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.
authors.affiliation: Department of Surgery (Otolaryngology), Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Rybalchenko
authors.forename: Joseph
authors.initials: J
authors.lastname: Santos-Sacchi
mesh_terms: D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000493:pharmacokinetics*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D025802:Electric Capacitance; D004553:Electric Conductivity; D005682:Gadolinium / Q000494:pharmacology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008627:Mercuric Chloride / Q000494:pharmacology; D017551:Microdialysis; D009544:Niflumic Acid / Q000494:pharmacology; D000442:Octanols / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D013451:Sulfonic Acids / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D000442:Octanols; C498722:Pres protein, Cavia porcellus; D011506:Proteins; D013451:Sulfonic Acids; D009544:Niflumic Acid; D008627:Mercuric Chloride; D005682:Gadolinium; D002229:Carbenoxolone