The effects of Tmc1 Beethoven mutation on mechanotransducer channel function in cochlear hair cells

The Journal of General Physiology
Maryline BeurgRobert Fettiplace

Abstract

Sound stimuli are converted into electrical signals via gating of mechano-electrical transducer (MT) channels in the hair cell stereociliary bundle. The molecular composition of the MT channel is still not fully established, although transmembrane channel-like protein isoform 1 (TMC1) may be one component. We found that in outer hair cells of Beethoven mice containing a M412K point mutation in TMC1, MT channels had a similar unitary conductance to that of wild-type channels but a reduced selectivity for Ca(2+). 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+). Consistent with this idea, the adaptive shift in the current-displacement relationship when hair bundles were bathed in endolymph-like Ca(2+) saline was usually abolis...Continue Reading

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Citations

Jul 15, 2016·Biophysical Journal·Robert Fettiplace
Nov 29, 2016·Nature Neuroscience·Zizhen WuUlrich Mueller
Sep 22, 2017·The Journal of General Physiology·Osvaldo Alvarez, Ramon Latorre
Aug 30, 2017·Cold Spring Harbor Perspectives in Biology·Avinash JaiganeshMarcos Sotomayor
Oct 7, 2017·The Journal of Physiology·Maryline Beurg, Robert Fettiplace
Aug 8, 2018·Cold Spring Harbor Perspectives in Medicine·Christopher L Cunningham, Ulrich Müller
Oct 7, 2018·Cold Spring Harbor Perspectives in Medicine·David P CoreyJeffrey R Holt
Oct 5, 2019·Cellular and Molecular Life Sciences : CMLS·Xiaomin YueRui Xiao
Mar 14, 2020·Human Molecular Genetics·Zongwei ChenBrian M McDermott
Sep 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Maryline BeurgRobert Fettiplace
May 15, 2018·Frontiers in Cellular Neuroscience·Xufeng Qiu, Ulrich Müller
Apr 27, 2020·Hearing Research·Philipp NiggemannZheng-Yi Chen
Apr 20, 2021·Cellular and Molecular Life Sciences : CMLS·Shuang LiuWei Xiong
Dec 8, 2020·Annual Review of Biophysics·Wang Zheng, Jeffrey R Holt
Aug 20, 2021·The Journal of General Physiology·Maryline BeurgRobert Fettiplace
Sep 14, 2021·Frontiers in Cell and Developmental Biology·Anthony W PengAnthony J Ricci
Oct 8, 2021·Journal of the Association for Research in Otolaryngology : JARO·Jeffrey R HoltTeresa Nicolson

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