Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea

Maryline Beurg, Runjia Cui, Adam C. Goldring, Seham Ebrahim, Robert Fettiplace () and Bechara Kachar ()
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Maryline Beurg: University of Wisconsin School of Medicine and Public Health
Runjia Cui: National Institutes of Health
Adam C. Goldring: University of Wisconsin School of Medicine and Public Health
Seham Ebrahim: National Institutes of Health
Robert Fettiplace: University of Wisconsin School of Medicine and Public Health
Bechara Kachar: National Institutes of Health

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Functional mechanoelectrical transduction (MET) channels of cochlear hair cells require the presence of transmembrane channel-like protein isoforms TMC1 or TMC2. We show that TMCs are required for normal stereociliary bundle development and distinctively influence channel properties. TMC1-dependent channels have larger single-channel conductance and in outer hair cells (OHCs) support a tonotopic apex-to-base conductance gradient. Each MET channel complex exhibits multiple conductance states in ~50 pS increments, basal MET channels having more large-conductance levels. Using mice expressing fluorescently tagged TMCs, we show a three-fold increase in number of TMC1 molecules per stereocilium tip from cochlear apex to base, mirroring the channel conductance gradient in OHCs. Single-molecule photobleaching indicates the number of TMC1 molecules per MET complex changes from ~8 at the apex to ~20 at base. The results suggest there are varying numbers of channels per MET complex, each requiring multiple TMC1 molecules, and together operating in a coordinated or cooperative manner.

Date: 2018
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DOI: 10.1038/s41467-018-04589-8

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