The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells.
Bottom Line: The Ca(2+)-dependent adaptation that adjusts the operating range of the channel was also impaired in Beethoven mutants, with reduced shifts in the relationship between MT current and hair bundle displacement for adapting steps or after lowering extracellular Ca(2+); these effects may be attributed to the channel's reduced Ca(2+) permeability.Moreover, the density of stereociliary CaATPase pumps for Ca(2+) extrusion was decreased in the mutant.The results suggest that a major component of channel adaptation is regulated by changes in intracellular Ca(2+).
Affiliation: Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706.Show MeSH
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Mentions: MT currents from OHCs of wild-type (Tmc1+/+) and littermate mutant (Tmc1Bth/Bth) Beethoven mice were recorded during hair bundle displacements with a piezoelectric fluid jet (Kros et al., 1992; Kim and Fettiplace, 2013). The maximum amplitude of the MT current was similar at least up to postnatal day (P) 9 in all genotypes tested, indicating that, unlike dn mutation in Tmc1 (Kim and Fettiplace, 2013), the Beethoven mutation does not impair mechanotransduction in apical OHCs. Because early on the bundles have a normal shape, a corollary is that the single–MT channel conductance was unaffected by the Beethoven mutation (Fig. 1, A–E). Although, as observed previously, there was an increase in OHC MT channel conductance from apex to base (Beurg et al., 2014, 2015), the conductance at neither location was reduced relative to wild type in Tmc1Bth/Bth. The basal values are most diagnostic, because they show a marked twofold reduction in the Tmc1−/− (Beurg et al., 2014), but here there was no significant difference between the wild-type and Beethoven mutant. There was also no effect of the Beethoven mutation on the MT channel conductance in IHCs (Fig. 1 E).
Affiliation: Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706.