title: Mechanotransduction current is essential for stability of the transducing stereocilia in mammalian auditory hair cells.
abstract: Mechanotransducer channels at the tips of sensory stereocilia of inner ear hair cells are gated by the tension of 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links are tensioned at rest, resulting in a continuous influx of Ca2+into the cell. Here, we show that this constitutive Ca2+influx, usually considered as potentially deleterious for hair cells, is in fact essential for stereocilia stability. In the auditory hair cells of young postnatal mice and rats, a reduction in mechanotransducer current, via pharmacological channel blockers or disruption of tip links, leads to stereocilia shape changes and shortening. These effects occur only in stereocilia that harbor mechanotransducer channels, recover upon blocker washout or tip link regeneration and can be replicated by manipulations of extracellular Ca2+or intracellular Ca2+buffering. Thus, our data provide the first experimental evidence for the dynamic control of stereocilia morphology by the mechanotransduction current.
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States.
authors.forename: A Catalina
authors.identifier: 0000-0001-9157-8390
authors.initials: AC
authors.lastname: Vélez-Ortega
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Freeman
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States.
authors.forename: Artur A
authors.initials: AA
authors.lastname: Indzhykulian
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grossheim
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, United States.
authors.forename: Gregory I
authors.identifier: 0000-0002-9810-5024
authors.initials: GI
authors.lastname: Frolenkov
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000502:physiology* / Q000648:ultrastructure*; D040542:Mechanotransduction, Cellular; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D017207:Rats, Sprague-Dawley; D059547:Stereocilia / Q000502:physiology* / Q000648:ultrastructure*
chemical_list: D002118:Calcium
keywords: actin; calcium; cell biology; deafness; hair cells; mechanotransduction; mouse; neuroscience; rat; stereocilia