Mechanical Gating of the Auditory Transduction Channel TMC1 Involves the Fourth and Sixth Transmembrane Helices

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Jul 20

PMID 35857511

Authors

Nurunisa Akyuz

K Domenica Karavitaki

Bifeng Pan

Panos I Tamvakologos

Kelly P Brock

Yaqiao Li

Debora S Marks

David P Corey

Affiliations

Soon will be listed here.

Abstract

The transmembrane (TM) channel-like 1 (TMC1) and TMC2 proteins play a central role in auditory transduction, forming ion channels that convert sound into electrical signals. However, the molecular mechanism of their gating remains unknown. Here, using predicted structural models as a guide, we probed the effects of 12 mutations on the mechanical gating of the transduction currents in native hair cells of -null mice expressing virally introduced TMC1 variants. Whole-cell electrophysiological recordings revealed that mutations within the pore-lining TM4 and TM6 helices modified gating, reducing the force sensitivity or shifting the open probability of the channels, or both. For some of the mutants, these changes were accompanied by a change in single-channel conductance. Our observations are in line with a model wherein conformational changes in the TM4 and TM6 helices are involved in the mechanical gating of the transduction channel.

Citing Articles

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