title: Fast adaptation and Ca2+ sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells.
abstract: In inner ear hair cells, activation of mechanotransduction channels is followed by extremely rapid deactivation that depends on the influx of Ca(2+) through these channels. Although the molecular mechanisms of this "fast" adaptation are largely unknown, the predominant models assume Ca(2+) sensitivity as an intrinsic property of yet unidentified mechanotransduction channels. Here, we examined mechanotransduction in the hair cells of young postnatal shaker 2 mice (Myo15(sh2/sh2)). These mice have no functional myosin-XVa, which is critical for normal growth of mechanosensory stereocilia of hair cells. Although stereocilia of both inner and outer hair cells of Myo15(sh2/sh2) mice lack myosin-XVa and are abnormally short, these cells have dramatically different hair bundle morphology. Myo15(sh2/sh2) outer hair cells retain a staircase arrangement of the abnormally short stereocilia and prominent tip links. Myo15(sh2/sh2) inner hair cells do not have obliquely oriented tip links, and their mechanosensitivity is mediated exclusively by "top-to-top" links between equally short stereocilia. In both inner and outer hair cells of Myo15(sh2/sh2) mice, we found mechanotransduction responses with a normal "wild-type" amplitude and speed of activation. Surprisingly, only outer hair cells exhibit fast adaptation and sensitivity to extracellular Ca(2+). In Myo15(sh2/sh2) inner hair cells, fast adaptation is disrupted and the transduction current is insensitive to extracellular Ca(2+). We conclude that the Ca(2+) sensitivity of the mechanotransduction channels and the fast adaptation require a structural environment that is dependent on myosin-XVa and is disrupted in Myo15(sh2/sh2) inner hair cells, but not in Myo15(sh2/sh2) outer hair cells.
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Stepanyan
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov