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

Nozomu Matsumoto, Rei Kitani, Anastasiya Maricle, Melissa Mueller, Federico Kalinec

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18 Citations (Scopus)

Abstract

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 phosphor- ylation 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.

Original languageEnglish
Pages (from-to)2067-2076
Number of pages10
JournalBiophysical Journal
Volume99
Issue number7
DOIs
Publication statusPublished - Oct 6 2010

All Science Journal Classification (ASJC) codes

  • Biophysics

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