsic voltage sensor. Instead, we suggest an allosteric modulation of prestin by Cl- and other anions. Finally, we hypothesize that prestin sensitivity to anion flux through the mechanically activated lateral membrane can provide a driving force that circumvents the membrane's low-pass filter, thus permitting amplification at high acoustic frequencies.

AB - Outer hair cells underlie high frequency cochlear amplification in mammals. Fast somatic motility can be driven by voltage-dependent conformational changes in the motor protein, prestin, which resides exclusively within lateral plasma membrane of the cell. Yet, how a voltage-driven motor could contribute to high frequency amplification, despite the low-pass membrane filter of the cell, remains an enigma. The recent identification of prestin's Cl- sensitivity revealed an alternative mechanism in which intracellular Cl- fluctuations near prestin could influence the motor. We report the existence of a stretch-sensitive conductance within the lateral membrane that passes anions and cations and is gated at acoustic rates. The resultant intracellular Cl- oscillations near prestin may drive motor protein transitions, as evidenced by pronounced shifts in prestin's state-probability function along the voltage axis. The sensitivity of prestin's state probability to intracellular Cl- levels betokens a more complicated role for Cl- than a simple extrinsic voltage sensor. Instead, we suggest an allosteric modulation of prestin by Cl- and other anions. Finally, we hypothesize that prestin sensitivity to anion flux through the mechanically activated lateral membrane can provide a driving force that circumvents the membrane's low-pass filter, thus permitting amplification at high acoustic frequencies.

UR - http://www.scopus.com/inward/record.url?scp=0037444687&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037444687&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2002.036434

DO - 10.1113/jphysiol.2002.036434

M3 - Article

C2 - 12562920

AN - SCOPUS:0037444687

VL - 547

SP - 873

EP - 891

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 3

ER -