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ROCK-dependent and ROCK-independent Control of Cochlear Outer Hair Cell Electromotility
- Source :
- Journal of Biological Chemistry. 278:35644-35650
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Outer hair cell electromotility is crucial for the proper function of the cochlear amplifier, the active process that enhances sensitivity and frequency discrimination of the mammalian ear. Previous work (Kalinec, F., Zhang, M., Urrutia, R., and Kalinec, G. (2000) J. Biol. Chem. 275, 28000-28005) has suggested a role for Rho GTPases in the regulation of outer hair cell electromotility, although the signaling pathways mediated by these enzymes remain to be established. Here we have investigated the cellular and molecular mechanisms underlying the homeostatic regulation of the electromotile response of guinea pig outer hair cells. Our findings defined a ROCK-mediated signaling cascade that continuously modulates outer hair cell electromotility by selectively targeting the cytoskeleton. A distinct ROCK-independent pathway functions as a fast resetting mechanism for this system. Neither pathway affects the function of prestin, the unique molecular motor of outer hair cells. These results extend our understanding of a basic mechanism of both normal human hearing and deafness, revealing the key role of the cytoskeleton in the regulation of outer hair cell electromotility and suggesting ROCK as a molecular target for modulating the function of the cochlear amplifier.
- Subjects :
- Cochlear amplifier
Patch-Clamp Techniques
Pyridines
Guinea Pigs
Protein Serine-Threonine Kinases
Biology
Models, Biological
Biochemistry
Membrane Potentials
Cell Movement
otorhinolaryngologic diseases
Molecular motor
medicine
Animals
Patch clamp
Enzyme Inhibitors
Cytoskeleton
Prestin
Molecular Biology
rho-Associated Kinases
Intracellular Signaling Peptides and Proteins
Cell Biology
Anatomy
Amides
Immunohistochemistry
Acetylcholine
Cell biology
Electrophysiology
Hair Cells, Auditory, Outer
Kinetics
medicine.anatomical_structure
biology.protein
Calmodulin-Binding Proteins
sense organs
Hair cell
Signal transduction
Function (biology)
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 278
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....523334a923da2fa80326a668a2ab4f7b