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

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.

SUBMITTER: Beurg M 

PROVIDER: S-EPMC5988745 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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

Beurg Maryline M   Cui Runjia R   Goldring Adam C AC   Ebrahim Seham S   Fettiplace Robert R   Kachar Bechara B  

Nature communications 20180605 1

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 ~  ...[more]