TMC1 and TMC2 Are Components of the Mechanotransduction Channel in Hair Cells of the Mammalian Inner Ear

Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea. •Hair cells that express either Tmc1 or Tmc2 have distinct biophysical properties•A Tmc1 point mutation yields reduced calcium selectivity and single-channel current•TMC1 and TMC2 are components of the hair cell mechanotransduction channel•We propose TMC1 and TMC2 heteromultimerize to yield a range of channel properties Pan et al. assess the role of TMC1 and TMC2 in hair cell mechanotransduction and find that they contribute to mechanotransduction channel permeation properties. Their data support the proposal that TMC1 and TMC2 are components of the hair cell channel that converts mechanical information into electrical signals.