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

J Physiol. 2003 Mar 15;547(Pt 3):873-91. doi: 10.1113/jphysiol.2002.036434. Epub 2003 Jan 31.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbenoxolone / pharmacology
  • Cell Membrane / metabolism
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / metabolism
  • Chlorides / pharmacokinetics*
  • Cyclooxygenase Inhibitors / pharmacology
  • Electric Capacitance
  • Electric Conductivity
  • Gadolinium / pharmacology
  • Guinea Pigs
  • Hair Cells, Auditory, Outer / metabolism*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Mechanotransduction, Cellular / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mercuric Chloride / pharmacology
  • Microdialysis
  • Niflumic Acid / pharmacology
  • Octanols / pharmacology
  • Proteins / metabolism
  • Sulfonic Acids / metabolism

Substances

  • Chloride Channels
  • Chlorides
  • Cyclooxygenase Inhibitors
  • Octanols
  • Pres protein, Cavia porcellus
  • Proteins
  • Sulfonic Acids
  • Niflumic Acid
  • Mercuric Chloride
  • Gadolinium
  • Carbenoxolone