Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein.
Outer hair cells (OHCs) of the mammalian cochlea actively change their cell length in response to changes in membrane potential. This electromotility, thought to be the basis of cochlear amplification, is mediated by a voltage-sensitive motor molecule recently identified as the membrane protein prestin. Here, we show that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well as the characteristic nonlinear charge movement ("gating currents") driving the underlying structural rearrangements of the protein. The results support a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule and thus trigger the conformational changes required for motility of OHCs.
Oliver
D
D
Department of Physiology II, University of Tübingen, 72074 Tübingen, Germany.
He
D Z
DZ
Klöcker
N
N
Ludwig
J
J
Schulte
U
U
Waldegger
S
S
Ruppersberg
J P
JP
Dallos
P
P
Fakler
B
B
D019943:Amino Acid Substitution; D000818:Animals; D027321:Anion Transport Proteins; D000838:Anions / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D016466:CHO Cells; D002412:Cations / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D006224:Cricetinae; D004553:Electric Conductivity; D004594:Electrophysiology; D018072:Hair Cells, Auditory, Outer / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; D000838:Anions; D001639:Bicarbonates; D002412:Cations; D002712:Chlorides; D011506:Proteins; C409207:Slc26a5 protein, rat; D000076988:Sulfate Transporters