Pivotal role of actin depolymerization in the regulation of cochlear outer hair cell motility

Biophys J. 2010 Oct 6;99(7):2067-76. doi: 10.1016/j.bpj.2010.08.015.


Cochlear outer hair cells undergo reversible changes in shape when externally stimulated. This response, known as OHC motility, is a central component of the cochlear amplifier, the mechanism responsible for the high sensitivity of mammalian hearing. We report that actin depolymerization, as regulated by activation/inhibition of LIMK/cofilin-mediated pathways, has a pivotal role in OHC motility. LIMK-mediated cofilin phosphorylation, which inhibits the actin depolymerizing activity of this protein, increases both electromotile amplitude and total length of guinea pig OHCs. In contrast, a decrease in cofilin phosphorylation reduces both OHC electromotile amplitude and OHC length. Experiments with acetylcholine and lysophosphatidic acid indicate that the effects of these agents on OHC motility are associated with regulation of cofilin phosphorylation via different signaling cascades. On the other hand, nonlinear capacitance measurements confirmed that all observed changes in OHC motile response were independent of the performance of the motor protein prestin. Altogether, these results strongly support the hypothesis that the cytoskeleton has a major role in the regulation of OHC motility, and identify actin depolymerization as a key process for modulating cochlear amplification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism*
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Movement* / drug effects
  • Cell Separation
  • Guinea Pigs
  • Hair Cells, Auditory, Outer / cytology*
  • Hair Cells, Auditory, Outer / drug effects
  • Hair Cells, Auditory, Outer / enzymology
  • Hair Cells, Auditory, Outer / metabolism*
  • Lim Kinases / metabolism
  • Lysophospholipids / pharmacology
  • Models, Biological
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Receptors, Lysophosphatidic Acid / metabolism
  • Signal Transduction / drug effects
  • Thiazolidines / pharmacology
  • rho-Associated Kinases / metabolism


  • Actin Depolymerizing Factors
  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • Thiazolidines
  • Lim Kinases
  • rho-Associated Kinases
  • Acetylcholine
  • lysophosphatidic acid
  • latrunculin A