Fast adaptation and Ca 2+ sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells

Ruben Stepanyan, Gregory I. Frolenkov

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 (Myol5 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 Myol5 sh2/sh2 mice lack myosin-XVa and are abnormally short, these cells have dramatically different hair bundle morphology. MyolS sh2/sh2 Outer hair cells retain a staircase arrangement of the abnormally short stereocilia and prominent tip links. Myol5 sh2/sh2inner 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 Myol5 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. In Myol5 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 Myol5 sh2/sh2 inner hair cells, but not in Myol5 sh2/sh2 outer hair cells.

Original languageEnglish
Pages (from-to)4023-4034
Number of pages12
JournalJournal of Neuroscience
Volume29
Issue number13
DOIs
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Neuroscience (all)

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