Rho GTPases Mediate the Regulation of Cochlear Outer Hair Cell Motility by Acetylcholine

Outer hair cells are the mechanical effectors of the cochlear amplifier, an active process that improves the sensitivity and frequency discrimination of the mammalian ear. In vivo , the gain of the cochlear amplifier is regulated by the efferent neurotransmitter acetylcholine through the modulation...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-09, Vol.275 (36), p.28000-28005
Main Authors: Kalinec, F, Zhang, M, Urrutia, R, Kalinec, G
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Actins - physiology
Animals
cdc42 GTP-Binding Protein - metabolism
Cochlea - physiology
Cytoskeleton - drug effects
Cytoskeleton - physiology
Cytoskeleton - ultrastructure
Guinea Pigs
Hair Cells, Auditory - drug effects
Hair Cells, Auditory - physiology
In Vitro Techniques
Movement - drug effects
Movement - physiology
rac1 GTP-Binding Protein - metabolism
rho GTP-Binding Proteins - metabolism
rhoA GTP-Binding Protein - metabolism
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Summary:Outer hair cells are the mechanical effectors of the cochlear amplifier, an active process that improves the sensitivity and frequency discrimination of the mammalian ear. In vivo , the gain of the cochlear amplifier is regulated by the efferent neurotransmitter acetylcholine through the modulation of outer hair cell motility. Little is known, however, regarding the molecular mechanisms activated by acetylcholine. In this study, intracellular signaling pathways involving the small GTPases RhoA, Rac1, and Cdc42 have been identified as regulators of outer hair cell motility. Changes in cell length (slow motility) and in the amplitude of electrically induced movement (fast motility) were measured in isolated outer hair cells patch clamped in whole-cell mode, internally perfused through the patch pipette with different inhibitors and activators of these small GTPases while being externally stimulated with acetylcholine. We found that acetylcholine induces outer hair cell shortening and a simultaneous increase in the amplitude of fast motility through Rac1 and Cdc42 activation. In contrast, a RhoA- and Rac1-mediated signaling pathway induces outer hair cell elongation and decreases fast motility amplitude. These two opposing processes provide the basis for a regulatory mechanism of outer hair cell motility.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M004917200