Electrophysiological Recordings of Voltage-Dependent and Mechanosensitive Currents in Sensory Hair Cells of the Auditory and Vestibular Organs of the Mouse

Indzhykulian, Artur A.; Johnson, Stuart L.; Géléoc, Gwenaëlle S. G.

doi:10.1007/978-1-0716-2022-9_10

Cited by 1 publication

(1 citation statement)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used an AAV (adeno-associated virus) gene delivery approach (3) to express mutant TMC1 channels in hair cells of Tmc1/2 double-knockout (DKO) mice. We then recorded currents from cochlear hair cells while simultaneously stimulating them with probes to deflect stereocilia (14). Comparing the mechanical activation curves of mutated TMC1 channels with those of wild-type (WT)-TMC1, we provide evidence for a model of transduction wherein conformational changes involving TM4 and TM6 of TMC1 are critical for channel opening induced by hair bundle deflection.…”

Section: Introductionmentioning

confidence: 99%

Mechanical gating of the auditory transduction channel TMC1 involves the fourth and sixth transmembrane helices

et al. 2022

View full text Add to dashboard Cite

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 Tmc1/2 -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.

show abstract

Section: Introductionmentioning

confidence: 99%